Cerebrovascular complications of bacterial meningitis in adults Hans-Walter Pfister, MD; Gian Domenico Borasio, MD; Ulrich Dirnagl, MD; Michael Bauer, MD; and Karl Max Einhaupl, MD

~~

~

Article abstract-We performed a prospective study of the type, frequency, temporal profile, and prognostic role of cerebrovascular complications in 86 adults with bacterial meningitis. Cerebral angiography was performed in 27 patients (31.4%) who had focal deficits either clinically, on cranial CT, or both, and in patients who had persistent coma without explained cause despite 3 days of antibiotic therapy. Alterations of the vessel systems, including involvement of major arteries a t the base of the brain, medium-sized arteries, small vessels, and major sinuses and cortical veins, were present in 13 of the 27 patients who had angiography. Typical cerebrovascular complications were arterial narrowing of the supraclinoid portion of the internal carotid artery; vessel wall irregularities, focal dilatations, and occlusions of distal branches of the middle cerebral artery; focal abnormal parenchymal blush; and thrombosis of the sagittal superior sinus and cortical veins. Prognosis for those patients with cerebrovascular complications was unfavorable. Six patients died, one remained in a vegetative state, four were moderately or slightly disabled, and only two recovered completely. The study showed that angiographically documented cerebrovascular complications are the most frequent intracranial complications in bacterial meningitis of the adult (37.1%) and are major determinants in the prognosis of this disease. NEUROLOGY 1992;42:1497-1504

Despite the improvement of antimicrobial therapy during the last decades, mortality rate and sequelae due to bacterial meningitis in the adult remain high.lV2The unfavorable clinical outcome is often due t o i n t r a c r a n i a l complications s u c h as brain edema, hydrocephalus, and cerebrovascular compliThe cations during the acute phase of the involvement of cerebral vessels during bacterial meningitis became evident from (1)autopsy studies that showed arteritis a n d t h r ~ m b o p h l e b i t i s ~(2) -~; reports of angiographic changes of cerebral arteries, including vessel wall irregularities, vasospasm, focal dilatation, occlusion, and septic sinus venous t h r o m b ~ s i s ~(3) - ~clinical ~; observations that showed alterations in cerebral blood flowl3-l5and Doppler blood flow velocity16; and (4)CT studies that revealed brain infarctions due to cerebrovascular complication^.^^-^^ I n addition, alterations of cerebral blood flow were found in animal models of bacterial m e n i n g i t i ~ . ~ ~ - ~ ~ Most of the clinical reports on cerebrovascular complications d u r i n g b a c t e r i a l m e n i n g i t i s stem from cases involving infants and children where Haemophilus influenzae is the most frequent etioThus far, there has been no syslogic agent.10J2,27-29 tematic clinical study on cerebrovascular complicat i o n s in b a c t e r i a l meningitis of the adult. We

prospectively investigated the type, frequency, temporal profile, and prognostic role of complications during the acute phase of bacterial meningitis in adults, and present the results on the cerebrovascular complications. Methods. Patients. The study was performed on 86 consecutive adult patients, admitted between 1984 and 1989 to the Department of Neurology, Klinikum Groahadern, Munich, with the diagnosis of bacterial meningitis. All the patients met the following diagnostic criteria: (1) detection of the bacterial microorganism in the CSF by at least one of the following methods-microscopic examination of a gram-stained smear, culture for bacterial pathogens, or detection of bacterial antigen using the latex agglutination method; or (2) CSF pleocytosis of >1,000 white blood cells per p1 with >60% polymorphonuclear leukocytes and clinical symptoms and signs of bacterial meningitis including stiff neck, headache, fever, photophobia, and elevated white blood cell count in blood; or (3) both. Patients with meningitis due to primary intracranial bacterial suppurative infections, eg, brain abscess o r intracranial empyema, were excluded. Antibiotic therapy varied during the observation period, but most patients were treated according to the following guidelines: when the bacterial microorganism was undefined, intravenous penicillin G o r cefotaxime was given to previously healthy patients; cefotaxime and fosfomycin were given

From t h e Departments of Neurology (Drs. Pfister, Borasio, Dirnagl, a n d Einhaupl) a n d Radiology (Dr. Bauer), University of Munich, Klinikum GroRhadern, Munich, Germany. Received December 10, 1991. Accepted for publication in final form January 29, 1992. Address correspondence and reprint requests to Dr. Hans-Walter Pfister, Department of Neurology, Ludwig-Maximilians-Universityof Munich, Kliuikum GroBhadern, Marchioninistrane 15, 8000 Munich 70, Germany.

