INT’L. J. PSYCHIATRY IN MEDICINE, Vol. 21(1) 1-15,1991
NEUROPSYCHIATRIC ASPECTS OF STROKE
MACE BECKSON, M.D. JEFFREY L. CUMMINGS, M.D.
West Los Angeles Veterans Affairs Medical Center and Departments of Neurology and Psychiatry and Biobehavioral Sciences UCLA School of Medicine
ABSTRACT
Neuropsychiatric disorders following stroke are common, and pathologic involvement of specific regions or functional systems results in behavioral syndromes similar to idiopathic psychiatric syndromes. Depression occurs in up to half of all stroke patients and is most frequently associated with left anterior cortical and subcortical infarctions. Mood changes interfere with cognitive, functional and social recovery. Treatment with heterocyclic antidepressants, stimulants, and electroconvulsive therapy is efficacious in most patients. Mania, delusions, hallucinations, personality alterations, obsessive-compulsive disorder, and changes in sexual behavior are less common but have also been described in post-stroke patients. Each behavioral syndrome is associated with a specific pattern of brain involvement. Investigation of these phenomena contributes to understanding the cerebral basis of psychiatric disorders. (Int’l. J. Psychiatry in Medicine 21 :1-15, 1991)
Key Words: Stroke, personality, depression, obsession, mania, compulsion, delusion, sexual behavior, hallucination, neuropsychiatry
Stroke is the most common serious neurologic disorder in the world, accounting for half of all acute hospitalizations for neurologic disease [l, 21. The prevalence of stroke rises steadily throughout the life course: it affects 10/100,OOO of those under age thirty-five, 200/100,000 in the thirty-five to forty-four year old age group, 440/100,000 of forty-five to fifty-four year olds, 810/100,OOO of fifty-five 1
0 1991, Baywood Publishing Co., Inc.
doi: 10.2190/EUMY-3MGP-MWB2-CWG9 http://baywood.com
2 / BECKSON AND CUMMINGS
Table 1. Vascular Territories and Anatomic Locations of Infarctions Associated with Neuropsychiatric Disorders
Syndrome
Vascular Territory
Major depression
Left middle cerebral artery
Minor depression
Left or right middle cerebral artery Right middle, posterior, or anterior cerebral artery
Mania
Delusions
Left or right middle cerebral artery
Visual hallucinations
Carotid/ophthalmic arteries Basilar artery Left or right posterior cerebral arteries Basilar artery
Auditory hallucinations Personality alterations Apathetic
Anterior cerebral artery
Akinetic mutism
Bilateral anterior cerebral artery; bilateral medial penetratingarteries
Disinhibited, tactless
Anterior cerebral artery aneurysm
Obsessive-compulsive disorder Kluver-Bucy syndrome Rage
Penetrating branches of anterior and middle cerebral arteries Bilateral posterior cerebral arteries Bilateral posterior cerebral arteries
Lesion Location Left frontal cortex [13] Left caudate nucleus [19] Left or right temporoparietal regions [4] Right thalamus, perithalamic, temporobasal, or inferior frontal region [19, 39-42] Temporoparietal cortical regions or subcortical gray and white matter [43-531 Retina and optic nerve [56, 571 Midbrain [58-621 Geniculocalcarine radiations [63,641 Pons [66,67l Medial, superior frontal cortex; paramedian thalamic nuclei; bilateral globus pallidus; dorsolateralcaudate nucleus [68, 751 Bilateral anterior cingulate gyri; septohypothalamic area; mesodiencephalic junction area [76-781 Inferior medial frontal lobe; ventromedial caudate nucleus PO, 791 Bilateral caudate nucleus [82]
Bilateral medial temporal lobes
[MI Bilateral medial occipital and occipitotemporaljunctions
[W Hypersexualii Exhibitionism Hyposexuality
Penetratingbranch of posterior cerebral artery Anterior cerebral artery aneurysm Right middle cerebral artery
Right thalamus [80] Inferior medial frontal lobe [80] Right hemisphere [81]
NEUROPSYCHIATRICASPECTS OF STROKE / 3
to sixty-four year olds, 3560/100,000 of those sixty-five to seventy-four, and 5970/100,000 of those over age seventy-five [2]. It is the third most common cause of death in the United States and most European countries. Seventy percent of stroke survivors are left with sufficient disability to limit vocational capacity [l,21. Recent studies indicate that 77 percent of strokes are thromboembolic in origin (30% thrombotic, 22% embolic, 25% uncertain) and in 23 percent the stroke is hemorrhagic (11%intracranial hemorrhage, 12% subarachnoid hemorrhage) [3]. Hypertension is the single most pervasive risk factor of stroke; other riskenhancing factors include ischemic heart disease, valvular heart disease, cardiac arrhythmias, diabetes mellitus, polycythemia, cigarette smoking, physical inactivity, hyperlipidemia, hypercholesterolemia, and family history of cerebrovascular disease [l]. Most investigations of the consequences of stroke have focused on physical disabilities such as paralysis, sensory loss, gait disturbances, and visual impairment. Specific neurobehavioral deficit syndromes including post-stroke aphasia and amnesia have also been intensively studied. Until recently there has been little attention to the neuropsychiatric sequelae of stroke. Current observations demonstrate that neuropsychiatric disorders are frequent after stroke and that lesions of specific regions or functional systems of the brain result in behavioral syndromes similar to idiopathic psychiatric conditions. In this review, the neuropsychiatric disorders observed in conjunction with cerebrovascular disease are described and the relationship between specific types of behavioral alterations and localized infarctions are emphasized (Table 1). Post-stroke depression, mania, delusions, hallucinations, and personality alterations are presented. Deficit syndromes such as aphasia, amnesia, and multiinfarct dementia will not be addressed.
POST-STROKE DEPRESSION Depression after cerebral ischemic injury occurs in 30 to 50 percent of patients [4-61. Robinson and colleagues have used criteria of the third edition of the Diagnostic and Statistical Manual of Mental Disorders [7] to separate post-stroke depression into diagnostic categories of major depression and minor depression (dysthymic disorder) [4, 5, 81. Using the Hamilton Depression Scale [9] and the Present State Examination [lo], they found similar scores and syndrome profiles with forty-three patients with post-stroke major depression were compared with forty-three patients with idiopathic or functional major depression [ll].A twoyear longitudinal study of hospitalized stroke patients who manifested major depression revealed that the depressed mood tended to resolve in the first year after the stroke, while patients with minor depression continued to exhibit depressive symptoms throughout the two year period [12]. The relative frequency of major and minor depressive syndromes among patients with post-stroke
4 / BECKSONAND CUMMINGS
depression has varied among studies [5, 13, 141. Severity of depression does not correlate closely with severity of physical impairment, implicating a specific association between brain lesion and mood change beyond the expected psychological response to disability [4, 161. Robinson and co-workers demonstrated an increased frequency and severity of depression following left compared to right hemisphere injury [5, 131. For example, in one study, they found depression and vegetative symptoms in fourteen of twenty-two patients with left hemisphere injury and in only two of fourteen patients with right hemisphere injury [13]. In a study of left-handed stroke victims, Robinson et al. found a pattern of mood disorder identical to that of right-handed patients [171. This implies that hemispheric lateralization of post-stroke depression is independent of cerebral motor dominance, as reflected in handedness. Its relationship to language dominance remains to be determined. Robinson and colleagues also demonstrated that intrahemispheric lesion location is related to mood disorder in stroke patients [13]. Major, but not minor, depressive syndromes were significantly more frequent among patients with left anterior lesions (defined as a lesion having its anterior border proximal to 40%of the anterior-posterior distance on computerized tomography) than left posterior lesions or lesions in any other location. Minor depression occurred with either right or left hemisphere parietal-occipitallesions [4]. Among patients with left anterior infarctions, depression severity correlated with proximity of the lesion to the left frontal pole. Studies assessing the relationship of mood to intrahemispheric location of right hemispheric lesions have produced conflicting results, including an inverse correlation between proximity to the right frontal pole and depression, a curvilinear relationship, and no relationship [13, 141. Lipsey et al. found that in patients with bilateral brain injury secondary to stroke or trauma, those with left anterior brain injury were significantly more depressed than those without a lesion in this location [18]. In a comparison of cortical and subcortical lesions, Starkstein et al. found that left-sided subcortical lesions were associated with the same high frequency and severity of depression as left cortical lesions; left subcortical lesions were found to have a higher frequency of depression than right subcortical lesions; and the correlation of proximity to the frontal pole with severity of depression was also as strong for left subcortical lesions as for left cortical lesions [19]. A major depressive syndrome was consistently associated with lesions in the head of the left caudate nucleus. Studies of patients with cerebellar and brainstem infarctions revealed a lower frequency of depression compared with infarctions in the middle cerebral artery distribution (35% compared with 48%), and cerebellarbrainstem lesions showed no specific correlation between lesion location and depression [20]. In an investigation of patients with left anterior lesions who failed to become depressed, Starkstein et al. studied thirteen pairs of patients matched for lesion size and location but differing in the presence of a major depressive syndrome
NEUROPSYCHIATRIC ASPECTS OF STROKE / 5
[21]. Patients who developed post-stroke depression had a greater lateral ventricle-to-brain ratio and a larger third ventricle-to-brain ratio. It was hypothesized that pre-existing subcortical atrophy was an important predisposing factor for post-stroke depression. Prior psychiatric illness may also determine some aspects of post-stroke depression; patients who developed depression after right-hemisphere injury had a greater frequency of psychiatric disorder in their families than those who exhibited no post-stroke depression [22]. This inherited vulnerability to depression following stroke was not apparent in patients with left-brain injuries and depression. Using the Mini-Mental State Examination [Z],it has been demonstrated that patients with post-stroke major depression following left hemisphere injury have greater cognitive impairmentwhen compared with nondepressed patients [21,24]. In addition, Bolla-Wilson et al. found that depressed patients had deficits in orientation, language, executive/motor,and frontal lobe domains that were greater than predicted by the lesion per se [24]. These patients manifested cognitive deficits associated with major depression (dementia of depression) beyond those expected with left frontal lesions. Furthermore, it was found that among patients with right hemisphere stroke, those with major depression performed no worse than nondepressed patients in any of nine cognitive domains tested [24]. It was concluded that the effect of post-stroke major depression causing dementia of depression depended on laterality of the lesion. The dexamethasone suppression test @ST) has also been evaluated in poststroke depression. Patients with moderate to severe post-stroke major depression failed to suppress serum cortisol levels after administration of dexamethasone [16]. However, while sensitivity of the DST in this condition has been estimated at 67 percent, a false positive rate of 30 percent (correlated with large lesion volumes) limits the utility of the test as a diagnostic marker [25]. Pharmacotherapy has proved to be useful in post-stroke depression. A doubleblind randomized prospective study showed nortriptyline to have significantly greater efficacy than placebo [26]. Patients with higher serum levels (100 ng/ml) and treated for longer periods (6 weeks rather than 4 weeks) had greater resolution of their mood disorder. In another prospective double-blind study, trazodone was found to be associated with a greater trend toward improvement than placebo [27]. A retrospective study of methylphenidate in post-stroke depression revealed a 52 percent response rate, with efficacy usually evident within the first forty-eight hours of treatment [B].Laterality of lesion and dose were not correlated with response. Electroconvulsive treatment (ECT) may be efficacious in post-stroke depression but is under-utilized [29]. A retrospective chart review revealed that twelve of fourteen patients with post-stroke depression treated with ECT showed marked improvement in mood. In addition, five of six patients with cognitive impairment in addition to depression improved in both domains after ECT [301.
