Handbook of Clinical Neurology, Vol. 121 (3rd series) Neurologic Aspects of Systemic Disease Part III Jose Biller and Jose M. Ferro, Editors © 2014 Elsevier B.V. All rights reserved

Chapter 107

Iatrogenic neurology LUCIANO A SPOSATO1 AND OSVALDO FUSTINONI2,3* Department of Clinical Neurological Sciences, London Health Sciences Centre, University of Western Ontario, London, Ontario, Canada


2 3

INEBA Institute of Neurosciences, Buenos Aires, Argentina

Faculty of Medicine, University of Buenos Aires, Buenos Aires, Argentina

INTRODUCTION Disease due to healthcare interventions is an important clinical problem that has remained unchanged for decades (Darchy et al., 1999). Iatrogenic disease due to drugs (60%), surgical (22%) and medical acts (18%) accounts for more than 12% of admissions in intensive care, with a 13% fatality rate and important financial costs, and equals noniatrogenic disease in severity, mortality, and length of stay. Advanced age and the number of prescribed drugs are the salient risk factors, with a rate of preventable disease of 51% (Darchy et al., 1999). Although iatrogenic neurologic disease may be more devastating due to the higher potential irreversibility of nervous system involvement, it has only been addressed in more recent years (Biller, 1998). This chapter will describe iatrogenic neurologic adverse effects and disorders induced by the administration of pharmacological agents prescribed for the clinical treatment and prevention of medical disease.

NEUROLOGIC ADVERSE EFFECTS OF CARDIOVASCULAR AND ANTITHROMBOTIC DRUGS Antihypertensive agents Aggressive blood pressure lowering in the course of stroke or malignant hypertension may induce neurologic worsening by hypoperfusion of brain ischemic areas (Choi et al., 2008). Current AHA/ASA Guidelines for early stroke management recommend “a cautious approach

to the treatment of arterial hypertension (Class I, Level of Evidence C),” and that “medications should be withheld unless the systolic blood pressure is greater than 220 mm Hg or the diastolic blood pressure less than 120 mm Hg (Class I, Level of Evidence C) (Adams et al., 2007). b-Adrenergic blockers often induce bradycardia and consequent symptoms of low cerebral blood flow (somnolence, unsteadiness, blurred vision, confusion, syncope). All other antihypertensive drugs may cause similar symptoms as a consequence of relative hypotension, which may appear even at therapeutic doses if the patient’s cerebral blood flow autoregulation curve is shifted to the right. Other less frequent and specific neurologic adverse effects of the most commonly used antihypertensive agents appear in Table 107.1. The neurologic side-effects of diuretics are almost invariably caused by their effect on electrolyte metabolism, such as hyponatremia (seizures and encephalopathy), hypokalemia (hypokalemic periodic paralysis), hyperkalemia (hyperkalemic periodic paralysis in the case of potassium-sparing agents such as spironolactone), and hypomagnesemia (myalgias, muscle cramps, tetany, carpopedal spasm, seizures). More specifically, loop diuretics and distal convoluted tubule agents (thiazides), produce hypokalemic, hypochloremic, metabolic alkalosis that responds to potassium chloride, and hyponatremia, which may cause permanent neurologic damage. Dose-related reversible or irreversible ototoxicity may complicate treatment with loop agents. Carbonic anhydrase inhibitors

*Correspondence to: Osvaldo Fustinoni, M.D., Professor of Neurology, Buenos Aires University Medical School, Chief, Cerebrovascular Diseases, INEBA - Instituto de Neurociencias, Buenos Aires, Guardia Vieja 4435, C1192AAW Buenos Aires Argentina. Tel/Fax: þ54-11-4867-7700/7735, 4805-8897, E-mail: [email protected]



Table 107.1 Neurologic adverse effects of most commonly used antihypertensive agents Group


Adverse effects

a-Adrenergic blockers


b-Adrenergic blockers

Propranolol Atenolol

Cataplexy in narcoleptics (Guilleminault et al., 1988) Myotonia (Satya-Murti et al., 1977) Delirium (Arber, 1988) Visual effects (Kummar and Clooney, 1990) Fulminant myasthenia gravis (Confavreux et al., 1990) Rhabdomyolysis (Willis et al., 1990) Tingling and micturition impairment (Bailey, 1977) Delirium (Hoffmann and Ladogana, 1981) Myalgias (Schwarz, 1987) Parkinsonism and chorea (Yamadori and Albert, 1972) Myoclonic dystonia (De Medina et al., 1986) Magnesium sulphate neuromuscular blockade worsening (Snyder and Cardwell, 1989) Myopathy (Phillips and Muller, 1998) Parkinsonism (Teive et al., 2002) Parkinsonism (Dick and Barold, 1989) Myoclonus (Jeret et al., 1992) Myopathy (Ahmad, 1993) Lambert–Eaton syndrome (Ueno and Hara, 1992) Parkinsonism (Padrell et al., 1995) Worsening of neuromuscular diseases (Swash and Ingram, 1992) Carbamazepine toxicity (Macphee et al., 1986) Peripheral neuropathy (Hormigo and Alves, 1992) Pseudopolymyalgia rheumatica (Leloe¨t et al., 1989) Parkinsonism (Sarma et al., 2008) Delirium, encephalopathy, thiocyanate poisoning (Harmon and Wohlreich, 1995)

Acebutolol Labetalol a2-Adrenergic agonists

Clonidine Methyldopa

Calcium channel blockers


Amlodipine Diltiazem


Angiotensin-converting enzyme inhibitors Angiotensin receptor blockers Vasodilators

Enalapril Losartan Sodium nitroprusside

(acetazolamide) produce less hypokalemia and volume depletion but commonly induce often symptomatic metabolic acidosis. The potassium-sparing agents also limit proton excretion, and spironolactone may produce metabolic acidosis (Greenberg, 2000).

Antiarrythmics, inotropes, and coronary artery dilators The various neurologic adverse effects of antiarrythmics are thought to be a consequence of their interference with central or peripheral nervous conduction. Cardiac inotropes influence the force of myocardial muscular contraction, either by increasing it (positive inotropes), or decreasing it (negative inotropes). Common positive inotropes include glycosides (digitalis) and catecholamines (dopamine, dobutamine, isoproterenol, adrenaline/epinephrine and noradrenaline/ norepinephrine). Negative inotropes include diltiazem,

verapamil, quinidine, procainamide and flecainide, all antiarrythmic agents as well. Coronary vasodilators are mainly represented by nitroglycerin-derived nitrates, which are potent vasodilators and may also decrease blood pressure (nitroprusside). The frequent headaches induced by nitrates are attributed to associated vasodilation of the intracranial vessels. The neurotoxic effects of the most commonly used antiarrythmics, inotropes, and coronary artery dilators are listed in Table 107.2.

Antilipemic drugs: HMG-CoA reductase inhibitors (statins) and other antilipemic drugs The most salient and severe side-effect of statins is rhabdomyolysis, thought to be due to increased membrane fluidity caused by reduction of the cholesterol content of the sarcolemmal phospholipid bilayer. Myalgias occur in less than 1%, and severe myopathy in less than 0.1% of



Table 107.2 Neurologic adverse effects of most commonly used antiarrythmics, inotropes and coronary artery dilators Group


Adverse effects



Peripheral neuropathy (Fraser et al., 1985) Myopathy (Roth et al., 1990) Optic neuropathy (Feiner et al., 1987) Pseudotumor cerebri (Grogan and Narkun, 1987) Parkinsonism and movement disorders (Werner and Olanow, 1989) Ataxia (Krauser et al., 2005) Peripheral neuropathy (Palace et al., 1992) Dystonia (Miller and Jankovic, 1992) Neuromuscular weakness (Ferrick and Power, 1990) Seizures (Kennedy et al., 1989) Dysarthria and visual hallucinations (Ramhamadany et al., 1986) Ataxic-myoclonic encephalopathy (Ghika et al., 1994) Seizures and encephalopathy (Crampton and Oriscello, 1968) “Doom anxiety” and delirium (Saravay et al., 1987) Tremor, ataxia, diplopia, blurred vision, visual hallucinations (Campbell, 1987) “Cinchonism”: headache, flushing, mydriasis, visual changes (Fisher, 1981) Myasthenia gravis worsening (also with propafenone and procainamide) (Kornfield et al., 1976) Delirium (Marriott, 1968) Photopsias (Oishi et al., 2006) Dyschromatopsias, acquired color vision deficiency (Lawrenson et al., 2002) Visual acuity decrease (Nagai et al., 2001) Trigeminal neuralgia (Bernat and Sullivan, 1979) Chorea (Wedzicha et al., 1984) Bilateral retinal infarction (Opremcak and Davidorf, 1985) Headache (Mueller and Meienberg, 1983) Intracranial hypertension (Ahmad, 1991)


Lidocaine Mexiletine Quinidine


Glycosides (digitalis) Dopamine

Coronary artery vasodilators


patients treated. Risk factors for myopathy are advanced age, impaired general or nutritional status, comorbidities, intercurrent surgery, and associated treatment with multiple medications. Associated drugs or nutrients that increase the risk include fibrates, nicotinamide, ciclosporin, azoles, macrolid antibiotics, erythromycin, clarithromycin, HIV-protease inhibitors, nefazodone, verapamil, amiodarone, alcohol, grapefruit juice. This is due to their interaction with cytochrome P450 and other hepatic uptake transporters which also metabolize statins (Neuvonen et al., 2006). Serum lipid, creatine kinase (CK) levels, and hepatic function should be assessed before starting treatment. Patients should be monitored for the risk of rhabdomyolysis with clinical follow-up, serum CK and thyroid-stimulating hormone (TSH) levels, especially if muscle symptoms develop. Statins should be discontinued if CK normal levels increase beyond 10 times The intensity of cytotoxicity, which is independent of their cholesterol-lowering effect, has been described as high for cerivastatin and simvastatin, intermediate for atorvastatin, and low for rosuvastatin and pravastatin The incidence of rhabdomyolisis is higher

with statins oxidized by cytochrome P450 3A4 (CYP3A4), such as simvastatin or atorvastatin, than with those not oxidized by CYP3A4, such as pravastatin or fluvastatin. In large systematic reviews, there is no excess of hepatic, renal, or cerebral disease with statins, although an increased incidence of peripheral neuropathy has been reported (Law and Rudnicka, 2006). Less common neurologic adverse effects of statins and other antilipemic drugs are listed in Table 107.3.

Thrombolytics The most salient neurologic complication of thrombolytic therapy, whether indicated for cardiovascular or cerebrovascular disease, is intracranial hemorrhage (IH). Ischemic stroke (IS) may also occur. The average frequency of stroke after therapeutic thrombolysis for noncerebral thrombotic disease, mainly acute myocardial infarction (AMI), was not higher than 2.5% in the 1990s (Sloan, 1998), and has since decreased. Several thrombolytic agents have been implicated:



Table 107.3 Other neurologic adverse effects of most commonly used antilipemic drugs Group


Adverse effects

HMG-CoA reductase inhibitors (statins)

Lovastatin Pravastatin Simvastatin Clofibrate Gemfibrozil Ezetimibe

Parkinsonism (Muller et al., 1995) Mitochondrial myopathy (England et al., 1995) Mitochondrial myopathy, MELAS (Chariot et al., 1993) Myopathy, cardiomyopathy (Smals et al., 1977) Myopathy (Magarian et al., 1991) Myopathy (Havranek et al., 2006) Polymyositis (Garcı´a-Valladares and Espinoza, 2010)

Fibrates Cholesterol intestinal absorption inhibitors

streptokinase (SK), recombinant tissue plasminogen activator (rt-PA, alteplase), reteplase, tenecteplase, and others. A higher stroke risk has been reported for alteplase and reteplase, with no difference in overall mortality (Dundar et al., 2003). Risk factors for IH after cardiac thrombolysis include age, hypertension, type and dosage of thrombolytic agent, associated antithrombotic therapy, prior cranial trauma and prior cerebrovascular disease, and for IS, age, hypertension, prior coronary artery disease or bypass graft (CABG), diabetes, and prior stroke. The American College of Chest Physicians has recommended against the administration of thrombolytic therapy in patients with AMI and with any history of intracranial hemorrhage, closed head trauma, or ischemic stroke within the previous 3 months (Menon et al., 2004). Thrombolysis administered for IS is associated with a higher rate of intracerebral hemorrhage (ICH), due to the intrinsic risk of spontaneous hemorrhagic transformation of the cerebral infarct (hemorrhagic infarction). Currently, rt-PA is the only approved thrombolytic agent for acute IS. Streptokinase is not recommended due to its high risk of ICH and death. Urokinase did not attain FDA approval status in the US. Other agents for the specific treatment of ischemic stroke are under investigation. By intravenous (systemic) infusion, rt-PA has been approved worlwide for the treatment of acute IS up to 4.5 hours from its onset, and is beneficial under strict inclusion/exclusion criteria (Del Zoppo et al., 2009). The treatment carries nevertheless a 10-fold higher risk of symptomatic ICH (overall risk around 5%, varying on the definitions used). If the established inclusion/ exclusion criteria are not met, the risk is higher. There is, however, no increase in mortality. Other less common complications of thrombolytic therapy are spinal epidural hematoma (Sawin et al., 1995), low back pain (Fishwick et al., 1995), angioneurotic orolingual edema (Hill et al., 2000), Guillain–Barre´ syndrome (Barnes and Hughes, 1992) and neuromuscular complications due to local hematoma (Cadman, 1995).

Anticoagulants Bleeding is the salient risk of any anticoagulant therapy, and ICH is the most frequent severe bleeding complication of anticoagulation.

HEPARINS AND HEPARINOIDS In acute stroke, subcutaneous unfractionated heparin (UFH) significantly decreases its recurrence, but causes a threefold increase in ICH (IST Collaborative Group, 1997). Consequently, heparin and urgent anticoagulation in general are currently not recommended for the treatment of acute stroke (Adams et al., 2007). The ICH risk of intavenous heparin for the treatment of AMI and deep vein thrombosis is less than 1% (Handley et al., 1972). Heparin may cause thrombocytopenia. Late heparininduced thrombocytopenia (HIT), appearing several days after initiation of treatment and often undiagnosed, may result in secondary platelet activation causing venous and arterial thrombotic events (Otis and Zehnder, 2010). Alternative nonheparin anticoagulants that inhibit thrombin directly, such as argatroban and lepirudin, are approved treatment options for HIT (Hook and Abrams, 2010). Other agents are under study. In the prevention of deep vein thrombosis and venous thromboembolism, low molecular weight heparins (LMWH) (enoxaparin, dalteparin, nadroparin, ardeparin, certoparin), compared to UFH, significantly reduce thrombosis, major hemorrhage, and mortality. Although hemorrhage with LMWH can still occur, fixed dose LMWH is more effective and safer than adjusted dose UFH in this setting (Erkens and Prins, 2010).

COUMARINS Coumarin drugs (warfarin, dicumarol, phenprocoumon, acenocumarol), interfering with vitamin K-dependent coagulation factors, are of benefit in the prevention of thromboembolic events when indicated, but concomitantly increase hemorrhagic risk. Coumarin-related ICH

IATROGENIC NEUROLOGY is a dreaded complication with a poor prognosis, that may occur even at therapeutic levels of anticoagulation. It is generally rapidly evolving, multilocular, and confluent and, characteristically, shows a liquid level in brain imaging studies. Risk factors for ICH in coumarin-treated patients are age, hypertension, diabetes, intensity of anticoagulation, stroke of arterial mechanism, amyloid angiopathy, and symptomatic intracranial arterial stenosis. Other rarer central nervous system bleeds can occur. A growing concern, especially when anticoagulation is an issue, is the finding of cerebral microbleeds in brain MRI echogradient-sequences of asymptomatic elderly individuals. Microbleeds are more prevalent in the presence of hypertension, lacunes, and white matter changes (Roob et al., 1999). However, the hemorrhagic risk of anticoagulation in such patients has not been established. Warfarin, unlike heparin, crosses the placenta and is teratogenic, causing bone disease (chondrodystrophia punctata), mental retardation, optic atrophy, hydrocephalus, schizencephaly, and the Dandy–Walker malformation (Ginsberg et al., 1989). Urgent reversal of anticoagulation is obtained with fresh frozen plasma or dose-adjusted protamine sulphate, in the case of heparin, or fresh frozen plasma and vitamin K, in the case of coumarins. Prothrombin complex concentrate of factors II, VII, IX, X, proteins C and S may also reverse warfarin anticoagulation.

DIRECT THROMBIN AND FACTOR XA INHIBITORS Direct thrombin and factor Xa inhibitors (DTIs and DFXaIs) inhibit thrombin and coagulation factor Xa directly, without modifying the hepatic synthesis of coagulation factors, and may thus overcome the limitations of conventional anticoagulants, especially the need of INR monitoring. At the time of writing, lepirudin, desirudin, bivalirudin, and argatroban are the FDAapproved DTIs in North America. New oral direct inhibitors are most promising as they may eventually replace conventional vitamin K antagonists for chronic oral anticoagulation. Dabigatran etexilate, apixaban, and rivaroxaban are currently the most studied drugs in this emerging group. DTI dabigatran, as well as DFXaIs rivaroxaban and apixaban, have been recently approved by the US Food and Drug Administration (FDA) for stroke prevention in atrial fibrillation. All have been found to be at least as effective as warfarin with comparable or even better bleeding risks. A recent meta-analysis comparing DTIs (ximelagatran, dabigatran, and desirudin) versus vitamin K antagonists or LMWH for prevention of venous thromboembolism after orthopedic replacements concluded that DTIs are as effective as LMWH and vitamin K antagonists, but show higher mortality and cause more bleeding


(ximelagatran especially, but not desirudin) than LMWH (although not warfarin) (Salazar et al., 2010).

Antiplatelet agents Aspirin is an anticyclooxygenase platelet inhibitor of proven benefit in the prevention of IS and AMI. When indicated following acute IS, it does not cause a major risk of ICH at a daily maximum dose of 300 mg (Sandercock et al., 2008). Up to a quarter of complying patients on treatment may be at persistent risk of vascular events because of lack of response to aspirin (aspirin “resistance”) (Krasopoulos et al., 2008). Dipyridamole is a platelet phosphodiesterase and adenosine reuptake inhibitor of proven benefit for the prevention of IS, in an extended release formulation, in association with aspirin. It may cause headache as a side-effect, prevailing in women, normotensives, and nonsmokers (Halkes et al., 2009). Ticlopidine and clopidogrel are thienopyridines that inhibit the ADP-dependent activation of platelet aggregation, and prevent IS and other thrombotic events with a somewhat higher benefit than aspirin. Individually they do not increase the risk of ICH, but clopidogrel in association with aspirin has been shown to increase both systemic and ICH (ACTIVE Investigators, 2009). This association (so-called “dual” antiplatelet therapy) has not otherwise proven to be of further benefit in the prevention of IS. Clopidogrel “resistance” has also been documented and linked to an increased vascular risk (Sofi et al., 2010). The recently approved thienopyridine prasugrel is a more consistent platelet inhibitor than clopidogrel. Although it has not been formally studied in cerebrovascular disease, prasugrel has been related to a higher risk of ICH and should presently be avoided in patients with prior stroke (Testa et al., 2010). Glycoprotein (GP) IIb-IIIa inhibitors (abciximab, tirofiban, eptifibatide) block the binding of fibrinogen to platelets, thereby inhibiting aggregation. They have shown some benefit in the treatment of acute coronary syndromes, but with higher risk of major bleeding, including ICH. The efficacy of these agents in stroke has not been proven (De Luca et al., 2009). There are as yet no data regarding the risk/benefit of triple antiplatelet therapy (adding GPIIb/IIIa inhibitors to a dual antiplatelet regimen) in preventing IS.

NEUROLOGIC ADVERSE EFFECTS OFANTIEPILEPTIC AND ANTISPASTIC DRUGS Antiepileptic drugs The neurologic adverse effects of most commonly used antiepileptic drugs (AEDs) are presented in Table 107.4.



Table 107.4 Neurologic adverse effects of most commonly used anticonvulsant drugs Drug

Adverse effects

Benzodiazepines Phenytoin

Cognitive impairment (Stewart, 2005) Cerebellar atrophy (Ney et al., 1994) Peripheral neuropathy (Shorvon and Reynolds, 1982) Mania (Drake and Peruzzi, 1986) Oculogyric crisis (Gorman and Barkley, 1995) Neurologic consequences of hyponatremia (Lahr, 1985) Hyperactivity (Wolf and Forsythe, 1978) Irritability and sleep disturbances (Camfield et al., 1979) Depression (Brent et al., 1987) Tremor (Karas et al., 1983) Hyperammonemic encephalopathy (Sunkavalli et al., 2011) Hearing loss (Hori et al., 2003) Dyskinesia and akathisia (Ehyai et al., 1978) Lupus with cerebral involvement (Casteels et al., 1998) Depression (Phabphal and Udomratn, 2010) Speech disturbances (Cramer et al., 1999) Peripheral visual field deficit (Willmore et al., 2009) Psychiatric and behavioral changes (Guberman, 1996) Agitation, confusion, and hallucinations (Beran and Gibson, 1998) Aggressive behavior (Litzinger et al., 1995) Neurologic consequences of hyponatremia (Van Amelsvoort et al., 1994) Depression (Andersohn et al., 2010) Irritability and behavioral changes (Mula et al., 2003) Tremor (Schachter, 1999) Psychomotor agitation (Chadwick and Marson, 2005)



Valproic acid

Ethosuximide Topiramate Vigabatrin Lamotrigine Gabapentin Oxcarbazepine Levetiracetam Tiagabine Zonisamide

Cognitive impairment is shared by most anticonvulsant drugs, an important issue since cognitive dysfunction is common among epileptic patients. Gabapentin, tiagabine, lamotrigine, oxcarbazepine, and levetiracetam are not associated with significant deleterious changes on cognitive functions. Movement disorders including parkinsonism, chorea, dystonia, asterixis, dyskinesias, hemiballism, and athetosis are less frequently found but can be seen with most anticonvulsant drugs: phenytoin, carbamazepine, valproic acid, ethosuximide, lamotrigine, and gabapentin (Kennedy and Lhatoo, 2008). Seizure exacerbation has also been described in children and adults as a consequence of clonazepam, phenytoin, carbamazepine, valproic acid, ethosuximide, topiramate, gabapentin, lamotrigine, oxcarbazepine, and tiagabine (Kennedy and Lhatoo, 2008).

