Outcome of heparin-treated patients with acute cerebral venous sinus thrombosis: influence of the temporal pattern of intracerebral haemorrhage.

BACKGROUND AND PURPOSE: The influence of temporal patterns of intracerebral haemorrhage (ICH) on the outcome of heparin-treated patients with cerebral venous sinus thrombosis (CVST) has not been examined systematically. METHODS: Temporal patterns of ICH and their influence on survival without disability (modified Rankin Scale score ≤1 point) at hospital discharge were examined in 141 consecutive hospital-admitted patients with acute CVST who were treated with intravenous unfractionated heparin. RESULTS: Of all 141 patients (median age 40 years; 73% women), 59 (42%) had ICH at the time of diagnosis (early ICH). Of these, seven (12%) subsequently had extension of ICH and 13 (22%) had additional ICHs at other locations (delayed ICH). Of 82 patients without early ICH, nine (11%) later had delayed ICH. After a median hospital stay of 26 days, 107 patients (76%) were discharged without disability. Patients with early ICH were less likely to survive without disability until discharge than those without early ICH [63% vs. 85%; risk ratio (RR) 0.73; P = 0.005]. The association was attenuated after adjusting for age, sex and impaired consciousness on admission (RR 0.83; P = 0.03). Taking temporal patterns of ICH into account, early ICH with subsequent complication (extension or delayed ICH) had a larger influence on survival without disability (RR 0.57; 95% confidence interval 0.35-0.95) than early ICH without complications (RR 0.78; 95% confidence interval 0.67-0.91). CONCLUSIONS: Heparin-treated CVST patients were less likely to survive without disability when ICH was present on admission. This association may largely be driven by subsequent extension of haemorrhage or additionally occurring delayed haemorrhage.

Prevalence of stroke and stroke symptoms: a population-based survey of 28,090 participants.

BACKGROUND: Stroke is associated with a considerable burden of disease worldwide. Data about prevalence needs regular updating to facilitate health care planning and resource allocation. The purpose of the present study was to determine stroke prevalence in a large urban population in an easy and reliable way. METHODS: In a population survey a total of 75,720 households with at least 1 person >or=50 years received information about stroke symptoms by mail. In addition, the Stroke Symptom Questionnaire assessing the prevalence of stroke and of stroke symptoms was sent. Stroke prevalence was determined by a single physician-diagnosed stroke-screening question or by the combination of the latter with reported visual impairment and/or articulation problems in the past. RESULTS: A total of 28,090 persons responded (37.5%). Mean (+/-SD) age was 64.4 +/- 9.7 years, 62.9 +/- 8.9 for men (43.3%), and 65.5 +/- 10.2 for women. Of all participants 2.7% reported impaired vision, 2.8% facial weakness, 2.8% articulation problems, 3.9% limb weakness, and 5% sensory disturbances. A total of 4.5% reported a physician-diagnosed stroke (women 4.3%; men 4.9%). Combining reported stroke history with reported impaired vision and/or articulation problems, the prevalence of stroke increased to 7.6% (men 8.4%; women 7.2%). Factors associated with higher prevalence were higher age, male gender, non-German nationality, lower education, positive family history of stroke, and living alone. CONCLUSIONS: The combination of questions concerning a prior stroke and stroke symptoms is a useful and easy approach to assess prevalence. It results in prevalence numbers which might compensate for an underestimation of stroke numbers.

Vertebral artery dissections after chiropractic neck manipulation in Germany over three years.