6 / BECKSONAND CUMMINGS
In summary, the similarities in symptomatology, natural history, cognitive impairment, biological markers, and treatment response between post-stroke depression and idiopathic depression imply that the neurobiology of mood changes after. stroke may be highly relevant in understanding the pathophysiology of “idiopathic” or “functional” depressive disorders. The Occurrence and course of post-stroke depression is influenced by lateralityof lesion, intrahemispheric lesion location, presence of pre-lesion atrophy, and presence of personal or family history of psychiatric illness. Interruption of ascending transmitter pathways, asymmetrical distribution of transmitters to the hemispheres and altered compensatory biochemical responses to brain injury may be important neurologic mechanisms underlying these observations [S, 31341.
POSTSTROKE MANIA Post-stroke mania is much less common than post-stroke depression. Dunne et al. identified three cases of post-stroke mania among 661 patients with strokes confirmed by computerized tomography or autopsy, and Robinson et al. identified two cases in a series of 500 consecutive stroke patients [35,36]. Emergence of this syndrome may require an hereditary predisposition as well as an appropriately placed lesion. Starkstein and colleagues found that patients with post-stroke mania often had a family history of mood disorders and that the post-stroke mania patients were more likely to have a family history of psychiatric illness than patients with post-stroke depression [36, 371. The existence of cerebral atrophy also appeared to increase the vulnerability to mania following stroke [19]. There is a marked predominance of right-sided lesions among patients exhibiting post-stroke mania. In most cases the lesion has been in the right hemisphere in the area of the thalamus, perithalamic region, basotemporal lobe, or inferior medial frontal lobe anterior to the third ventricle [19,38-43]. Mania may occur immediately after stroke or may be delayed for up to three years. In some cases, a single manic episode is experienced, whereas in others the patients manifest recurrent episodes of depression and mania closely imitating the course of bipolar mood disorders [42]. The clinical phenomenology of mania following stroke is also very similar to that of idiopathic manic episodes: elation, hyperactivity, insomnia, pressured speech, grandiosity, and flight of ideas are the most common symptoms [36]. Post-stroke mania is treated with the same agents utilized in the treatment of idiopathic manic syndromes and systematic differences in responsiveness have not been observed. Lithium, neuroleptics, and anticonvulsants administered in conventional dosages have been successful in controlling the manic behavior [421.
NEUROPSYCHIATRIC ASPECTS OF STROKE 1 7
POSTSTROKE DELUSIONAL DISORDERS The prevalence of delusions following stroke is unknown. Of 661 patients reviewed by Dunne et al., two were delusional in the acute post-stroke period and two more exhibited delusional syndromes within the first year following the cerebrovascular event [35].There have been no comprehensive assessments of acute and deferred psychosis following stroke. Delusions have been observed after both right and left hemispheric injuries and most lesions have involved the temporoparietal region or subcortical structures. Peroutka et al. and Berthier and Starkstein reported patients with the abrupt onset of delusions and auditory, visual, and tactile hallucinations following right temporoparietal infarctions [43,441. Levine and Finklestein reported eight patients with delusions and hallucinations following injuries (stroke or trauma) to the right temporoparietal region [45].In this study, psychotic episodes were closely related to the occurrence of seizures. Cutting included two patients with right parietal stroke among seventy-four patients with organic delusional disorders [&I. Flynn et al. reported a unique patient with more right than left-sided subcortical ischemic injury who manifested the delusion of parasitosis [46].The parasitic “infestation” remained confined to the left side of the body. Reduplication delusions such as Capgras syndrome (the conviction that someone familiar has been replaced by an identical appearing imposter) and Frkgoli syndrome (the belief that familiar persons are disguised as others) have been observed following stroke and are more often associated with right than left hemisphere infarctions [48,49]. Delusions have also been reported with left brain strokes. Signer et al. reviewed the psychiatric hospitalizationsof aphasic patients and found a significant association between left posterior lesions and psychosis, whereas left anterior lesions were more often associated with depression [50].The occurrence of delusions was not greater in those with seizures. Subcortical lacunar infarctions have also been identified in a number of patients with late-onset psychotic disorders [51-531,and multiple deep ischemic lesions are present in most patients with vascular dementia where the prevalence of delusions approaches 50 percent [54]. Post-stroke delusions resemble those of idiopathic psychiatric disorders such as schizophrenia, although visual hallucinations are more common in patients with Unique delusions the former and auditory hallucinations with the latter [&I. occurring exclusively in patients with focal cerebral injuries and not observed in schizophrenia include anosognosia (the delusion that hemiparetic limbs are not paralyzed) and reduplicative paramnesia (the belief that one is simultaneously in two locations). Both these disorders are most common with infarctions of the right hemisphere, although anosognosia has also been observed with left-sided lesions [55]. Neuroleptic agents are the drugs of choice for the treatment of post-stroke delusions. There is little information available concerning the relative efficacy of these agents in idiopathic and organic disorders.
8 / BECKSON AND CUMMINGS
POST-STROKE HALLUCINATIONS Visual hallucinations may occur with vascular lesions anywhere between the retina and the occipital cortex. Retinal ischemia associated with amaurosis fugax is associated with hallucinations in approximately one-third of patients. They report scintillations, colors, abnormal brightness, and flashing lights [56]. Optic nerve lesions can also produce visual hallucinations: the syndrome of auditoryvisual synesthesia in which sudden loud sounds induce photisms (unformed visual hallucinations) has been described in patients with optic nerve ischemia [57]. Midbrain vascular lesions are associated with the syndrome of peduncular hallucinosis. This unusual disorder is comprised of vivid visual hallucinations that typically exhibit a diurnal pattern, appearing in the evening. There is often an accompanying affect of interest and amusement. The syndrome typically persists for only a few days following the vascular event [58-601. It usually follows basilar artery branch thrombosis but has also been observed with pontine hemorrhage [61,62]. Lesions of the geniculocalcarine radiations produce homonymous visual field defects and are commonly associated with visual hallucinations. In a comprehensive study, Kolmel examined ninety-six patients with homonymous hemianopias, most secondary to vascular disease [63]. Forty-two percent experienced unformed hallucinations in the hemianopic field. Colored phosphenes occurred in 27 percent, phosphenes with heterogeneous colors and shapes in 18percent, and colored patterns in 15 percent (some patients experienced more than one type of hallucination). In most cases the hallucinations began within a few hours of onset of the visual field defect and disappearedwithin ten days. In a series of 120 patients with visual field defects, Kolmel reported that sixteen (13%) experienced complex visual hallucinations including lilliputians, marching armies of peasant women, and visions of one’s self (heutoscopy) [a]. The hallucinations appeared within hours to days of onset of the stroke and resolved in concert with the visual improvement in cases where the visual field defect remitted, and spontaneously over the course of weeks or months if the visual field defect persisted. The lesions associated with both unformed and complex hallucinationswere usually occipital in location and involved the left and right hemispheres approximately equally. These “release” hallucinations must be distinguished from the brief stereotyped visual hallucinations that may occur in the course of seizures [65]. The latter are treated with anticonvulsant agents. Auditory hallucinations are an uncommon complication of cerebrovascular disease. Unformed sounds, clicks, and poorly intelligible voices have been described following brainstem strokes, particularly pontine hemorrhages [66,67]. Formed hallucinations of human voices may also occur in conjunction with persecutory delusions. Likewise, tactile hallucinations are rare in stroke syndromesbut may accompany delusional parasitosis associated with cerebrovascular disease [47].
NEUROPSYCHIATRIC ASPECTS OF STROKE / 9
POST-STROKE PERSONALITY ALTERATIONS Changes in personality associated with specific stroke syndromes are largely unexplored. The most dramatic alterations occur in patients with infarctions of the frontal lobes. Identifiable personality patterns are described following lesions of the superior medial and of the inferior medial frontal cortex. Unilateral lesions of the superior medial frontal lobe in the distribution of the anterior cerebral artery involve the cingulate gyms and the supplementary motor area and cause transient hypokinesia, slowness, and paucity of verbal output [68]. A similar but persistent syndrome has been observed in patients with infarction of the globus pallidus. The patients are quiet, laconic, indifferent to personal circumstances, and unmotivated [69]. Mendez et al. observed that apathy also dominated the clinical syndrome associated with dorsolateral infarctions of the caudate nucleus, and bilateral paramedian thalamic infarction results in an apathetic syndrome with diminished motivation and interest punctuated by periods of irritability, euphoria, and brief labile outbursts [70-731. Apathy is also the most common personality change observed in patients with vascular dementia with multiple subcortical infarctions [74]. The frontal lobe, caudate nucleus, globus pallidus, and thalamus are linked together in a functional unit and lesions of any of the structures within the complex produce a similar disorder with apathic behavior [75]. A more marked syndrome of apathy, the akinetic mute state, occurs with bilateral infarctions of the anterior medial frontal cortex (bilateral anterior cingulate gyri), inferior frontal lobe in the region of the septum and septohypothalamic junction, or in the posterior hypothalamic region involving the medial thalamus, subthalamus, and midbrain tegmentum [76-781. Behavioral changes associated with inferior frontal injury are common, may be marked, and contrast sharply with the apathy noted in patients with superior medial frontal infarction. Patients exhibit a behavioral syndrome characterized as euphoric, tactless, irritable, lacking judgment, impulsive, and outspoken. In a study of behavior change following rupture of anterior cerebral artery aneurysms by Logue et al., 19 percent of seventy-nine patients were euphoric, 32 percent worried less, 18percent exhibited affective flattening, 38 percent were emotionally labile, 27 percent were more irritable, 33 percent were more outspoken, 13 percent were tactless, and 46 percent exhibited diminished interest and conscientiousness [79]. A similar disinhibited state has been reported in patients with lesions of the ventromedial caudate nucleus [70].