Antispastic drugs There are several drugs with antispastic effect. Benzodiazepines, gabapentin, baclofen, tizanidine, and clonidine are centrally acting drugs. Dantrolene and botulinum toxin type A have peripheral action.

The efficacy of antispastic agents is marginal and adverse effects are so common that this can limit their usefulness. Antispastic drugs act by decreasing muscle tone, thus one of the most frequent adverse effects is impaired movement performance. Drowsiness is the most frequent adverse symptom in patients treated with tizanidine, dantrolene is associated with weakness, drowsiness, and malaise, while baclofen produces sedation, dizziness, and muscle weakness (Montane´ et al., 2004). Botulinum toxin type A is injected locally. This exotoxin of the anaerobic bacterium Clostridium botulinum is irreversibly bound to the presynaptic neuron at the neuromuscular junction and disrupts peptides necessary for the release of acetylcholine, causing a flaccid muscle paralysis. Common neurologic indications include blepharospasm, cervical dystonia, hemifacial spasm, and spasticity. Following injection, muscular function recovers after 4–6 months. The most frequent neurologic adverse effect of botulinum toxin type A is muscle weakness, generally due to local extension of the antispastic effect to the wrong or undesired muscles, inducing ptosis, diplopia, lack of eyelid occlusion, or cervical, facial or limb

IATROGENIC NEUROLOGY weakness, depending on the site of injection. It can sometimes spread to cause generalized weakness, dysphagia, dysarthria, and dyspnea (Bhatia et al., 1999).



Table 107.5 Other neurologic adverse effects of commonly used antiparkinsonian drugs Drug

Adverse effects

Dopamine agonists

Compulsive behavior (i.e., pathological gambling) (Dodd et al., 2005) Uncontrollable somnolence (Avorn et al., 2005) Insomnia (Horn and Stern, 2004) Dizziness (Etminan et al., 2003) Orthostatic hypotension (Horn and Stern, 2004) Levodopa phobia (Kurlan, 2005) Serotonin syndrome (Bainbridge et al., 2008) Headache, dizziness, somnolence (Horn and Stern, 2004) Somnolence/insomnia (Horn and Stern, 2004) Confusion (Horn and Stern, 2004) Insomnia (Thornton et al., 1980) Headache (Horn and Stern, 2004) Serotonin syndrome (Bainbridge et al., 2008) Confusion (Horn and Stern, 2004)

Antiparkinsonian drugs Almost every antiparkinsonian agent, including levodopa, dopamine agonists, MAO B inhibitors, anticholinergics, and amantadine, can produce hallucinations, mostly visual (Burn and Tr€oster, 2004). They are considered benign when insight is preserved. When there is no insight they are regarded as malignant and a manifestation of psychosis. They may also be accompanied by delusional symptoms. Psychosis is present in up to a quarter of patients with Parkinson’s disease and constitutes the main predictor of institutionalization. Patients treated with antiparkinsonian drugs are at much higher risk of developing psychosis than nontreated patients. All the centrally acting drugs used to treat motor symptoms in Parkinson’s disease have been associated with psychosis (Goetz, 1999). Anticholinergic treatment is associated with chronic cognitive impairment (Cooper et al., 1992). Dopaminergic drugs (dopamine agonists and levodopa) can improve cognitive performance in early Parkinson’s disease but a relative “hyperdopaminergic” state may impair cognitive functioning in later stages (Kulisevsky, 2000). Amantadine and selegiline may also be associated with cognitive dysfunction (Elmer, 2004). Dopamine dysregulation syndrome, in patients treated with dopaminergic agents, is characterized by a compulsive use of drugs, beyond that needed to achieve relief of motor symptoms, resulting in harmful consequences, such as stereotypies or punding, euphoria, hypomania, delusions, paranoia, aggressive behavior, social or relationship breakdown, seeking/craving or hoarding medication, and withdrawal symptoms (Burn and Tr€ oster, 2004). Dyskinesias are common complications of dopaminergic treatment of Parkinson’s disease. They comprise ballism, chorea, dystonia, myoclonus, and tics. They can occur in coincidence with peak blood levels of dopaminergic drugs (peak dose dyskinesias), with rising and falling blood concentrations (diphasic dyskinesias), or when levels are low (off dyskinesias). Motor fluctuations are also common with the use of levodopa. Wearing off is the predictable recurrence of parkinsonian motor and nonmotor symptoms that

Levodopa COMT inhibitors Anticholinergics MAO B inhibitors


precedes and usually improves after the scheduled intake doses of antiparkinsonian medication. The “onoff” phenomenon is characterized by rapid and mostly random periods of change from a medication-related motor state to a parkinsonian state. Symptoms of parkinsonian autonomic dysfunction such as orthostatic hypotension, constipation, urinary retention, and abnormal salivation can be exacerbated by dopaminergic agents, amantadine, anticholinergics, and COMT inhibitors (Dewey, 2004). Other frequent neurologic adverse effects of most commonly used antiparkinsonian drugs are shown in Table 107.5.

Antidepressant drugs (See Table 107.6.)

Cognition drugs They comprise the agents used for the treatment of degenerative and vascular dementias. There are currently two groups of drugs available for the treatment of dementias: (1) cholinesterase inhibitors (donepezil, rivastigmine, and galantamine), and (2) NMDA receptor antagonists (memantine).



Table 107.6

Table 107.7

Common neurologic adverse effects of most antidepressants

Common neurologic adverse effects of cognition drugs


Adverse effects


Confusion (Uher et al., 2009) Cognitive dysfunction (Uher et al., 2009) Orthosthatic hypotension (Uher et al., 2009) Blurred vision (Uher et al., 2009) Seizures (Kumlien and Lundberg, 2010) Serotonin syndrome (Bainbridge et al., 2008) Aggressive behavior (Moore et al., 2010) Decreased lacrimation (Malone et al., 1992) Insomnia (Papakostas and Fava, 2006)

MAOA inhibitors





Trazodone and nefazodone


Serotonin syndrome (Bainbridge et al., 2008) Orthostatic hypotension (Nair et al., 1995) Insomnia (Nair et al., 1995) Extrapyramidal symptoms (Gerber and Lynd, 1998) Sexual dysfunction (Montejo et al., 2001) Isomnia (Uher et al., 2009) Seizures (Kumilen and Lundberg, 2010) Serotonin syndrome (Mason et al., 2000) Hallucinations (Capaldi and Carr, 2010) Suicidal ideation (Mann et al., 2006) Aggressive behavior (Moore et al., 2010) Oculogyric dystonic reaction (Patel and Simon, 2006) Insomnia (Perahia et al., 2006) Serotonin syndrome (Hadikusumo and Ng, 2009) Aggressive behavior (Moore et al., 2010) Somnolence (Papakostas, 2007) Insomnia (Papakostas et al., 2008a) Aggressive behavior (Moore et al., 2010) Insomnia (Papakostas et al., 2008b) Seizures (Kumilen and Lundberg, 2010) Insomnia (Thase et al., 2005) Serotonin syndrome (Thorpe et al., 2010) Aggressive behavior (Moore et al., 2010) Priapism (Davis et al., 1997) Insomnia (Beasley et al., 1991) Serotonin syndrome (Bainbridge et al., 2008) Aggressive behavior (Moore et al., 2010) Confusion (Davis et al., 1997) Visual disturbances (Davis et al., 1997) Palinopsia (Hughes and Lessell, 1990) Insomnia (Green, 2011) Headache (Green, 2011)


Adverse effects


Seizures (Kumlien and Lundberg, 2010) Agitation (Turon-Estrada et al., 2003) Insomnia (Hogan et al., 2008) Headache (Hogan et al., 2008) Hallucinations (Sobow and Kloszewska, 2006) Vertigo (Sobow and Kloszewska, 2006) Seizures (Kumlien and Lundberg, 2010) Headache (Hogan et al., 2008) Insomnia (Kavirajan and Schneider, 2007) Headache (Hogan et al., 2008) Headache (Hogan et al., 2008) Confusion (Hogan et al., 2008) Seizures (Babai et al., 2010)

Rivastigmine Galantamine Memantine

Dizziness has been reported with the use of cholinesterase inhibitors and memantine (Hogan et al., 2008). Adverse events of cholinesterase inhibitors and memantine are shown in Table 107.7.

NEUROLOGIC ADVERSE EFFECTS OFANTIPSYCHOTICS, SEDATIVES, AND HYPNOTICS Antipsychotics and dopamine receptor-blocking drugs The salient clinical features and management of antipsychotics and dopamine receptor-blocking drugs (DRBDs) are listed in Table 107.8. Antipsychotics may also cause or worsen cognitive impairment and induce anticholinergic side-effects. Clozapine requires blood cell count monitoring for possible agranulocytosis. Other atypical antipsychotic adverse effects include hyperglycemia and dyslipidemia (mostly clozapine and olanzapine), hyperprolactinemia (mostly amisulpride, risperidone), prolongation of heart rate-corrected QT interval (all, but mostly ziprasidone, sertindole), weight gain (mostly clozapine, olanzapine), postural hypotension and seizures (mostly clozapine) (Haddad and Sharma, 2007). Nonantipsychotic DRBDs such as metoclopramide, domperidone, and droperidol (see digestive tract drugs), and promethazine, cinarizine and flunarizine (Mangone and Herskovits, 1989) may have similar though usually milder adverse effects.

Table 107.8 Dopamine receptor-blocking drugs: adverse effects, salient features, and management DRBD adverse effect

Salient features


Acute dystonia

Usually begins early after commencing DRBD Tongue “thickness” or protrusion, brisk jaw or head movements, grimacing, twisted or crooked posturing (“Pisa” syndrome), oculogyric crisis, throat “tightness,” laryngeal spasm

Akathisia (“acute” akathisia)

Generally begins after weeks/months of DRBD Restlessness, fidgetiness, jumpiness, compulsion to move, pacing, foot-tapping or shifting, stomping, swinging Improves with DRBD removal

Neuroleptic malignant syndrome

Begins tipically after a few weeks of DRBD Fever, rigidity, tremor, confusion, dysautonomia (sweating, hypotension, arrhythmias, incontinence) High CK (>1000 U) and GPT, proteinuria, myoglobinuria Eventually, rhabdomyolysis, disseminated intravascular coagulation, acute renal failure Also seen in Parkinson’s disease, after withdrawal of dopaminergic drugs, dehydration, infections and “wearing off” (Ikebe et al., 2003) Generally begins after weeks/months of DRBD Common parkinsonism features, but symmetric “Rabbit” syndrome Appears mostly after months/years, or on discontinuation or dose reduction of DRBD Several clinical syndromes: Classic: oral-lingual: tongue pressing or rolling (“bonbon” sign), protruding (“fly-catcher’s” sign), chewing, cheek blowing Stereotypic: pelvic: “copulatory” rocking respiratory: panting, puffing, gasping, wheezing vocal: moaning, humming finger: “piano playing” chorea Withdrawal-emergent syndrome: transient chorea after sudden removal of DRBD Tardive akathisia: worsens with DRBD removal Tardive dystonia: face, neck, trunk, often painful Other: myoclonus, tremor, tics, orogenital pain

Discontinuation of DRBD Biperiden 2–8 mg/day Benztropine 1–2 mg IV Diphenhydramine 10–50 mg IV Diazepam 5–10 mg IV Discontinuation of DRBD Change to other neuroleptics Propranolol 40–120 mg/day Biperiden 2–8 mg/day Trihexyphenidyl 2–10 mg/day Consider related conditions: catatonia (Vesperini et al., 2010), serotonin syndrome (Carbone, 2000) Discontinuation of DRBD Oral dantrolene sodium 200–400 mg/day Bromocriptine 10–30 mg/day Dopaminergics resumption if due to its withdrawal Alkalinize urine to prevent myoglobinuria

Neuroleptic-induced parkinsonism Tardive dyskinesia

DRBD, dopamine receptor-blocking drug; CK, creatine kinase; GTP, glutamic-pyruvic transaminase; IV, intravenous.

Discontinuation of DRBD or dopamine-depleting (reserpine, tetrabenazine) drug Anticholinergics Discontinuation of DRBD Initial worsening, thenceforth slow improvement through months, may persist Avoid anticholinergics



Sedatives and hypnotics Barbiturates and benzodiazepines may cause varying and well known dose-dependent degrees of sedation: slowed thinking, cognitive impairment, somnolence or drowsiness, incoordination, ataxia, hypotonia, dysarthria, nystagmus, delirium, coma. Benzodiazepine dependence may occur with therapeutic doses, through the appearance of withdrawal symptoms upon abrupt discontinuation (anxiety, tremor, eventually seizures) that may be controlled by progressive dose tapering (O’Brien, 2005). Carbamazepine as an adjunctive therapy has shown some benefit in reducing benzodiazepine withdrawal severity, significantly improving drug-free outcome (Denis et al., 2006). Benzodiazepines may specifically cause anterograde amnesia, especially for events occurring near the time of their peak plasma concentrations (Buffett-Jerrott and Stewart, 2002). Paradoxical aggressive reactions (physical aggression, rape, impulsive decision making, violence, and autoaggressiveness) may also occur (Saı¨as and Gallarda, 2008).

NEUROLOGIC ADVERSE EFFECTS OF PSYCHOSTIMULANTS AND RELATED DRUGS The clinical effects of psychostimulants include increased alertness, wakefulness, activity and drive, enhanced attention, concentration, and memory, and mood improvement. Adverse effects include insomnia, restlessness, agitation, tremor, irritability and aggression, anxiety or panic, malaise, dizziness, nausea or vomiting, abdominal pain, headache, anorexia and weight loss. Associated adrenergic effects include mydriasis, dry mouth, hypertension, tachycardia, hyperthermia and hyperhydrosis. Most psychostimulants act by inhibiting the reuptake of selective neurotransmitters, such as epinephrine, norepinephrine, dopamine, and serotonin. The most commonly used drugs with psychostimulant-like effect today include atomoxetine, methylphenidate, bupropion, and modafinil. Atomoxetine, introduced as “the first nonstimulant for the management of ADHD,” is thought to enhance noradrenergic function via selective inhibition of the presynaptic norepinephrine transporter (Corman et al., 2004). Pemoline, introduced in the 1980s to treat attention deficity hyperactivity disorder (ADHD), has been discontinued in the US and several other countries because of liver toxicity, and overwhelmingly replaced by methylphenidate, and, increasingly, atomoxetine for that indication (Garnock-Jones and Keating, 2009). Bupropion is mainly a norepinephrine reuptake inhibitor which has shown

benefit for smoking cessation. Modafinil increases monoamine release and hypothalamic histamine levels. Exacerbation of the tics in Tourette’s syndrome has been linked to the use of psychostimulants indicated for the frequent coexistence of ADHD. However, whereas individual patients may eventually undergo an increase in tics, group data have not shown a significant adverse effect. Psychostimulants, used with caution, are therefore not considered today contraindicated in persons with tics and ADHD (Erenberg, 2005). Reported adverse effects of psychostimulants also include chorea (Weiner et al., 1978), growth retardation (Correll and Carlson, 2006), and hypomania (Masand et al., 1995). However, mania and other possible psychiatric effects, such as “behavioral rebound,” withdrawal risk, and psychosis are presently controversial. Concerns have been raised whether to continue or withdraw psychostimulants in adult patients treated for ADHD since childhood, and showing other psychiatric symtpoms (Ashton et al., 2006). On the other hand, the belief that stimulants are contraindicated in mania has been challenged. ADHD and mania share symptoms or pathogenetic mechanisms. Patients with features of both ADHD and psychosis (“ADHD psychosis”) do benefit from treatment with psychostimulants, possibly by improvement of frontal lobe dysfunction (Opler et al., 2001). Psychostimulants have a low risk and might thus even be a treatment option for mania (Hegerl et al., 2010). Other specific neurologic adverse efects of psychostimulants appear in Table 107.9. Recreationally used or abused psychostimulants, such as amfetamines (dextramfetamine, methamfetamine, MDMA or “ecstasy”, MDEA or “eve”), sympathomimetics (phenylpropanolamine, ephedrine), and cocaine may cause movement disorders, seizures, ischemic and hemorrhagic stroke, and severe withdrawal symptoms, other than the general neuropsychiatric and cardiovascular effects mentioned above.

NEUROLOGIC ADVERSE EFFECTS OF ANTIBACTERIAL, ANTIVIRAL, ANTIFUNGAL, ANTIPARASITIC DRUGS, AND VACCINES Antibacterial agents (antibiotics) About 80% of the adverse effects of antibacterial agents are the result of allergic reactions. Neurologic complications, mostly ototoxicty and seizures, are much less frequent. Serious neurologic complications are generally related to inadequate dose management in patients with renal failure. Imipenem and cefepime are the antibacterial agents with the highest neurotoxic risk.


Antiparasitic agents

Other neurologic adverse effects of most commonly used psychostimulants and related drugs Drug

Adverse effects


Stuttering (Burd and Kerbeshian, 1991) Paroxysmal kinesigenic dystonia (Gay and Ryan, 1994) Cerebral arteritis Priapism (Schwartz and Rushton, 2004) Akathisia (Almeida et al., 2006) Rabbit syndrome (Mendhekar and Duggal, 2006) Orofacial and extremity dyskinesia (Bala´zs et al., 2007) Enuresis (Ghanizadeh, 2008) Bruxism (Mendhekar and Andrade, 2008) Excessive talking (Ghanizadeh, 2009) Complex visual hallucinations (Halevy and Shuper, 2009) Acute urinary retention (Desarkar and Sinha, 2006) Suicidal ideation (Bangs et al., 2008) Bruxism worsening (Mendhekar and Lohia, 2009) Priapism (Levenson, 1995) Rhabdomyolysis (David and Esquenazi, 1999) Tactile hallucinations (Charuvastra and Yaeger, 2006) Acute dystonia (Wang et al., 2007) Neck and shoulder pain (Sansone and Sansone, 2009) Seizures (Starr et al., 2009) Serotonin syndrome (Thorpe et al., 2010) Cataplexy worsening (Poza, 2003) Hyperkinetic nondystonic movement disorder (Luborzewski et al., 2006) Visual and cenesthetic hallucinations (Oulis et al., 2008)





The neurologic adverse effects of the most frequently used antibacterial agents are shown in Table 107.10.

Antiviral agents The neurologic adverse effects of the most frequently used antiviral agents are shown in Table 107.11.

Systemic antifungal agents The most frequently encountered adverse effects of systemic antifungal agents are shown in Table 107.12.

The salient neurologic adverse effects of the most frequently used antiparasitic agents are shown in Table 107.13.

Vaccines The reported neurologic adverse effects of the most frequently used vaccines are shown in Table 107.14, but it must be pointed out that no clear causal association could be confirmed for some of the adverse effects shown.

NEUROLOGIC ADVERSE EFFECTS OF ANTINEOPLASTIC AND IMMUNOMODULATORY DRUGS Antineoplastic drugs The most prevalent neurologic complication of chemotherapy is peripheral neuropathy. Encephalopathy is also relatively frequent, especially after repeated intrathecal administration. The most common adverse effects of antineoplastic agents are shown in Table 107.15.

Immunomodulatory drugs Common adverse effects of immunomodulatory agents are shown in Table 107.16.

NEUROLOGIC ADVERSE EFFECTS OF ANTI-INFLAMMATORY, ANALGESIC, AND ANTIALLERGIC DRUGS Anti-inflammtory and analgesic drugs CORTICOSTEROIDS Corticosteroids or glucocorticoids commonly used as anti-inflammatory agents have a central stimulating effect and may cause well-known behavioral changes, such as insomnia, hyperactivity, logorrea, hallucinations, agressiveness, mania, and delirium (“steroid psychosis”). Longer treatment with corticosteroids can induce dose-dependent depression and memory decline, often during the first few weeks of therapy, with changes in the temporal lobe detected by structural, functional, and spectroscopic imaging. Lithium and phenytoin may prevent the mood symptoms, whereas lamotrigine and memantine can partially reverse the memory changes. Both alterations may also revert with dose reduction or discontinuation. The symptoms and treatment response have been likened to those of bipolar disorder (Brown, 2009).