August 1992 NEUROLOGY 42 1497

to patients with a parameningeal infectious focus such as otitis, mastoiditis, sinusitis, or a remote focus of infection or previous traumatic brain injury (fosfomycinwas added because of its antistaphylococcal activity); cefotaxime, fosfomycin, and ampicillin were given to patients with underlying debilitating disease; and cefotaxime, fosfomycin, and aminoglycoside were given to patients with

nosocomial meningitis. The results of antimicrobial susceptibility tests determined antibiotics for culture-positive patients. All patients were evaluated at least once a day during hospitalization by neurologic examination and Glasgow Coma Scale (GCS) score.3oThe patients were followed until death or discharge from the hospital. The outcome was assessed on the basis of the following grading scale: death, vegetative state, severe disability (totally dependent), moderate disability (capable of leading relatively normal life with assistance), slight disability (capable of leading relatively normal autonomous life), and complete recovery. Cerebral angiography. To detect cerebrovascular complications of meningitis, cerebral angiography was performed on admission or during the hospital stay if at least one of the following criteria was fulfilled: focal deficits either clinically (eg, hemiparesis, focal seizures) or on cranial CT (eg, infarction, focal brain edema); or no improvement of a comatose patient (GCS score less than 8) after 3 days of adequate antibiotic therapy, provided that other causes for coma (eg, metabolic or pharmacologic causes, hydrocephalus, o r brain abscess) were excluded. Bilateral carotid angiography combined with unilateral vertebral angiography was performed in seven patients, sole bilateral carotid angiography in 13 patients, sole unilateral carotid angiography in three patients, and unilateral carotid angiography combined with unilateral vertebral angiography in four patients. Cut-film angiography was carried out in 24 patients and arterial digital subtraction angiography i n three patients. Selective injections were performed in all vertebral angiographies and in 40 of 47 carotid angiographies. Cranial CT. CT was performed in patients (1)with GCS scores less than 8, (2) with focal neurologic deficits, including focal epileptic seizure, and (3) whose condition did not improve or even deteriorated during the first 3 days of antibiotic therapy. CT was performed using a Siemens Somatom 2 until 1985 and a Siemens Somatom DRH from 1985 to 1989. Axial sections were made parallel t o the canthomeatal line with a slice thickness of 4 mm in the posterior fossa and 8 mm in the supratentoria1 region. Intravenous contrast material was administered in 10 patients. Nondiagnostic scans due to motion artifact were not included for evaluation; in these patients repeat CTs were performed.

Results. Patients. Of the 86 patients admitted, 47 were men a n d 39 women. Forty-seven patients were initially admitted to our department, 39 were referred from other hospitals. Twenty patients were previously healthy a n d 65 h a d underlying risk factors including parameningeal infections (20 patients), pneumonia (21, bacterial endocarditis (4), psoas abscess (I),diabetes mellitus (51, chronic alcoholism (111, i m m u n o s u p p r e s s i v e t h e r a p y because of ulcerative colitis and multiple sclerosis (a), congenital h e a r t defect (single ventricle, l), splenectomy (41,malignancies (61, previous head 1498 NEUROLOGY 42 August 1992

t r a u m a (171, previous surgical procedure in t h e region of paranasal sinuses or the ear or a previous neurosurgical procedure (11).Five patients had a history of a previous episode of bacterial meningitis 6 months to 11 years before the current acute disease. On admission, 11 patients had GCS scores less than 5, 25 between 6 and 10, and 50 between 11 and 15. Seizures occurred within the first 3 weeks of the disease in 2 1 patients (24.4%). One of these patients had status epilepticus. Cranial nerve pares e s occurred in four p a t i e n t s (4.7%), including bilateral abducens paresis (2 patients), one-sided facial palsy (l),and bilateral ophthalmoplegia (1). Five patients had a petechial rash on admission. In four of these patients, meningococcal infection w a s p r e s e n t , the f i f t h h a d s e p s i s d u e t o Staphylococcus aureus. In 60 patients (70%), the bacterial microorganisms were identified in the CSF by at least one of three methods: positive CSF culture in 50 patients (58%),solely positive CSF Gram’s stain in seven (8%),and solely positive CSF antigen test in three (3%).Microorganisms included Streptococcus pneumoniae (n = 301, Neisseria meningitidis (51, H influenzae (6), S aureus (5), Staphylococcus epidermidis (11, Listeria monocytogenes (2), Streptococcus viridans (21, group B streptococci (l),Escherichia coli (2, in one patient combined with S aureus), Pseudomonas aeruginosa (l), gram-positive diplococci (51, gram-negative cocci (11, and gram-negative rods (1).In five patients with negative bacteriologic findings in the CSF, a positive blood culture revealed S pneumoniae (n = l),N meningitidis ( l ) , Fusobacterium speciale (11, Serratia marcescens (11, and S aureus plus S viridans (1). Cerebrovascular complications. Cerebral angiography was performed in 27 patients (31.4%)-21 because of a focal neurologic deficit or a focal CT deficit or both, three because of a persistent coma despite 3 days of adequate antibiotic therapy, and three because of clinical signs of herniation and CT findings of brain swelling. Angiography was performed between the first and the 21st day after the onset of the disease (median, 3rd day). We did not observe complications of cerebral angiography in any of the patients. Angiographic changes of cerebral arteries, major sinuses, and cortical veins were identified in 13 of 27 patients (48.1%; figure). The clinical data of the 13 patients are summarized in the table. The vascular changes revealed by angiography were classified according to the different vessel segments involved: (1)major arteries at the base of the brain-arterial narrowing of the supraclinoid portion of the internal carotid artery (2 patients) or the cerebellar arteries (posterior inferior cerebellar artery a n d anterior inferior cerebellar artery, 1 patient), or occlusion of the posterior cerebral artery (1 patient); (2) medium-sized arteries-vessel wall irregularities with narrowed and ectatic segments, and obstructions of branches of the mid-