MISCELLANEOUS POSTSTROKE NEUROPSYCHIATRIC SYNDROMES In addition to the relatively well recognized consequences of stroke described above, a variety of less well known neuropsychiatric disorders have been observed following localized cerebrovascular injuries. Alterations in sexual
10 I BECKSON AND CUMMINGS
behavior, obsessive-compulsive disorders, Kluver-Bucy syndrome, and rage syndromes have all been described following localized ischemic injuries. A variety of types of change in sexual behavior have been observed as a consequence of vascular lesions. Miller et al. reported one patient with exhibitionism following rupture of an anterior cerebral artery aneurysm and another with abnormal hypersexuality associated with a right-sided thalamic hemorrhage [80]. Coslett and Heilman found that diminished sexual function was more prevalent following right than left hemisphere infarctions [81]. Sixty-seven percent of men with right hemisphere lesions experienced reduced libido compared to 21 percent of those with left hemisphere strokes. Obsessive and compulsive behaviors including counting objects and stereotyped motor behavior have been observed with bilateral infarctions of the caudate nuclei [82]. The Kluver-Bucy syndrome is a complex disorder consisting of placidity, hyperorality, altered sexual behavior, visual agnosia, and hypermetamorphosis [83]. It occurs in patients with bilateral medial temporal injury, including bilateral temporal lobe infarction [a]. Rage with biting, spitting, shouting, and swearing has been observed as a consequence of bilateral infarctions of the medial occipital and occipito-temporal junction regions [85].
SECONDARYBEHAVIORALCONSEQUENCESOF CARDIOVASCULAR DISEASE Stroke patients often harbor other manifestations of vascular disease or take medications that may impact behavior and should be considered in the differential diagnosis of post-stroke behavioral changes. Ischemic cardiac disease with congestive heart failure and cerebral anoxia may lead to delirium with hallucinations, delusions, or mood changes. Similarly, renal failure secondary to vascular pathology may produce hallucinations, delusions, and mood alterations. Drugs administered to manage vascular problems may also have substantial behavioral effects. Antihypertensive agents may produce depression, mania, delusions, or hallucinations. Finally, infarctions may lead to seizures with complex ictal and interictal behavioral syndromes [86].
SUMMARY A variety of neuropsychiatric syndromes may be observed following cerebrovascular insults to the brain. Depression is the most commonly observed post-stroke syndrome, but mania, delusions, hallucinations, personality alterations, obsessive-compulsive disorder, and changes in sexual behavior have also been described. Neuropsychiatricsyndromes are not contingent on specific lesion sites with the same predictability as deficit syndromes such as aphasia and
NEUROPSYCHIATRICASPECTS OF STROKE / 11
amnesia. Nevertheless, regional relationships are evident and disruption of specific structures or functional systems is an important element influencing the behavioral consequences of focal lesions and ischemic injuries (see Table 1). Further investigation of functional-anatomic brain systems will improve the understanding of how such behavioral syndromes are mediated. Investigation of the neuropsychiatric consequences of stroke aids in identifying brain areas involved in specific behavioral disturbances and contributes to understanding the cerebral basis of psychiatric disorders. ACKNOWLEDGMENTS
This project was supported by the Department of Veterans Affairs. Ms.Norene Hiekel prepared the manuscript. REFERENCES 1. V. Hachinski and J. W. Norris, TheAcute Stroke, F. A. Davis, Philadelphia, 1985. 2. P. A. Wolf, W. B. Kannel, and J. Verter, Cerebrovascular Disease in the Elderly: Epidemiology, in ClinicalNeurology ofAging, M. L. Albert (ed.), Oxford, New York, pp. 458-477,1984. 3. L. R. Caplan and R. W. Stein, Stroke: A Clinical Approach, Butterworths, Boston, 1986. 4. R. G. Robinson, L. B. Starr, K. L Kubos, et al., A Two Year Longitudinal Study of Post-Stroke Mood Disorder: Findings during the Initial Evaluation, Stroke, 14, pp. 736-741,1983. 5 . R. G. Robinson and T. R. Price, Post-Stroke Depressive Disorders: A Follow-up Study of 103 Patients, Stroke, 13, pp. 63541,1982. 6. D. Sinyor, P. Jacques, D. A. Kaloupek, et al., Post-Stroke Depression and Lesion Location: An Attempted Replication,Brain, 109, pp. 537-546,1986. 7. American Psychiatric Association,Diagnostic and Statistical Manual of Mental Disorders, (3rd Edition), American Psychiatric Association, Washington, D.C., 1980. 8. S. E. Starkstein and R. G. Robinson, Affective Disorders and Cerebral Vascular Disease, British Journal of Psychiatry, 154, pp. 170-182,1989. 9. M. A. Hamilton, A Rating Scale for Depression,Journal of Neurology, Neurosurgery, and Psychiatry, 23, pp. 56-62,1960. 10. J. K. Wing, J. E. Cooper, and N. Santorius, Measurement and Classification of Psychiatric Symptoms, Cambridge University Press, London, 1974. 11. J. R. Lipsey, W. C. Spencer, P. V. Rabins, and R. G. Robinson, Phenomenological Comparison of Post-Stroke Depression and Functional Depression,American Journal of Psychiatry, 143, pp. 527-529, 1986. 12. R. G . Robinson, P. L. Bolduc, and T. R. Price, Two Year Longitudinal Study of Post-Stroke Mood Disorders Diagnosis and Outcome at One and Two Years, Stroke, 18, pp. 837-843,1987. 13. R. G . Robinson, K. L. Kubos, L. B. Skirr, et al., Mood Disorders in Stroke Patients: Importance of Location of Lesion, Brain, 107, pp. 81-93,1984a.
12 / BECKSON AND CUMMINGS
14. M. R. Eastwood, S. Rifat, H. Nobbs, et al., Mood Disorder Following Cerebrovascular Accident, British Journal of Psychiatry, 154, pp. 195-200, 1989. 15. M. F. Folstein, R. Mailberger, and P. R. McHugh, Mood Disorders as a Specific Complication of Stroke, Journal of Neurology, Neurosurgery and Psychiatry, 40, pp. 1018-1020,1977. 16. S. Finklestein, L. I. Benowitz, R. Baldessarini, et al., Mood, Vegetative Disturbance, and Dexamethasone Suppression Test after Stroke, Annals of Neurology, 12, pp. 463468,1982. 17. R. G. Robinson, J. R. Lipsey, K. Bolla-Wilson, et al., Mood Disorders in Left-Handed Stroke Patients, Anierican Journal of Psychiatry, 142, pp. 1424-1429, 1985. 18. J. R. Lipsey, R. G. Robinson, G. D. Pearlson, et al., Mood Change Following Bilateral Hemisphere Brain Injury, British Journal of Psychiatry, 143, pp. 266-273,1983. 19. S. E. Starkstein, R. G. Robinson, and T. R. Price, Comparison of Cortical and Subcortical Lesions in the Production of Post-Stroke Mood Disorders, Brain, 110, pp. 10451059,1987. 20. S. E. Starkstein, R. G. Robinson, and T. R. Price, Depressive Disorders Following Posterior Circulation as Compared with Middle Cerebral Artery Infarcts, Brain, 111, pp. 375387,1988. 21. S. E. Starkstein, R. G. Robinson, and T. R. Price, Comparison of Patients with and without Post-Stroke Major Depression Matched for Size and Location of Lxsion, Archives of General Psychiatry, 45, pp. 247-252,1988. 22. S. E. Starkstein, R. G. Robinson, M. A. Honig, et al., Mood Changes after Right-Hemisphere Lesions, British Journal of Psychiatry, 155, pp. 79-85, 1989. 23. M. F. Folstein, S. F. Folstein, and P. R. McHugh, Mini-Mental State: A Practical Method for Grading the Cognitive State of Patients, for the Clinician, Journal of Psychiatric Research, 12, pp. 189-198, 1975. 24. K. Bolla-Wilson, R. G. Robinson, S. E. Starkstein, et al., Lateralization of Dementia of Depression in Stroke Patients, Anierican Journal of Psychiatry, 146, pp. 627634, 1989. 25. R. Lipsey, R. G. Robinson, G. D. Pearlson, et al., The Dexamethasone Suppression Test and Mood Following Stroke, American Journal of Psychiatry, 142, pp. 318-323, 1985. 26. R. Lipsey, R. G. Robinson, G. D. Pearlson, et al., Nortriptyline Treatment of PostStroke Depression A Double-Blind Study, TheLancet, 84, pp. 297-300, 1984. 27. M. J. Reding, L. A. Orto, S. W. Winter, et al., Antidepressant Therapy after Stroke: A Double-Blind Trial, Archives of Neurology, 43, pp. 763-765,1986. 28. V. R. Lingam, L. W. Lazarus, L. Groves, et al., Methylphenidate in Treating PostStroke Depression, Journal of Clinical Psychiatry, 49, pp. 151-153,1988. 29. H. Feibel and C. J. Springer, Depression and Failure to Resume Social Activities after Stroke, Archives of Physical Medicine and Rehabilitation, 63, p. 276, 1982. 30. G. B. Murray, V. S. Shea, and D. K. Conn, Electroconvulsive Therapy for Post-Stroke Depression, Journal of Clinical Psychiatry, 47, pp. 258-260,1986. 31. V. M. Pickel, M. Segal, and F. E. Bloom, A Radio-auto-graphic Study of the Efferent Pathways of the Nucleus Locus Ceruleus, Journal of Comparative Neurology, 155, pp. 1542,1974.