Vertebral artery dissection (VAD) has been observed in association with chirotherapy of the neck. However, most publications describe only single case reports or a small number of cases. We analyzed data from neurological departments at university hospitals in Germany over a three year period of time of subjects with vertebral artery dissections associated with chiropractic neck manipulation. We conducted a country-wide survey at neurological departments of all medical schools to identify patients with VAD after chirotherapy followed by a standardized questionnaire for each patient. 36 patients (mean age 40 + 11 years) with VAD were identified in 13 neurological departments. Clinical symptoms consistent with VAD started in 55% of patients within 12 hours after neck manipulation. Diagnosis of VAD was established in most cases using digital subtraction angiography (DSA), magnetic resonance angiography (MRA) or duplex sonography. 90% of patients admitted to hospital showed focal neurological deficits and among these 11 % had a reduced level of consciousness. 50% of subjects were discharged after 20 +/- 14 hospital days with focal neurological deficits, 1 patient died and 1 was in a persistent vegetative state. Risk factors associated with artery dissections (e. g. fibromuscular dysplasia) were present in only 25% of subjects. In summary, we describe the clinical pattern of 36 patients with vertebral artery dissections and prior chiropractic neck manipulation.

Brain HMPAO-SPECT and ocular microangiopathic syndrome in HIV-1-infected patients.

OBJECTIVE: The pathogenesis of neurologic and neuropsychologic dysfunction in HIV-1 infection is unclear. The purpose of the study was to determine an association between cerebral perfusion and HIV-1-related ocular microangiopathic syndrome. METHODS: We studied 28 HIV-1-infected patients, seven of whom presented with asymptomatic HIV infection, nine with lymphadenopathy syndrome or AIDS-related complex, and 12 with AIDS. Cerebral perfusion was semi-quantitatively measured by single photon emission computed tomography of the brain using technetium-99 hexamethyl-propylenamine oxime (HMPAO-SPECT). The conjunctival manifestation of HIV-1-related microangiopathic syndrome was measured by a rating scale determining blood-flow sludging and, retinal cotton-wool spots were counted. CD4 count, neopterin, beta 2-microglobulin (beta 2M), haemoglobin, and age were determined as putative confounding variables. RESULTS: Mean conjunctival sludge in patients with normal HMPAO-SPECT findings was 1.3 +/- 0.5 (mean +/- s.e.m.); no cotton-wool spots were present. In patients with slightly impaired HMPAO-SPECT, it was 2.1 +/- 0.6 and mean cotton-wool spot count was 1.1 +/- 0.4. In patients with severely impaired HMPAO-SPECT, mean conjunctival sludge was 4.5 +/- 0.3 and mean cotton-wool spot count was 4.9 +/- 1.1 HMPAO-SPECT findings were closely associated with conjunctival sludge (r = 0.72; P < 0.001) and number of cotton-wool spots (r = 0.78; P < 0.001), whereas only a slight association with staging of HIV disease was found (P = 0.052). Analysis of covariance controlling for CD4 count neopterin, beta 2M, age, and haemoglobin demonstrated a significant difference between the three HMPAO-SPECT groups for both the number of cotton-wool spots (P < 0.001) and the conjunctival sludge rating (P < 0.001). CONCLUSION: There was a close association between severity of HIV-1-related ocular microangiopathic syndrome and severity of cerebral hypoperfusion. Microvascular alterations might contribute to the pathogenesis of neurological and neuropsychological symptoms in patients with HIV-1 disease. Furthermore, the conjunctival sludge rating and the number of cotton-wool spots might be appropriate indicators for severity of microvascular changes of the central nervous system [corrected].

Three-dimensional reconstruction of the rat brain cortical microcirculation in vivo.

We used confocal laser scanning microscopy (CLSM) to investigate the morphology and three-dimensional relationships of the microcirculation of the superficial layers of the rat brain cortex in vivo. In anesthetized rats equipped with a closed cranial window (dura mater removed), after i.v. injection of 3 mg/100 g of body weight of fluorescein in 0.5 ml of saline, serial optical sections of the brain cortex intraparenchymal microcirculation were taken. Excitation was at a wavelength of 488 nm (argon laser), and emission was collected above 515 nm. CLSM provided images of brain vessels with sufficient signal-to-noise ratio for three-dimensional reconstructions down to a depth of 250 microns beneath the surface of the brain. Compared to conventional fluorescence microscopy, CLSM has a much higher axial resolution and higher depth of penetration. Laser light-induced intravascular aggregates, irregularities of erythrocyte flow, or microvascular occlusions ("light and dye injury") were not apparent in the current experimental paradigm. CLSM is a promising new tool for in vivo visualization of the cerebral microcirculation. Future studies have to characterize the potential damage to the tissue dye mechanisms.