B

C Figure. Different angiographic features of cerebrovascular complications in bacterial meningitis. (A) Lateral subtraction view from a common carotid injection in a 48-year-old patient with meningitis due to S viridans (table, patient I): severe narrowing in the supraclinoid portion of the right internal carotid artery (long arrow), ectatic (triangle) and narrowed (short arrow) segments in the middle cerebral artery distribution. (B) Left carotid angiography (lateral subtraction view from a common carotid injection) in an 87-year-oldpatient with pneumococcal meningitis revealed a focal abnormal parenchymal blush in the parietal region (open arrows) and a n early filling vein (closed arrow), thus indicating cortical hyperemia (table, patient 4). (C) Left carotid angiography (lateral view from a selective internal carotid artery injection) in a 49-year-old patient with purulent meningitis and positive blood culture for Serratia marcescens revealed segments of narrowing (closed arrow) and ectasia (triangle) in the distribution of the middle cerebral artery, and the early evidence of a n abnormal parenchymal blush (open arrows) (table, patient 8). (D) Left carotid angiography (lateral subtraction view from a selective internal carotid injection) in a 44-year-old patient with pneumococcal meningitis disclosed nonvisualization of parts of the superior sagittal sinus (short arrow), broken bridging veins (long arrow), and presence of cork-screw veins (open arrow) (table, patient 10).

dle cerebral artery (3 patients); (3) small vesselsfocal abnormal parenchymal blush with an early filling vein (1 patient), or prolonged circulation time of the middle cerebral artery territory with pooling of contrast probably in the capillaries (1 patient); (4)major sinuses and cerebral cortical veins-nonvisualization of a part of the superior sagittal sinus indicating septic thrombosis of this

sinus (2 patients), or nonvisualization of cortical veins, presence of cork-screw veins, venous dilatation, a n d venous collaterals indicating septic thrombosis of cortical ascending veins (2 patients). In those patients with cerebrovascular findings on angiography, we have considered other factors t h a t may contribute t o these findings. None of these patients had previous radiation, evidence for August 1992 NEUROLOGY 42 1499

'able. Clinical data of 13 patients with bacterial meningitis and cerebrovascularcomplications Pt no. Age ~.(.ye)/ Micro-organism

Sex

intheCSF

Clinical f i n d i n g s on a d m i s s i o n

1 48N

Streptococcus viridans

Comatose, spastic quadriparesis

2 66N

Pneumococci

Comatose, L hemiparesis

Findings on CT D a y of ( d a y ofCT admission" investigation*) 12

7

D a y of Angiographic a n g i o g r a p h y * findings

Hydrocephalus, ventricular empyema (12th1, infarction in R MCA distribution (15th)

InSarction in

Clinical course, outcome ( d a y after onset of disease)

20

Narrowing of supraclinoid portion of R ICA, vessel wall irregularities in R ACA and R MCA distribution

Died (37th)

8

Narrowing of supraclinoid portions of both ICAs Moderate improvement of narrowing

Pulmonary embolism, cardiac arrest ( X t h ) , vegetative state (48th)

R MCA distribution (7th) 16

3 41lM

Nogrowthf

Somnolent. ataxia

1

Cerebellar infarction L, thalamic infarction L (1st)

3

Narrowing of L AICA and PICA

Alcoholic delirium tremens (6th), complete recovery (11th)

4

Pneumococci

Comatose, R hemiparesis, R focal seizure

1

Normal ( l s t , 5th)

3

Focal abnormal parenchymal blush L in the parietal region with an early filling vein

Multiple myeloma with renal failure, died (17th)

5 43lM

Pneumococci

Comatose

3

Normal (3rd, 7th), infarction in R MCA distribution (11th)

3

Prolonged circulation time Died (21st) for t h e R MCA territory, pooling of contrast material

6 66N

Pneumococci

Comatose

6

Multiple infarctions frontotemporoparietal WL (6th)

6

Narrowing and occlusions of peripheral branches of both MCAs

7 37iF

Nogrowth$

Confused, R homonymous hemianopia, Wernicke's aphasia

3

InSarction in L posterior cerebral artery distribution and thalamic infarction L (3rd)

11

Occlusion of L posterior Moderate disability cerebral artery, vessel wall (confusion, R irregularities of hemianopia) (20th) peripheral branches of L MCA

8 49N

Nogrowthg

Comatose, spastic limbs

4

Normal (4th), multiple infarctions frontoparietal WL (20th)

5 21

Nonnal Vessel wall irregularities and ectasia of peripheral branches of both MCAs, focal abnormal parenchymal blush L Improvement o f abnormalities

Moderate disability (confusion, spastic limbs) (49th)

87iF

37

Septic shock, Adult respiratory distress syndrome, died (17th)

9 18/M

Nogrowth

Comatose, spastic limbs

3

Multiple infarctions frontotemporoparietal R L (3rd)

3

Faint filling of both MCAs and ACAs

Moderate disability (confusion, spastic limbs) (29th)

10 44lF

Pneumococci

Comatose, abnormal posturing R arm, forced conjugate gaze (6th day)

1

Normal (1st)

6

Thromhosis of parts of the superior sagittal sinus, broken bridging veins, presence of corkscrew veins

Retroperitoneal bleeding during IV heparin, hypovolemic shock ( l l t h ) , pulmonary embolism, cardiac arrest (26th), vegetative state, died (46th)

11 361n

Listeria mono rytogenes

Comatose

1

Gyral enhancement. brain swelling (1st)

2

Thrombosis of parts of t h e superior sagittal sinus

Died (3rd)

12 53lF

Pneumococci

Comatose

1

Gyral enhancement (1st)

5

Occlusion of frontal ascending cortical veins 1, with collaterals

Complete recovery (24th)

13 56iF

Meningococci

L hemiparesis, L focal seizure

2

Infarction parietal R (4th)

5

Occlusion of parietal ascending cortical veins R Normal findings

Slight disability (L hemiparesis) (29th)

19 After onset of meningitis.

-1 Fusobacterium sneciale in blood culture $ Staphylococcus aureus plus Streptococcus viridans

in blood culture.