NEUROPSYCHIATRICASPECTS OF STROKE I 13
32. J. H. Morrison, M. E. MolIiver, and R. Grzanna, Noradrenergic Innervation of the Cerebral Cortex: Widespread Effects of Local Cortical Lesions, Science, 205, pp. 313316,1979. 33. R. G. Robinson, Differential Behavioral and Biochemical Effects of Right and Left Hemispheric Cerebral Infarction in the Rat, Science, 205, pp. 707-710, 1979. 34. H. S. Mayberg, R. G. Robinson, D. F. Wong, et al., PET Imaging of Cortical S2-Serotonin Receptors Following Stroke: Lateralized Changes and Relationship to Depression, American Journal of Psychiatry, 145, pp. 937-943,1988. 35. J. W. Dunne, P. J. Leedman, and R. H. Edk, Inobvious Stroke: A Cause of Delirium and Dementia, Australian and New Zealand Journal of Medicine, 16, pp. 771-778,1986. 36. R. G. Robinson, J. D. Boston, S. E. Starkstein, et al., Comparison of Mania and Depression after Brain Injury: Causal Factors, American Journal of Psychiatry, 145, pp. 172-178, 1988. 37. S. E. Starkstein, R. G. Robinson, M. L. Berthier, et al., Differential Mood Changes Following Basal Ganglia vs. Thalamic Lesions, Archives of Neurology, 45, pp. 725730,1988. 38. J. Bogousslavsky, M. Ferrazzini, F. Regli, et al., Manic Delirium and Frontal-Like Syndrome with Paramedian Infarction in the Right Thalamus, Journal of Neurology, Neurosurgery, and Psychiatry, 51, pp. 117-119,1988. 39. M. R. Cohen and R. W. Niska, Localized Right Cerebral Hemisphere Dysfunction and Recurrent Mania, American Journal of Psychiatry, 137, pp. 847-848,1980. 40. J. L. Cummings and M. F. Mendez, Secondary Mania with Focal Cerebrovascular Lesions, American Journal of Psychiatry, 141, pp. 1084-1087,1984. 41. P. J. M. Van Der Lugt and A. P. DeVisser, Two Patients with a Vital Expansive Syndrome Following a Cerebrovascular Accident, Psychiatrica, Neurologica, and Neurochirugia, 70, pp. 349-359, 1967. 42. S. E. Starkstein and R. G. Robinson, Affective Disorders and Cerebral Vascular Disease, British Journal of Psychiatry, 154, pp. 170-182,1989. 43. S. J. Peroutka, B. Sohmer, A. J. Kumar, et al., Hallucinations and Delusions Following a Right Temporoparietooccipital Infarction, The Johns Hopkins Medical Journal, 151, pp. 181-185,1982. 44. M. Berthier and S. E. Starkstein, Acute Atypical Psychosis Following a Right Hemisphere Stroke, AcfaNeurologica Belgica, 87, pp. 125-131,1987. 45. D. N. Levine and S. Finklestein, Delayed Psychosis after Right Temporoparietal Stroke or Trauma: Relation to Epilepsy, Neurology, 32, pp. 267-273,1982. 46. J. Cutting, The Phenomenology of Acute Organic Psychosis, British Journal of Psychiatry, 151, pp. 324-332,1987. 47. F. G. Flynn, J. L. Cummings, J. Scheibel, et al., Monosymptomatic Delusions of Parasitosis Associated with Ischemic Cerebrovascular Disease, Journal of Geriatric Psychiatry and Neurology, 2, pp. 134-139,1989. 48. T. E. Feinberg and R. M. Shapiro, Misidentification-Reduplication and the Right Hemisphere, Neuropsychiatry, Neuropsychology, and Behavioral Neurology, 2, pp. 3948,1989. 49. K. W. de Pauw, T. K. Szulecka, and T. L. Poltock, Frkgoli Syndrome after Cerebral Infarction, The Journal of Nervous and Mental Disease, 175, pp. 433437,1987.
14 / BECKSON AND CUMMINGS
50. S. Signer, J. L. Cummings, D. F. Benson, Delusions and Mood Changes in Patients with Chronic Aphasia, Journal of Neuropsychiatry and Clinical Neuroscience, I , pp. 4 0 4 , 1 9 8 9 . 51. B. L. Miller, D. F. Benson, J. L. Cummings, et al., Late-life Paraphrenia: An Organic Delusional Syndrome, Journal of Clinical Psychiatry, 47, pp. 204-207, 1986. 52. B. L. Miller, I. M. Lesser, K. Boone, et al., Brain White-Matter Lesions and Psychosis, British Journal of Psychiatry, 155, pp. 73-78,1989. 53. A. Pakalnis, M. E. Drake, Jr., et al., Right Parietooccipital Lacunar Infarctions with Agitation, Hallucinations, and Delusions, Psychosomatics, 28, pp. 95-96, 1987. 54. J. L. Cummings, B. L. Miller, M. A. Hill, et al., Neuropsychiatric Aspects of Vascular Dementia and Dementia of the Alzheimer Type, Archives of Neurology, 44, pp. 389393,1987. 55. J. L. Cummings, Organic Delusions, British Journal of Psychiatry, 146, pp. 184-197, 1985. 56. J. A. Goodwin, P. B. Gorelick, and C. M. Helgason, Symptoms of Amaurosis Fugax in Atherosclerotic Carotid Artery Disease, Neurology, 37,pp. 829-832,1987. 57. L. Jacobs, A. Arpik, D. Bozian, et al., Auditory-Visual Synesthesia, Archives of NeuroZogy, 38, pp. 211-216, 1981. 58. W. M. Feinberg and S. 2. Rapcsak, “Peduncular Hallucinosis” Following Paramedian Thalamic Infarction, Neurology, 39,pp. 1525-1536,1989. 59. T. J. Geller and S. N. Bellur, Peduncular Hallucinosis Magnetic Resonance Imaging Confirmation of Mesencephalic Infarction during Life, Annals of NeuroZogy, 21, pp. 602404,1987. 60. J. Rozanski, Peduncular Hallucinosis Following Vertebral Angiography, Neurology, 2, pp. 341-349,1952. 61. L. R. Caplan, “Top of the Basilar” Syndrome, Neurology, 30, pp. 72-79,1980. 62. K. Nakajima, Clinicopathologic Study of Pontine Hemorrhage, Stroke, 14, pp. 485493,1983. 63. H. W. Kolmel, Coloured Patterns in Hemianopic Fields, Brain, 107, pp. 155-167, 1984. 64. H. W. Kolmel, Complex Visual Hallucinations in the Hemianopic Field, Journal of Neurology, Neurosurgery, and Psychiatry, 48, pp. 29-38,1985. 65. J. L. Cummings and B. L. Miller, Visual Hallucinations, WesternJournal OfMedicine, 146,pp. 46-51,1987. 66. G. D. Cascino and R. D. Adams, Brainstem Auditory Hallucinosis, Neurology, 36, pp. 1042-1047,1986. 67. D. J. Lanska, J. Lanska, and M. F. Mendez, Brainstem Auditory Hallucinosis, Neurology,37,p. 1685,1987. 68. M. Verfaellie and K. M.Heilman, Response Preparation and Response Inhibition after Lesions of the Medial Frontal Lobe, Archives of Neurology, 44, pp. 1265-1271,1987. 69. R. L. Strub, Frontal Lobe Syndrome in a Patient with Bilateral Globus Pallidus Lesions, Archives of Neurology, 46, pp. 1024-1027,1989. 70. M. F. Mendez, N. L. Adams, and K. S. Lewandowski, Neurobehavioral Changes Associated with Caudate Lesions, Neurology, 39, pp. 349-354, 1989.
NEUROPSYCHIATRICASPECTS OF STROKE / 15
71. M. Gentilini, E. De Renzi, and G. Crisis, Bilateral Paramedian Thalamic Artery Infarcts: Report of Eight Cases, Journal of Neurology, Neurosurgery, Psychiatry, SO, pp. 900-909,1987. 72. A. Guberman and D. Shlss, The Syndrome of Bilateral Paramedian Thalamic Infarction, Neurology, 33, pp. 540-546,1983. 73. D. I. Katz,M. P. Alexander, and A. M. Mandell, Dementia Following Strokes in the Mesencephalon and Diencephalon, Archives of Neurology, 44, pp. 1127-1133, 1987. 74. L. Dian, J. L. Cummings, S. Petry, et al., Personality Alterations in Vascular Dementia, Psychosomatics, (in press). 75. G. E. Alexander, M. R. DeLong, and P. Strick, Parallel Organization of Functionally Segregated Circuits Linking Basal Ganglia and Cortex, Annual Review of Neuroscience, 9, pp. 357-381,1986. 76. R. W. Barris and H. R. Schuman, Bilateral Anterior Cingulate Gyms Lesions, Neurology, 3, pp. 44-52,1953. 77. J. M. Nielsen and L. L. Jacobs, Bilateral Lesions of the Anterior Cingulate Gyms, Bulletin of the Los Angeles Neurological Society, 16, pp. 231-234,1951. 78. J. M. Segarra, Cerebral Vascular Disease and Behavior, Archives of Neurology, 22, pp. 408-418,1970. 79. V. Logue, J. Dunvard, R. T. C. Pratt, et al., The Quality of Survival after Rupture of an Anterior Cerebral Aneurysm, British Jourml of Psychiaby, 114, pp. 137-160, 1968. 80. B. L. Miller, J. L. Cummings, H. Mclntyre, et al., Hypersexuality or Altered Sexual Preference Following Brain Injury, Journal of Neurology, Neurosurgery, and Psychiatry, 49, pp. 8674373,1986. 81. H. B. Coslett and K. M. Heilman, Male Sexual Function, Archives of Neurology, 43, pp. 1036-1039,1986. 82. B. Croisile, D. Tourniare, C. Confavreux, et al., Bilateral Damage to the Head of the Caudate Nuclei, Annals of Neurology, 25, pp. 313-314,1989. 83. R. Lilly, J. L. Cummings, D. F. Benson, et al., The Human Kluver-Bucy Syndrome, Neurology, 33, pp. 1141-1145,1983. 84. D. Shraberg and L. Weisberg, The Kluver-Bucy Syndrome in Man, The Journal of Nervous andMenta1 Disease, 166, pp. 130-134,1978. 85. J. L. Medina, F. A. Rubino, and E. Ross, Agitated Delirium Caused by Infarctions of the Hippocampal Formation and Fusiform and Lingual Gyri: A Case Report, NeurolO ~ Y ,24, pp. 1181-1183,1974. 86. J. Cummings, ClinicalNeuropsychiutry, Grune and Stratton, New York, 1985.