Table 107.10 Neurologic adverse effects of the most frequently used antibacterial drugs Group

Adverse effects


Seizures (Meropol et al., 2008) Penicillin psychosis (Hoigne’s syndrome) (Rao, 1999) Aseptic meningitis (Prieto-Gonza´lez et al., 2011) Delirium (Tong et al., 2004) Benign intracranial hypertension (Schmitt and Krivit, 1969) Seizures (Chow et al., 2005) Delirium (Chow et al., 2003) Encephalopathy (Roncon-Albuquerque et al., 2009) Dysgeusia (Noel et al., 2008) Agitation and confusion (Slaker and Danielson, 1991) Elevated creatine phosphokinase (Talbot et al., 2007) Vestibular toxicity (Sennesael et al., 1982) Psychosis, aphasia, and dizziness (Mitropoulos et al., 2007) Headache (Dauner et al., 2010) Aseptic meningitis (Nakajima et al., 2007) Hearing loss (Schmutzhard et al., 1995) Seizures (Schranz, 1998) Headache (Bazan et al., 2009) Stroke-like symptoms and delirium (Duquaine et al., 2011) Hearing loss (Schmutzhard et al., 1995) Vertigo (Duque et al., 1991) Insomnia (Matthews and Lancaster, 2009) Encephalopathy (Ferna´ndez-Torre et al., 2004) Paresthesiae (Gotuzzo et al., 1994) Hearing loss (Pedrajas et al., 1993) Hearing loss (Moore et al., 1984) Vestibular toxicity (Darlington and Smith, 2003) Neuromuscular blockade (Snavely and Hodges, 1984) Musical hallucinations (Tanriverdi et al., 2001) Psychosis (Kane and Byrd, 1975) Polyneuropathy/encephalopathy (Bischoff et al., 1977) Aseptic meningitis (Granowitz and Brown, 2008) Optic neuritis (Bucy, 1937) Confusion (Lehr, 1957) Psychosis Multiple peripheral neuropathy (Blankenhorn, 1938) Seizures (Meropol et al., 2008) Vertigo (Granowitz and Brown, 2008) Pseudotumor cerebri (Tabibian and Gutie´rrez, 2009) Headache (Doan et al., 2006) Vestibular dysfunction (Fanning et al., 1977) Visual disturbances (Aagaard and Hansen, 2010) Neuromuscular blockade (Bezzi and Gessa, 1961) Hearing loss (Ress and Gross, 2000) Headache and dizziness (Hopkins, 1991) Dysgeusia (Snyman et al., 2009) Hallucinations and seizures (Schiff et al., 2010) Psychosis, anxiety, confusion, and restlessness (Aagaard and Hansen, 2010) Headache and dizziness (Nguyen and Chung, 2005) Dysgeusia (Kasbekar and Acharya, 2005)



Monobactams Aminoglycosides







Table 107.10 Continued Group

Adverse effects


Hearing loss (Farber and Moellering, 1983) Headache and dizziness (Noel et al., 2008) Dysgeusia (Leonard and Rybak, 2008) Seizures (Aagaard and Hansen, 2010) Elevated creatine phosphokinase (Canto´n et al., 2010) Headache, drowsiness, and dizziness (Radner, 1973) Headache, insomnia, and seizures (Owens and Ambrose, 2005) Dysgeusia and seizures (Noel, 2009) Seizures (Walton et al., 1997) Dysgeusia (Geddes, 1999) Peripheral neuropathy (Lode, 2010) Psychosis and anxiety (Stahlmann and Lode, 2003) Delirium (Slobodin et al., 2009) Dizziness (Anzueto et al., 2002) Neuromuscular blockade (Tang and Schroeder, 1968), Headache, insomnia, and dizziness (Fung et al., 2001)

Lipopeptides Rifamycins Fluoroquinolones

Lincosamides Oxazolidinone Other agents Metronidazole





Cerebellar dysfunction (Kusumi et al., 1980) Peripheral neuropathy (Coxon and Pallis, 1976) Seizures (Frytak et al., 1978) Optic neuritis (Lasky et al., 1957) Peripheral neuropathy (Wallenstein and Snyder, 1952) Ophthalmoplegia (Hill and Armstrong, 1950) Neuromuscular blockade (Fogdall and Miller, 1974) Hearing loss, visual disturbances, paresthesiae, vertigo, confusion, hallucinations, seizures, and ataxia (Falagas and Kasiakou, 2006) Seizures (Sullivan et al., 1998) Optic neuritis (Kass et al., 1957) Peripheral neuropathy (Goldman and Braman, 1972) Encephalopathy (Adams and White, 1965) Aseptic meningitis (Granowitz and Brown, 2008)

By an uncertain mechanism, corticosteroids may induce exacerbation of myasthenia gravis symptoms, especially at initiation of therapy, in up to 50% of patients. Predictors of exacerbation appear to be old age, predominant bulbar symptoms, and clinical severity of the disease, rather than a high initial dose (Bae et al., 2006). Proximal progressive lower limb girdle myopathy is a frequent complication of prolonged steroid therapy. It may extend to upper limbs, and occasionally present as an acute quadriplegic myopathy after high intravenous doses (Hirano et al., 1992). Other rarer reported adverse effects of steroids are optic neuropathy with fluprednisolone (Teus et al., 1991) and pseudotumor cerebri on steroid withdrawal (Lessell, 1992).

NONSTEROIDAL ANTI-INFLAMMATORY DRUGS Non-selective COX inhibitors Aspirin has antiplatelet effects that have been dealt with earlier in this chapter. Its most common side-effect is gastrointestinal bleeding linked to inhibition of anticyclooxygenase-1 (COX-1). Aspirin administered in children with high fever may cause Reye syndrome believed to be due to impaired oxidation on the long chain hydroxyacyl-CoA dehydrogenase enzyme (Glasgow, 2006). However, the cause– effect relationship between aspirin and Reye syndrome has recently been put into question (Schr€or, 2007). Reye syndrome has also been linked to the use of phenothiazines and antiemetics (Casteels-Van Daele et al., 2000).



Table 107.11 Neurologic adverse effects of the most frequently used antiviral drugs Drug Nonretroviral agents: Anti-herpesviridae agents

Anti-influenza agents*

Antihepatitis agents*{{ Other nonretroviral agents Retroviral agents: Nucleoside reverse transcriptase inhibitors

Non-nucleoside reverse transcriptase inhibitors

Fusion inhibitors CCR5 antagonists

Adverse effects

Delirium (Revankar et al., 1995) Encephalopathy (Onuigbo et al., 2009) Seizures (Fan-Harvard et al., 2009) Aseptic meningitis (Olin and Gugliotta, 2003) Psychosis (Yang et al., 2007) Headache, insomnia, peripheral neuropathy, and paresthesia (Curran and Noble, 2001) Depression (Sirota et al., 1988) Confusion and ataxia (Martinez-Diaz and Hsia, 2011) Headache (Dutkowski et al., 2010) Dizziness (Choo et al., 2011) Insomnia and hallucinations (Jefferson et al., 2006) Depression (Chung and Joung, 2010) Myopathy (Tak et al., 2010) Tetany secondary to hypocalcemia or hypomagnesemia (Muller et al., 2007) Psychosis (Quarantini et al., 2006) Psychosis (Maxwell et al., 1988) Depression (Foster et al., 2004) Migraine and mood changes (Colebunders et al., 2002) Sleep disturbances and peripheral neuropathy (Sharma et al., 2008) Seizures (D’Silva et al., 1995) Psychosis (Wise et al., 2002) Cognitive impairment (Prime and French, 2001) Insomnia, vivid dreams, and night terrors (Cespedes and Aberg, 2006) Mania (Shah and Balderson, 2003) Delirium and behavioral changes (de la Garza et al., 2001) Depression Insomnia, peripheral neuropathy, and headache (Fung and Guo, 2004) Dizziness and insomnia (Lieberman-Blum et al., 2008)

*Adverse effects of interferons and amantadine have been addressed in other sections. { Adverse effects of lamivudine are included in the NRTI group. { Ribavirin is included in the group of other nonretroviral agents.

Acute aspirin/salicylate intoxication, accidental or voluntary, presents as hyperpnea, sweating, tinnitus, deafness, encephalopathy (confusion, stupor, seizures) and metabolic acidosis, and can be confirmed by measuring plasma salicylate concentrations. Gastric emptying, forced alkaline diuresis, and eventually hemodialysis are accepted therapeutic interventions (Pearlman and Gambhir, 2009). Consensus management guidelines have been published (Chyka et al., 2007). Aspirin and salicylates are ototoxic, causing usually reversible tinnitus, high frequency hearing loss, and alterations of perceived sounds. Salicylates act as competitive inhibitors of Cl-anions at the anion-binding site of prestin, the motor protein of the outer hair cell. Regular use of aspirin, non-steroidal antiinflammatory

drugs (NSAIDs), and acetaminophen/paracetamol may cause hearing loss (Curhan et al., 2010). Aseptic ibuprofen-induced meningitis, often recurrent, may occur with therapeutic doses, especially in patients with an autoimmune connective tissue disorder. It presents as an acute meningeal or meningoencephalopathic syndrome, sometimes with focal neurologic signs (Agus et al., 1990). The cerebrospinal fluid shows elevated neutrophils and protein, and, unlike acute bacterial meningitis, normal glucose. Symptoms abate on discontinuation. Screening for autoimmune disease has been recommended in previously healthy patients with ibuprofen-related meningoencephalitis (Rodrı´guez et al., 2006). Diclofenac is a NSAID inhibiting COX-1, COX-2, and prostaglandin synthesis. Nonselective COX inhibitors



Table 107.12

Selective COX-2 inhibitors

Neurologic adverse effects of most frequently used antifungal drugs

Selective COX-2 inhibitors, especially rofecoxib, have been associated with an increased risk of thromboembolic vascular events, possibly stroke, either through prothrombotic effects or blood pressure destabilization (Farkouh and Greenberg, 2009). Other COX-2 inhibitors include celecoxib, parecoxib, valdecoxib, etoricoxib, and lumiracoxib.


Adverse effects


Benign intracranial hypertension (Heudier et al., 1992) Seizures (Aruna et al., 2000) Delirium and depression (Weddington, 1982) Headache and dizziness (Bodhe et al., 2002) Visual loss (Li and Lai, 1989) Recurrent hemiparesis (Devuyst et al., 1995) Myelopathy (Carnevale et al., 1980) Leukoencephalopathy (Liu et al., 1995) Anxiety, confusion, and insomnia Visual disturbances (Herbrecht et al., 2002) Hallucinations (Cleveland and Campbell, 1995) Vertigo (Costa et al, 1994) Headache and dizziness (Tucker et al., 1990) Sexual dysfunction (Terrell, 1999) Cerebellar syndrome (Cubo Delgado et al., 1997) Headache (Mayr et al., 2011) Dizziness (Menichetti, 2009) Insomnia (Hiemenz et al., 2005) Sexual dysfunction (Hull and Vismer, 1992)


Pyrimidine analogs Echinocandins


may have an increased risk of cardiovascular thromboembolic adverse effects, and diclofenac-related stroke has been reported (Kornowski et al., 1995). Other neurologic or neurologically related adverse effects induced by diclofenac include myoclonus/myoclonic encephalopathy (Sa´nchez Valiente, 1995), corneal disorders either with oral or topical use of the drug (Zanini et al., 2006), and, in association with mefenamic acid, another NSAID, pediatric posterior reversible leukoencephalopathy (Yokobori et al., 2006). Naproxen, a nonselective COX inhibitor, has been reported to cause hearing loss, sometimes irreversible (Chapman, 1982). Both naproxen and phenylbutazone, another NSAID now in scant use because of agranulocytosis risk, in combination with misoprostol, a prostaglandin E1 analog preventing the development of NSAID-induced gastric ulcers, have been reported to cause ataxia and other neurosensory effects (Huq, 1990).

OPIATES AND OPIOIDS Both opiates and opioids have narcotic and analgesic effects. Opioids, predominantly, are as a rule used today for the treatment of chronic pain, mostly related to cancer, but also to selected cases of headache, neuralgias, facial, radicular, rheumatic, and low back pain. Drowsiness, somnolence, stupor, shallow respiration, pinpoint pupils, bradycardia, and hypothermia are classic narcotic effects of opioids. Opioid withdrawal symptoms, also well known, include agitation, sweating, shivering, piloerection, abdominal pain, vomiting and diarrhea. Naloxone may reverse the narcotic symptoms as well as precipitate withdrawal. Sedation and cognitive changes can occur on initiation of therapy with opioids (Swegle and Logemann, 2006). Cognitive changes have been reported in patients on long-term therapy (Larsen et al., 1999), but psychological measures and pain severity seem to be more predictive of cognitive decrements than specific opioids or daily dose (Brown et al., 2006). Opioid-induced dose-related myoclonus may appear with various agents, including methadone (Ito and Liao, 2008). It occurs particularly in the perioperative setting, in patients on chronic opioid therapy, and with coexisting dehydration or renal disease (Mercadante, 1998). Prolonged opioid treatment may result in opioidinduced hyperalgesia, with worsening pain despite accelerating opioid doses, and abnormal pain sensitivity and symptoms such as allodynia (Mitra, 2008). Intrathecal use of opioids may increase the likelihood of adverse events (Ruan, 2007).

FLUPIRTINE Flupirtine, an aminopyridine, is a centrally acting nonopioid, non-NSAID, nonsteroidal analgesic, a selective neuronal potassium channel opener and NMDA receptor antagonist, used in Europe for treating fibromyalgia and other types of back pain. It is not commercialized in the U.S.A. Reported cases of flupirtine-induced neurologic toxicity include “paradoxical cerebral cortical



Table 107.13 Neurologic adverse effects of most frequently used antiparasitic drugs Drug

Adverse effects


Vertigo (Knopp et al., 2010) Headache and dysgeusia (Can˜ete et al., 2006) Encephalopathy (Blum et al., 2001) Dizziness (Keystone and Murdoch, 1979) Blurred vision, optic neuritis, and seizures (Bagheri et al., 2004) Post-ivermectin Loa loa encephalopathy (Kamgno et al., 2008) Myalgia, dizziness, and headache (Bussaratid et al., 2005) Optic neuritis (Bagheri et al., 2004) Neuromuscular blockade (Ojewole, 1984) Headache and myalgia (Pani et al., 2005) Sleepiness, headache, and dizziness (Bagheri et al., 2004) Seizures (Hewagama et al., 2010) Vertigo and headache (Yangco et al., 1987) Psychosis (Zaki et al., 2009) Ototoxicity (Bortoli and Santiago, 2007) Seizures (Marquardt and Albertson, 2001) Cinchonism (Wolf et al., 1992) Dizziness, sleep disturbances, anxiety, and psychosis (Toovey, 2009) Fatigue and dysgeusia (Fung and Doan, 2005) Headache and dysgeusia (Kapoor et al., 1999)


Other anthelmintics


Agents for other parasitic infections

hyperexcitability” entailing an increased risk of seizures (Hoffmann et al., 2004), and, more specifically, a clinical syndrome of headache, blurred vision, confusion, ataxia, syncope, and, characteristically, green urine (Hufschmidt et al., 2009).

OTHER ANTI-INFLAMMATORY AND ANALGESIC DRUGS Acute colchicine poisoning causes abdominal pain, vomiting, metabolic acidosis, pancytopenia, lifethreatening cardiac arrythmias, hypotension, respiratory distress, and hypocalcemia. Rhabdomyolysis, peripheral neuropathy, and ascending paralysis may occur a few days after exposure (Maxwell et al., 2002). Longer use of colchicine may induce axonal peripheral neuropathy and associated vacuolar myopathy with elevated CK levels (colchicine myoneuropathy), especially in patients with altered renal function, that may resolve on discontinuation of the drug (Kuncl et al., 1987). Gold salts can cause peripheral neuropathy, sometimes with segmental demyelination and axonal degeneration, a Guillain–Barre´-type syndrome, cranial nerve palsies, encephalopathy showing white matter lesions on contrast CT, and associated myokimia or generalized muscle fasciculations. Both symptoms and lesions revert on withdrawal (Schlumpf et al., 1983; Fam et al., 1984; Perry and Jacobsen, 1984).

ANTIMIGRAINE AGENTS Ergotamine Long-term use of ergotamine may cause the so called “ergotism,” characterized by headache and an intensive generalized, even gangrenous, vasoconstriction of small and large blood vessels. Angiography may show arterial narrowing, tapering, or segmented stenosis in different vascular territories (Ruano-Caldero´n and Zermen˜oPohls, 2005). Ergot vasospasm and ischemia may involve the cerebral arteries, producing various ischemic syndromes with neurologic and neuropsychiatric manifestations. Convulsive ergotism, with generalized tonic-clonic seizures, may be due to ischemia or other unclear mechanisms. Neurologic adverse effects of ergotamine toxicity are summarized in Table 107.17. Patients taking ergotamine, ergotamine derivatives and other vasoconstrictive medications may undergo a specific reversible cerebral vasoconstriction (“Call– Fleming”) syndrome. Patients present with sudden, severe, and recurrent (“thunderclap”) headache, and may have seizures, focal motor signs, bilateral paramedian hyperintense diffuse lesions on MRI with a nonvascular distribution, and characteristic (“string of beads”) vasospasm on angiography, mostly resolving spontaneously or on withdrawal of the medication. Localized cortical subarachnoid hemorrhages and later cerebral ischemic events may occur (Ducros, 2010).



Table 107.14 Reported neurologic adverse effects of vaccines included in recommended immunization schedules Drug

Adverse effects

Hepatitis B

Guillain–Barre´ syndrome and optic neuritis (Shaw et al., 1998) Multiple sclerosis (Herroelen et al., 1991) Ototoxicity (DeJonckere and de Surge`res, 2001) Cerebellar ataxia (Deisenhammer et al., 1994) Transverse myelitis (Tartaglino et al., 1995) Irritability (Cheuvart et al., 2009) Guillain–Barre´ syndrome (Pollard and Selby, 1978) Encephalomyelitis (Schwarz et al., 1988) Transverse myelitis (Whittle and Robertson, 1977) Optic neuritis and myelitis (Topaloglu et al., 1992) Peripheral neuropathy (Baust et al., 1979) Febrile and afebrile seizures (Barlow et al., 2001) Seizures (Kulenkampff et al., 1974) Hypotonic/hyporesponsive episodes (DuVernoy and Braun, 2000) Guillain–Barre´ syndrome (Gervaix et al., 1993) Giant cell arteritis (Perez et al., 2000) Seizures, encephalopathy, ataxia, insomnia, meningitis, and hypotonic/hyporesponsive episodes (Wise et al., 2004) Paralytic poliomyelitis (Nathanson and Kew, 2010) Guillain–Barre´ syndrome (Kinnunen et al., 1989) Encephalitis (Landrigan and Witte, 1973) Subacute sclerosing panencephalitis (Modlin et al., 1977) Febrile and afebrile seizures (Griffin et al., 1991) Cranial neuropathy (Chan et al., 1980) Optic neuritis (Kazarian and Gager, 1978) Peripheral neuropathy (Schaffner et al., 1974) Aseptic meningitis (Fujinaga et al., 1991) Transverse myelitis and optic neuritis (Kline et al., 1982) Encephalitis (Gilden et al., 2000) Behavioral changes and delirium (George and Benonis, 2003) Encephalitis (Goulleret et al., 2010) Herpes zoster ophthalmicus and encephalitis (Chouliaras et al., 2010) Headache (Mick, 2010) Meningitis and Guillain–Barre´ syndrome (De Wals et al., 2009)

Rotavirus DT and DTP

Haemophilus influenzae type b4 Pneumococcal Poliovirus Measles, mumps, and rubella

Varicella Hepatitis A Zoster


Triptans The most salient potential complication of triptans is coronary spasm and acute myocadial infarction. Concerns have been raised about the risk of serotonin syndrome when triptans are used in association with selective serotonin reuptake inhibitors (SSRIs), usually indicated for affective disorders, and the FDA in the US has suggested that fatal serotonin syndrome (SS) is possible in that case. However, the evidence for this risk is uncertain and such a concern has recently been put into question (Gillman, 2010). Rare reported neurologic side-effects of triptans have included triptan-induced daily headache (G€ obel et al., 1996), axial dystonia (Oterino and Pascual,

1998), postpartum cerebral angiopathy in association with dihydroergotamine (Granier et al., 1999) and acute pathologic laughter (Barbanti et al., 2008).

Antiallergic drugs: antihistamines (H1-receptor antagonists) Diphenhydramine poisoning may induce a central anticholinergic syndrome with clouding of consciousness, optical/acoustic hallucinatory psychosis, fever, and dry skin and mouth (Lang et al., 1995). The most common neurologic symptoms for fatal cases of diphenhydramine intoxication have been seizures and/or sympathetic pupil responses (Nine and Rund, 2006). Other rarer toxic



Table 107.15 Common neurologic adverse effects of antineoplastic agents Group

Adverse effects

Alkylating agents

Seizures (Salloum et al., 1997) Blurred vision (Kende et al., 1979) Confusion (Tashima, 1975) Retinal hemorrhages and diplopia (Burns, 1992) Visual loss (Shapiro et al., 1992) Myoclonus (Wyllie et al., 1997) Hallucinations (Walsh et al., 1984) Encephalopathy (Nicolao and Giometto, 2003) Peripheral neuropathy (Patel et al., 1997) Headache (Middleton et al., 2000) Seizures (Tfayli et al., 1999) Visual disturbances (Ostrow et al., 1978) Encephalopathy (Lyass et al., 1998) Peripheral neuropathy (Roelofs et al., 1984) Cranial neuropathy (Bokemeyer et al., 1998) Muscle cramps (Siegal and Haim, 1990) Stroke (Doll et al., 1986) Hearing loss (Extra et al., 1998) Paraparesis and quadriparesis (Cheson et al., 1994) Cerebellar dysfunction (Herzig et al., 1987) Aseptic meningitis (Nelson and Frank, 1981) Locked-in syndrome (Kleinschmidt-DeMasters and Yeh, 1992) Encephalopathy (Hwang et al., 1985) Myeloencephalopathy (Resar et al., 1993) Leukoencephalopathy (Lien et al., 1991) Posterior reversible encephalopathy (Russell et al., 2001) Peripheral neuropathy (Dormann et al., 1998) Stroke-like syndrome (Yim et al., 1991) Encephalopathy (Nieto et al., 1999) Coma (Whittaker et al., 1973) Cortical blindness (Byrd et al., 1981) Hallucinations (Ghosh et al., 1994) Lethargy (Brown et al., 2000) Transient dysarthria (Baz et al., 2001) Peripheral neuropathy (Hilkens et al., 1996) Cranial neuropathy (Delaney, 1982) Autonomic disturbances (Carmichael et al., 1970) Optic neuropathy (Capri et al., 1994) Myalgias (McGuire et al., 1989) Stroke (Kukla et al., 1982) Myeloencephalopathy (Arico et al., 1990) Encephalopathy (Pisoni et al., 2001) TIA (Schachter and Freeman, 1982) Stroke (Doll and Yarbro, 1992) Encephalopathy (Pirzada et al., 2000) Multifocal inflammatory leukoencephalopathy (Hook et al., 1992) Subacute leucoencephalopathy (Kuzuhara et al., 1987) Wernicke–Korsakoff-like syndrome (Heier et al., 1986) Cerebellar dysfunction (Riehl and Brown, 1964) Optic neuropathy (Adams et al., 1984) Focal dystonia (Brashear and Siemers, 1997) Acute parkinsonian syndrome (Bergevin et al., 1975) Stroke (Doll and Yarbro, 1992)