B

Serratia marcesccns in blood culture.

MCA ICA ACA AICA PICA

Middle cerebral artery Internal carotid a r t e r j Anterior cerebral artery. Anterior inferior cerebellar artery Posterior inferior cerehellar artery.

a hypercoagulable state, concomitant CNS infection other than bacterial meningitis, or preexisting arteriosclerotic changes. One patient (no. 9) had a history of a brain trauma 1%years before bacterial meningitis. It is unlikely that the angiographic findings in this patient were directly related to the brain trauma. One patient (no. 6) had infective 1500 NEUROLOGY 42 August 1992

endocarditis; the angiographic findings in this patient may have been caused by septic embolism. Seven of 13 patients with angiographically documented cerebrovascular complications had brain infarctions on CT at the time of angiography. In addition, two patients developed brain infarctions d u r i n g t h e course of t h e disease. Follow-up

angiograms were performed i n three patients (table, nos. 2, 8, and 13). Angiographic abnormalities moderately improved in patient 2, showed a mild improvement in patient 8, and had completely normalized at follow-up in patient 13. Cerebral angiography was normal i n 14 patients. The angiography was performed in 12 of these patients because of a clinical focal deficit (hemiparesis, 6; aphasia, 1;ataxia, 1; focal epileptic seizures, 2; locked-in syndrome, 1; bilateral ophthalmoplegia, 1). CT showed normal findings in five of these 12 patients, generalized brain edema in two patients, right frontal bleeding and focal brain edema (11, focal swelling of the right hemisphere (1,follow-up normalized), hypodense mesencephalic and diencephalic area (1,follow-up normalized), a n d brain infarctions (2). Cerebral angiography did not reveal cerebrovascular complications in two patients who had clinical symptoms of herniation and brain swelling on CT. Temporal profile of cerebrovascular complications. Septic sinus venous thrombosis was diagnosed during the first week of the disease in all patients. Cerebral arterial complications were diagnosed during this period in five patients. In four patients, the angiographic diagnosis of cerebral arterial complication was made during the second and third week of disease (table, nos. 1,2, 7, and 8). In one of these four patients, in whom arterial narrowing was angiographically documented in the supraclinoid portion of the internal carotid artery on the 20th day of the disease, the arterial vascular complication probably developed earlier. The patient was comatose and had a tetraspastic syndrome from the 12th day of disease (patient 1).In another patient, vessel wall irregularities were observed at angiography on the 21st day of disease (patient 8). A previous angiography in this patient on the 5th day of disease was normal (patient 8). Clinical outcome. The clinical outcome was as follows: 16 patients (18.6%) died, two (2.3%) remained in a vegetative state, seven (8.1%)were severely disabled, five (5.8%) had moderate o r slight disability, and 56 (65.1%) recovered completely. The highest rate of complications and mortality occurred in pneumococcal meningitis. Of 30 patients with pneumococcal meningitis, 15 had an unfavorable course: 10 died, one was in a vegetative state, and four had severe or moderate disability. The prognosis of bacterial meningitis when cerebrovascular complications existed was extremely poor (table). Six patients died, one was in a vegetative state, four had moderate or slight disability, and only two patients recovered completely. Four patients with cerebrovascular arterial complications were treated with corticosteroids, two of them with dexamethasone (patients 3 and 9), and two with prednisolone (patients 2 and 8). All four patients improved clinically during therapy. In one of these patients, the angiographic and clinical findings initially improved; however, pulmonary

embolism and cardiac arrest determined the unfavorable outcome in this patient (patient 2). Three patients with septic sinus venous thrombosis (table, patients 10 t o 12) were treated with dose-adjusted IV heparin to maintain the partial thromboplastin time at 1.5 to 2 times control. One of these patients completely recovered (patient 12). One patient had fulminant sinus thrombosis with clinical signs of herniation when heparin therapy was started and subsequently died (patient 11). One p a t i e n t with s i n u s thrombosis initially improved during heparin therapy. The dosage of heparin in this patient had to be reduced 5 days after the onset of treatment because of retroperitoneal bleeding. Pulmonary embolism, with consecutive hypoxic brain damage, occurred 2 weeks later, thus resulting in the death of this patient (patient 10).