Direct reprint requests to: Jeffrey L. Cummings, M.D. Neurobehavior Unit (Bldg. 256B) West Los Angeles VAMC Brentwood Division 11301Wilshire Blvd. Los Angeles, CA 90073
NEUROPSYCHIATRIC ASPECTS OF STROKE
MACE BECKSON, M.D. JEFFREY L. CUMMINGS, M.D.
West Los Angeles Veterans Affairs Medical Center and Departments of Neurology and Psychiatry and Biobehavioral Sciences UCLA School of Medicine
ABSTRACT
Neuropsychiatric disorders following stroke are common, and pathologic involvement of specific regions or functional systems results in behavioral syndromes similar to idiopathic psychiatric syndromes. Depression occurs in up to half of all stroke patients and is most frequently associated with left anterior cortical and subcortical infarctions. Mood changes interfere with cognitive, functional and social recovery. Treatment with heterocyclic antidepressants, stimulants, and electroconvulsive therapy is efficacious in most patients. Mania, delusions, hallucinations, personality alterations, obsessive-compulsive disorder, and changes in sexual behavior are less common but have also been described in post-stroke patients. Each behavioral syndrome is associated with a specific pattern of brain involvement. Investigation of these phenomena contributes to understanding the cerebral basis of psychiatric disorders. (Int’l. J. Psychiatry in Medicine 21 :1-15, 1991)
Key Words: Stroke, personality, depression, obsession, mania, compulsion, delusion, sexual behavior, hallucination, neuropsychiatry
Stroke is the most common serious neurologic disorder in the world, accounting for half of all acute hospitalizations for neurologic disease [l, 21. The prevalence of stroke rises steadily throughout the life course: it affects 10/100,OOO of those under age thirty-five, 200/100,000 in the thirty-five to forty-four year old age group, 440/100,000 of forty-five to fifty-four year olds, 810/100,OOO of fifty-five 1
0 1991, Baywood Publishing Co., Inc.
doi: 10.2190/EUMY-3MGP-MWB2-CWG9 http://baywood.com
2 / BECKSON AND CUMMINGS
Table 1. Vascular Territories and Anatomic Locations of Infarctions Associated with Neuropsychiatric Disorders
Syndrome
Vascular Territory
Major depression
Left middle cerebral artery
Minor depression
Left or right middle cerebral artery Right middle, posterior, or anterior cerebral artery
Mania
Delusions
Left or right middle cerebral artery
Visual hallucinations
Carotid/ophthalmic arteries Basilar artery Left or right posterior cerebral arteries Basilar artery
Auditory hallucinations Personality alterations Apathetic
Anterior cerebral artery
Akinetic mutism
Bilateral anterior cerebral artery; bilateral medial penetratingarteries
Disinhibited, tactless
Anterior cerebral artery aneurysm
Obsessive-compulsive disorder Kluver-Bucy syndrome Rage
Penetrating branches of anterior and middle cerebral arteries Bilateral posterior cerebral arteries Bilateral posterior cerebral arteries
Lesion Location Left frontal cortex [13] Left caudate nucleus [19] Left or right temporoparietal regions [4] Right thalamus, perithalamic, temporobasal, or inferior frontal region [19, 39-42] Temporoparietal cortical regions or subcortical gray and white matter [43-531 Retina and optic nerve [56, 571 Midbrain [58-621 Geniculocalcarine radiations [63,641 Pons [66,67l Medial, superior frontal cortex; paramedian thalamic nuclei; bilateral globus pallidus; dorsolateralcaudate nucleus [68, 751 Bilateral anterior cingulate gyri; septohypothalamic area; mesodiencephalic junction area [76-781 Inferior medial frontal lobe; ventromedial caudate nucleus PO, 791 Bilateral caudate nucleus [82]
Bilateral medial temporal lobes
[MI Bilateral medial occipital and occipitotemporaljunctions
[W Hypersexualii Exhibitionism Hyposexuality
Penetratingbranch of posterior cerebral artery Anterior cerebral artery aneurysm Right middle cerebral artery
Right thalamus [80] Inferior medial frontal lobe [80] Right hemisphere [81]
NEUROPSYCHIATRICASPECTS OF STROKE / 3
to sixty-four year olds, 3560/100,000 of those sixty-five to seventy-four, and 5970/100,000 of those over age seventy-five [2]. It is the third most common cause of death in the United States and most European countries. Seventy percent of stroke survivors are left with sufficient disability to limit vocational capacity [l,21. Recent studies indicate that 77 percent of strokes are thromboembolic in origin (30% thrombotic, 22% embolic, 25% uncertain) and in 23 percent the stroke is hemorrhagic (11%intracranial hemorrhage, 12% subarachnoid hemorrhage) [3]. Hypertension is the single most pervasive risk factor of stroke; other riskenhancing factors include ischemic heart disease, valvular heart disease, cardiac arrhythmias, diabetes mellitus, polycythemia, cigarette smoking, physical inactivity, hyperlipidemia, hypercholesterolemia, and family history of cerebrovascular disease [l]. Most investigations of the consequences of stroke have focused on physical disabilities such as paralysis, sensory loss, gait disturbances, and visual impairment. Specific neurobehavioral deficit syndromes including post-stroke aphasia and amnesia have also been intensively studied. Until recently there has been little attention to the neuropsychiatric sequelae of stroke. Current observations demonstrate that neuropsychiatric disorders are frequent after stroke and that lesions of specific regions or functional systems of the brain result in behavioral syndromes similar to idiopathic psychiatric conditions. In this review, the neuropsychiatric disorders observed in conjunction with cerebrovascular disease are described and the relationship between specific types of behavioral alterations and localized infarctions are emphasized (Table 1). Post-stroke depression, mania, delusions, hallucinations, and personality alterations are presented. Deficit syndromes such as aphasia, amnesia, and multiinfarct dementia will not be addressed.
POST-STROKE DEPRESSION Depression after cerebral ischemic injury occurs in 30 to 50 percent of patients [4-61. Robinson and colleagues have used criteria of the third edition of the Diagnostic and Statistical Manual of Mental Disorders [7] to separate post-stroke depression into diagnostic categories of major depression and minor depression (dysthymic disorder) [4, 5, 81. Using the Hamilton Depression Scale [9] and the Present State Examination [lo], they found similar scores and syndrome profiles with forty-three patients with post-stroke major depression were compared with forty-three patients with idiopathic or functional major depression [ll].A twoyear longitudinal study of hospitalized stroke patients who manifested major depression revealed that the depressed mood tended to resolve in the first year after the stroke, while patients with minor depression continued to exhibit depressive symptoms throughout the two year period [12]. The relative frequency of major and minor depressive syndromes among patients with post-stroke
4 / BECKSONAND CUMMINGS
depression has varied among studies [5, 13, 141. Severity of depression does not correlate closely with severity of physical impairment, implicating a specific association between brain lesion and mood change beyond the expected psychological response to disability [4, 161. Robinson and co-workers demonstrated an increased frequency and severity of depression following left compared to right hemisphere injury [5, 131. For example, in one study, they found depression and vegetative symptoms in fourteen of twenty-two patients with left hemisphere injury and in only two of fourteen patients with right hemisphere injury [13]. In a study of left-handed stroke victims, Robinson et al. found a pattern of mood disorder identical to that of right-handed patients [171. This implies that hemispheric lateralization of post-stroke depression is independent of cerebral motor dominance, as reflected in handedness. Its relationship to language dominance remains to be determined. Robinson and colleagues also demonstrated that intrahemispheric lesion location is related to mood disorder in stroke patients [13]. Major, but not minor, depressive syndromes were significantly more frequent among patients with left anterior lesions (defined as a lesion having its anterior border proximal to 40%of the anterior-posterior distance on computerized tomography) than left posterior lesions or lesions in any other location. Minor depression occurred with either right or left hemisphere parietal-occipitallesions [4]. Among patients with left anterior infarctions, depression severity correlated with proximity of the lesion to the left frontal pole. Studies assessing the relationship of mood to intrahemispheric location of right hemispheric lesions have produced conflicting results, including an inverse correlation between proximity to the right frontal pole and depression, a curvilinear relationship, and no relationship [13, 141. Lipsey et al. found that in patients with bilateral brain injury secondary to stroke or trauma, those with left anterior brain injury were significantly more depressed than those without a lesion in this location [18]. In a comparison of cortical and subcortical lesions, Starkstein et al. found that left-sided subcortical lesions were associated with the same high frequency and severity of depression as left cortical lesions; left subcortical lesions were found to have a higher frequency of depression than right subcortical lesions; and the correlation of proximity to the frontal pole with severity of depression was also as strong for left subcortical lesions as for left cortical lesions [19]. A major depressive syndrome was consistently associated with lesions in the head of the left caudate nucleus. Studies of patients with cerebellar and brainstem infarctions revealed a lower frequency of depression compared with infarctions in the middle cerebral artery distribution (35% compared with 48%), and cerebellarbrainstem lesions showed no specific correlation between lesion location and depression [20]. In an investigation of patients with left anterior lesions who failed to become depressed, Starkstein et al. studied thirteen pairs of patients matched for lesion size and location but differing in the presence of a major depressive syndrome
NEUROPSYCHIATRIC ASPECTS OF STROKE / 5
[21]. Patients who developed post-stroke depression had a greater lateral ventricle-to-brain ratio and a larger third ventricle-to-brain ratio. It was hypothesized that pre-existing subcortical atrophy was an important predisposing factor for post-stroke depression. Prior psychiatric illness may also determine some aspects of post-stroke depression; patients who developed depression after right-hemisphere injury had a greater frequency of psychiatric disorder in their families than those who exhibited no post-stroke depression [22]. This inherited vulnerability to depression following stroke was not apparent in patients with left-brain injuries and depression. Using the Mini-Mental State Examination [Z],it has been demonstrated that patients with post-stroke major depression following left hemisphere injury have greater cognitive impairmentwhen compared with nondepressed patients [21,24]. In addition, Bolla-Wilson et al. found that depressed patients had deficits in orientation, language, executive/motor,and frontal lobe domains that were greater than predicted by the lesion per se [24]. These patients manifested cognitive deficits associated with major depression (dementia of depression) beyond those expected with left frontal lesions. Furthermore, it was found that among patients with right hemisphere stroke, those with major depression performed no worse than nondepressed patients in any of nine cognitive domains tested [24]. It was concluded that the effect of post-stroke major depression causing dementia of depression depended on laterality of the lesion. The dexamethasone suppression test @ST) has also been evaluated in poststroke depression. Patients with moderate to severe post-stroke major depression failed to suppress serum cortisol levels after administration of dexamethasone [16]. However, while sensitivity of the DST in this condition has been estimated at 67 percent, a false positive rate of 30 percent (correlated with large lesion volumes) limits the utility of the test as a diagnostic marker [25]. Pharmacotherapy has proved to be useful in post-stroke depression. A doubleblind randomized prospective study showed nortriptyline to have significantly greater efficacy than placebo [26]. Patients with higher serum levels (100 ng/ml) and treated for longer periods (6 weeks rather than 4 weeks) had greater resolution of their mood disorder. In another prospective double-blind study, trazodone was found to be associated with a greater trend toward improvement than placebo [27]. A retrospective study of methylphenidate in post-stroke depression revealed a 52 percent response rate, with efficacy usually evident within the first forty-eight hours of treatment [B].Laterality of lesion and dose were not correlated with response. Electroconvulsive treatment (ECT) may be efficacious in post-stroke depression but is under-utilized [29]. A retrospective chart review revealed that twelve of fourteen patients with post-stroke depression treated with ECT showed marked improvement in mood. In addition, five of six patients with cognitive impairment in addition to depression improved in both domains after ECT [301.