Role of nitric oxide synthase inhibition in leukocyte-endothelium interaction in the rat pial microvasculature.

We investigated the role of nitric oxide (NO) in leukocyte-endothelium interaction, blood-brain barrier (BBB) function and oxygen free-radical production in the rat pial microcirculation. In a closed cranial window preparation (dura removed) over the parietal cortex of pentobarbital-anesthetized Wistar rats, NO synthase (NOS) was inhibited by systemic and/or topical application of N omega-nitro-L-arginine (L-NNA) under physiological conditions and during leukotriene B4 (LTB4) activation. Circulating leukocytes were labeled by intravenous injection of rhodamine 6G. We used a confocal laser scanning microscope (CLSM) and studied leukocyte rolling and sticking in pial veins and arteries before and after NOS inhibition. At the end of the experiments, sodium-fluorescein was injected intravenously to test BBB integrity. Brain cortex oxygen free-radical production was investigated in the cranial window preparation using lucigenin-enhanced chemiluminescence (CL). L-NNA application did not lead to significant changes in leukocyte-endothelium interaction, BBB function, and oxygen free-radical production under physiological conditions [leukocyte-endothelium interaction: control (n = 5), L-NNA systemically (n = 5), L-NNA topically (n = 5): at baseline rollers/100 microns: 0.76 +/- 0.55, 0.64 +/- 0.94, 0.44 +/- 0.55 and stickers/100 microns: 0.90 +/- 0.28, 0.76 +/- 0.24, 0.84 +/- 0.42; at 60 min rollers/100 microns: 1.49 +/- 0.66, 1.21 +/- 0.99, 0.67 +/- 0.66 and stickers/100 microns: 1.04 +/- 0.20, 1.19 +/- 0.23, 1.21 +/- 0.54; oxygen free-radical production (n = 4): CL count before L-NNA application 35 +/- 17 cps, after 1 h of topical superfusion of L-NNA 38 +/- 14 cps; p < 0.05]. In contrast to the results achieved under physiological conditions, a significant further increase of rolling leukocytes and BBB permeability occurred due to NOS inhibition under LTB4-activated conditions [76 +/- 47% significant (p < or = 0.01, n = 7) further increase of rollers/100 microns due to 60 min L-NNA application following the activation period of 120 min LTB4 superfusion]. Our results support a modulatory role for NO in leukocyte-endothelium interaction and BBB permeability in the pial microcirculation when this interaction is increased.

Microvascular changes during the early phase of experimental bacterial meningitis.

We investigated the temporal profile of the changes in regional CBF (rCBF) and intracranial pressure (ICP) during the early phase of pneumococcal meningitis in the rat. rCBF, as measured by laser-Doppler flowmetry, and ICP were continuously monitored during 6 h post infection (p.i.). Brain edema formation was assessed by brain water content determinations. Meningitis was induced by intracisternal injection of 75 microliters of 10(7) colony-forming units/ml pneumococci (n = 7). In control animals (n = 6), saline was injected. There was no change in the rCBF or ICP of controls throughout the experiment. However, there was a dramatic increase in rCBF and ICP associated with brain edema formation in untreated meningitis animals. rCBF increased to 135.3 +/- 33.8% (mean +/- SD) in the untreated animals at 1 h p.i. and reached 211.1 +/- 40.5% at 6 h p.i. (p less than 0.05 compared with controls). ICP increased from 2.9 +/- 1.4 to 10.4 +/- 4.7 mm Hg at 6 h p.i. (p less than 0.05 compared with controls). Brain water content was significantly elevated (79.69 +/- 0.24 compared with 78.94 +/- 0.16% in the control group, p less than 0.05). We investigated the effect of dexamethasone (3 mg/kg i.p.), which was given prior to the induction of meningitis (n = 3) or at 2 h after pneumococcal injection (n = 5), indomethacin (10 mg/kg i.v., n = 5), and superoxide dismutase (SOD; 132,000 U/kg i.v. per 6 h, n = 6).(ABSTRACT TRUNCATED AT 250 WORDS)

The trigeminal nerve and augmentation of regional cerebral blood flow during experimental bacterial meningitis.