Platinum-based agents


Plant alkaloids

Antitumor antibiotics

Fluorinated pyrimidines



Table 107.15 Continued Group

Adverse effects

Tyrosine kinase inhibitors Bortezomib

Headache (Giampaglia et al., 2010) Peripheral neuropathy (Richardson et al., 2006) Stroke (Guo et al., 2010) Encephalopathy (Leonard and Kay, 1986) Ischemic and hemorrhagic stroke (Feinberg and Swenson, 1988) Headache and idiopathic intracranial hypertension (Bigby and Stern, 1988) Cerebellar dysfunction (Bernstein and Leventhal-Rochon, 1996) Depression and suicide (Jacobs et al., 2001) Myalgias/rhabdomyolysis (Trauner and Ruben, 1999) Stroke (Royer et al., 2002) Peripheral neuropathy (La Rocca et al., 1990) Disorientation, visual and hearing loss (Hussain et al., 2000) Stroke (Laterra et al., 2004) Somnolence (Singhal et al., 1999) Peripheral neuropathy (Molloy et al., 2001) Seizures (Fine et al., 2000) Stroke (Ortin et al., 2006)

L-Asparaginase Retinoids



Table 107.16 Common neurologic adverse effects of immunomodulatory agents Group

Adverse effects


Encephalopathy and parkinsonism (Meyers et al., 1991a) Confusion, lethargy, and dizziness (Weiss, 1998) Depression and suicide (Jonasch and Haluska, 2001) Paranoid psychosis (Schafer and Schwaiger, 2003) Cognitive impairment (Valentine et al., 1998) Hearing loss (Kanda et al., 1994) Oculomotor nerve paralysis (Bauherz et al., 1990) Peripheral neuropathy (Bernsen et al., 1988) Spastic diplegia (Barlow et al., 1998) Seizures and vegetative state (Meyers et al., 1991b) Encephalopathy (Siegel and Puri, 1991) Acute fatal leukoencephalopathy (Vecht et al., 1990) Transient visual loss (Bernard et al., 1990) Peripheral neuropathy (Loh et al., 1992) Cerebellar dysfunction (Meyers and Yung, 1993). Transient dysarthria (Baz et al., 2001) Multifocal inflammatory leukoencephalopathy (Kimmel et al., 1995) Insomnia, headache and dizziness (Parkinson et al., 1977) Progressive multifocal leukoencephalopathy (Carson et al., 2009) Hemorrhagic stroke (Ranpura et al., 2010) Hypophysitis (Blansfield et al., 2005) Uveitis (Weber et al., 2008) Cerebral aspergillosis (Amadori et al., 2010)



Monoclonal antibodies



Table 107.17 Neurologic adverse effects of ergotamine toxicity Drug

Adverse effects

Ergotamine tartrate

Coma (Hudgson and Hart, 1964) Peroneal nerve palsy (Merhoff and Porter, 1974) Transient monocular blindness (Merhoff and Porter, 1974) Headache (Wainscott et al., 1974) Homonymous hemianopia, hemiplegia, uninhibited behavior (Senter et al., 1976) Neuropsychiatric symptoms (Fl€ ugel et al., 1977) Paraplegia (Lenger, 1984) Bilateral focal cortical atrophy/ infarcts (Fincham et al., 1985) Carotid artery territory infarct (Berlit et al., 1986) Bilateral ischemic optic neuropathy (Sommer et al., 1998) Dystonia and reflex sympathetic dystrophy (Merello et al., 1991)

effects observed have been rhabdomyolysis (Emadian et al., 1996) and opsoclonus (Irioka et al., 2009). Cetirizine has been reported to cause sedation and mental performance changes (Spangler and Brunton, 2006), oculogyric crises (Fraunfelder and Fraunfelder, 2004), and dystonia (Esen et al., 2008). Cyproheptadine may cause anticholergic delirium (Scott et al., 2007). Choreoathetosis has also been observed (Samie and Ashton, 1989).

NEUROLOGIC ADVERSE EFFECTS OF HORMONES, HORMONE-RELATED AND METABOLISM DRUGS Hormones and hormone-related drugs Estrogens given in contraceptive doses may have prothrombotic effects and increase stroke risk, both ischemic and hemorrhagic, whether in higher (more than 50 mg per pill) or lower doses (Collaborative Group, 1973; Stadel, 1981). Smoking and migraine increase this risk (Tzourio et al., 1995). Progestogens increase the hazard of venous thromboembolism and may contribute to stroke risk (Jick et al., 1995). There has been a long-standing controversy about the benefit of hormone replacement therapy in postmenopausal women, through possible vascular and cognition protective effects. However, an excess risk of stroke, cognitive decline and dementia was observed with

combined estrogen/progestogen replacement therapy in large randomized studies (Shumaker et al., 2003; Wassertheil-Smoller et al., 2003), and the US Preventive Services Task Force has discouraged or not recommended its use (Humphrey et al., 2002). Oral contraceptives are also known to cause chorea (Nausieda et al., 1979). Agents that inhibit or block natural endogenous hormones and have neurologic side-effects are listed in Table 107.18. Sildenafil may cause headache and eventually cluster headache (de L Figuerola et al., 2006). Visual adverse effects have been described in some patients, such as increased brightness of lights, blue-tinged or blurry vision (Laties and Sharlip, 2006). They are usually transient, appear after higher doses, and are attributed to associated inhibition of the retinal PDE6. Serious ophthalmic side-effects may occur, generally after longer exposure to the drug: branch retinal artery occlusion (Tripathi and O’Donnell, 2000), central serous chorioretinopathy (Allibhai et al., 2004), anterior and posterior ischemic optic neuropathy (Pomeranz and Bhavsar, 2005; Su et al., 2008), acute angle-closure glaucoma (Ramasamy et al., 2007), optic atrophy (Sowka et al., 2007), and stepwise decline in visual field (Pepin and Pitha-Rowe, 2008). Priapism (Sur and Kane, 2000), tonic-clonic seizures (Gilad et al., 2002), vestibular dysfunction (Hamzavi et al., 2002), and amnesia and aggressive behavior (Milman and Arnold, 2002) have also been reported. Intracerebral hemorrhage (McGee et al., 2005), sudden sensorineural hearing loss (Snodgrass et al., 2010) and epileptic seizures (Koussa et al., 2006) have been linked to vardenafil, and transient global amnesia to tadalafil (Schiefer and Sparing, 2005), both sildenafil-related drugs.

Metabolism drugs Long-term ingestion of allopurinol may rarely cause axonal peripheral neuropathy, receding after discontinuation (Azulay et al., 1993). Oral glucose lowering drugs include sulfonylureas and biguanides. Their most frequent side-effect is hypoglycemia. Hypoglycemic encephalopathy can develop insidiously and result in disabling residual neurologic deficits if not recognized in time (Turkington, 1977). Chlorpropamide can cause optic neuropathy (Wymore and Carter, 1982). Biguanides may induce lactic acidosis and encephalopathy, but encephalopathy without lactic acidosis has also been reported (Jung et al., 2009). Vitamins may be neurotoxic (Snodgrass, 1992). Pseudotumor cerebri (benign intracranial hypertension) linked to vitamin A (Drouet and Valance, 1998) and pyridoxine-generated peripheral neuropathy (Scott



Table 107.18 Neurologic adverse effects of most commonly used antihormonal drugs Group


Adverse effects

Antithyroid agents


Prolactin blocking agents

Bromocriptine Cabergoline

Anti-osteoporotic agents (diphosphonates) Antiandrogens and antigonadotrophin-releasing agents Antiestrogens


Optic neuritis (Sponzilli et al., 1979) Cerebral vasculitis (Tripodi et al., 2008) Postpartum cerebral angiopathy (Chartier et al., 1997) Puerperal seizures (von Werder, 1996) Cerebrospinal fluid leakage (Netea-Maier et al., 2006) SUNCT syndrome (Jime´nez Caballero, 2007) Pathological gambling and hypersexuality (Falhammar and Yarker, 2009) Chiasmal herniation and secondary deterioration of visual field (Raverot et al., 2009) Priapism (De La Pen˜a Zarzuelo et al., 2010) Transient cranial neuropathy (de Klerk et al., 1996)


Atypical absence seizures (Akaboshi and Takeshita, 2000)


Retinopathy (Nayfield and Gorin, 1996) Cerebral venous sinus thrombosis (Bushnell and Goldstein, 2004)

et al., 2008) are well-established neurologic adverse effects of vitamins. The initiation of vitamin B12 treatment for cyanocobalamin deficiency has been reported to eventually induce seizures (Benbir et al., 2007) and involuntary movements (tremor, myoclonus) (Ozdemir et al., 2010). Vitamin D has also been related to pseudotumor cerebri (Alpan et al., 1991). Prolonged vitamin D administration may result in muscle calcinosis due to hypercalcemia (Chiricone et al., 2003). Drug-induced hypercalcemia is caused by increased bone resorption (vitamin D and vitamin A intoxication), increased gastrointestinal absorption (vitamin D intoxication, excessive calcium intake) or increased renal tubule reabsorption (thiazide diuretics) of calcium (Sato, 2006). The administration of high levels of vitamin E is contraindicated in subjects who are receiving vitamin K antagonists as anticoagulant therapy (Machlin, 1989).

NEUROLOGIC ADVERSE EFFECTS OF RESPIRATORY TRACT DRUGS Bronchodilators with b-stimulating adrenergic effect may cause classic adrenergic reactions. Tremor may sometimes be intense and disabling (Ozog and Lerner, 1989). Posterior reversible encephalopathy has been observed in relation to pseudoephedrine (Ebbo et al., 2010). Theophylline may induce seizures and nonconvulsive status epilepticus (Paloucek and Rodvold, 1988; Krieger and Takeyasu, 1999).

Dextromethorphan, alone or in association, has been observed to cause distonic reaction (Warden et al., 1997), agitated psychosis, and ataxia (Roberge et al., 1999; Price and Lebel, 2000).

NEUROLOGIC ADVERSE EFFECTS OF GENITOURINARY AND DIGESTIVE TRACT DRUGS Smooth muscle spasmolytic drugs with anticholinergic antimuscarinic action all entail a risk of anticholinergic delirium: sudden confusion, distractibility, dysarthria, logorrhea, dry mouth, restlessness, tremor, and visual hallucinations (Lipowski, 1990). Agents stimulating uterine contractility to induce labor have been associated with postpartum cerebral angiopathy and hypertensive encephalopathy (Garre´ et al., 1978; Chartier et al., 1997; Sato et al., 2004). Antiemetic and gastroprokinetic drugs may cause extrapiramidal side-effects. Related antiemetic agents with an indirect parasympathomimetic effect may also induce extrapyramidal toxicity. The neurologic adverse effects of antiemetics appear in Table 107.19. Gastric H2-receptor inhibitors have been associated with some neurologic side-effects, including confusion (Sonnenblick and Yinnon, 1986), extrapyramidal and cerebellar syndrome with encephalopathy (Handler et al., 1982), and hemiballism (Elzinga-Huttenga et al., 2006). Gastric protonic pump inhibitors have been associated with central fever with severe myalgia (Grattagliano



Table 107.19 Neurologic adverse effects of most commonly used antiemetic drugs Drug

Adverse effects


Myoclonus (Hyser and Drake, 1983) Parkinsonism, tardive dyskinesia, tardive dystonia, akathisia (Miller and Jankovic, 1989) Acute dyskinesia (Andrejak et al., 1990) Dystonic reaction (Guala et al., 1992) Oculogyric crisis (Lou and Abou-Zeid, 2006) Oculogyric crisis (Shafrir et al., 1985) Acute dyskinesia (Andrejak et al., 1990) Acute dystonia (Yamada et al., 2010) Syncope associated with QT prolongation (Gray, 1998) Akathisia, abnormal movements (Elzinga-Huttenga et al., 2006) Transient dyskinesia (Martı´nez-Martı´n, 1993) Parkinsonism, tardive dyskinesia (Sempere et al., 1994) Acute dystonic reaction (Sprung et al., 2003) Oromandibular/limb dystonia, oculogyric crisis, multifocal encephalopathy (Ritter et al., 2003)

Domperidone Droperidol Cisapride Clebopride Ondansetron

et al., 2005), myopathy (Clark and Strandell, 2006), and panic attacks and confusion (Polimeni et al., 2007).

CONCLUSION Almost every drug can produce neurologic adverse effects. The compelling evidence of the frequency of iatrogenic pharmacologic disease is large enough to warrant its consideration as a differential diagnosis when assessing the neurologically ill patient.

REFERENCES Aagaard L, Hansen EH (2010). Adverse drug reactions reported for systemic antibacterials in Danish children over a decade. Br J Clin Pharmacol 70: 765–768. ACTIVE Investigators, Connolly SJ, Pogue J, Hart RG et al. (2009). Effect of clopidogrel added to aspirin in patients with atrial fibrillation. N Engl J Med 360: 2066–2078. Adams P, White C (1965). Isoniazid-induced encephalopathy. Lancet 1: 680–682. Adams JW, Bofenkamp TM, Kobrin J et al. (1984). Recurrent acute toxic optic neuropathy secondary to 5-FU. Cancer Treat Rep 68: 565–566. Adams HP Jr, del Zoppo G, Alberts MJ et al. (2007). Guidelines for the early management of adults with ischemic stroke. Stroke 38: 1655–1711. Agus B, Nelson J, Kramer N et al. (1990). Acute central nervous system symptoms caused by ibuprofen in connective tissue disease. J Rheumatol 17: 1094–1096. Ahmad S (1991). Nitroglycerin and intracranial hypertension. Am Heart J 121: 1850–1851. Ahmad S (1993). Diltiazem myopathy. Am Heart J 126: 1494–1495.

Akaboshi S, Takeshita K (2000). A case of atypical absence seizures induced by leuprolide acetate. Pediatr Neurol 23: 266–268. Allibhai ZA, Gale JS, Sheidow TS (2004). Central serous chorioretinopathy in a patient taking sildenafil citrate. Ophthalmic Surg Lasers Imaging 35: 165–167. Almeida MS, Padala PR, Bhatia S (2006). Methylphenidateinduced akathisia in a patient with multiple sclerosis. Prim Care Companion J Clin Psychiatry 8: 379–380. Alpan G, Glick B, Peleg O et al. (1991). Pseudotumor cerebri and coma in vitamin D-dependent rickets. Clin Pediatr (Phila) 30: 254–256. Amadori S, Suciu S, Selleslag D et al. (2010). Randomized trial of two schedules of low-dose gemtuzumab ozogamicin as induction monotherapy for newly diagnosed acute myeloid leukaemia in older patients not considered candidates for intensive chemotherapy. A phase II study of the EORTC and GIMEMA leukaemia groups (AML-19). Br J Haematol 149: 376–382. Andersohn F, Schade R, Willich SN et al. (2010). Use of antiepileptic drugs in epilepsy and the risk of self-harm or suicidal behavior. Neurology 75: 335–440. Andrejak M, Masmoudi K, Mizon JP (1990). Acute dyskinesia after the ingestion of antiemetics leading to emergency hospitalization. Therapie 45: 33–35. Anzueto A, Gotfried M, Wikler MA et al. (2002). Efficacy and tolerability of gatifloxacin in community treatment of acute exacerbations of chronic bronchitis. Clin Ther 24: 906–917. Arber N (1988). Delirium induced by atenolol. BMJ 297: 1048. Arico M, Nespoli L, Porta F et al. (1990). Severe acute encephalopathy following inadvertent intrathecal doxorubicin administration. Med Pediatr Oncol 18: 261–263. Aruna AS, AL-Sammarra SA, AL-Humaidan AS (2000). Amphotericin B-induced seizures in a patient with AIDS. HIV Clin 12: 6–8.

IATROGENIC NEUROLOGY Ashton H, Gallagher P, Moore B (2006). The adult psychiatrist’s dilemma: psychostimulant use in attention deficit/ hyperactivity disorder. J Psychopharmacol 20: 602–610. Avorn J, Schneeweiss S, Sudarsky L et al. (2005). Sudden uncontrollable somnolence and medication use in Parkinson disease. Arch Neurol 62: 1242–1248. Azulay JP, Blin O, Valentin P et al. (1993). Regression of allopurinol-induced peripheral neuropathy after drug withdrawal. Eur Neurol 33: 193–194. Babai S, Auriche P, Le-Loue¨t H (2010). Comparison of adverse drug reactions with donepezil versus memantine: analysis of the French Pharmacovigilance Database. Therapie 65: 255–259. Bae JS, Go SM, Kim BJ (2006). Clinical predictors of steroidinduced exacerbation in myasthenia gravis. J Clin Neurosci 13: 1006–1010. Bagheri H, Simiand E, Montastruc JL et al. (2004). Adverse drug reactions to anthelmintics. Ann Pharmacother 38: 383–388. Bailey RR (1977). Scalp tingling and difficulty in micturition in patients on labetalol. Lancet 2: 720–721. Bainbridge JL, Page RL 2nd, Ruscin JM (2008). Elucidating the mechanism of action and potential interactions of MAO-B inhibitors. Neurol Clin 26 (3 Suppl): 85–96. Bala´zs J, Besnyo M, Ga´doros J (2007). Methylphenidateinduced orofacial and extremity dyskinesia. J Child Adolesc Psychopharmacol 17: 378–381. Bangs ME, Tauscher-Wisniewski S, Polzer J et al. (2008). Meta-analysis of suicide-related behavior events in patients treated with atomoxetine. J Am Acad Child Adolesc Psychiatry 47: 209–218. Barbanti P, Fabbrini G, Berardelli A (2008). Acute pathological laughter induced by sumatriptan. Cephalalgia 28: 92–93. Barlow CF, Priebe CJ, Mulliken JB et al. (1998). Spastic diplegia as a complication of interferon alfa-2a treatment of hemangiomas of infancy. J Pediatr 132: 527–530. Barlow WE, Davis RL, Glasser JW et al. (2001). The risk of seizures after receipt of whole-cell pertussis or measles, mumps, and rubella vaccine. N Engl J Med 345: 656–661. Barnes D, Hughes RA (1992). Guillain–Barre´ syndrome after treatment with streptokinase. BMJ 304: 1225. Bauherz G, Soeur M, Lustman F (1990). Oculomotor nerve paralysis induced by alpha II-interferon. Acta Neurol Belg 90: 111–114. Baust W, Meyer D, Wachsmuth W (1979). Peripheral neuropathy after administration of tetanus toxoid. J Neurol 222: 131–133. Baz DV, Bofill JS, Nogueira JA (2001). Irinotecan-induced dysarthria. J Natl Cancer Inst 93: 1419–1420. Bazan JA, Martin SI, Kaye KM (2009). Newer beta- lactam antibiotics: doripenem, cef tobiprole, ceftaroline, and cefepime. Infect Dis Clin North Am 23: 983–996. Beasley CM Jr, Dornseif BE, Pultz JA et al. (1991). Fluoxetine versus trazodone: efficacy and activating-sedating effects. J Clin Psychiatry 52: 294–299. Benbir G, Uysal S, Saltik S et al. (2007). Seizures during treatment of vitamin B12 deficiency. Seizure 16: 69–73.


Beran RG, Gibson RJ (1998). Aggressive behaviour in intellectually challenged patients with epilepsy treated with lamotrigine. Epilepsia 39: 280–282. Bergevin PR, Patwardhan VC, Weissman J et al. (1975). Letter: Neurotoxicity of 5-fluorouracil. Lancet 1: 410. Berlit P, Gerhardt H, Huck K et al. (1986). Ergotism with cerebral complications. Case report and review of the literature. Schweiz Med Wochenschr 116: 440–445. Bernard JT, Ameriso S, Kempf RA et al. (1990). Transient focal neurologic deficits complicating interleukin-2 therapy. Neurology 40: 154–155. Bernat JL, Sullivan JK (1979). Trigeminal neuralgia from digitalis intoxication. JAMA 241: 164. Bernsen PL, Wong Chung RE, Vingerhoets HM et al. (1988). Bilateral neuralgic amyotrophy induced by interferon treatment. Arch Neurol 45: 449–451. Bernstein AL, Leventhal-Rochon JL (1996). Neurotoxicity related to the use of topical tretinoin (Retin-A). Ann Intern Med 124: 227–228. Bezzi G, Gessa GL (1961). Influence of antibiotics on the neuromuscular transmission in mammals. Antibiot Chemother 11: 710–714. Bhatia KP, M€ unchau A, Thompson PD et al. (1999). Generalised muscular weakness after botulinum toxin injections for dystonia: a report of three cases. J Neurol Neurosurg Psychiatry 67: 90–93. Bigby M, Stern RS (1988). Adverse reactions to isotretinoin. A report from the Adverse Drug Reaction Reporting System. J Am Acad Dermatol 18: 543–552. Biller J (1998). Iatrogenic Neurology. ButterworthHeinemann, Boston and Oxford. Bischoff A, Meier C, Roth F et al. (1977). Gentamicin neurotoxicity (polyneuropathy-encephalopathy). Schweiz Med Wochenschr 107: 3–8. Blankenhorn MA (1938). Multiple peripheral neuritis occurring with sulfonamide therapy. JAMA 111: 2103. Blansfield JA, Beck KA, Tran K et al. (2005). Cytotoxic T-lymphocyte-associated antigen-4 blockage can induce autoimmune hypophysitis in patients with metastatic melanoma and renal cancer. J Immunother 28: 593–598. Blum J, Wiestner A, Fuhr P et al. (2001). Encephalopathy following Loa loa treatment with albendazole. Acta Trop 78: 63–65. Bodhe PV, Kotwani RN, Kirodian BG et al. (2002). Open label, randomised, comparative phase III safety and efficacy study with conventional amphotericin B and liposomal amphotericin B in patients with systemic fungal infection. J Assoc Physicians India 50: 662–670. Bokemeyer C, Berger CC, Hartmann JT et al. (1998). Analysis of risk factors for cisplatin induced ototoxicity in patients with testicular cancer. Br J Cancer 77: 1355–1362. Bortoli R, Santiago M (2007). Chloroquine ototoxicity. Clin Rheumatol 26: 1809–1810. Brashear A, Siemers E (1997). Focal dystonia after chemotherapy: a case series. J Neurooncol 34: 163–167. Brent DA, Crumrine PK, Varma RR et al. (1987). Phenobarbital treatment and major depressive disorder in children with epilepsy. Pediatrics 80: 909–917.