Discussion. In this prospective study, the most common intracranial complications in adults with bacterial meningitis were angiographically documented cerebrovascular lesions. We detected cerebrovascular complications in 13 of 35 (37.1%) patients with intracranial complications, followed in frequency by brain swelling detected on CT (n = 121, hydrocephalus (lo), and intracerebral hemorrhage (2). The spectrum of cerebrovascular complications was considerable, involving large arteries at the base of the brain, medium-sized arteries, small pial and intraparenchymatous vessels, and major sinuses and cortical veins. One type of cerebrovascular complication associated with bacterial meningitis is the narrowing of large arteries at the base of the brain. This narrowing often occurs at the supraclinoid portion of the internal carotid artery as shown in the present study and by others.10-12,28,31 This is the site where the internal carotid, basilar, and vertebral arteries and their primary branches are bathed within heavy subarachnoid exudate in the cisterns and the subarachnoid spaces.32The arterial narrowing is considered t o be caused by several mechanisms, either alone o r i n combination, including (1) encroachment by the inflammatory subarachnoid purulent e x ~ d a t e ~ ,(2) ~ ,infiltration ~,~~; of the arterial wall by inflammatory cells with the phenomena of intimal thickening, subintimal infiltration of the arterial wall, arterial wall edema, and infiltration of the whole vessel wall ( v a s ~ u l i t i s ) ~and - ~ ;(3) an active vascular response t o t h e infection ( v a s o ~ p a s m )The . ~ ~angiographic ~~~~~ findings of marked narrowing of large arteries at the base of the brain in bacterial meningitis often resemble vasospasm associated with subarachnoid hemorr h a g e secondary t o a n e u r y s m r ~ p t u r e . ~ ~ , ~ Neuropathologic findings have shown that areas of angiographically demonstrated narrowing, dilatations, and even occlusions in bacterial meningitis have no histologically inflammatory correlate.8,28 The pathogenesis of arterial spasm is unknown. In animal models of bacterial meningitis, vasoconAugust 1992 NEUROLOGY 42 1501

sis i n four patients i n the current study. The stricting substances, such as platelet-activating anatomic bases for the inflammatory involvement factor,34.35 were detected in the CSF and may be of cerebral veins within the subarachnoid spaces candidates for arterial constrictions. However, the are the thin collagenous wall, the sparse muscle role of these mediators in humans with bacterial cells, and little elastic tissue. Compared with the meningitis has yet to be determined. conditions in arteries, the slow blood flow in veins The second type of cerebrovascular complication enhances the possibility of adherence of white involves t h e medium-sized a r t e r i e s . Leptoblood cells to the vessel wall and migration through meningeal arterial branches may be involved either the walls. Septic thrombosis of the superior sagittal due t o the meningitic process or due t o embolism in sinus may be caused by the spread of infection from infective e n d ~ c a r d i t i sNeurologic .~~ complications of the meninges to the sinus via the diploic veins.40In infective endocarditis include meningitis, brain a neuropathologic survey, Dodge and Swartz6 found abscess, nonfocal encephalopathy, and ischemic or thrombosis of small cortical veins in five of 30 hemorrhagic ~ t r o k e .In ~~ the , ~current ~ study, one of autopsied cases of bacterial meningitis. Adams et the patients with involvement of the medium-sized a15 found cerebral thrombophlebitis in four of 14 arteries had infective endocarditis as shown at fatal cases of H influenzae meningitis. In a retroautopsy (table, patient 6). Diagnosis of infective spective study of 790 cases of bacterial meningitis, endocarditis may be difficult in a patient who priDiNubile et a141 found cortical thrombophlebitis, marily presents with symptoms and signs of bacteeither diagnosed clinically or at autopsy, in 10 rial meningitis because (1)bacteremia is also a frepatients. quent finding in patients with primary bacterial Cerebrovascular complications i n bacterial meningitis but without infective endocarditis, and meningitis may lead to an increase in intracranial (2) vegetations due to infective endocarditis may be pressure by different mechanisms including (1) missed by echocardiography. vasogenic brain edema as a result of endothelial The third type of cerebrovascular complication concerns the small pial and intraparenchymatous damage, (2) cytotoxic brain edema as a result of vessels. Dodge and Swartz6 found polymorphobrain infarction, and (3) increased intracranial nuclear infiltration extending via the Virchowblood volume, especially in sinus venous thromboRobin spaces t o the subintimal regions of small sis. There is a risk of cortical necrosis when cerearteries and veins in 12 of 30 patients with bacteribral perfusion pressure, defined as the difference al meningitis in an autopsy study. A corresponding between systemic mean arterial blood pressure and finding on angiography is different fast outflow of intracranial pressure, decreases a s a result of the contrast material from different regions of the increased intracranial pressure.42 In addition, elesame vascular territory. A focal hypervascular patvated intracranial pressure may cause cerebral tern, which appears as blush, represents dilating herniati~n.~~ supplying arteries, arterioles and capillaries, and Cerebral angiography was normal in 14 patients premature venous filling.7,9,33 This focal hyperperfuwho had focal neurologic deficits. Involvement of sion may be caused by a t least three different cerebral arterioles or venules that could not be mechanisms: (1)a local loss of cerebral autoregulavisualized by cerebral angiography, or metabolic tion as a result of cerebral ischemia; (2) a localized changes due to bacterial meningitis, may have decrease in extracellular space pH9a3;or (3) the libaccounted for the focal neurologic deficits in these eration of vasodilating mediators during t h e patients. We have recently shown that patients inflammatory process, as shown i n a n animal with bacterial meningitis who presented with focal model of pneumococcal meningitis.26Paulson et all3 neurologic deficits had normal cerebral angiographdemonstrated impaired cerebral autoregulation in ic findings but pathologic patterns on HMPAOhumans with pneumococcal meningitis using the SPECT investigation (Forderreuther et al, unpub133xenonintra-arterial injection method. In addilished data). Therefore, it may be that the true fretion, in a rabbit model of pneumococcal meningitis, quency of cerebrovascular complications is underthere was disturbed cerebral autoregulation at 16 estimated when the data are based solely on an to 20 hours after intracisternal pneumococcal chalangiographic study. Another possible drawback lenge by means of the microsphere t e ~ h n i q u e . ~ 5 might be our reliance on CT (in addition to clinical Andersen et a139found a decreased intracerebral factors) a s one of the criteria for choosing the pH during experimental pneumococcal meningitis patients to study with angiography. Presumably, if in a rabbit model. An increase of regional cerebral all patients with bacterial meningitis were studied blood flow was present during the early phase of with MRI, the increased sensitivity of MRI t o experimental pneumococcal meningitis in the rat26 detect parenchymal ischemic changes would have and in the rabbit,24suggesting that oxygen-derived increased the population t o study with angiografree radicals are involved in the increase of regionphy. This may also have decreased the percentage al cerebral blood flow in the early phase of the disof positive arteriograms in our group of patients. ease.26 The prognosis of cerebrovascular complications The fourth type of cerebrovascular complication was poor. In the present series, only two of 13 involves major sinuses a n d cortical veins. patients completely recovered. Effective therapy for Angiography revealed septic sinus venous thrombocerebrovascular complications during bacterial 1502 NEUROLOGY 42 August 1992