6 / BECKSONAND CUMMINGS
In summary, the similarities in symptomatology, natural history, cognitive impairment, biological markers, and treatment response between post-stroke depression and idiopathic depression imply that the neurobiology of mood changes after. stroke may be highly relevant in understanding the pathophysiology of “idiopathic” or “functional” depressive disorders. The Occurrence and course of post-stroke depression is influenced by lateralityof lesion, intrahemispheric lesion location, presence of pre-lesion atrophy, and presence of personal or family history of psychiatric illness. Interruption of ascending transmitter pathways, asymmetrical distribution of transmitters to the hemispheres and altered compensatory biochemical responses to brain injury may be important neurologic mechanisms underlying these observations [S, 31341.
POSTSTROKE MANIA Post-stroke mania is much less common than post-stroke depression. Dunne et al. identified three cases of post-stroke mania among 661 patients with strokes confirmed by computerized tomography or autopsy, and Robinson et al. identified two cases in a series of 500 consecutive stroke patients [35,36]. Emergence of this syndrome may require an hereditary predisposition as well as an appropriately placed lesion. Starkstein and colleagues found that patients with post-stroke mania often had a family history of mood disorders and that the post-stroke mania patients were more likely to have a family history of psychiatric illness than patients with post-stroke depression [36, 371. The existence of cerebral atrophy also appeared to increase the vulnerability to mania following stroke [19]. There is a marked predominance of right-sided lesions among patients exhibiting post-stroke mania. In most cases the lesion has been in the right hemisphere in the area of the thalamus, perithalamic region, basotemporal lobe, or inferior medial frontal lobe anterior to the third ventricle [19,38-43]. Mania may occur immediately after stroke or may be delayed for up to three years. In some cases, a single manic episode is experienced, whereas in others the patients manifest recurrent episodes of depression and mania closely imitating the course of bipolar mood disorders [42]. The clinical phenomenology of mania following stroke is also very similar to that of idiopathic manic episodes: elation, hyperactivity, insomnia, pressured speech, grandiosity, and flight of ideas are the most common symptoms [36]. Post-stroke mania is treated with the same agents utilized in the treatment of idiopathic manic syndromes and systematic differences in responsiveness have not been observed. Lithium, neuroleptics, and anticonvulsants administered in conventional dosages have been successful in controlling the manic behavior [421.
NEUROPSYCHIATRIC ASPECTS OF STROKE 1 7
POSTSTROKE DELUSIONAL DISORDERS The prevalence of delusions following stroke is unknown. Of 661 patients reviewed by Dunne et al., two were delusional in the acute post-stroke period and two more exhibited delusional syndromes within the first year following the cerebrovascular event [35].There have been no comprehensive assessments of acute and deferred psychosis following stroke. Delusions have been observed after both right and left hemispheric injuries and most lesions have involved the temporoparietal region or subcortical structures. Peroutka et al. and Berthier and Starkstein reported patients with the abrupt onset of delusions and auditory, visual, and tactile hallucinations following right temporoparietal infarctions [43,441. Levine and Finklestein reported eight patients with delusions and hallucinations following injuries (stroke or trauma) to the right temporoparietal region [45].In this study, psychotic episodes were closely related to the occurrence of seizures. Cutting included two patients with right parietal stroke among seventy-four patients with organic delusional disorders [&I. Flynn et al. reported a unique patient with more right than left-sided subcortical ischemic injury who manifested the delusion of parasitosis [46].The parasitic “infestation” remained confined to the left side of the body. Reduplication delusions such as Capgras syndrome (the conviction that someone familiar has been replaced by an identical appearing imposter) and Frkgoli syndrome (the belief that familiar persons are disguised as others) have been observed following stroke and are more often associated with right than left hemisphere infarctions [48,49]. Delusions have also been reported with left brain strokes. Signer et al. reviewed the psychiatric hospitalizationsof aphasic patients and found a significant association between left posterior lesions and psychosis, whereas left anterior lesions were more often associated with depression [50].The occurrence of delusions was not greater in those with seizures. Subcortical lacunar infarctions have also been identified in a number of patients with late-onset psychotic disorders [51-531,and multiple deep ischemic lesions are present in most patients with vascular dementia where the prevalence of delusions approaches 50 percent [54]. Post-stroke delusions resemble those of idiopathic psychiatric disorders such as schizophrenia, although visual hallucinations are more common in patients with Unique delusions the former and auditory hallucinations with the latter [&I. occurring exclusively in patients with focal cerebral injuries and not observed in schizophrenia include anosognosia (the delusion that hemiparetic limbs are not paralyzed) and reduplicative paramnesia (the belief that one is simultaneously in two locations). Both these disorders are most common with infarctions of the right hemisphere, although anosognosia has also been observed with left-sided lesions [55]. Neuroleptic agents are the drugs of choice for the treatment of post-stroke delusions. There is little information available concerning the relative efficacy of these agents in idiopathic and organic disorders.
8 / BECKSON AND CUMMINGS
POST-STROKE HALLUCINATIONS Visual hallucinations may occur with vascular lesions anywhere between the retina and the occipital cortex. Retinal ischemia associated with amaurosis fugax is associated with hallucinations in approximately one-third of patients. They report scintillations, colors, abnormal brightness, and flashing lights [56]. Optic nerve lesions can also produce visual hallucinations: the syndrome of auditoryvisual synesthesia in which sudden loud sounds induce photisms (unformed visual hallucinations) has been described in patients with optic nerve ischemia [57]. Midbrain vascular lesions are associated with the syndrome of peduncular hallucinosis. This unusual disorder is comprised of vivid visual hallucinations that typically exhibit a diurnal pattern, appearing in the evening. There is often an accompanying affect of interest and amusement. The syndrome typically persists for only a few days following the vascular event [58-601. It usually follows basilar artery branch thrombosis but has also been observed with pontine hemorrhage [61,62]. Lesions of the geniculocalcarine radiations produce homonymous visual field defects and are commonly associated with visual hallucinations. In a comprehensive study, Kolmel examined ninety-six patients with homonymous hemianopias, most secondary to vascular disease [63]. Forty-two percent experienced unformed hallucinations in the hemianopic field. Colored phosphenes occurred in 27 percent, phosphenes with heterogeneous colors and shapes in 18percent, and colored patterns in 15 percent (some patients experienced more than one type of hallucination). In most cases the hallucinations began within a few hours of onset of the visual field defect and disappearedwithin ten days. In a series of 120 patients with visual field defects, Kolmel reported that sixteen (13%) experienced complex visual hallucinations including lilliputians, marching armies of peasant women, and visions of one’s self (heutoscopy) [a]. The hallucinations appeared within hours to days of onset of the stroke and resolved in concert with the visual improvement in cases where the visual field defect remitted, and spontaneously over the course of weeks or months if the visual field defect persisted. The lesions associated with both unformed and complex hallucinationswere usually occipital in location and involved the left and right hemispheres approximately equally. These “release” hallucinations must be distinguished from the brief stereotyped visual hallucinations that may occur in the course of seizures [65]. The latter are treated with anticonvulsant agents. Auditory hallucinations are an uncommon complication of cerebrovascular disease. Unformed sounds, clicks, and poorly intelligible voices have been described following brainstem strokes, particularly pontine hemorrhages [66,67]. Formed hallucinations of human voices may also occur in conjunction with persecutory delusions. Likewise, tactile hallucinations are rare in stroke syndromesbut may accompany delusional parasitosis associated with cerebrovascular disease [47].
NEUROPSYCHIATRIC ASPECTS OF STROKE / 9
POST-STROKE PERSONALITY ALTERATIONS Changes in personality associated with specific stroke syndromes are largely unexplored. The most dramatic alterations occur in patients with infarctions of the frontal lobes. Identifiable personality patterns are described following lesions of the superior medial and of the inferior medial frontal cortex. Unilateral lesions of the superior medial frontal lobe in the distribution of the anterior cerebral artery involve the cingulate gyms and the supplementary motor area and cause transient hypokinesia, slowness, and paucity of verbal output [68]. A similar but persistent syndrome has been observed in patients with infarction of the globus pallidus. The patients are quiet, laconic, indifferent to personal circumstances, and unmotivated [69]. Mendez et al. observed that apathy also dominated the clinical syndrome associated with dorsolateral infarctions of the caudate nucleus, and bilateral paramedian thalamic infarction results in an apathetic syndrome with diminished motivation and interest punctuated by periods of irritability, euphoria, and brief labile outbursts [70-731. Apathy is also the most common personality change observed in patients with vascular dementia with multiple subcortical infarctions [74]. The frontal lobe, caudate nucleus, globus pallidus, and thalamus are linked together in a functional unit and lesions of any of the structures within the complex produce a similar disorder with apathic behavior [75]. A more marked syndrome of apathy, the akinetic mute state, occurs with bilateral infarctions of the anterior medial frontal cortex (bilateral anterior cingulate gyri), inferior frontal lobe in the region of the septum and septohypothalamic junction, or in the posterior hypothalamic region involving the medial thalamus, subthalamus, and midbrain tegmentum [76-781. Behavioral changes associated with inferior frontal injury are common, may be marked, and contrast sharply with the apathy noted in patients with superior medial frontal infarction. Patients exhibit a behavioral syndrome characterized as euphoric, tactless, irritable, lacking judgment, impulsive, and outspoken. In a study of behavior change following rupture of anterior cerebral artery aneurysms by Logue et al., 19 percent of seventy-nine patients were euphoric, 32 percent worried less, 18percent exhibited affective flattening, 38 percent were emotionally labile, 27 percent were more irritable, 33 percent were more outspoken, 13 percent were tactless, and 46 percent exhibited diminished interest and conscientiousness [79]. A similar disinhibited state has been reported in patients with lesions of the ventromedial caudate nucleus [70].