Brown ES (2009). Effects of glucocorticoids on mood, memory, and the hippocampus. Treatment and preventive therapy. Ann N Y Acad Sci 1179: 41–55. Brown JV III, Peters WA III, Rettenmaier MA et al. (2000). A phase I trial of a 3-day topotecan Q 21 days for recurrent epithelial cancers of the ovary, fallopian tube, and peritoneum. Gynecol Oncol 79: 495–498. Brown RT, Zuelsdorff M, Fleming M (2006). Adverse effects and cognitive function among primary care patients taking opioids for chronic nonmalignant pain. J Opioid Manag 2: 137–146. Bucy PC (1937). Toxic optic neuritis resulting from sulfanilamide. JAMA 109: 1007–1008. Buffett-Jerrott SE, Stewart SH (2002). Cognitive and sedative effects of benzodiazepine use. Curr Pharm Des 8: 45–58. Burd L, Kerbeshian J (1991). Stuttering and stimulants. J Clin Psychopharmacol 11: 72–73. Burn DJ, Tr€oster AI (2004). Neuropsychiatric complications of medical and surgical therapies for Parkinson’s disease. J Geriatr Psychiatry Neurol 17: 172–180. Burns LJ (1992). Ocular toxicities of chemotherapy. Semin Oncol 19: 492–500. Bushnell CD, Goldstein LB (2004). Risk of ischemic stroke with tamoxifen treatment for breast cancer: a metaanalysis. Neurology 63: 1230–1233. Bussaratid V, Krudsood S, Silachamroon U et al. (2005). Tolerability of ivermectin in gnathostomiasis. Southeast Asian J Trop Med Public Health 36: 644–649. Byrd RL, Rohrbaugh TM, Raney RB Jr et al. (1981). Transient cortical blindness secondary to vincristine therapy in childhood malignancies. Cancer 47: 37–40. Cadman PJ (1995). Case report: femoral nerve palsy complicating femoral artery puncture and intra-arterial thrombolysis. Clin Radiol 50: 345–346. Camfield CS, Chaplin S, Doyle AB et al. (1979). Side effects of phenobarbital in toddlers; behavioral and cognitive aspect. J Pediatr 95: 361–365. Campbell RWF (1987). Mexiletine. N Engl J Med 316: 29–34. Can˜ete R, Escobedo AA, Gonza´lez ME et al. (2006). A randomized, controlled, open-label trial of a single day of mebendazole versus a single dose of tinidazole in the treatment of giardiasis in children. Curr Med Res Opin 22: 2131–2136. Canto´n R, Ruiz-Garbajosa P, Chaves RL et al. (2010). A potential role for daptomycin in enterococcal infections: what is the evidence? J Antimicrob Chemother 65: 1126–1136. Capaldi VF 2nd, Carr RB (2010). Citalopram-induced hallucinations and delusions in a young adult. Gen Hosp Psychiatry 32: 648.e1–648.e3. Capri G, Munzone E, Tarenzi E et al. (1994). Optic nerve disturbances: a new form of paclitaxel neurotoxicity. J Natl Cancer Inst 86: 1099–1101. Carbone JR (2000). The neuroleptic malignant and serotonin syndromes. Emerg Med Clin North Am 18: 317–325. Carmichael SM, Eagleton L, Ayers CR et al. (1970). Orthostatic hypotension during vincristine therapy. Arch Intern Med 126: 290–293.

Carnevale NT, Galgiani JN, Stevens DA et al. (1980). Amphotericin B-induced myelopathy. Arch Intern Med 140: 1189–1192. Carson KR, Focosi D, Major EO et al. (2009). Monoclonal antibody-associated progressive multifocal leucoencephalopathy in patients treated with rituximab, natalizumab, and efalizumab: a review from the Research on Adverse Drug Events and Reports (RADAR) project. Lancet Oncol 10: 816–824. Casteels K, Van Geet C, Wouters K (1998). Ethosuximideassociated lupus with cerebral and renal manifestations. Eur J Pediatr 157: 780. Casteels-Van Daele M, Van Geet C, Wouters C et al. (2000). Reye syndrome revisited: a descriptive term covering a group of heterogeneous disorders. Eur J Pediatr 159: 641–648. Cespedes MS, Aberg JA (2006). Neuropsychiatric complications of antiretroviral therapy. Drug Saf 29: 865–874. Chadwick DW, Marson AG (2005). Zonisamide add-on for drug-resistant epilepsy. Cochrane Database Syst Rev 4: CD001416. Chan CC, Sogg RL, Steinman L (1980). Isolated oculomotor palsy after measles immunization. Am J Ophthalmol 89: 446–448. Chapman P (1982). Naproxen and sudden hearing loss. J Laryngol Otol 96: 163–166. Chariot P, Abadia R, Danan C et al. (1993). Simvastatininduced rhabdomyolisis followed by a MELAS syndrome. Am J Med 94: 109–110. Chartier JP, Bousigue JY, Teisseyre A et al. (1997). Postpartum cerebral angiopathy of iatrogenic origin. Rev Neurol (Paris) 153: 212–214. Charuvastra A, Yaeger D (2006). Tactile hallucinations associated with therapeutic doses of bupropion in 2 patients. J Clin Psychiatry 67: 1820–1821. Cheson BD, Vena DA, Foss FM et al. (1994). Neurotoxicity of purine analogs: a review. J Clin Oncol 12: 2216–2228. Cheuvart B, Friedland LR, Abu-Elyazeed R et al. (2009). The human rotavirus vaccine RIX4414 in infants: a review of safety and tolerability. Pediatr Infect Dis J 28: 225–232. Chiricone D, De Santo NG, Cirillo M (2003). Unusual cases of chronic intoxication by vitamin D. J Nephrol 16: 917–921. Choi JH, Choi KD, Kim JS et al. (2008). Simultaneous posterior ischemic optic neuropathy, cerebral border zone infarction, and spinal cord infarction after correction of malignant hypertension. J Neuroophthalmol 28: 198–201. Choo D, Hossain M, Liew P et al. (2011). Side effects of oseltamivir in end-stage renal failure patients. Nephrol Dial Transplant 26: 2339–2344. Chouliaras G, Spoulou V, Quinlivan M et al. (2010). Vaccineassociated herpes zoster ophthalmicus and encephalitis in an immunocompetent child. Pediatrics 125: e969–e972. Chow KM, Szeto CC, Hui ACF et al. (2003). Retrospective review of neurotoxicity induced by cefepime and ceftazidime. Pharmacotherapy 23: 369–373. Chow KM, Hui AC, Szeto CC (2005). Neurotoxicity induced by beta-lactam antibiotics: from bench to bedside. Eur J Clin Microbiol Infect Dis 24: 649–653.

IATROGENIC NEUROLOGY Chung S, Joung YS (2010). Oseltamivir (Tamiflu) induced depressive episode in a female adolescent. Psychiatry Investig 7: 302–304. Chyka PA, Erdman AR, Christianson G et al. (2007). Salicylate poisoning: an evidence-based consensus guideline for out-of-hospital management. Clin Toxicol (Phila) 45: 95–131. Clark DW, Strandell J (2006). Myopathy including polymyositis: a likely class adverse effect of proton pump inhibitors? Eur J Clin Pharmacol 62: 473–479. Cleveland KO, Campbell JW (1995). Hallucinations associated with itraconazole therapy. Clin Infect Dis 21: 456. Colebunders R, Hilbrands R, De Roo A et al. (2002). Neuropsychiatric reaction induced by abacavir. Am J Med 113: 616. Collaborative Group for the Study of Stroke in Young Women (1973). Oral contraception and increased risk of cerebral ischemia or thrombosis. N Engl J Med 288: 871–878. Confavreux C, Charles N, Aimard G (1990). Fulminant myasthenia gravis soon after initiation of acebutolol therapy. Eur Neurol 30: 279–281. Cooper JA, Sagar HJ, Doherty SM et al. (1992). Different effects of dopaminergic and anticholinergic therapies on cognitive and motor function in Parkinson’s disease. A follow-up study of untreated patients. Brain 115: 1701–1725. Corman SL, Fedutes BA, Culley CM (2004). Atomoxetine: the first nonstimulant for the management of attention-deficit/ hyperactivity disorder. Am J Health Syst Pharm 61: 2391–2399. Correll CU, Carlson HE (2006). Endocrine and metabolic adverse effects of psychotropic medications in children and adolescents. J Am Acad Child Adolesc Psychiatry 45: 771–791. Costa I, Castanet J, Lacour JP et al. (1994). Vertigo and hypokalemia: two rare side effects of itraconazole. Therapie 49: 149. Coxon A, Pallis CA (1976). Metronidazole neuropathy. J Neurol Neurosurg Psychiatry 39: 403–405. Cramer J, Fisher R, Ben-Menachem E et al. (1999). New antiepileptic drugs: a comparison of key clinical trials. Epilepsia 40: 590–600. Crampton RS, Oriscello RG (1968). Petit and grand mal convulsions during lidocaine hydrochloride treatment of ventricular tachycardia. JAMA 204: 201–204. Cubo Delgado E, Sanz Boza R, Garcia Urra D et al. (1997). Acute cerebellopathy as a probable toxic effect of flucytosine. Eur J Clin Pharmacol 51: 505–506. Curhan SG, Eavey R, Shargorodsky J et al. (2010). Analgesic use and the risk of hearing loss in men. Am J Med 123: 231–237. Curran M, Noble S (2001). Valganciclovir. Drugs 61: 1145–1150. D’Silva M, Leibowitz D, Flaherty JP et al. (1995). Seizure associated with zidovudine. Lancet 346: 452. Darchy B, Le Mie`re E, Figue´re´do B et al. (1999). Iatrogenic diseases as a reason for admission to the intensive care unit: incidence, causes, and consequences. Arch Intern Med 159: 71–78.


Darlington CL, Smith PF (2003). Vestibulotoxicity following aminoglycoside antibiotics and its prevention. Curr Opin Investig Drugs 4: 841–846. Dauner DG, Nelson RE, Taketa DC et al. (2010). Ceftobiprole: a novel, broad-spectrum cephalosporin with activity against methicillin-resistant Staphylococcus aureus. Am J Health Syst Pharm 67: 983–993. David D, Esquenazi J (1999). Rhabdomyolysis associated with bupropion treatment. J Clin Psychopharmacol 19: 185–186. Davis R, Whittington R, Bryson HM (1997). Nefazodone. A review of its pharmacology and clinical efficacy in the management of major depression. Drugs 53: 608–636. de Klerk JM, Zonnenberg BA, Krouwer HG et al. (1996). Transient cranial neuropathy in prostatic cancer with bone metastases after rhenium-186-HEDP treatment. J Nucl Med 37: 465–467. de L Figuerola M, Bruera O, Leston J et al. (2006). Cluster headache attack due to sildenafil intake. Cephalalgia 26: 617–619. de la Garza CL, Paoletti-Duarte S, Garcia-Martin C et al. (2001). Efavirenz induced psychosis. AIDS 15: 1911–1912. de La Pen˜a Zarzuelo E, Herna´ndez Can˜as V, Llorente Abarca C (2010). Priapism secondary to treatment due to cabergoline: the first description of this association. Actas Urol Esp 34: 487–488. de Luca G, Navarese E, Marino P (2009). Risk profile and benefits from Gp IIb-IIIa inhibitors among patients with ST-segment elevation myocardial infarction treated with primary angioplasty: a meta-regression analysis of randomized trials. Eur Heart J 30: 2705–2713. De Medina A, Biasini O, Rivera A et al. (1986). Nifedipine and myoclonic dystonia. Ann Intern Med 104: 125. De Wals P, Deceuninck G, Ouakki M et al. (2009). Analysis of mortality following a mass immunization campaign with serogroup C meningococcal conjugate vaccine: methodological difficulties and imperfect solutions. Vaccine 27: 3223–3227. Deisenhammer F, Pohl P, Bosch S et al. (1994). Acute cerebellar ataxia after immunisation with recombinant hepatitis B vaccine. Acta Neurol Scand 89: 462–463. DeJonckere PH, de Surge`res GG (2001). Acute tinnitus and permanent audiovestibular damage after hepatitis B vaccination. Int Tinnitus J 7: 59–61. del Zoppo GJ, Saver JL, Jauch EC et al. (2009). Expansion of the time window for treatment of acute ischemic stroke with intravenous tissue plasminogen activator: a science advisory from the American Heart Association/American Stroke Association. Stroke 40: 2945–2948. Delaney P (1982). Vincristine-induced laryngeal nerve paralysis. Neurology 32: 1285–1288. Denis C, Fatse´as M, Lavie E et al. (2006). Pharmacological interventions for benzodiazepine mono-dependence management in outpatient settings. Cochrane Database Syst Rev 3: CD005194. Desarkar P, Sinha VK (2006). Acute urinary retention associated with atomoxetine use. Aust N Z J Psychiatry 40: 936. Devuyst O, Goffin E, van Ypersele de Strihou C (1995). Recurrent hemiparesis under amphotericin B for



Candida albicans peritonitis. Nephrol Dial Transplant 10: 699–701. Dewey RB Jr (2004). Autonomic dysfunction in Parkinson’s disease. Neurol Clin 22(3 Suppl): S127–S139. Dick RS, Barold SS (1989). Diltiazem-induced parkinsonism. Am J Med 87: 95–96. Doan TL, Fung HB, Mehta D et al. (2006). Tigecycline: a glycylcycline antimicrobial agent. Clin Ther 28: 1079–1106. Dodd ML, Klos KJ, Bower JH et al. (2005). Pathological gambling caused by drugs used to treat Parkinson disease. Arch Neurol 62: 1377–1381. Doll DC, Yarbro JW (1992). Vascular toxicity associated with antineoplastic agents. Semin Oncol 19: 580–596. Doll DC, List AF, Greco FA et al. (1986). Acute vascular ischemic events after cisplatin-based combination chemotherapy for germ-cell tumors of the testis. Ann Intern Med 105: 48–51. Dormann AJ, Grunewald T, Wigginghaus B et al. (1998). Gemcitabine-associated autonomic neuropathy. Lancet 351: 644. Drake ME, Peruzzi WT (1986). Manic state with carbamazepine therapy of seizures. J Natl Med Assoc 78: 1105–1110. Drouet A, Valance J (1998). Benign intracranial hypertension and chronic hypervitaminosis A. Rev Neurol (Paris) 154: 253–256. Ducros A (2010). Reversible cerebral vasoconstriction syndrome. Rev Neurol (Paris) 166: 365–376. Dundar Y, Hill R, Dickson R et al. (2003). Comparative efficacy of thrombolytics in acute myocardial infarction: a systematic review. QJM 96: 103–113. Duquaine S, Kitchell E, Tate T et al. (2011). Central nervous system toxicity associated with ertapenem use. Ann Pharmacother 45: e6. Duque A, Altimiras J, Garcı´a-Cases C et al. (1991). Vertigo caused by intravenous imipenem/cilastatin. DICP 25: 1009. Dutkowski R, Smith JR, Davies BE (2010). Safety and pharmacokinetics of oseltamivir at standard and high dosages. Int J Antimicrob Agents 35: 461–467. DuVernoy TS, Braun MM (2000). Hypotonic-hyporesponsive episodes reported to the Vaccine Adverse Event Reporting System (VAERS), 1996–1998. Pediatrics 106: E52. Ebbo M, Benarous L, Thomas G et al. (2010). Posterior reversible encephalopathy syndrome induced by a cough and cold drug containing pseudoephedrine. Rev Med Interne 31: 440–444. Ehyai A, Kilroy AW, Fenichel GM (1978). Dyskinesia and akathisia induced by ethosuximide. Am J Dis Child 132: 527–528. Elmer L (2004). Cognitive issues in Parkinson’s disease. Neurol Clin 22(Suppl 1): 91–106. Elzinga-Huttenga J, Hekster Y, Bijl A et al. (2006). Movement disorders inducedby gastrointestinal drugs: two paediatric cases. Neuropediatrics 37: 102–106. Emadian SM, Caravati EM, Herr RD (1996). Rhabdomyolysis: a rare adverse effect of diphenhydramine overdose. Am J Emerg Med 14: 574–576. England JD, Walsh JC, Stewart P et al. (1995). Mitochondrial myopathy developing on treatment with the HMG CoA

reductase inhibitors – simvastatin and pravastatin. Aust N Z J Med 25: 374–375. Erenberg G (2005). The relationship between Tourette syndrome, attention deficit hyperactivity disorder, and stimulant medication: a critical review. Semin Pediatr Neurol 12: 217–221. Erkens PM, Prins MH (2010). Fixed dose subcutaneous low molecular weight heparins versus adjusted dose unfractionated heparin for venous thromboembolism. Cochrane Database Syst Rev 9: CD001100. Esen I, Demirpence S, Yis U et al. (2008). Cetirizine-induced dystonic reaction in a 6-year-old boy. Pediatr Emerg Care 24: 627–628. Etminan M, Gill S, Samii A (2003). Comparison of the risk of adverse events with pramipexole and ropinirole in patients with Parkinson’s disease. A meta-analysis. Drug Saf 26: 439–444. Extra JM, Marty M, Brienza S et al. (1998). Pharmacokinetics and safety profile of oxaliplatin. Semin Oncol 25: 13–22. Falagas ME, Kasiakou SK (2006). Toxicity of polymyxins: a systematic review of the evidence from old and recent studies. Crit Care 10: R27. Falhammar H, Yarker JY (2009). Pathological gambling and hypersexuality in cabergoline-treated prolactinoma. Med J Aust 190: 97. Fam AG, Gordon DA, Sarkozi J et al. (1984). Neurologic complications associated with gold therapy for rheumatoid arthritis. J Rheumatol 11: 700–706. Fan-Harvard P, Sanchorawala V, Oh J et al. (2009). Concurrent use of foscarnet and ciprofloxacin may increase the propensity for seizures. Ann Pharmacother 28: 869–872. Fanning WL, Gump DW, Sofferman RA (1977). Side effects of minocycline: a double-blind study. Antimicrob Agents Chemother 11: 712–717. Farber BF, Moellering RC Jr (1983). Retrospective study of the toxicity of preparations of vancomycin from 1974 to 1981. Antimicrob Agents Chemother 23: 138–141. Farkouh ME, Greenberg BP (2009). An evidence-based review of the cardiovascular risks of nonsteroidal antiinflammatory drugs. Am J Cardiol 103: 1227–1237. Feinberg WM, Swenson MR (1988). Cerebrovascular complications of L-asparaginase therapy. Neurology 38: 127–133. Feiner LA, Younge BR, Kazmier FJ et al. (1987). Optic neuropathy and amiodarone therapy. Mayo Clin Proc 62: 702–717. Ferna´ndez-Torre JL, Velasco M, Gutie´rrez R et al. (2004). Encephalopathy secondary to imipenem therapy. Clin EEG Neurosci 35: 100–103. Ferrick KJ, Power M (1990). Profound exacerbation of neuromuscualar weakness by flecainide. Am Heart J 119: 414–415. Fincham RW, Perdue Z, Dunn VD (1985). Bilateral focal cortical atrophy and chronic ergotamine abuse. Neurology 35: 720–722. Fine HA, Figg WD, Jaeckle K et al. (2000). Phase II trial of the antiangiogenic agent thalidomide in patients with recurrent high-grade gliomas. J Clin Oncol 18: 708–715. Fisher CM (1981). Visual disturbances associated with quinidine and quinine. Neurology 31: 1569–1571.

IATROGENIC NEUROLOGY Fishwick D, Prasan A, Adams P (1995). Thrombolysis and low back pain. BMJ 310: 504. Fl€ ugel KA, Niedermaier K, Lang E (1977). The neuropsychiatric symptomatology of chronic ergotamine tartrate intoxication. Casuistic contribution to pharmacogenetic ergotism. Nervenarzt 48: 441–445. Fogdall RP, Miller RD (1974). Prolongation of a pancuronium-induced neuromuscular blockade by polymyxin B. Anesthesiology 40: 84–87. Foster R, Taylor C, Everall IP et al. (2004). More on abacavirinduced neuropsychiatric reactions. AIDS 18: 2449. Fraser AG, McQueen INF, Watt AH et al. (1985). Peripheral neuropathy during longterm high-dose amiodarone therapy. J Neurol Neurosurg Psychiatry 48: 576–578. Fraunfelder FW, Fraunfelder FT (2004). Oculogyric crisis in patients taking cetirizine. Am J Ophthalmol 137: 355–357. Frytak S, Moertel CH, Childs DS et al. (1978). Neurologic toxicity associated with high-dose metronidazole therapy. Ann Intern Med 88: 361–362. Fujinaga T, Motegi Y, Tamura H et al. (1991). A prefecturewide survey of mumps meningitis associated with measles, mumps and rubella vaccine. Pediatr Infect Dis J 10: 204–209. Fung HB, Doan TL (2005). Tinidazole: a nitroimidazole antiprotozoal agent. Clin Ther 27: 1859–1884. Fung HB, Guo Y (2004). Enfuvirtide: a fusion inhibitor for the treatment of HIV infection. Clin Ther 26: 352–378. Fung HB, Kirschenbaum HL, Ojofeitimi BO (2001). Linezolid: an oxazolidinone antimicrobial agent. Clin Ther 23: 356–391. Garcia-Valladares I, Espinoza LR (2010). Ezetimibe-induced relapsing polymyositis. J Rheumatol 37: 472. Garnock-Jones KP, Keating GM (2009). Atomoxetine: a review of its use in attention-deficit hyperactivity disorder in children and adolescents. Paediatr Drugs 11: 203–226. Garre´ M, Oudry B, Thomas R et al. (1978). Acute hypertensive encephalopathy post partum after using methyl ergometrin. Nouv Presse Med 7: 467. Gay CT, Ryan SG (1994). Paroxysmal kinesigenic dystonia after methylphenidate administration. J Child Neurol 9: 45–46. Geddes AM (1999). Grepafloxacin: an overview of antibacterial activity, pharmacokinetics, clinical efficacy and safety. Expert Opin Investig Drugs 8: 487–505. George DL, Benonis JG (2003). Neurological adverse event after administration of the hepatitis A vaccine. Am J Med 115: 587. Gerber PE, Lynd LD (1998). Selective serotonin-reuptake inhibitor-induced movement disorders. Ann Pharmacother 32: 692–698. Gervaix A, Caflisch M, Suter S et al. (1993). Guillain–Barre´ syndrome following immunization with Haemophilus influenzae type b conjugate vaccine. Eur J Pediatr 152: 613–614. Ghanizadeh A (2008). Methylphenidate-associated enuresis in attention deficit hyperactivity disorder. J Pediatr Urol 4: 306–307. Ghanizadeh A (2009). Excessive talking triggered by methylphenidate in a boy with ADHD. Pharmacopsychiatry 42: 35–36.