meningitis is still unknown. The beneficial effect of chance to reduce mortality lies in early detection corticosteroids has been demonstrated in animal and improved treatment of the complications arismodels of bacterial m e n i n g i t i ~ . ~Corticosteroids ~,~~-~~ ing during the disease. reduced intracranial pressure, brain edema formation, and the degree of meningeal inflammation, Acknowledgments improved disturbances of CSF hydrodynamics, and prevented changes in cerebral blood flow. Previous We thank Dr. H. Steinhoff who performed some of the cerebral controlled studies in humans with bacterial meninangiographies, and Mary J. Finke for manuscript preparation. gitis did not give evidence for a beneficial effect of corticosteroids in bacterial m e n i n g i t i ~ However, .~~ there was a beneficial effect of dexamethasone in References placebo-controlled double-blind studies in children 1. Swartz MN. Bacterial meningitis: more involved than just with bacterial meningitis most often suffering from the meninges. N Engl J Med 1984;311:912-914. H influenzae r n e n i n g i t i ~ .In ~ ~addition, .~~ in an open 2. B r u y n GAW, K r e m e r H P H , deMarie S, P a d b e r g GW, randomized study, dexamethasone reduced mortalHermans J , van Furth R. Clinical evaluation of pneumoity in adults with pneumococcal m e n i n g i t i ~ In .~~ coccal meningitis in adults over a twelve-year period. Eur J patients with bacterial endocarditis and septic Clin Microbiol Infect Dis 1989;8:695-700. 3. Pfister HW. Complicated purulent meningitis of the adult: embolism, corticosteroids are not recommended persisting high mortality caused by vasculitis and increased and may even worsen the thrombosis. Four-day intracranial pressure. Nervenarzt 1989;60:249-254. dexamethasone therapy is currently used at our 4. Cairns H, Russell DS. Cerebral arteritis and phlebitis i n department in patients with angiographic findings pneumococcal meningitis. J Pathol Bacteriol 1946;58:649-665. 5. Adams RD, Kubik CS, Bonner FJ. The clinical and pathologof cerebrovascular arterial complications not relatical a s p e c t s of influenza1 m e n i n g i t i s . Arch P e d i a t r ed to septic embolism, and in four of our patients 1948;65:354-376, 408-441. seemed to be beneficial. However, these results are 6. Dodge PR, Swartz MN. Bacterial meningitis: a review of insufficient to give any recommendation for cortiselected aspects. N Engl J Med 1965;272:1003-1010. costeroid therapy in adults with cerebrovascular 7. Ferris EJ, Rudikoff JC, Shapiro JH. Cerebral angiography of bacterial infection. Radiology 1968;90:727-734. complications of bacterial meningitis, and further 8. Davis DO, Dilenge D, Schlaepper W. Arterial dilatation in controlled studies are warranted. purulent meningitis. J Neurosurg 1970;32:112-115. Anticoagulation of septic sinus venous thrombo9. Leeds NE, Goldberg HI. Angiographic manifestations in sis in bacterial meningitis is c o n t r o ~ e r s i a l . ~ ~ ~cerebral ~ ~ ~ inflammatory ~~ disease. Radiology 1971;98:595-604. 10. Thomas VH, Hopkins IJ. Arteriographic demonstration of Southwick et a140suggested that anticoagulants are v a s c u l a r lesions i n t h e s t u d y of neurologic deficit i n contraindicated in septic sinus thrombosis because advanced Haemophilus influenzae meningitis. Dev Med this condition is often associated with venous hemChild Neurol 1972;14:783-787. orrhagic infarctions. However, studies in aseptic 11. Rainiondi AJ, DiRocco C. Cerebral angiography in meningosinus venous thrombosis have shown that intracerebral inflammatory diseases in infancy and childhood: a study of thirty-five cases. Neurosurgery 1978;3:37-44. cerebral hemorrhage is not a contraindication for 12. Igarashi M, Gilmartin RC, Gerald B, Wilburn F, Jabbour heparin therapy,53and anticoagulation with doseJT. Cerebral arteritis and bacterial meningitis. Arch Neurol adjusted intravenous heparin may be an effective 1984;41:531-535. treatment in such patients. There are no prospec13. Paulson OB, Brodersen P, Hansen EL, Kristensen HS. Regional cerebral blood flow, cerebral metabolic rate of oxytive controlled studies in the treatment of septic gen, and cerebrospinal fluid acid-base variables in patients sinus venous thrombosis. Despite the advent of with acute meningitis and with acute encephalitis. Acta Med antibiotic therapy, the mortality r a t e of septic Scand 1974;196:191-198. thrombosis of the superior sagittal sinus is still 14. Ashwal S, Stringer W, Tomasi L, Schneider S, Thompson J, 78%,40 and t h a t of cortical thrombophlebitis is Perkin R. Cerebral blood flow and carbon dioxide reactivity in children with bacterial meningitis. J Pediatr 1990;117:523-530. 50%.41Controlled studies are needed to answer the 15. Gordon I, Orton M, Hughes T, Dinwiddie R. Evaluation of question of whether patients with septic sinus regional cerebral perfusion (rCBF) in acute neurological disvenous thrombosis, including patients with a n orders in childhood [abstract]. J Nucl Med 1991;32:943. intracerebral hemorrhage, will benefit from hep16. McMenamin JB, Volpe J J . Bacterial meningitis in infancy: effects on intracranial pressure and cerebral blood flow arin therapy. velocity. Neurology 1984;34:500-504. In conclusion, our data show that cerebrovascu17. Stovring J , Snyder RD. Computed tomography in childhood lar complications are frequent during bacterial bacterial meningitis. J Pediatr 1980;966:820-823. meningitis in adults and constitute a major deter18. Weisberg LA. C e r e b r a l computerized tomography i n minant for the prognosis of this disease. They may i n t r a c r a n i a l i n f l a m m a t o r y d i s o r d e r s . Arch Neurol 1980;37:137-142. be overlooked without a systematic search using 19. Snyder RD, Stovring J , Cushing AH, Davis LE, Hardy TL. angiography or CT. Transcranial Doppler sonograCerebral infarction in childhood bacterial meningitis. J phy may be useful in detecting involvement of Neurol Neurosurg Psychiatry 1981;44:581-585. great arteries at the base of the brain. However, 20. Packer RJ, Bilaniuk LT, Zimmerman RA. CT parenchymal abnormalities in bacterial meningitis: clinical significance. J changes of small vessels, major sinuses, and cortiComput Assist Tomogr 1982;6:1064-1068. cal veins cannot be detected by this technique. 21. Dunn DW, Daum RS, Weisberg L, Vargas R. Ischemic cereBecause it is doubtful that further development of brovascular complications of Haemophilus influenme meninantimicrobial therapy will substantially improve gitis: t h e value of computed tomography. Arch Neurol the prognosis of bacterial meningitis of adults, the 1982:39:650-652. August 1992 NEUROLOGY 42 1503