We investigated whether trigeminal nerve fibers contribute to enhanced regional cerebral blood flow (rCBF) in a rat model of experimental bacterial meningitis. rCBF was measured continuously for 6 h by laser Doppler flowmetry through thinned bone over the frontal cortex. Meningitis was induced with pneumococcal cell wall components and confirmed by a significant increase of (a) leukocytes within the cerebrospinal fluid, (b) brain water content, (c) intracranial pressure and (d) rCBF. The increase of rCBF was significantly attenuated (p < 0.05) at 3, 4, 5, and 6 h in animals after a chronic (200 +/- 21% versus 138 +/- 13% at 6 h on the intact and denervated sides, respectively) but not after an acute section of the nasociliary branch of the trigeminal nerve. We conclude that elevations in blood flow during the early phase of bacterial meningitis are mediated in part by the trigeminal nerve, probably by local perivascular release of neuropeptides from afferent axons innervating the meninges.

Heparin inhibits leukocyte rolling in pial vessels and attenuates inflammatory changes in a rat model of experimental bacterial meningitis.

Heparin is a natural proteoglycan that was first described in 1916. In addition to its well characterized effect on blood coagulation, it is becoming clear that heparin also modulates inflammatory processes on several levels, including the interference with leukocyte-endothelium interaction. Anecdotal observations suggest a better clinical outcome of heparin-treated patients with bacterial meningitis. The authors demonstrate that heparin, a glycosaminoglycan, inhibits significantly in the early phase of experimental pneumococcal meningitis the increase of 1) regional cerebral blood flow (125 +/- 18 versus 247 +/- 42%), 2) intracranial pressure (4.5 +/- 2.0 versus 12.1 +/- 2.2 mm Hg), 3) brain edema (brain water content: 78.23 +/- 0.33 versus 79.49 +/- 0.46%), and 4) influx of leukocytes (571 +/- 397 versus 2400 +/- 875 cells/microL) to the cerebrospinal fluid compared with untreated rats. To elucidate the possible mechanism of this observation, the authors investigated for the first time leukocyte rolling in an inflammatory model in brain venules by confocal laser scanning microscopy in vivo. Heparin significantly attenuates leukocyte rolling at 2, 3, and 4 hours (2.8 +/- 1.3 versus 7.9 +/- 3.2/100 microm/min), as well as leukocyte sticking at 4 hours (2.1 +/- 0.4 versus 3.5 +/- 1.0/100 microm/min) after meningitis induction compared with untreated animals. The authors conclude that heparin can modulate acute central nervous system inflammation and, in particular, leukocyte-endothelium interaction, a key process in the cascade of injury in bacterial meningitis. They propose to evaluate further the potential of heparin in central nervous system inflammation in basic and clinical studies.

Nitric oxide scavenging by hemoglobin or nitric oxide synthase inhibition by N-nitro-L-arginine induces cortical spreading ischemia when K+ is increased in the subarachnoid space.