Ghika J, Goy JJ, Naegeli C et al. (1994). Acute reversible ataxo-myoclonic encephalopathy with flecainide therapy. Schweiz Arch Neurol Psychiatr 145: 4–6. Ghosh K, Sivakumaran M, Murphy P et al. (1994). Visual hallucinations following treatment with vincristine. Clin Lab Haematol 16: 355–357. Giampaglia M, Chiuri VE, Tinelli A et al. (2010). Lapatinib in breast cancer: clinical experiences and future perspectives. Cancer Treat Rev 36(Suppl 3): S72–S79. Gilad R, Lampl Y, Eshel Y et al. (2002). Tonic-clonic seizures in patients taking sildenafil. BMJ 325: 869. Gilden DH, Kleinschmidt-DeMasters BK, LaGuardia JJ et al. (2000). Neurologic complications of the reactivation of varicella-zoster virus. N Engl J Med 342: 635–645. Gillman PK (2010). Triptans, serotonin agonists, and serotonin syndrome (serotonin toxicity): a review. Headache 50: 264–272. Ginsberg JS, Hirsh J, Turner DC et al. (1989). Risks to the fetus of anticoagulant therapy during pregnancy. Thromb Haemost 61: 197–203. Glasgow JF (2006). Reye’s syndrome: the case for a causal link with aspirin. Drug Saf 29: 1111–1121. G€ obel H, Stolze H, Heinze A et al. (1996). Easy therapeutical management of sumatriptan-induced daily headache. Neurology 47: 297–298. Goetz CG (1999). Hallucinations Parkinson’s disease clinical syndrome. Adv Neurol 80: 419–423. Goldman AL, Braman SS (1972). Isoniazid: a review with emphasis on adverse effects. Chest 62: 71–77. Gorman M, Barkley GL (1995). Oculogyric crisis induced by carbamazepine. Epilepsia 36: 1158–1160. Gotuzzo E, Echevarrı´a J, Carrillo C et al. (1994). Randomized comparison of aztreonam and chloramphenicol in treatment of typhoid fever. Antimicrob Agents Chemother 38: 558–562. Goulleret N, Mauvisseau E, Essevaz-Roulet M et al. (2010). Safety profile of live varicella virus vaccine (Oka/ Merck): five-year results of the European Varicella Zoster Virus Identification Program (EU VZVIP). Vaccine 28: 5878–5882. Granier I, Garcia E, Geissler A et al. (1999). Postpartum cerebral angiopathy associated with the administration of sumatriptan and dihydroergotamine – a case report. Intensive Care Med 25: 532–534. Granowitz EV, Brown RB (2008). Antibiotic adverse reactions and drug interactions. Crit Care Clin 34: 421–442. Grattagliano I, Portincasa P, Mastronardi M et al. (2005). Esomeprazole-induced central fever with severe myalgia. Ann Pharmacother 39: 757–760. Gray VS (1998). Syncopal episodes associated with cisapride and concurrent drugs. Ann Pharmacother 32: 648–651. Green B (2011). Focus on agomelatine. Curr Med Res Opin 27: 745–749. Greenberg A (2000). Diuretic complications. Am J Med Sci 319: 10–24. Griffin MR, Ray WA, Mortimer EA et al. (1991). Risk of seizures after measles-mumps-rubella immunization. Pediatrics 88: 881–885.



Grogan WA, Narkun DM (1987). Pseudotumor cerebri with amiodarone. J Neurol Neurosurg Psychiatry 50: 651. Guala A, Mittino D, Fabbrocini P et al. (1992). Familial metoclopramide-induced dystonic reactions. Mov Disord 7: 385–386. Guberman A (1996). Vigabatrin. Can J Neurol Sci 23: S13–S17. Guilleminault C, Mignot E, Aldrich M et al. (1988). Prazosin contraindicated in patients with narcolepsy. Lancet 2: 511. Guo HF, Su HL, Mao JJ et al. (2010). Stroke after treatment with bortezomib and dexamethasone in a Chinese patient with extramedullary relapse of multiple myeloma. Int J Clin Pharmacol Ther 48: 776–778. Haddad PM, Sharma SG (2007). Adverse effects of atypical antipsychotics: differential risk and clinical implications. CNS Drugs 21: 911–936. Hadikusumo B, Ng B (2009). Serotonin syndrome induced by duloxetine. Aust N Z J Psychiatry 43: 581–582. Halevy A, Shuper A (2009). Methylphenidate induction of complex visual hallucinations. J Child Neurol 24: 1005–1007. Halkes PH, van Gijn J, Kappelle LJ et al. (2009). Risk indicators for development of headache during dipyridamole treatment after cerebral ischaemia of arterial origin. J Neurol Neurosurg Psychiatry 80: 437–439. Hamzavi J, Schmetterer L, Formanek M (2002). Vestibular symptoms as a complication of sildenafil: a case report. Wien Klin Wochenschr 114: 54–55. Handler CE, Besse CP, Wilson AO (1982). Extrapyramidal and cerebellar syndrome with encephalopathy associated with cimetidine. Postgrad Med J 58: 527–528. Handley AJ, Emerson PA, Fleming PR (1972). Heparin in the prevention of deep vein thrombosis after myocardial infarction. BMJ 2: 436–438. Harmon C, Wohlreich MM (1995). Sodium nitroprussideinduced delirium. Psychosomatics 36: 83–85. Havranek JM, Wolfsen AR, Warnke GA et al. (2006). Monotherapy with ezetimibe causing myopathy. Am J Med 119: 285–286. Hegerl U, Himmerich H, Engmann B et al. (2010). Mania and attention-deficit/hyperactivity disorder: common symptomatology, common pathophysiology and common treatment? Curr Opin Psychiatry 23: 1–7. Heier MS, Heintz R, Fossa SD (1986). Wernicke–Korsakofflike syndrome in patients with colorectal carcinoma treated with high-dose doxifluridine (50 -dFUrd). Acta Neurol Scand 74: 240–244. Herbrecht R, Denning DW, Patterson TF et al. (2002). Voriconazole versus amphotericin B for primary therapy of invasive aspergillosis. N Engl J Med 347: 408–415. Herroelen L, de Keyser J, Ebinger G (1991). Central-nervoussystem demyelination after immunisation with recombinant hepatitis B vaccine. Lancet 338: 1174–1175. Herzig RH, Hines JD, Herzig GP et al. (1987). Cerebellar toxicity with high-dose cytosine arabinoside. J Clin Oncol 5: 927–932. Heudier P, Chichmanian RM, Taillan B et al. (1992). Druginduced benign intracranial hypertension. A propos of a

case with amphotericin B. Review of the literature. Therapie 47: 403–407. Hewagama SS, Darby JD, Sheorey H et al. (2010). Seizures related to praziquantel therapy in neurocysticercosis. Med J Aust 193: 246–247. Hiemenz J, Cagnoni P, Simpson D et al. (2005). Pharmacokinetic and maximum tolerated dose study of micafungin in combination with fluconazole versus fluconazole alone for prophylaxis of fungal infections in adult patients undergoing a bone marrow or peripheral stem cell transplant. Antimicrob Agents Chemother 49: 1331–1336. Hilkens PH, Verweij J, Stoter G et al. (1996). Peripheral neurotoxicity induced by docetaxel. Neurology 46: 104–108. Hill CFL, Armstrong JV (1950). Treatment of typhoid fever with chloramphenicol. Lancet 2: 802–804. Hill MD, Barber PA, Takahashi J et al. (2000). Anaphylactoid reactions and angioedema during alteplase treatment of acute ischemic stroke. CMAJ 162: 1281–1284. Hirano M, Ott BR, Raps EC et al. (1992). Acute quadriplegic myopathy: a complication of treatment with steroids, nondepolarizing blocking agents, or both. Neurology 42: 2082–2087. Hoffmann WF, Ladogana L (1981). Delirium secondary to clonidine therapy. N Y State J Med 81: 382–383. Hoffmann O, Gommert LR, Egert M (2004). Paradoxical cerebral cortical hyperexcitability following flupirtine overdose. J Toxicol Clin Toxicol 42: 913–916. Hogan DB, Bailey P, Black S et al. (2008). Diagnosis and treatment of dementia: 5. Nonpharmacologic and pharmacologic therapy for mild to moderate dementia. CMAJ 179: 1019–1026. Hook KM, Abrams CS (2010). Treatment options in heparininduced thrombocytopenia. Curr Opin Hematol 17: 424–431. Hook CC, Kimmel DW, Kvols LK et al. (1992). Multifocal inflammatory leukoencephalopathy with 5-fluorouracil and levamisole. Ann Neurol 31: 262–267. Hopkins S (1991). Clinical toleration and safety of azithromycin. Am J Med 91: 40S–45S. Hori A, Kataoka S, Sakai K et al. (2003). Valproic acidinduced hearing loss and tinnitus. Intern Med 42: 1153–1154. Hormigo A, Alves M (1992). Peripheral neuropathy in a patient receiving enalapril. BMJ 305: 1332. Horn S, Stern MB (2004). The comparative effects of medical therapies for Parkinson’s disease. Neurology 63(Suppl 2): 7–12. Hudgson P, Hart JA (1964). Acute ergotism. Med J Aust 2: 589–591. Hufschmidt A, Krisch A, Peschen I (2009). A girl with headache, confusion and green urine. J Neurol 256: 1169–1170. Hughes MS, Lessell S (1990). Trazodone-induced palinopsia. Arch Ophthalmol 108: 399–400. Hull PR, Vismer HF (1992). Treatment of cutaneous sporotrichosis with terbinafine. Br J Dermatol 126(Suppl. 39): 51–55. Humphrey LL, Takano LMA, Chan BKS (2002). Postmenopausal Hormone Replacement Therapy and Cardiovascular Disease [Internet]. Agency for Healthcare

IATROGENIC NEUROLOGY Research and Quality (US), Rockville, MD. Available from: http://www.ncbi.nlm.nih.gov/bookshelf/br.fcgi?book¼es10. Huq M (1990). Neurological adverse effects of naproxen and misoprostol combination. Br J Gen Pract 40: 432. Hussain M, Fisher EI, Petrylak DP et al. (2000). Androgen deprivation and four courses of fixed schedule suramin treatment in patients with newly diagnosed metastatic prostate cancer: a Southwest Oncology Group Study. J Clin Oncol 18: 1043–1049. Hwang TL, Yung WK, Estey EH et al. (1985). Central nervous system toxicity with highdose Ara-C. Neurology 35: 1475–1479. Hyser CL, Drake ME Jr (1983). Myoclonus induced by metoclopramide therapy. Arch Intern Med 143: 2201–2202. Ikebe S, Harada T, Hashimoto T et al. (2003). Prevention and treatment of malignant syndrome in Parkinson’s disease: a consensus statement of the malignant syndrome research group. Parkinsonism Relat Disord 9(Suppl 1): S47–S49. International Stroke Trial Collaborative Group (1997). The International Stroke Trial (IST): a randomised trial of aspirin, subcutaneous heparin, both, or neither among 19435 patients with acute ischaemic stroke. Lancet 349: 1569–1581. Irioka T, Yamanami A, Uchida N et al. (2009). Opsoclonus caused by diphenhydramine self-poisoning. J Neuroophthalmol 29: 72–73. Ito S, Liao S (2008). Myoclonus associated with high-dose parenteral methadone. J Palliat Med 11: 838–841. Jacobs DG, Deutsch NL, Brewer M (2001). Suicide, depression, and isotretinoin: is there a casual link? J Am Acad Dermatol 45: S168–S175. Jefferson T, Demicheli V, Rivetti D et al. (2006). Antivirals for influenza in healthy adults: systematic review. Lancet 367: 303–313. Jeret JS, Somasundaram M, Asaikar S (1992). Diltiazeminduced myoclonus. N Y State J Med 92: 447–448. Jick H, Jick SS, Gurewich V et al. (1995). Risk of idiopathic cardiovascular death and nonfatal venous thromboembolism in women using oral contraceptives with differing progestagen components. Lancet 346: 1589–1593. Jime´nez Caballero PE (2007). SUNCT syndrome in a patient with prolactinoma and cabergoline-induced attacks. Cephalalgia 27: 76–78. Jonasch E, Haluska FG (2001). Interferon in oncological practice: review of interferon biology, clinical applications and toxicities. Oncologist 6: 34–55. Jung EY, Cho HS, Seo JW et al. (2009). Metformin-induced encephalopathy without lactic acidosis in a patient with contraindication for metformin. Hemodial Int 13: 172–175. Kamgno J, Boussinesq M, Labrousse F et al. (2008). Encephalopathy after ivermectin treatment in a patient infected with Loa loa and Plasmodium spp. Am J Trop Med Hyg 78: 546–551. Kanda Y, Shigeno K, Kinoshita N et al. (1994). Sudden hearing loss associated with interferon. Lancet 343: 1134–1135. Kane FJ Jr, Byrd G (1975). Acute toxic psychosis associated with gentamicin therapy. South Med J 68: 1283–1285.


Kapoor K, Chandra M, Nag D et al. (1999). Evaluation of metronidazole toxicity: a prospective study. Int J Clin Pharmacol Res 19: 83–88. Karas BJ, Wilder BJ, Hammond EJ et al. (1983). Treatment of valproate tremors. Neurology 33: 1380–1382. Kasbekar N, Acharya PS (2005). Telithromycin: the first ketolide for the treatment of respiratory infections. Am J Health Syst Pharm 62: 905–916. Kass I, Mandel W, Cohen H et al. (1957). Isoniazid as a cause of optic neuritis and atrophy. JAMA 164: 1740–1743. Kavirajan H, Schneider LS (2007). Efficacy and adverse effects of cholinesterase inhibitors and memantine in vascular dementia: a meta-analysis of randomised controlled trials. Lancet Neurol 6: 782–792. Kazarian EL, Gager WE (1978). Optic neuritis complicating measles, mumps, and rubella vaccination. Am J Ophthalmol 86: 544–547. Kende G, Sirkin SR, Thomas PR et al. (1979). Blurring of vision: a previously undescribed complication of cyclophosphamide therapy. Cancer 44: 69–71. Kennedy GM, Lhatoo SD (2008). CNS adverse events associated with antiepileptic drugs. CNS Drugs 22: 739–760. Kennedy A, Thomas P, Sheridan DJ (1989). Generalized seizures as the presentation of flecainide toxicity. Eur Heart J 10: 950–954. Keystone JS, Murdoch JK (1979). Mebendazole. Ann Intern Med 91: 582–586. Kimmel DW, Wijdicks EF, Rodriguez M (1995). Multifocal inflammatory leukoencephalopathy associated with levamisole therapy. Neurology 45: 374–376. Kinnunen E, Fa¨rkkila¨ M, Hovi T et al. (1989). Incidence of Guillain–Barre´ syndrome during a nationwide oral poliovirus vaccine campaign. Neurology 39: 1034–1036. Kleinschmidt-DeMasters BK, Yeh M (1992). “Locked-in syndrome” after intrathecal cytosine arabinoside therapy for malignant immunoblastic lymphoma. Cancer 70: 2504–2547. Kline LB, Margulies SL, Oh SJ (1982). Optic neuritis and myelitis following rubella vaccination. Arch Neurol 39: 443–444. Knopp S, Mohammed KA, Speich B et al. (2010). Albendazole and mebendazole administered alone or in combination with ivermectin against Trichuris trichiura: a randomized controlled trial. Clin Infect Dis 51: 1420–1428. Kornfield P, Horowitz SH, Genkins G et al. (1976). Myasthenia gravis unmasked by antiarrhythmic agents. Mt Sinai J Med 43: 10–14. Kornowski R, Pines A, Levo Y (1995). Ischemic stroke following an intramuscular injection of diclofenac. Case report. Angiology 46: 1145–1147. Koussa S, Hage Chahine S, Tohme´ A et al. (2006). Epileptic seizures and vardenafil. Rev Neurol (Paris) 162: 651–652. Krasopoulos G, Brister SJ, Beattie WS et al. (2008). Aspirin “resistance” and risk of cardiovascular morbidity: systematic review and meta-analysis. BMJ 336: 195–198. Krauser DG, Segal AZ, Kligfield P (2005). Severe ataxia caused by amiodarone. Am J Cardiol 96: 1463–1464.



Krieger AC, Takeyasu M (1999). Nonconvulsive status epilepticus in theophylline toxicity. J Toxicol Clin Toxicol 37: 99–101. Kukla LJ, McGuire WP, Lad T et al. (1982). Acute vascular episodes associated with therapy for carcinomas of the upper aerodigestive tract with bleomycin, vincristine, and cisplatin. Cancer Treat Rep 66: 369–370. Kulenkampff M, Schwartzman JS, Wilson J (1974). Neurological complications of pertussis inoculation. Arch Dis Child 49: 46–49. Kulisevsky J (2000). Role of dopamine in learning and memory: implications for the treatment of cognitive dysfunction in patients with Parkinson’s disease. Drugs Aging 16: 365–379. Kumlien E, Lundberg PO (2010). Seizure risk associated with neuroactive drugs: data from the WHO adverse drug reactions database. Seizure 19: 69–73. Kummar KL, Clooney TG (1990). Visual symptoms after atenolol therapy for migraine. Ann Intern Med 112: 712–713. Kuncl RW, Duncan G, Watson D et al. (1987). Colchicine myopathy and neuropathy. N Engl J Med 316: 1562–1568. Kurlan R (2005). “Levodopa phobia”: a new iatrogenic cause of disability in Parkinson disease. Neurology 64: 923–924. Kusumi RK, Plouffe JF, Wyatt RH et al. (1980). Central nervous system toxicity associated with metronidazole therapy. Ann Intern Med 93: 59–60. Kuzuhara S, Ohkoshi N, Kanemaru K et al. (1987). Subacute leucoencephalopathy induced by carmofur, a 5fluorouracil derivative. J Neurol 234: 365–370. La Rocca RV, Meer J, Gilliatt RW et al. (1990). Suramininduced polyneuropathy. Neurology 40: 954–960. Lahr MB (1985). Hyponatremia during carbamazepine therapy. Clin Pharmacol Ther 37: 693–696. Landrigan PJ, Witte JJ (1973). Neurologic disorders following live measles-virus vaccination. JAMA 223: 1459–1462. Lang K, Sigusch H, M€ uller S (1995). An anticholinergic syndrome with hallucinatory psychosis after diphenhydramine poisoning. Dtsch Med Wochenschr 120: 1695–1698. Larsen B, Otto H, Dorscheid E et al. (1999). Effects of longterm opioid therapy on psychomotor function in patients with cancer pain or non-malignant pain. Anaesthesist 48: 613–624. Lasky MA, Pincus MH, Katlan NR (1957). Bilateral optic neuritis following chloramphenicol therapy. JAMA 151: 1403–1404. Laterra JJ, Grossman SA, Carson KA et al. (2004). Suramin and radiotherapy in newly diagnosed glioblastoma: phase 2 NABTT CNS Consortium study. Neuro Oncol 6: 15–20. Laties A, Sharlip I (2006). Ocular safety in patients using sildenafil citrate therapy for erectile dysfunction. J Sex Med 3: 12–27. Law M, Rudnicka AR (2006). Statin safety: a systematic review. Am J Cardiol 97: 52C–60C. Lawrenson JG, Kelly C, Lawrenson AL et al. (2002). Acquired colour vision deficiency in patients receiving digoxin maintenance therapy. Br J Ophthalmol 86: 1259–1261. Lehr D (1957). Clinical toxicity of sulfonamides. Ann N Y Acad Sci 69: 417–447.

Leloe¨t X, Moore N, Deshayes P (1989). Pseudopolymyalgia rheumatica during treatment with enalapril. BMJ 298: 325. Lenger R (1984). Ergot poisoning in paraplegia. Paraplegia 22: 42–44. Leonard JV, Kay JD (1986). Acute encephalopathy and hyperammonaemia complicating treatment of acute lymphoblastic leukaemia with asparaginase. Lancet 1: 162–163. Leonard SN, Rybak MJ (2008). Telavancin: an antimicrobial with a multifunctional mechanism of action for the treatment of serious gram-positive infections. Pharmacotherapy 28: 458–468. Lessell S (1992). Pediatric pseudotumor cerebri (idiopathic intracranial hypertension). Surv Ophthalmol 37: 155–166. Levenson JL (1995). Priapism associated with bupropion treatment. Am J Psychiatry 152: 813. Li PK, Lai KN (1989). Amphotericin B induced ocular toxicity in cryptococcal meningitis. Br J Ophthalmol 73: 397–398. Lieberman-Blum SS, Fung HB, Bandres JC (2008). Maraviroc: a CCR5-receptor antagonist for the treatment of HIV-1 infection. Clin Ther 30: 1228–1250. Lien HH, Blomlie V, Saeter G et al. (1991). Osteogenic sarcoma: MR signal abnormalities of the brain in asymptomatic patients treated with high-dose methotrexate. Radiology 179: 547–550. Lipowski ZJ (1990). Acute Confusional States. New York and Oxford, pp. 229–238. Litzinger MJ, Wiscombe N, Hanny A et al. (1995). Increased seizures and aggression seen in persons with mental retardation and epilepsy treated with Neurontin [abstract]. Epilepsia 36(Suppl 4): 71. Liu JS, Chang YY, Chen WH et al. (1995). Amphotericin Binduced leukoencephalopathy in a patient with cryptococcal meningitis. J Formos Med Assoc 94: 432–434. Lode H (2010). Safety and tolerability of commonly prescribed oral antibiotics for the treatment of respiratory tract infections. Am J Med 123 (4 Suppl): S26–S38. Loh FL, Herskovitz S, Berger AR et al. (1992). Brachial plexopathy associated with interleukin-2 therapy. Neurology 42: 462–463. Lou E, Abou-Zeid N (2006). A case of metoclopramideinduced oculogyric crisis in a 16-year-old girl with cystic fibrosis. South Med J 99: 1290–1291. Luborzewski A, Regen F, Schindler F et al. (2006). Modafinilinduced reversible hyperkinetic nondystonic movement disorder in a patient with major depressive disorder. J Neuropsychiatry Clin Neurosci 18: 248–249. Lyass O, Lossos A, Hubert A et al. (1998). Cisplatin-induced non-convulsive encephalopathy. Anticancer Drugs 9: 100–104. Machlin LJ (1989). Use and safety of elevated dosages of vitamin E in adults. Int J Vitam Nutr Res Suppl 30: 56–68. Macphee GJ, McInnes GT, Thompson GG et al. (1986). Verapamil potentiates carbamazepine neurotoxicity: a clinically important inhibitory interaction. Lancet 1: 700–703. Magarian GJ, Lucas LM, Colley C (1991). Gemfibrozilinduced myopathy. Arch Intern Med 151: 1873–1874.