MISCELLANEOUS POSTSTROKE NEUROPSYCHIATRIC SYNDROMES In addition to the relatively well recognized consequences of stroke described above, a variety of less well known neuropsychiatric disorders have been observed following localized cerebrovascular injuries. Alterations in sexual
10 I BECKSON AND CUMMINGS
behavior, obsessive-compulsive disorders, Kluver-Bucy syndrome, and rage syndromes have all been described following localized ischemic injuries. A variety of types of change in sexual behavior have been observed as a consequence of vascular lesions. Miller et al. reported one patient with exhibitionism following rupture of an anterior cerebral artery aneurysm and another with abnormal hypersexuality associated with a right-sided thalamic hemorrhage [80]. Coslett and Heilman found that diminished sexual function was more prevalent following right than left hemisphere infarctions [81]. Sixty-seven percent of men with right hemisphere lesions experienced reduced libido compared to 21 percent of those with left hemisphere strokes. Obsessive and compulsive behaviors including counting objects and stereotyped motor behavior have been observed with bilateral infarctions of the caudate nuclei [82]. The Kluver-Bucy syndrome is a complex disorder consisting of placidity, hyperorality, altered sexual behavior, visual agnosia, and hypermetamorphosis [83]. It occurs in patients with bilateral medial temporal injury, including bilateral temporal lobe infarction [a]. Rage with biting, spitting, shouting, and swearing has been observed as a consequence of bilateral infarctions of the medial occipital and occipito-temporal junction regions [85].
SECONDARYBEHAVIORALCONSEQUENCESOF CARDIOVASCULAR DISEASE Stroke patients often harbor other manifestations of vascular disease or take medications that may impact behavior and should be considered in the differential diagnosis of post-stroke behavioral changes. Ischemic cardiac disease with congestive heart failure and cerebral anoxia may lead to delirium with hallucinations, delusions, or mood changes. Similarly, renal failure secondary to vascular pathology may produce hallucinations, delusions, and mood alterations. Drugs administered to manage vascular problems may also have substantial behavioral effects. Antihypertensive agents may produce depression, mania, delusions, or hallucinations. Finally, infarctions may lead to seizures with complex ictal and interictal behavioral syndromes [86].
SUMMARY A variety of neuropsychiatric syndromes may be observed following cerebrovascular insults to the brain. Depression is the most commonly observed post-stroke syndrome, but mania, delusions, hallucinations, personality alterations, obsessive-compulsive disorder, and changes in sexual behavior have also been described. Neuropsychiatricsyndromes are not contingent on specific lesion sites with the same predictability as deficit syndromes such as aphasia and
NEUROPSYCHIATRICASPECTS OF STROKE / 11
amnesia. Nevertheless, regional relationships are evident and disruption of specific structures or functional systems is an important element influencing the behavioral consequences of focal lesions and ischemic injuries (see Table 1). Further investigation of functional-anatomic brain systems will improve the understanding of how such behavioral syndromes are mediated. Investigation of the neuropsychiatric consequences of stroke aids in identifying brain areas involved in specific behavioral disturbances and contributes to understanding the cerebral basis of psychiatric disorders. ACKNOWLEDGMENTS
This project was supported by the Department of Veterans Affairs. Ms.Norene Hiekel prepared the manuscript. REFERENCES 1. V. Hachinski and J. W. Norris, TheAcute Stroke, F. A. Davis, Philadelphia, 1985. 2. P. A. Wolf, W. B. Kannel, and J. Verter, Cerebrovascular Disease in the Elderly: Epidemiology, in ClinicalNeurology ofAging, M. L. Albert (ed.), Oxford, New York, pp. 458-477,1984. 3. L. R. Caplan and R. W. Stein, Stroke: A Clinical Approach, Butterworths, Boston, 1986. 4. R. G. Robinson, L. B. Starr, K. L Kubos, et al., A Two Year Longitudinal Study of Post-Stroke Mood Disorder: Findings during the Initial Evaluation, Stroke, 14, pp. 736-741,1983. 5 . R. G. Robinson and T. R. Price, Post-Stroke Depressive Disorders: A Follow-up Study of 103 Patients, Stroke, 13, pp. 63541,1982. 6. D. Sinyor, P. Jacques, D. A. Kaloupek, et al., Post-Stroke Depression and Lesion Location: An Attempted Replication,Brain, 109, pp. 537-546,1986. 7. American Psychiatric Association,Diagnostic and Statistical Manual of Mental Disorders, (3rd Edition), American Psychiatric Association, Washington, D.C., 1980. 8. S. E. Starkstein and R. G. Robinson, Affective Disorders and Cerebral Vascular Disease, British Journal of Psychiatry, 154, pp. 170-182,1989. 9. M. A. Hamilton, A Rating Scale for Depression,Journal of Neurology, Neurosurgery, and Psychiatry, 23, pp. 56-62,1960. 10. J. K. Wing, J. E. Cooper, and N. Santorius, Measurement and Classification of Psychiatric Symptoms, Cambridge University Press, London, 1974. 11. J. R. Lipsey, W. C. Spencer, P. V. Rabins, and R. G. Robinson, Phenomenological Comparison of Post-Stroke Depression and Functional Depression,American Journal of Psychiatry, 143, pp. 527-529, 1986. 12. R. G . Robinson, P. L. Bolduc, and T. R. Price, Two Year Longitudinal Study of Post-Stroke Mood Disorders Diagnosis and Outcome at One and Two Years, Stroke, 18, pp. 837-843,1987. 13. R. G . Robinson, K. L. Kubos, L. B. Skirr, et al., Mood Disorders in Stroke Patients: Importance of Location of Lesion, Brain, 107, pp. 81-93,1984a.
12 / BECKSON AND CUMMINGS
14. M. R. Eastwood, S. Rifat, H. Nobbs, et al., Mood Disorder Following Cerebrovascular Accident, British Journal of Psychiatry, 154, pp. 195-200, 1989. 15. M. F. Folstein, R. Mailberger, and P. R. McHugh, Mood Disorders as a Specific Complication of Stroke, Journal of Neurology, Neurosurgery and Psychiatry, 40, pp. 1018-1020,1977. 16. S. Finklestein, L. I. Benowitz, R. Baldessarini, et al., Mood, Vegetative Disturbance, and Dexamethasone Suppression Test after Stroke, Annals of Neurology, 12, pp. 463468,1982. 17. R. G. Robinson, J. R. Lipsey, K. Bolla-Wilson, et al., Mood Disorders in Left-Handed Stroke Patients, Anierican Journal of Psychiatry, 142, pp. 1424-1429, 1985. 18. J. R. Lipsey, R. G. Robinson, G. D. Pearlson, et al., Mood Change Following Bilateral Hemisphere Brain Injury, British Journal of Psychiatry, 143, pp. 266-273,1983. 19. S. E. Starkstein, R. G. Robinson, and T. R. Price, Comparison of Cortical and Subcortical Lesions in the Production of Post-Stroke Mood Disorders, Brain, 110, pp. 10451059,1987. 20. S. E. Starkstein, R. G. Robinson, and T. R. Price, Depressive Disorders Following Posterior Circulation as Compared with Middle Cerebral Artery Infarcts, Brain, 111, pp. 375387,1988. 21. S. E. Starkstein, R. G. Robinson, and T. R. Price, Comparison of Patients with and without Post-Stroke Major Depression Matched for Size and Location of Lxsion, Archives of General Psychiatry, 45, pp. 247-252,1988. 22. S. E. Starkstein, R. G. Robinson, M. A. Honig, et al., Mood Changes after Right-Hemisphere Lesions, British Journal of Psychiatry, 155, pp. 79-85, 1989. 23. M. F. Folstein, S. F. Folstein, and P. R. McHugh, Mini-Mental State: A Practical Method for Grading the Cognitive State of Patients, for the Clinician, Journal of Psychiatric Research, 12, pp. 189-198, 1975. 24. K. Bolla-Wilson, R. G. Robinson, S. E. Starkstein, et al., Lateralization of Dementia of Depression in Stroke Patients, Anierican Journal of Psychiatry, 146, pp. 627634, 1989. 25. R. Lipsey, R. G. Robinson, G. D. Pearlson, et al., The Dexamethasone Suppression Test and Mood Following Stroke, American Journal of Psychiatry, 142, pp. 318-323, 1985. 26. R. Lipsey, R. G. Robinson, G. D. Pearlson, et al., Nortriptyline Treatment of PostStroke Depression A Double-Blind Study, TheLancet, 84, pp. 297-300, 1984. 27. M. J. Reding, L. A. Orto, S. W. Winter, et al., Antidepressant Therapy after Stroke: A Double-Blind Trial, Archives of Neurology, 43, pp. 763-765,1986. 28. V. R. Lingam, L. W. Lazarus, L. Groves, et al., Methylphenidate in Treating PostStroke Depression, Journal of Clinical Psychiatry, 49, pp. 151-153,1988. 29. H. Feibel and C. J. Springer, Depression and Failure to Resume Social Activities after Stroke, Archives of Physical Medicine and Rehabilitation, 63, p. 276, 1982. 30. G. B. Murray, V. S. Shea, and D. K. Conn, Electroconvulsive Therapy for Post-Stroke Depression, Journal of Clinical Psychiatry, 47, pp. 258-260,1986. 31. V. M. Pickel, M. Segal, and F. E. Bloom, A Radio-auto-graphic Study of the Efferent Pathways of the Nucleus Locus Ceruleus, Journal of Comparative Neurology, 155, pp. 1542,1974.