We investigated the combined effect of increased brain topical K+ concentration and reduction of the nitric oxide (NO.) level caused by nitric oxide scavenging or nitric oxide synthase (NOS) inhibition on regional cerebral blood flow and subarachnoid direct current (DC) potential. Using thiopental-anesthetized male Wistar rats with a closed cranial window preparation, brain topical superfusion of a combination of the NO. scavenger hemoglobin (Hb; 2 mmol/L) and increased K+ concentration in the artificial cerebrospinal fluid ([K+]ACSF) at 35 mmol/L led to sudden spontaneous transient ischemic events with a decrease of CBF to 14+/-7% (n=4) compared with the baseline (100%). The ischemic events lasted for 53+/-17 minutes and were associated with a negative subarachnoid DC shift of -7.3+/-0.6 mV of 49+/-12 minutes' duration. The combination of the NOS inhibitor N-nitro-L-arginine (L-NA, 1 mmol/L) with [K+]ACSF at 35 mmol/L caused similar spontaneous transient ischemic events in 13 rats. When cortical spreading depression was induced by KCl at a 5-mm distance, a typical cortical spreading hyperemia (CSH) and negative DC shift were measured at the closed cranial window during brain topical superfusion with either physiologic artificial CSF (n=5), or artificial CSF containing increased [K+]ACSF at 20 mmol/L (n=4), [K+]ACSF at 3 mmol/L combined with L-NA (n=10), [K+]ACSF at 10 mmol/L combined with L-NA (five of six animals) or [K+]ACSF at 3 mmol/L combined with Hb (three of four animals). Cortical spreading depression induced longlasting transient ischemia instead of CSH, when brain was superfused with either [K+]ACSF at 20 mmol/L combined with Hb (CBF decrease to 20+/-20% duration 25+/-21 minutes, n=4), or [K+]ACSF at 20 mmol/L combined with L-NA (n=19). Transient ischemia induced by NOS inhibition and [K],ACSF at 20 mmol/L propagated at a speed of 3.4+/-0.6 mm/min, indicating cortical spreading ischemia (CSI). Although CSH did not change oxygen free radical production, as measured on-line by in vivo lucigenin-enhanced chemiluminescence, CSI resulted in the typical radical production pattern of ischemia and reperfusion suggestive of brain damage (n=4). Nimodipine (2 microg/kg body weight/min intravenously) transformed CSI back to CSH (n=4). Vehicle had no effect on CSI (n=4). Our data suggest that the combination of decreased NO. levels and increased subarachnoid K+ levels induces spreading depression with acute ischemic CBF response. Thus, a disturbed coupling of metabolism and CBF can cause ischemia. We speculate that CSI may be related to delayed ischemic deficits after subarachnoid hemorrhage, a clinical condition in which the release of Hb and K+ from erythrocytes creates a microenvironment similar to the one investigated here.

Spectrum of complications during bacterial meningitis in adults. Results of a prospective clinical study.

OBJECTIVE: To determine systematically central nervous system and systemic complications during the acute phase of adult bacterial meningitis. DESIGN: Prospective clinical study. SETTING: University referral center, Department of Neurology. PATIENTS: A total of 86 consecutive patients between the ages of 15 and 87 years who had bacterial meningitis. MEASUREMENTS: Central nervous system complications, including brain swelling, hydrocephalus, brain abscess, subdural empyema, or subdural effusion (using computed tomography) and cerebrovascular involvement (using cerebral angiography), systemic complications, including septic shock, disseminated intravascular coagulation, adult respiratory distress syndrome, or septic or reactive arthritis, and typical complications arising during intensive care therapy. RESULTS: Of the 86 adult patients with bacterial meningitis, complications developed in 43 patients. The major central nervous system complications included angiographically documented cerebrovascular involvement (15.1% of the patients [13/86 patients]), brain swelling (14.0% [12/86]), hydrocephalus (11.6% [10/86]), and intracerebral hemorrhage (2.3% [2/86]), while septic shock (11.6% [10/86]), adult respiratory distress syndrome (3.5% [3/86]), and disseminated intravascular coagulation (8.1% [7/86]) dominated among the patients with systemic complications. Seven patients had cerebral herniation, three with a lethal course. The overall mortality was 18.6% [16/86] and was 10 of 30 (3.33%) in pneumococcal meningitis. CONCLUSIONS: Clinical and autopsy studies showed that the major determinants for the lethal outcome were primarily central nervous system complications in six patients, systemic complications in five, and a combination of both in another five. The identification of the various complications and their time of expected occurrence may help to develop additional treatment regimens in bacterial meningitis in adults.