IATROGENIC NEUROLOGY Malone DA Jr, Camara EG, Krug JH Jr (1992). Ophthalmologic effects of psychotropic medications. Psychosomatics 33: 271–277. Mangone CA, Herskovits E (1989). Extrapyramidal and depressive side reactions with flunarizine and cinarizine. J Neurol Neurosurg Psychiatry 52: 288–289. Mann JJ, Emslie G, Baldessarini RJ et al. (2006). ACNP Task Force report on SSRIs and suicidal behavior in youth. Neuropsychopharmacology 31: 473–492. Marquardt K, Albertson TE (2001). Treatment of hydroxychloroquine overdose. Am J Emerg Med 19: 420–424. Marriott HJ (1968). Delirium from digitalis toxicity. JAMA 203: 156. Martinez-Diaz GJ, Hsia R (2011). Altered mental status from acyclovir. J Emerg Med 41: 55–58. Martı´nez-Martı´n P (1993). Transient dyskinesia induced by clebopride. Mov Disord 8: 125–126. Masand PS, Pickett P, Murray GB (1995). Hypomania precipitated by psychostimulant use in depressed medically ill patients. Psychosomatics 36: 145–147. Mason PJ, Morris VA, Balcezak TJ (2000). Serotonin syndrome: presentation of 2 cases and review of the literature. Medicine (Baltimore) 79: 201–209. Matthews SJ, Lancaster JW (2009). Doripenem monohydrate, a broad-spectrum carbapenem antibiotic. Clin Ther 31: 42–63. Maxwell S, Scheftner WA, Kessler HA et al. (1988). Manic syndrome. JAMA 259: 3406–3407. Maxwell MJ, Muthu P, Pritty PE (2002). Accidental colchicine overdose. A case report and literature review. Emerg Med J 19: 265–267. Mayr A, Aigner M, Lass-Fl€orl C (2011). Anidulafungin for the treatment of invasive candidiasis. Clin Microbiol Infect 17(Suppl 1): 1–12. McGee HT, Egan RA, Clark WM (2005). Visual field defect and intracerebral hemorrhage associated with use of vardenafil (Levitra). Neurology 64: 1095–1096. McGuire WP, Rowinsky EK, Rosenshein NB et al. (1989). Taxol: a unique antineoplastic agent with significant activity in advanced ovarian epithelial neoplasms. Ann Intern Med 111: 273–279. Mendhekar DN, Andrade C (2008). Bruxism arising during monotherapy with methylphenidate. J Child Adolesc Psychopharmacol 18: 537–538. Mendhekar DN, Duggal HS (2006). Methylphenidate-induced rabbit syndrome. Ann Pharmacother 40: 2076. Mendhekar D, Lohia D (2009). Worsening of bruxism with atomoxetine: a case report. World J Biol Psychiatry 10: 671–672. Menichetti F (2009). Anidulafungin, a new echinocandin: effectiveness and tolerability. Drugs 69(Suppl 1): 95–97. Menon V, Harrington RA, Hochman JS et al. (2004). Thrombolysis and adjunctive therapy in acute myocardial infarction: the Seventh ACCP Conference on Antithrombotic and Thrombolytic Therapy. Chest 126 (Suppl 3): 549S–575S. Mercadante S (1998). Pathophysiology and treatment of opioid-related myoclonus in cancer patients. Pain 74: 5–9.


Merello MJ, Nogue´s MA, Leiguarda RC et al. (1991). Dystonia and reflex sympathetic dystrophy induced by ergotamine. Mov Disord 6: 263–264. Merhoff GC, Porter JM (1974). Ergot intoxication: historical review and description of unusual clinicalmanifestations. Ann Surg 180: 773–779. Meropol SN, Chan KA, Chen Z et al. (2008). Adverse events associated with prolonged antibiotic use. Pharmacoepidemiol Drug Saf 17: 523–532. Meyers CA, Yung WK (1993). Delayed neurotoxicity of intraventricular interleukin-2: a case report. J Neurooncol 15: 265–267. Meyers CA, Scheibel RS, Forman AD (1991a). Persistent neurotoxicity of systemically administered interferon-alpha. Neurology 41: 672–676. Meyers CA, Obbens EA, Scheibel RS et al. (1991b). Neurotoxicity of intraventricularly administered alphainterferon for leptomeningeal disease. Cancer 68: 88–92. Mick G (2010). Vaccination: a new option to reduce the burden of herpes zoster. Expert Rev Vaccines 9(3Suppl): 31–35. Middleton MR, Grob JJ, Aaronson N et al. (2000). Randomized phase III study of temozolomide versus dacarbazine in the treatment of patients with advanced metastatic malignant melanoma. J Clin Oncol 18: 158–166. Miller LG, Jankovic J (1989). Metoclopramide-induced movement disorders. Clinical findings with a review of the literature. Arch Intern Med 149: 2486–2492. Miller LG, Jankovic J (1992). Persistent dystonia possibly induced by flecainide. Mov Disord 7: 62–63. Milman HA, Arnold SB (2002). Neurologic, psychological, and aggressive disturbances with sildenafil. Ann Pharmacother 36: 1129–1134. Mitra S (2008). Opioid-induced hyperalgesia: pathophysiology and clinical implications. J Opioid Manag 4: 123–130. Mitropoulos IF, Rotschafer JC, Rodvold KA (2007). Adverse events associated with the use of oral cephalosporins/ cephems. Diagn Microbiol Infect Dis 57(Suppl 3): 67S–76S. Modlin JF, Jabbour JT, Witte JJ et al. (1977). Epidemiologic studies of measles, measles vaccine, and subacute sclerosing panencephalitis. Pediatrics 59: 505–512. Molloy FM, Floeter MK, Syed NA et al. (2001). Thalidomide neuropathy in patients treated for metastatic prostate cancer. Muscle Nerve 24: 1050–1057. Montane´ E, Vallano A, Laporte JR (2004). Oral antispastic drugs in nonprogressive neurologic diseases. A systematic review. Neurology 63: 1357–1363. Montejo AL, Llorca G, Izquierdo JA et al. (2001). Incidence of sexual dysfunction associated with antidepressant agents: a prospective multicenter study of 1022 outpatients. Spanish Working Group for the Study of PsychotropicRelated Sexual Dysfunction. J Clin Psychiatry 62(Suppl 3): 10–21. Moore RD, Smith CR, Leitman PS (1984). Risk factors for the development of auditory toxicity in patients receiving aminoglycosides. J Infect Dis 149: 23–30. Moore TJ, Glenmullen J, Furberg CD (2010). Prescription drugs associated with reports of violence towards others. PLoS One 5: e15337.



Mueller RA, Meienberg O (1983). Hemicrania with oculosympathetic paresis from isosorbide dinitrate. N Engl J Med 308: 458–459. Mula M, Trimble MR, Yuen AW et al. (2003). Psychiatric adverse events during levetiracetam therapy. Neurology 61: 704–706. Muller T, Kuhn W, Pohlau D et al. (1995). Parkinsonism unmasked by lovastatin. Ann Neurol 37: 685–686. Muller MP, Dresser L, Raboud J et al. (2007). Adverse events associated with high-dose ribavirin: evidence from the Toronto outbreak of severe acute respiratory syndrome. Pharmacotherapy 27: 494–503. Nagai N, Ohde H, Betsuin Y et al. (2001). Two cases of digitalis toxicity with reversible and severe decrease of visual acuity. Nippon Ganka Gakkai Zasshi 105: 24–30. Nair NPV, Ahmed SK, Ng Ying Kin NMK et al. (1995). Reversible and selective inhibitors of monoamine oxidase A in the treatment of depressed elderly patients. Acta Psychiatr Scand 91(Suppl 386): 28–35. Nakajima W, Ishida A, Takahashi M et al. (2007). Aseptic meningitis associated with cephalosporins in an infant with trisomy 21. J Child Neurol 22: 780–782. Nathanson N, Kew OM (2010). From emergence to eradication: the epidemiology of poliomyelitis deconstructed. Am J Epidemiol 172: 1213–1229. Nausieda PA, Koller WC, Weiner WJ et al. (1979). Chorea induced by oral contraceptives. Neurology 29: 1605–1609. Nayfield SG, Gorin MB (1996). Tamoxifen-associated eye disease. A review. J Clin Oncol 14: 1018–1026. Nelson RW, Frank JT (1981). Intrathecal methotrexateinduced neurotoxicities. Am J Hosp Pharm 38: 65–68. Netea-Maier RT, van Lindert EJ, Timmers H et al. (2006). Cerebrospinal fluid leakage as complication of treatment with cabergoline for macroprolactinomas. J Endocrinol Invest 29: 1001–1005. Neuvonen PJ, Niemi M, Backman JT (2006). Drug interactions with lipid-lowering drugs: mechanisms and clinical relevance. Clin Pharmacol Ther 80: 565–581. Ney GC, Lantos G, Barr WB et al. (1994). Cerebellar atrophy in patients with long-term phenytoin exposure and epilepsy. Arch Neurol 51: 767–771. Nguyen M, Chung EP (2005). Telithromycin: the first ketolide antimicrobial. Clin Ther 27: 1144–1163. Nicolao P, Giometto B (2003). Neurological toxicity of ifosfamide. Oncology 65(Suppl 2): 11–16. Nieto Y, Cagnoni PJ, Bearman SI et al. (1999). Acute encephalopathy: a new toxicity associated with high-dose paclitaxel. Clin Cancer Res 5: 501–506. Nine JS, Rund CR (2006). Fatality from diphenhydramine monointoxication: a case report and review of the infant, pediatric, and adult literature. Am J Forensic Med Pathol 27: 36–41. Noel GJ (2009). A review of levofloxacin for the treatment of bacterial infections. Clin Med Ther 1: 433–458. Noel GJ, Strauss RS, Amsler K et al. (2008). Results of a doubleblind, randomized trial of ceftobiprole treatment of complicated skin and skin structure infections caused by grampositive bacteria. Antimicrob Agents Chemother 52: 37–44.

O’Brien CP (2005). Benzodiazepine use, abuse, and dependence. J Clin Psychiatry 66(Suppl 2): 28–33. Oishi A, Miyamoto K, Kashii S et al. (2006). Photopsia as a manifestation of digitalis toxicity. Can J Ophthalmol 41: 603–604. Ojewole JA (1984). Pharmacological analysis of the neuromuscular properties of diethylcarbamazine citrate in vitro. Methods Find Exp Clin Pharmacol 6: 91–101. Olin JL, Gugliotta JL (2003). Possible valacyclovir-related neurotoxicity and aseptic meningitis. Ann Pharmacother 37: 1814–1817. Onuigbo MA, Nye D, Iloanya PC (2009). Drug-induced encephalopathy secondary to non renal dosing of common medications in two dialysis patients. Adv Perit Dial 25: 89–91. Opler LA, Frank DM, Ramirez PM (2001). Psychostimulants in the treatment of adults with psychosis and attention deficit disorder. Ann N Y Acad Sci 931: 297–301. Opremcak EM, Davidorf FH (1985). Bilateral retinal infarction associated with high dose dopamine. Ann Ophthalmol 17: 141–144. Ortı´n X, Rodrı´guez-Luaces M, Calabuig M et al. (2006). Stroke in a multiple myeloma patient treated with thalidomide. J Stroke Cerebrovasc Dis 15: 283–285. Ostrow S, Hahn D, Wiernik PH et al. (1978). Ophthalmologic toxicity after cisdichlorodiammineplatinum (II) therapy. Cancer Treat Rep 62: 1591–1594. Oterino A, Pascual J (1998). Sumatriptan-induced axial dystonia in a patient with cluster headache. Cephalalgia 18: 360–361. Otis SA, Zehnder JL (2010). Heparin-induced thrombocytopenia: current status and diagnostic challenges. Am J Hematol 85: 700–706. Oulis P, Kouzoupis AV, Kontoangelos K et al. (2008). Visual and coenesthetic hallucinations associated with modafinil. J Clin Psychopharmacol 28: 251–252. Owens RC Jr, Ambrose PG (2005). Antimicrobial safety: focus on fluoroquinolones. Clin Infect Dis 41(Suppl 2): S144–S157. Ozdemir O, Baytan B, Gunes AM et al. (2010). Involuntary movements during vitamin B12 treatment. J Child Neurol 25: 227–230. Ozog D, Lerner C (1989). An exaggerated response to betaadrenergics. Ann Allergy 62: 11–13. Padrell MD, Navarro M, Faura CC et al. (1995). Verapamilinduced parkinsonism. Am J Med 99: 436. Palace J, Shah R, Clough C (1992). Flecainide induced peripheral neuropathy. BMJ 305: 810. Paloucek FP, Rodvold KA (1988). Evaluation of theophylline overdoses and toxicities. Ann Emerg Med 17: 135–144. Pani SP, Das LK, Vanamail P (2005). Tolerability and efficacy of a three-age class dosage schedule of diethylcarbamazine citrate (DEC) in the treatment of microfilaria carriers of Wuchereria bancrofti and its implications in mass drug administration (MDA) strategy for elimination of lymphatic filariasis (LF). J Commun Dis 37: 12–17. Papakostas GI (2007). Limitations of contemporary antidepressants: tolerability. J Clin Psychiatry 68(Suppl 10): 11–17.

IATROGENIC NEUROLOGY Papakostas GI, Fava M (2006). A metaanalysis of clinical trials comparing moclobemide with selective serotonin reuptake inhibitors for the treatment of major depressive disorder. Can J Psychiatry 51: 783–790. Papakostas GI, Homberger CH, Fava M (2008a). A metaanalysis of clinical trials comparing mirtazapine with selective serotonin reuptake inhibitors for the treatment of major depressive disorder. J Psychopharmacol 22: 843–848. Papakostas GI, Nelson JC, Kasper S et al. (2008b). A metaanalysis of clinical trials comparing reboxetine, a norepinephrine reuptake inhibitor, with selective serotonin reuptake inhibitors for the treatment of major depressive disorder. Eur Neuropsychopharmacol 18: 122–127. Parkinson DR, Cano PO, Jerry LM et al. (1977). Complications of cancer immunotherapy with levamisole. Lancet 1: 1129–1132. Patel OP, Simon MR (2006). Oculogyric dystonic reaction to escitalopram with features of anaphylaxis including response to epinephrine. Int Arch Allergy Immunol 140: 27–29. Patel SR, Vadhan-Raj S, Papadopolous N et al. (1997). Highdose ifosfamide in bone and soft tissue sarcoma. Results of phase II and pilot studies: dose-response and schedule dependence. J Clin Oncol 15: 2378–2384. Pearlman BL, Gambhir R (2009). Salicylate intoxication: a clinical review. Postgrad Med 121: 162–168. Pedrajas JM, Pieltain R, Mesa N et al. (1993). Aztreonam as monotherapy in urinary tract infections with a systemic repercussion in patients with a relative contraindication for the use of aminoglycosides. Rev Clin Esp 192: 256–259. Pepin S, Pitha-Rowe I (2008). Stepwise decline in visual field after serial sildenafil use. J Neuroophthalmol 28: 76–77. Perahia DGS, Wang F, Mallinckrodt CH et al. (2006). Duloxetine in the treatment of major depressive disorder: a placebo- and paroxetine-controlled trial. Eur Psychiatry 21: 367–378. Perez C, Loza E, Tinture T (2000). Giant cell arteritis after influenza vaccination. Arch Intern Med 160: 2677. Perry RP, Jacobsen ES (1984). Gold induced encephalopathy: case report. J Rheumatol 11: 233–234. Phabphal K, Udomratn P (2010). Topiramate-induced depression in cases using topiramate for migraine prophylaxis. Cephalalgia 30: 747–749. Phillips BB, Muller BA (1998). Severe neuromuscular complications possibly associated with amlodipine. Ann Pharmacother 32: 1165–1167. Pirzada NA, Ali II, Dafer RM (2000). Fluorouracil-induced neurotoxicity. Ann Pharmacother 34: 35–38. Pisoni R, Ruggenenti P, Remuzzi G (2001). Drug-induced thrombotic microangiopathy: incidence, prevention and management. Drug Saf 24: 491–501. Polimeni G, Cutroneo P, Gallo A et al. (2007). Rabeprazole and psychiatric symptoms. Ann Pharmacother 41: 1315–1317. Pollard JD, Selby G (1978). Relapsing neuropathy due to tetanus toxoid. Report of a case. J Neurol Sci 37: 113–125. Pomeranz HD, Bhavsar AR (2005). Nonarteritic ischemic optic neuropathy developing soon after use of sildenafil (Viagra): a report of seven new cases. J Neuroophthalmol 25: 9–13.


Poza JJ (2003). Cataplexy worsened by modafinil. Sleep 26: 489. Price LH, Lebel J (2000). Dextromethorphan-induced psychosis. Am J Psychiatry 157: 304. Prieto-Gonza´lez S, Escoda R, Coloma E et al. (2011). Amoxicillin-induced acute aseptic meningitis. J Clin Neurosci 18: 443–444. Prime K, French P (2001). Neuropsychiatric reaction induced by clarithromycin in a patient on highly active antiretroviral therapy (HAART). Sex Transm Infect 77: 297–298. Quarantini LC, Cruz SC, Batista-Neves SC et al. (2006). Psychosis during peginterferon-alpha 2a and ribavirin therapy: case report. Braz J Infect Dis 10: 406–407. Radner DB (1973). Toxicologic and pharmacologic aspects of rifampin. Chest 64: 213–216. Ramasamy B, Rowe F, Nayak H et al. (2007). Acute angleclosure glaucoma following sildenafil citrate-aided sexual intercourse. Acta Ophthalmol Scand 85: 229–230. Ramhamadany E, Mackenzie S, Ramsdale DR (1986). Dysarthria and visual hallucinations due to flecainide toxicity. Postgrad Med J 62: 61–62. Ranpura V, Hapani S, Wu S et al. (2010). Treatment-related mortality with bevacizumab in cancer patients. JAMA 305: 487–494. Rao R (1999). Penicillin psychosis in later life: Hoigne’s syndrome revisited. J Neuropsychiatry Clin Neurosci 11: 517–518. Raverot G, Jacob M, Jouanneau E et al. (2009). Secondary deterioration of visual field during cabergoline treatment for macroprolactinoma. Clin Endocrinol (Oxf) 70: 588–592. Resar LM, Phillips PC, Kastan MB et al. (1993). Acute neurotoxicity after intrathecal cytosine arabinoside in two adolescents with acute lymphoblastic leukemia of B-cell type. Cancer 71: 117–123. Ress BD, Gross EM (2000). Irreversible sensorineural hearing loss as a result of azithromycin ototoxicity: a case report. Ann Otol Rhinol Laryngol 109: 435–437. Revankar SG, Applegate AL, Markovitz DM (1995). Delirium associated with acyclovir treatment in a patient with renal failure. Clin Infect Dis 21: 435–436. Richardson PG, Briemberg H, Jagannath S et al. (2006). Frequency, characteristics, and reversibility of peripheral neuropathy during treatment of advanced multiple myeloma with bortezomib. J Clin Oncol 24: 3113–3120. Riehl JL, Brown WJ (1964). Acute cerebellar syndrome secondary to 5-fluorouracil therapy. Neurology 14: 961–967. Ritter MJ, Goodman BP, Sprung J et al. (2003). Ondansetroninduced multifocal encephalopathy. Mayo Clin Proc 78: 1150–1152. Roberge RJ, Hirani KH, Rowland PL 3rd et al. (1999). Dextromethorphan- and pseudoephedrine-induced agitated psychosis and ataxia: case report. J Emerg Med 17: 285–288. Rodrı´guez SC, Olguı´n AM, Miralles CP et al. (2006). Characteristics of meningitis caused by ibuprofen: report of 2 cases with recurrent episodes and review of the literature. Medicine (Baltimore) 85: 214–220. Roelofs RI, Hrushesky W, Rogin J et al. (1984). Peripheral sensory neuropathy and cisplatin chemotherapy. Neurology 34: 934–938.