NEUROPSYCHIATRICASPECTS OF STROKE I 13
32. J. H. Morrison, M. E. MolIiver, and R. Grzanna, Noradrenergic Innervation of the Cerebral Cortex: Widespread Effects of Local Cortical Lesions, Science, 205, pp. 313316,1979. 33. R. G. Robinson, Differential Behavioral and Biochemical Effects of Right and Left Hemispheric Cerebral Infarction in the Rat, Science, 205, pp. 707-710, 1979. 34. H. S. Mayberg, R. G. Robinson, D. F. Wong, et al., PET Imaging of Cortical S2-Serotonin Receptors Following Stroke: Lateralized Changes and Relationship to Depression, American Journal of Psychiatry, 145, pp. 937-943,1988. 35. J. W. Dunne, P. J. Leedman, and R. H. Edk, Inobvious Stroke: A Cause of Delirium and Dementia, Australian and New Zealand Journal of Medicine, 16, pp. 771-778,1986. 36. R. G. Robinson, J. D. Boston, S. E. Starkstein, et al., Comparison of Mania and Depression after Brain Injury: Causal Factors, American Journal of Psychiatry, 145, pp. 172-178, 1988. 37. S. E. Starkstein, R. G. Robinson, M. L. Berthier, et al., Differential Mood Changes Following Basal Ganglia vs. Thalamic Lesions, Archives of Neurology, 45, pp. 725730,1988. 38. J. Bogousslavsky, M. Ferrazzini, F. Regli, et al., Manic Delirium and Frontal-Like Syndrome with Paramedian Infarction in the Right Thalamus, Journal of Neurology, Neurosurgery, and Psychiatry, 51, pp. 117-119,1988. 39. M. R. Cohen and R. W. Niska, Localized Right Cerebral Hemisphere Dysfunction and Recurrent Mania, American Journal of Psychiatry, 137, pp. 847-848,1980. 40. J. L. Cummings and M. F. Mendez, Secondary Mania with Focal Cerebrovascular Lesions, American Journal of Psychiatry, 141, pp. 1084-1087,1984. 41. P. J. M. Van Der Lugt and A. P. DeVisser, Two Patients with a Vital Expansive Syndrome Following a Cerebrovascular Accident, Psychiatrica, Neurologica, and Neurochirugia, 70, pp. 349-359, 1967. 42. S. E. Starkstein and R. G. Robinson, Affective Disorders and Cerebral Vascular Disease, British Journal of Psychiatry, 154, pp. 170-182,1989. 43. S. J. Peroutka, B. Sohmer, A. J. Kumar, et al., Hallucinations and Delusions Following a Right Temporoparietooccipital Infarction, The Johns Hopkins Medical Journal, 151, pp. 181-185,1982. 44. M. Berthier and S. E. Starkstein, Acute Atypical Psychosis Following a Right Hemisphere Stroke, AcfaNeurologica Belgica, 87, pp. 125-131,1987. 45. D. N. Levine and S. Finklestein, Delayed Psychosis after Right Temporoparietal Stroke or Trauma: Relation to Epilepsy, Neurology, 32, pp. 267-273,1982. 46. J. Cutting, The Phenomenology of Acute Organic Psychosis, British Journal of Psychiatry, 151, pp. 324-332,1987. 47. F. G. Flynn, J. L. Cummings, J. Scheibel, et al., Monosymptomatic Delusions of Parasitosis Associated with Ischemic Cerebrovascular Disease, Journal of Geriatric Psychiatry and Neurology, 2, pp. 134-139,1989. 48. T. E. Feinberg and R. M. Shapiro, Misidentification-Reduplication and the Right Hemisphere, Neuropsychiatry, Neuropsychology, and Behavioral Neurology, 2, pp. 3948,1989. 49. K. W. de Pauw, T. K. Szulecka, and T. L. Poltock, Frkgoli Syndrome after Cerebral Infarction, The Journal of Nervous and Mental Disease, 175, pp. 433437,1987.
14 / BECKSON AND CUMMINGS
50. S. Signer, J. L. Cummings, D. F. Benson, Delusions and Mood Changes in Patients with Chronic Aphasia, Journal of Neuropsychiatry and Clinical Neuroscience, I , pp. 4 0 4 , 1 9 8 9 . 51. B. L. Miller, D. F. Benson, J. L. Cummings, et al., Late-life Paraphrenia: An Organic Delusional Syndrome, Journal of Clinical Psychiatry, 47, pp. 204-207, 1986. 52. B. L. Miller, I. M. Lesser, K. Boone, et al., Brain White-Matter Lesions and Psychosis, British Journal of Psychiatry, 155, pp. 73-78,1989. 53. A. Pakalnis, M. E. Drake, Jr., et al., Right Parietooccipital Lacunar Infarctions with Agitation, Hallucinations, and Delusions, Psychosomatics, 28, pp. 95-96, 1987. 54. J. L. Cummings, B. L. Miller, M. A. Hill, et al., Neuropsychiatric Aspects of Vascular Dementia and Dementia of the Alzheimer Type, Archives of Neurology, 44, pp. 389393,1987. 55. J. L. Cummings, Organic Delusions, British Journal of Psychiatry, 146, pp. 184-197, 1985. 56. J. A. Goodwin, P. B. Gorelick, and C. M. Helgason, Symptoms of Amaurosis Fugax in Atherosclerotic Carotid Artery Disease, Neurology, 37,pp. 829-832,1987. 57. L. Jacobs, A. Arpik, D. Bozian, et al., Auditory-Visual Synesthesia, Archives of NeuroZogy, 38, pp. 211-216, 1981. 58. W. M. Feinberg and S. 2. Rapcsak, “Peduncular Hallucinosis” Following Paramedian Thalamic Infarction, Neurology, 39,pp. 1525-1536,1989. 59. T. J. Geller and S. N. Bellur, Peduncular Hallucinosis Magnetic Resonance Imaging Confirmation of Mesencephalic Infarction during Life, Annals of NeuroZogy, 21, pp. 602404,1987. 60. J. Rozanski, Peduncular Hallucinosis Following Vertebral Angiography, Neurology, 2, pp. 341-349,1952. 61. L. R. Caplan, “Top of the Basilar” Syndrome, Neurology, 30, pp. 72-79,1980. 62. K. Nakajima, Clinicopathologic Study of Pontine Hemorrhage, Stroke, 14, pp. 485493,1983. 63. H. W. Kolmel, Coloured Patterns in Hemianopic Fields, Brain, 107, pp. 155-167, 1984. 64. H. W. Kolmel, Complex Visual Hallucinations in the Hemianopic Field, Journal of Neurology, Neurosurgery, and Psychiatry, 48, pp. 29-38,1985. 65. J. L. Cummings and B. L. Miller, Visual Hallucinations, WesternJournal OfMedicine, 146,pp. 46-51,1987. 66. G. D. Cascino and R. D. Adams, Brainstem Auditory Hallucinosis, Neurology, 36, pp. 1042-1047,1986. 67. D. J. Lanska, J. Lanska, and M. F. Mendez, Brainstem Auditory Hallucinosis, Neurology,37,p. 1685,1987. 68. M. Verfaellie and K. M.Heilman, Response Preparation and Response Inhibition after Lesions of the Medial Frontal Lobe, Archives of Neurology, 44, pp. 1265-1271,1987. 69. R. L. Strub, Frontal Lobe Syndrome in a Patient with Bilateral Globus Pallidus Lesions, Archives of Neurology, 46, pp. 1024-1027,1989. 70. M. F. Mendez, N. L. Adams, and K. S. Lewandowski, Neurobehavioral Changes Associated with Caudate Lesions, Neurology, 39, pp. 349-354, 1989.
NEUROPSYCHIATRICASPECTS OF STROKE / 15
71. M. Gentilini, E. De Renzi, and G. Crisis, Bilateral Paramedian Thalamic Artery Infarcts: Report of Eight Cases, Journal of Neurology, Neurosurgery, Psychiatry, SO, pp. 900-909,1987. 72. A. Guberman and D. Shlss, The Syndrome of Bilateral Paramedian Thalamic Infarction, Neurology, 33, pp. 540-546,1983. 73. D. I. Katz,M. P. Alexander, and A. M. Mandell, Dementia Following Strokes in the Mesencephalon and Diencephalon, Archives of Neurology, 44, pp. 1127-1133, 1987. 74. L. Dian, J. L. Cummings, S. Petry, et al., Personality Alterations in Vascular Dementia, Psychosomatics, (in press). 75. G. E. Alexander, M. R. DeLong, and P. Strick, Parallel Organization of Functionally Segregated Circuits Linking Basal Ganglia and Cortex, Annual Review of Neuroscience, 9, pp. 357-381,1986. 76. R. W. Barris and H. R. Schuman, Bilateral Anterior Cingulate Gyms Lesions, Neurology, 3, pp. 44-52,1953. 77. J. M. Nielsen and L. L. Jacobs, Bilateral Lesions of the Anterior Cingulate Gyms, Bulletin of the Los Angeles Neurological Society, 16, pp. 231-234,1951. 78. J. M. Segarra, Cerebral Vascular Disease and Behavior, Archives of Neurology, 22, pp. 408-418,1970. 79. V. Logue, J. Dunvard, R. T. C. Pratt, et al., The Quality of Survival after Rupture of an Anterior Cerebral Aneurysm, British Jourml of Psychiaby, 114, pp. 137-160, 1968. 80. B. L. Miller, J. L. Cummings, H. Mclntyre, et al., Hypersexuality or Altered Sexual Preference Following Brain Injury, Journal of Neurology, Neurosurgery, and Psychiatry, 49, pp. 8674373,1986. 81. H. B. Coslett and K. M. Heilman, Male Sexual Function, Archives of Neurology, 43, pp. 1036-1039,1986. 82. B. Croisile, D. Tourniare, C. Confavreux, et al., Bilateral Damage to the Head of the Caudate Nuclei, Annals of Neurology, 25, pp. 313-314,1989. 83. R. Lilly, J. L. Cummings, D. F. Benson, et al., The Human Kluver-Bucy Syndrome, Neurology, 33, pp. 1141-1145,1983. 84. D. Shraberg and L. Weisberg, The Kluver-Bucy Syndrome in Man, The Journal of Nervous andMenta1 Disease, 166, pp. 130-134,1978. 85. J. L. Medina, F. A. Rubino, and E. Ross, Agitated Delirium Caused by Infarctions of the Hippocampal Formation and Fusiform and Lingual Gyri: A Case Report, NeurolO ~ Y ,24, pp. 1181-1183,1974. 86. J. Cummings, ClinicalNeuropsychiutry, Grune and Stratton, New York, 1985.
Direct reprint requests to: Jeffrey L. Cummings, M.D. Neurobehavior Unit (Bldg. 256B) West Los Angeles VAMC Brentwood Division 11301Wilshire Blvd. Los Angeles, CA 90073