22. T a f t TA, C h u s i d M J , S t y J R . C e r e b r a l i n f a r c t i o n i n Haemophilus influenme type B meningitis. Clin Pediatr 1986;25:177-180. 23. Cabral DA, Flodmark 0, Farrell K, Speert DP. Prospective study of computed tomography in acute bacterial meningitis. J Pediatr 1987;111:201-205. 24. Tureen J . Cerebral blood flow and metabolism in experimental meningitis. Pediatr Infect Dis J 1989;8:917-918. 25. Tureen JH, Dworkin RJ, Kennedy SL, Sachdeva M, Sande MA. Loss of cerebrovascular autoregulation in experimental meningitis in rabbits. J Clin Invest 1990;85:577-581. 26. Pfister HW, Koedel U, Haberl RL, e t al. Microvascular changes during the early phase of experimental bacterial meningitis. J Cereb Blood Flow Metab 1990;10:914-922. 27. Gad0 M, Axley J , Appleton DB, Prensky DB. Angiography in the acute and posttreatment phases of Huemophilus influenzue meningitis. Radiology 1974;110:439-444. 28. Lyons EL, Leeds NE. The angiographic demonstration of arterial vascular disease in purulent meningitis. Radiology 1967;88:935-938. 29. Headings DL, Glasgow LA. Occlusion of the internal carotid artery complicating Huemophilus infZuenzae meningitis. Am J Dis Child 1977;131:854-856. 30. Teasdale G, Jennett B. Assessment of coma and impaired consciousness: a practical scale. Lancet 1975;2:81-84. 31. Yamashima T, Kashihara K, Ikeda K, Kubota T, Yamamoto S. Three phases of cerebral arteriopathy i n meningitis: vasospasm and vasodilatation followed by organic stenosis. Neurosurgery 1985;16:546-553. 32. Yasargil MG. Intracranial arteries. In: Microneurosurgery, vol 1. Microsurgical anatomy of the basal cisterns and vessels of the brain, diagnostic studies, general operative techniques and pathological considerations of the intracranial aneurysms. Stuttgart: Georg Thieme Verlag, 1984:54-143. 33. Raimondi AJ, DiRocco C. The physiopathogenetic basis for the ansographic diagnosis of bacterial infections of the brain and its coverings in children. Childs Brain 1979;5:1-13. 34. Tuomanen E. Molecular mechanisms of inflammation in experimental pneumococcal meningitis. Pediatr Infect Dis J 1987;6:1146-1149. 35. Arditi M, Manogue KR, Caplan M, Yogev R. Cerebrospinal fluid cachectidtumor necrosis factor-a and platelet-activating factor concentrations and seventy of bacterial meningitis in children. J Infect Dis 1990;162:139-147. 36. Alajouanine T, Castaigne P, Lhermitte F, Cambier J. The cerebral arteritis of bacteria1 endocarditis: its late complications. JAMA 1959;170:1858. 37. Salgado AV, Furlan AJ, Keys TF, Nichols TR, Beck GJ. Neurologic complications of endocarditis: a 12-year experience. Neurology 1989;39:173-178.