Roncon-Albuquerque R Jr, Pires I, Martins R et al. (2009). Ceftriaxone-induced acute reversible encephalopathy in a patient treated for a urinary tract infection. Neth J Med 67: 72–75. Roob G, Schmidt R, Kapeller P et al. (1999). MRI evidence of past cerebral microbleeds in a healthy elderly population. Neurology 52: 991–994. Roth RF, Itabashi H, Louie J et al. (1990). Amiodarone toxicity: myopathy and neuropathy. Am Heart J 119: 1223–1225. Royer B, Ziegler F, Muret P et al. (2002). Acitretin-associated thrombotic stroke. Ann Pharmacother 36: 1879–1882. Ruan X (2007). Drug-related side effects of long-term intrathecal morphine therapy. Pain Physician 10: 357–366. Ruano-Caldero´n LA, Zermen˜o-Pohls F (2005). Ergotism. A case report and review of the literature. Rev Neurol 40: 412–416. Russell MT, Nassif AS, Cacayorin ED et al. (2001). Gemcitabine associated posterior reversible encephalopathy syndrome: MR imaging and MR spectroscopy findings. Magn Reson Imaging 19: 129–132. Saı¨as T, Gallarda T (2008). Paradoxical aggressive reactions to benzodiazepine use: a review. Ence´phale 34: 330–336. Salazar CA, Malaga G, Malasquez G (2010). Direct thrombin inhibitors versus vitamin K antagonists or low molecular weight heparins for prevention of venous thromboembolism following total hip or knee replacement. Cochrane Database Syst Rev 4: CD005981. Salloum E, Khan KK, Cooper DL (1997). Chlorambucilinduced seizures. Cancer 79: 1009–1013. Samie MR, Ashton AK (1989). Choreoathetosis induced by cyproheptadine. Mov Disord 4: 81–84. Sa´nchez Valiente S (1995). Myoclonic encephalopathy induced by diclofenac treatment. Rev Neurol 23: 1226–1227. Sandercock PA, Counsell C, Gubitz GJ et al. (2008). Antiplatelet therapy for acute ischaemic stroke. Cochrane Database Syst Rev (3): CD000029. Sansone RA, Sansone LA (2009). Bupropion-induced neck and shoulder pain. Pharmacopsychiatry 42: 203–204. Saravay SM, Marke J, Steinberg MD et al. (1987). “Doom anxiety” and delirium in lidocaine toxicity. Am J Psychiatry 144: 159–163. Sarma GR, Kamath V, Mathew T et al. (2008). A case of parkinsonism worsened by losartan: a probable new adverse effect. Mov Disord 23: 1055. Sato K (2006). Drug-induced hypercalcemia. Clin Calcium 16: 67–72. Sato S, Shimizu M, Endo K (2004). Postpartum cerebral angiopathy – a case report the vasculopathy associated with co-administration of two vasoconstrictives, methylergometrine maleate and sumatriptan. Rinsho Shinkeigaku 44: 96–101. Satya-Murti S, Heiman T, Martı´nez LB (1977). Possible propranolol-myotonin association. N Engl J Med 297: 223–224. Sawin PD, Traynelis VC, Follett KA (1995). Spinal epidural hematoma following coronary thrombolysis with tissue plasminogen activator. Report of two cases. J Neurosurg 83: 350–353. Schachter SC (1999). Tiagabine. Epilepsia 40(Suppl 5): 17–22.

Schachter S, Freeman R (1982). Transient ischemic attack and adriamycin cardiomyopathy. Neurology 32: 1380–1381. Schafer M, Schwaiger M (2003). Incidence, pathoetiology and treatment of interferon-alpha induced neuropsychiatric side effects. Fortschr Neurol Psychiatr 71: 469–476. Schaffner W, Fleet WF, Kilroy AW et al. (1974). Polyneuropathy following rubella immunization. A follow-up study and review of the problem. Am J Dis Child 127: 684–688. Schiefer J, Sparing R (2005). Transient global amnesia after intake of tadalafil, a PDE-5 inhibitor: a possible association? Int J Impot Res 17: 383–384. Schiff E, May K, Goldstein LH (2010). Neuropsychiatric manifestations associated with azithromycin in two brothers. Eur J Clin Pharmacol 66: 1273–1275. Schlumpf U, Meyer M, Ulrich J (1983). Neurologic complications induced by gold treatment. Arthritis Rheum 26: 825–831. Schmitt BD, Krivit W (1969). Benign intracranial hypertension associated with a delayed penicillin reaction. Pediatrics 43: 50–53. Schmutzhard E, Williams KJ, Vukmirovits G et al. (1995). A randomised comparison of meropenem with cefotaxime or ceftriaxone for the treatment of bacterial meningitis in adults. Meropenem Meningitis Study Group. J Antimicrob Chemother 36(Suppl A): 85–97. Schranz J (1998). Comparisons of seizure incidence and adverse experiences between imipenem and meropenem. Crit Care Med 26: 1464–1466. Schr€ or K (2007). Aspirin and Reye syndrome: a review of the evidence. Paediatr Drugs 9: 195–204. Schwartz RH, Rushton HG (2004). Stuttering priapism associated with withdrawal from sustained-release methylphenidate. J Pediatr 144: 675–676. Schwarz KO (1987). Clonidine-induced myalgias. Med J Aust 147: 365. Schwarz G, Lanzer G, List WF (1988). Acute midbrain syndrome as an adverse reaction to tetanus immunization. Intensive Care Med 15: 53–54. Scott J, Pache D, Keane G et al. (2007). Prolonged anticholinergic delirium following antihistamine overdose. Australas Psychiatry 15: 242–244. Scott K, Zeris S, Kothari MJ (2008). Elevated B6 levels and peripheral neuropathies. Electromyogr Clin Neurophysiol 48: 219–223. Sempere AP, Duarte J, Palomares JM et al. (1994). Parkinsonism and tardive dyskinesia after chronic use of clebopride. Mov Disord 9: 114–115. Sennesael J, Verbeelen D, Lauwers S (1982). Ototoxicity associated with cephalexin in two patients with renal failure [Letter]. Lancet 2: 1154–1155. Senter HJ, Lieverman AN, Pinto R (1976). Cerebral manifestations of ergotism. Report of a case and review of the literature. Stroke 7: 88–92. Shafrir Y, Levy Y, Ben-Amitai D et al. (1985). Oculogyric crisis due to domperidone therapy. Helv Paediatr Acta 40: 95.

IATROGENIC NEUROLOGY Shah MD, Balderson K (2003). A manic episode associated with efavirenz therapy for HIV infection. AIDS 17: 1713–1714. Shapiro WR, Green SB, Burger PC et al. (1992). A randomized comparison of intra-arterial versus intravenous BCNU, with or without intravenous 5-fluorouracil, for newly diagnosed patients with malignant glioma. J Neurosurg 76: 772–781. Sharma A, Vora R, Modi M et al. (2008). Adverse effects of antiretroviral treatment. Indian J Dermatol Venereol Leprol 74: 234–237. Shaw FE Jr, Graham DJ, Guess HA et al. (1998). Postmarketing surveillance for neurologic adverse events reported after hepatitis B vaccination. Experience of the first three years. Am J Epidemiol 127: 337–352. Shorvon SD, Reynolds EH (1982). Anticonvulsant peripheral neuropathy: a clinical and electrophysiological study of patients on single drug treatment with phenytoin, carbamazepine or barbiturates. J Neurol Neurosurg Psychiatry 45: 620–626. Shumaker SA, Legault C, Rapp SR et al.WHIMS Investigators (2003). Estrogen plus progestin and the incidence of dementia and mild cognitive impairment in postmenopausal women: the Women’s Health Initiative Memory Study: a randomized controlled trial. JAMA 289: 2651–2662. Siegal T, Haim N (1990). Cisplatin-induced peripheral neuropathy. Frequent off-therapy deterioration, demyelinating syndromes, and muscle cramps. Cancer 66: 1117–1123. Siegel JP, Puri RK (1991). Interleukin-2 toxicity. J Clin Oncol 9: 694–704. Singhal S, Mehta J, Desikan R et al. (1999). Antitumor activity of thalidomide in refractory multiple myeloma. N Engl J Med 341: 1565–1571. Sirota P, Stoler M, Meshulam B (1988). Major depression with psychotic features associated with acyclovir therapy. Drug Intell Clin Pharm 22: 306–308. Slaker RA, Danielson B (1991). Neurotoxicity associated with ceftazidime therapy in geriatric patients with renal dysfunction. Pharmacotherapy 11: 351–352. Sloan MA (1998). Neurologic complications of thrombolytic therapy. In: J Biller (Ed.), Iatrogenic Neurology. Butterworth-Heinemann, Boston and Oxford, p. 336. Slobodin G, Elias N, Zaygraikin N et al. (2009). Levofloxacininduced delirium. Neurol Sci 30: 159–161. Smals AGH, Beex LVAM, Kloppenborg PWC (1977). Clofibrate-induced muscle damage with myoglobinuria and cardiomyopathy. N Engl J Med 296: 942. Snavely SR, Hodges GR (1984). The neurotoxicity of antibacterial agents. Ann Intern Med 101: 92–104. Snodgrass SR (1992). Vitamin neurotoxicity. Mol Neurobiol 6: 41–73. Snodgrass AJ, Campbell HM, Mace DL et al. (2010). Sudden sensorineural hearing loss associated with vardenafil. Pharmacotherapy 30: 112. Snyder SW, Cardwell MS (1989). Neuromuscular blockade with magnesium sulfate and nifedipine. Am J Obstet Gynecol 161: 35–36. Snyman JR, Schoeman HS, Grobusch MP et al. (2009). Generic versus non-generic formulation of extended-


release clarithromycin in patients with communityacquired respiratory tract infections: a prospective, randomized, comparative, investigator-blind, multicentre study. Clin Drug Investig 29: 265–274. Sobow T, Kloszewska I (2006). Cholinesterase inhibitors in the “real world” setting: rivastigmine versus donepezil tolerability and effectiveness study. Arch Med Sci 2: 194–198. Sofi F, Marcucci R, Gori AM et al. (2010). Clopidogrel non-responsiveness and risk of cardiovascular morbidity. An updated meta-analysis. Thromb Haemost 103: 841–848. Sommer S, Delemazure B, Wagner M et al. (1998). Bilateral ischemic optic neuropathy secondary to acute ergotism. J Fr Ophtalmol 21: 123–125. Sonnenblick M, Yinnon A (1986). Mental confusion as a side effect of ranitidine. Am J Psychiatry 143: 257. Sowka JW, Neiberg MN, Vollmer LA (2007). Optic atrophy after sildenafil use. Optometry 78: 122–128. Spangler DL, Brunton S (2006). Efficacy and central nervous system impairment of newer-generation prescription antihistamines in seasonal allergic rhinitis. South Med J 99: 593–599. Sponzilli T, Tarroni P, D’Amico A et al. (1979). Retrobulbar optic neuritis in the course of methimazole therapy (a clinical case). Riv Neurobiol 25: 233–238. Sprung J, Choudhry FM, Hall BA (2003). Extrapyramidal reactions to ondansetron: cross-reactivity between ondansetron and prochlorperazine? Anesth Analg 96: 1374–1376. Stadel BV (1981). Oral contraceptives and cardiovascular disease (second of two parts). N Engl J Med 305: 672–677. Stahlmann R, Lode H (2003). Fluoroquinolones in the elderly. Safety considerations. Drugs Aging 20: 289–302. Starr P, Klein-Schwartz W, Spiller H et al. (2009). Incidence and onset of delayed seizures after overdoses of extendedrelease bupropion. Am J Emerg Med 27: 911–915. Stewart SA (2005). The effects of benzodiazepines on cognition. J Clin Psychiatry 66(Suppl 2): 9–13. Su DH, Ang PS, Tow SL (2008). Bilateral posterior ischemic optic neuropathy associated with use of sildenafil. J Neuroophthalmol 28: 75. Sullivan EA, Geoffroy P, Weisman R et al. (1998). Isoniazid poisonings in New York City. J Emerg Med 16: 57–59. Sunkavalli KK, Iqbal FM, Singh B et al. (2011). Valproateinduced hyperammonemic encephalopathy: a case report and brief review of the literature. Am J Ther [Epub ahead of print]. Sur RL, Kane CJ (2000). Sildenafil citrate-associated priapism. Urology 55: 950. Swash M, Ingram DA (1992). Adverse effect of verapamil in myasthenia gravis. Muscle Nerve 15: 396–398. Swegle JM, Logemann C (2006). Management of common opioid-induced adverse effects. Am Fam Physician 74: 1347–1354. Tabibian JH, Gutie´rrez MA (2009). Doxycycline-induced pseudotumor cerebri. South Med J 102: 310–311.



Tak WY, Park SY, Cho CM et al. (2010). Clinical, biochemical, and pathological characteristics of clevudineassociated myopathy. J Hepatol 53: 261–266. Talbot GH, Thye D, Das A et al. (2007). Phase 2 study of ceftaroline versus standard therapy in treatment of complicated skin and skin structure infections. Antimicrob Agents Chemother 51: 3612–3616. Tang AH, Schroeder LA (1968). The effect of lincomycin on neuromuscular transmission. Toxicol Appl Pharmacol 12: 44–47. €r€ Tanriverdi N, Sayilgan MA, Ozc¸u umez G et al. (2001). Musical hallucinations associated with abruptly developed bilateral loss of hearing. Acta Psychiatr Scand 103: 153–155. Tartaglino LM, Heiman-Pattersson T, Friedman DP et al. (1995). MR imaging in a case of postvaccination myelitis. AJNR Am J Neuroradiol 16: 581–582. Tashima CK (1975). Immediate cerebral symptoms during rapid intravenous administration of cyclophosphamide (NSC-26271). Cancer Chemother Rep 59: 441–442. Teive HA, Germiniani FM, Werneck LC (2002). Parkinsonian syndrome induced by amlodipine: case report. Mov Disord 17: 833–835. Terrell CL (1999). Antifungal agents. Part II. The Azoles. Mayo Clin Proc 74: 78–100. Testa L, Bhindi R, Van Gaal WJ et al. (2010). What is the risk of intensifying platelet inhibition beyond clopidogrel? A systematic review and a critical appraisal of the role of prasugrel. QJM 103: 367–377. Teus MA, Teruel JL, Pascual J et al. (1991). Corticosteroidinduced toxic optic neuropathy. Am J Ophthalmol 112: 605–606. Tfayli A, Hentschel P, Madajewicz S et al. (1999). Toxicities related to intraarterial infusion of cisplatin and etoposide in patients with brain tumors. J Neurooncol 42: 73–77. Thase ME, Haight BR, Richard N et al. (2005). Remission rates following antidepressant therapy with bupropion or selective serotonin reuptake inhibitors: a meta-analysis of original data from 7 randomized controlled trials. J Clin Psychiatry 66: 974–981. Thornton C, Dore´ CJ, Elsworth JD et al. (1980). The effect of deprenyl, a selective monoamine oxidase B inhibitor, on sleep and mood in man. Psychopharmacology (Berl) 70: 163–166. Thorpe EL, Pizon AF, Lynch MJ et al. (2010). Bupropion induced serotonin syndrome: a case report. J Med Toxicol 6: 168–171. Tong MK, Siu YP, Yung CY et al. (2004). Piperacillin/tazobactam-induced acute delirium in a peritoneal dialysis patient. Nephrol Dial Transplant 19: 1341. Toovey S (2009). Mefloquine neurotoxicity: a literature review. Travel Med Infect Dis 7: 2–6. Topaloglu H, Berker M, Kansu T et al. (1992). Optic neuritis and myelitis after booster tetanus toxoid vaccination. Lancet 339: 178–179. Trauner MA, Ruben BS (1999). Isotretinoin induced rhabdomyolysis? A case report. Dermatol Online J 5: 2. Tripathi A, O’Donnell NP (2000). Branch retinal artery occlusion; another complication of sildenafil. Br J Ophthalmol 84: 934–935.

Tripodi PF, Ruggeri RM, Campennı` A et al. (2008). Central nervous system vasculitis after starting methimazole in a woman with Graves’ disease. Thyroid 18: 1011–1013. Tucker RM, Haq Y, Denning DW et al. (1990). Adverse events associated with itraconazole in 189 patients on chronic therapy. J Antimicrob Chemother 26: 561–566. Turkington RW (1977). Encephalopathy induced by oral hypoglycaemic drugs. Arch Intern Med 137: 1082–1083. Turon-Estrada A, Lo´pez-Pousa S, Gelada-Batlle E et al. (2003). Tolerance and adverse events of treatment with acetylcholinesterase inhibitors in a clinical sample of patients with very slight and mild Alzheimer s disease over a six-month period. Rev Neurol 36: 421–424. Tzourio C, Tehindrazanarivelo A, Igle´sias S et al. (1995). Case-control study of migraine and risk of ischaemic stroke in young women. BMJ 310: 830–833. Ueno S, Hara Y (1992). Lambert–Eaton myasthenic syndrome without anti-calcium channel antibody: adverse effect of calcium antagonist diltiazem. J Neurol Neurosurg Psychiatry 55: 409–410. Uher R, Farmer A, Henigsberg N et al. (2009). Adverse reactions to antidepressants. Br J Psychiatry 195: 202–210. Valentine AD, Meyers CA, Kling MA et al. (1998). Mood and cognitive side effects of interferon alfa therapy. Semin Oncol 25: 39–47. van Amelsvoort T, Bakshi R, Devaux CB et al. (1994). Hyponatremia associated with carbamazepine and oxcarbazepine therapy: a review. Epilepsia 35: 181–188. Vecht CJ, Keohane C, Menon RS et al. (1990). Acute fatal leukoencephalopathy after interleukin-2 therapy. N Engl J Med 323: 1146–1147. Vesperini S, Papetti F, Pringuey D (2010). Are catatonia and neuroleptic malignant syndrome related conditions? Ence´phale 36: 105–110. von Werder K (1996). Bromocriptine and puerperal seizures. Zentralbl Gynakol 118: 395–396. Wainscott G, Volans G, Wilkinson M (1974). Ergotamineinduced headaches. Br Med J 2: 724. Wallenstein L, Snyder J (1952). Neurotoxic reaction to chloromycetin. Ann Intern Med 36: 1526–1528. Walsh KP, Shelley RK, Daly PA (1984). Hallucinations: an unusual adverse reaction to chlorambucil. Ir Med J 77: 288–289. Walton GD, Hon JK, Mulpur TG et al. (1997). Ofloxacin-induced seizure. Ann Pharmacother 31: 1475–1477. Wang HY, Chou WJ, Huang TY et al. (2007). Acute dystonia resulting from abrupt bupropion discontinuation. Prog Neuropsychopharmacol Biol Psychiatry 31: 766–768. Warden CR, Diekema DS, Robertson WO (1997). Dystonic reaction associated with dextromethorphan ingestion in a toddler. Pediatr Emerg Care 13: 214–215. Wassertheil-Smoller S, Hendrix SL et al.WHI Investigators (2003). Effect of estrogen plus progestin on stroke in postmenopausal women: the Women’s Health Initiative: a randomized trial. JAMA 289: 2673–2684. Weber JS, Berman D, Siegel J et al. (2008). Safety and efficacy of ipilimumab with or without prophylactic budesonide in

IATROGENIC NEUROLOGY treatment-naive and previously treated patients with advanced melanoma. J Clin Oncol ASCO annual meeting proceedings. Part I, 26 May suppl 20: abstr 9010. Weddington WW Jr (1982). Delirium and depression associated with amphotericin B. Psychosomatics 23: 1076–1078. Wedzicha JA, Gibb WR, Lees AJ (1984). Chorea in digoxin toxicity. J Neurol Neurosurg Psychiatry 47: 419. Weiner WJ, Nausieda PA, Klawans HL (1978). Methylphenidate-induced chorea: case report and pharmacologic implications. Neurology 28: 1041–1044. Weiss K (1998). Safety profile of interferon-alfa therapy. Semin Oncol 25: 9–13. Werner EG, Olanow CW (1989). Parkinsonism and amiodarone therapy. Ann Neurol 25: 630–632. Whittaker JA, Parry DH, Bunch C et al. (1973). Coma associated with vincristine therapy. Br Med J 4: 335–337. Whittle E, Robertson NR (1977). Transverse myelitis after diphtheria, tetanus, and polio immunization. Br Med J 1: 1450. Willis JK, Tilton AH, Harkin JC et al. (1990). Reversible myopathy due to labetalol. Pediatr Neurol 6: 275–276. Willmore LJ, Abelson MB, Ben-Menachem E (2009). Vigabatrin: 2008 update. Epilepsia 50: 163–173. Wise MEJ, Mistry K, Reid S (2002). Neuropsychiatric complications of nevirapine treatment. BMJ 324: 879. Wise RP, Iskander J, Pratt RD et al. (2004). Postlicensure safety surveillance for 7-valent pneumococcal conjugate vaccine. JAMA 292: 1702–1710. Wolf SM, Forsythe A (1978). Behavior disturbance, phenobarbital, and febrile seizures. Pediatrics 61: 728–731. Wolf LR, Otten EJ, Spadafora MP (1992). Cinchonism: two case reports and review of acute quinine toxicity and treatment. J Emerg Med 10: 295–301.


Wyllie AR, Bayliff CD, Kovacs MJ (1997). Myoclonus due to chlorambucil in two adults with lymphoma. Ann Pharmacother 31: 171–174. Wymore J, Carter JE (1982). Chlorpropamide-induced optic neuropathy. Arch Intern Med 142: 381. Yamada S, Suzuki T, Oe K et al. (2010). Case of acute dystonia during epidural droperidol infusion to prevent postoperative nausea and vomiting. Masui 59: 238–241. Yamadori A, Albert ML (1972). Involuntary mopvement disorders caused by methyldopa. N Engl J Med 286: 610. Yang HH, Hsiao YP, Shih HC et al. (2007). Acyclovir-induced neuropsychosis successfully recovered after immediate hemodialysis in an end-stage renal disease patient. Int J Dermatol 46: 883–884. Yangco BG, De Lerma C, Lyman GH et al. (1987). Clinical study evaluating efficacy of praziquantel in clonorchiasis. Antimicrob Agents Chemother 31: 135–138. Yim YS, Mahoney DH Jr, Oshman DG (1991). Hemiparesis and ischemic changes of the white matter after intrathecal therapy for children with acute lymphocytic leukemia. Cancer 67: 2058–2061. Yokobori S, Yokota H, Yamamoto Y (2006). Pediatric posterior reversible leukoencephalopathy syndrome and NSAID-induced acute tubular interstitial nephritis. Pediatr Neurol 34: 245–247. Zaki SA, Mauskar A, Shanbag P (2009). Toxic psychosis due to chloroquine overdose: a case report. J Vector Borne Dis 46: 81–82. Zanini M, Savini G, Barboni P (2006). Corneal melting associated with topical diclofenac use after laser-assisted subepithelial keratectomy. J Cataract Refract Surg 32: 1570–1572.

Iatrogenic neurology.

Iatrogenic disease is one of the most frequent causes of hospital admissions and constitutes a growing public health problem. The most common type of ...
894KB Sizes 1 Downloads 0 Views