Cefotaxime vs penicillin G for acute neurologic manifestations in Lyme borreliosis. A prospective randomized study.

We randomly assigned 21 patients with painful Lyme neuroborreliosis radiculitis (Bannwarth's syndrome) and neuroborreliosis meningitis to a 10-day treatment with either penicillin G. 4 x 5 million U/d (n = 10) or cefotaxime sodium, 3 x 2 g/d (n = 11), intravenously. We were not able to demonstrate clinical differences between groups, either during the 10-day treatment period or at follow-up examination a mean of 7.7 months after antibiotic therapy. Cerebrospinal fluid cefotaxime concentrations reached the minimum inhibitory concentration at the 90% level for Borrelia burgdorferi in all patients, while none of the patients treated with penicillin G had cerebrospinal fluid concentrations above the minimum inhibitory concentration at the 90% value. We conclude that patients with acute neurologic manifestations of Lyme borreliosis may benefit from a 10-day treatment with cefotaxime or penicillin G. Cerebrospinal fluid antibiotic concentrations above the minimum inhibitory concentration at the 90% value, as observed in all patients treated with cefotaxime, offer the most hope for long-term prognosis.

Monitoring of venous hemodynamics in patients with cerebral venous thrombosis by transcranial Doppler ultrasound.

OBJECTIVES: To test the assumption that transcranial Doppler ultrasound (TCD) is able to detect and to monitor intracranial venous blood flow velocities in patients with confirmed cerebral venous thrombosis (CVT). DESIGN: Prospective case study in 18 patients. SETTING: Inpatient neurologic service in a university hospital. SUBJECTS AND METHODS: Serial TCD examinations were performed in 18 consecutive patients with CVT (14 females, 4 males) aged 16 to 64 years (mean+/-SD, 36.8+/-13.1 years) during a mean follow-up ranging from 34 to 783 days (mean+/-SD, 201+/-185 days) between 1993 and 1997. Venous TCD was performed with a 2-MHz range-gated transducer. RESULTS: Venous blood flow velocities were successfully measured in all patients. The highest measured velocities in the monitored intracranial venous vessels ranged from 20 to 150 cm/s (mean+/-SD, 58.9+/-38.8 cm/s), and the lowest were from 9 to 84 cm/s (mean+/-SD, 27.9+/-17.0 cm/s). Fifteen patients (83%) showed a decrease of velocities-2 of them after a transient increase during cessation of heparin therapy. The percentage of velocity decrease ranged from 34% to 73% (mean+/-SD, 56.4%+/-10.9%). A plateau phase, defined as no further decrease in velocities, was reached in these patients within 4 to 314 days (mean+/-SD, 59.9+/-73.7 days). Three patients (17%) showed no changes in velocities as defined by a limit of velocity variation of 30% during the course of CVT. High venous velocities were significantly associated with altered consciousness (P = .001). A nonsignificant relationship was observed with affliction of the superior sagittal sinus. No correlations were noted for onset of disease, initial motor deficits, and presence of bleeding. No predictive value was gained from analyzing the outcome in relation to absolute velocities or their decrease. CONCLUSIONS: Serial TCD studies allow monitoring of venous hemodynamics and collateral pathways in patients with CVT. Normal venous velocities in serial measurements, however, do not exclude a diagnosis of CVT.

Reduced cerebral blood flow in early stages of human immunodeficiency virus infection.

In order to determine if brain perfusion abnormalities, which are known in patients with acquiredimmunodeficiency syndrome dementia, occur in early stages of human immunodeficiency virus infection, technetium 99m hexamethyl-propyleneamine oxime-single-photon emission computed tomography studies were performed in 20 patients infected with human immunodeficiency virus who belonged to Walter Reed stages I through IV. None of these patients demonstrated signs of dementia or severe neurological dysfunction. Pathological patterns of hexamethyl-propyleneamine oxime uptake were seen in 14 patients, seven of whom had normal results during neurological examination. Only four patients had signs of cerebral atrophy on cranial computed tomographic scan. These data suggest that subtle changes in cerebral perfusion seem to arise early in the course of human immunodeficiency virus infection and may indicate human immunodeficiency virus encephalopathy before neurological symptoms or noticeable structural damage occurs.