1504 NEUROLOGY 42 August 1992

38. Kanter MC, Hart RG. Neurologic complications of infective endocarditis. Neurology 1991;41:1015-1020. 39. Andersen NEO, Gyring J , Hansen AJ, Laursen H, Siesjo BK. Brain acidosis in experimental pneumococcal meningitis. J Cereb Blood Flow Metab 1989;9:381-387. 40. Southwick FS, Richardson E P J r , Swartz MN. Septic thrombosis of the dural venous sinuses. Medicine 1986;65:82-106. 41. DiNubile MJ, Boom WH, Southwick FS. Septic cortical thrombophlebitis. J Infect Dis 1990;161:1216-1220. 42. Goitein KJ, Tamir 1. Cerebral perfusion pressure in central nervous system infections of infancy a n d childhood. J Pediatr 1983;103:40-43. 43. Horwitz SJ, Boxerbaum B, O’Bell J. Cerebral herniation in bacterial meningitis in childhood. Ann Neurol 1980;7:524528. 44. Scheld WM, Dacey RG, Winn HR, Welsh JE, Jane JA, Sande MA. Cerebrospinal fluid outflow resistance in rabbits with experimental meningitis. J Clin Invest 1980;66:243-253. 45. Tauber MG, Khayam-Bashi H, Sande MA. Effects of ampicillin and corticosteroids on brain water content, cerebrospinal fluid pressure, and cerebrospinal fluid lactate levels in experimental pneumococcal meningitis. J Infect Dis 1985;151:528-534. 46. Syrogiannopoulos GA, Olsen KD, Reisch JS, McCracken GH J r . Dexamethasone i n t h e t r e a t m e n t of experimental Huemophilus influenme type b meningitis. J Infect Dis 1987;155:213-219. 47. Havens PL, Wendelberger KJ, Hoffman GM. Corticosteroids a s adjunctive therapy i n bacterial meningitis. Am J Dis Child 1989;143:1051-1055. 48. Lebel MH, Frei B J , Syrogiannopoulos GA, et a l . Dexamethasone therapy for bacterial meningitis: results of two double-blind, placebo-controlled trials. N Engl J Med 1988;319:964-971. 49. Odio CM, Faingezicht I, Paris M, e t al. The beneficial effects of early dexamethasone administration in infants and child r e n w i t h b a c t e r i a l m e n i n g i t i s . N E n g l J Med 1991;324:1525-1531. 50. Girgis NI, F a r i d Z, M i k h a i l IA, F a r r a g I, S u l t a n Y , Kilpatrick ME. Dexamethasone treatment for bacterial meningitis i n children and adults. Pediatr Infect Dis J 1989;8:848-851. 51. Levine SR, Twyman RE, Gilman S. The role of anticoagulation in cavernous sinus thrombosis. Neurology 1988;38:517522. 52. S c h m u t z h a r d E , Aichner F , B e r e k K, e t al. A k u t e Komplikationen der Pneumokokken-Meningoenzephalitis. Intensivbehandlung 1989;14:91-95. 53. Einhaupl KM, Villringer A, Meister W, e t al. Heparin treatment in sinus venous thrombosis. Lancet 1991; 338:597-600.

Cerebrovascular complications of bacterial meningitis in adults Hans-Walter Pfister, Gian Domenico Borasio, Ulrich Dirnagl, et al. Neurology 1992;42;1497 DOI 10.1212/WNL.42.8.1497 This information is current as of August 1, 1992 Updated Information & Services

including high resolution figures, can be found at: http://www.neurology.org/content/42/8/1497.full.html

Citations

This article has been cited by 20 HighWire-hosted articles: http://www.neurology.org/content/42/8/1497.full.html##otherarticl es

Permissions & Licensing

Information about reproducing this article in parts (figures,tables) or in its entirety can be found online at: http://www.neurology.org/misc/about.xhtml#permissions

Reprints

Information about ordering reprints can be found online: http://www.neurology.org/misc/addir.xhtml#reprintsus

Neurology ® is the official journal of the American Academy of Neurology. Published continuously since 1951, it is now a weekly with 48 issues per year. Copyright © 1992 by the American Academy of Neurology. All rights reserved. Print ISSN: 0028-3878. Online ISSN: 1526-632X.

Cerebrovascular complications of bacterial meningitis in adults.

We performed a prospective study of the type, frequency, temporal profile, and prognostic role of cerebrovascular complications in 86 adults with bact...
2MB Sizes 0 Downloads 0 Views