Latent Lyme neuroborreliosis: presence of Borrelia burgdorferi in the cerebrospinal fluid without concurrent inflammatory signs.

Borrelia burgdorferi, the etiologic agent of Lyme borreliosis, was isolated from the CSF of a patient with elevated serum IgG antibody titers against B burgdorferi and a history of multiple tick bites. The absence of concurrent inflammatory signs of CSF as well as intrathecal antibody production indicates a phase of latent Lyme neuroborreliosis in which no tissue infection or reaction has yet occurred. Bilateral tinnitus was the only clinical symptom in this patient. The persistence of the bilateral tinnitus after antibiotic therapy did not support a causal relationship between this symptom and the borrelial infection.

Toxoplasmosis with early intracerebral hemorrhage in a patient with the acquired immunodeficiency syndrome.

Cerebral hemorrhage is a rare complication of the acquired immunodeficiency syndrome. We report a case of multifocal hemorrhage in a 37-year-old homosexual man with cerebral toxoplasmosis. Histopathologic examination, performed at cerebral autopsy, confirmed the findings on CT and MRI.

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 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 at 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.

Anti ICAM-1 (CD 54) monoclonal antibody reduces inflammatory changes in experimental bacterial meningitis.

We investigated whether monoclonal antibodies directed against intracellular adhesion molecule 1 (ICAM-1 mAb) inhibit brain edema, increase of intracranial pressure (ICP), regional cerebral blood flow (rCBF) and recruitment of white blood cells (WBC) into the cerebrospinal fluid (CSF) in the rat model of the early phase of bacterial meningitis. Brain edema was assessed by brain water content determinations. rCBF measured by laser Doppler flowmetry and ICP were recorded continuously for 6 h after intracisternal challenge. Meningitis was induced with pneumococcal cell walls (PCW). Increase of ICP and brain water content were significantly inhibited (P <0.05) by intravenous treatment with ICAM-1 mAb (TM-8, 1 mg/kg). Furthermore, ICAM-1 mAb treatment profoundly attenuated (P <0.05) rCBF increase and WBC invasion into the CSF. These results suggest that the ICAM-1 pathway is critically involved in the early phase of bacterial meningitis.

Tumour necrosis factor alpha induces only minor inflammatory changes in the central nervous system, but augments experimental meningitis.

Although tumour necrosis factor alpha is said to play a key role in bacterial meningitis and other CNS diseases, the effects of this pro-inflammatory cytokine have only been studied in part and are incompletely understood. In a rat model, we investigated the effect of intracisternal injection of recombinant rat-specific tumour necrosis factor alpha (5, 35, 70 and 280 microg tumour necrosis factor alpha) (i) alone, (ii) combined with pneumococcal cell wall components, on regional cerebral blood flow, intracranial pressure, white blood cell count in the cerebrospinal fluid, and brain water content. Tumour necrosis factor a dose-dependently caused an increase in regional cerebral blood flow (up to 221 +/- 43% of baseline values) over the six hour observation period and mild cerebrospinal fluid leukocytosis; intracranial pressure and brain water content were unchanged. Hypothesizing that regional cerebral blood flow changes are dependent on nitric oxide, tumour necrosis factor alpha-induced regional cerebral blood flow increase was abolished by Aminoguanidine, a selective inhibitor of inducible nitric oxide synthase. Combination of the lowest tumour necrosis factor alpha dose and a low dose pneumococcal cell wall preparation magnified the inflammatory effect of both. We conclude that intrathecally injected tumour necrosis factor alpha alone results in only minor inflammatory changes, whereas it dramatically augments experimental meningitis.