Blood biomarkers associated with inflammation predict poor prognosis in cerebral venous thrombosis:: a multicenter prospective observational study.

BACKGROUND AND PURPOSE: Experimental studies suggest inflammation can contribute to blood barrier disruption and brain injury in cerebral venous thrombosis (CVT). We aimed to determine whether blood biomarkers of inflammation were associated with the evolution of brain lesions, persistent venous occlusion or functional outcome in patients with CVT. METHODS: Pathophysiology of Venous Infarction-Prediction of Infarction and Recanalization in CVT (PRIORITy-CVT) was a multicenter prospective cohort study of patients with newly diagnosed CVT. Evaluation of neutrophil-to-lymphocyte ratio (NLR) and C-reactive protein (CRP) concentrations in peripheral blood samples was performed at admission in 62 patients. Additional quantification of interleukin (IL)-6 was performed at day 1, 3 and 8 in 35 patients and 22 healthy controls. Standardized magnetic resonance imaging was performed at day 1, 8 and 90. Primary outcomes were early evolution of brain lesion, early recanalization and functional outcome at 90 days. RESULTS: Interleukin-6 levels were increased in patients with CVT with a peak at baseline. IL-6, NLR and CRP levels were not related with brain lesion outcomes or early recanalization but had a significant association with unfavourable functional outcome at 90 days (IL-6: OR = 1.28, 95% CI: 1.05-1.56, P = 0.046; NLR: OR = 1.39, 95% CI: 1.4-1.87, P = 0.014; CRP: OR = 1.756, 95% CI: 1.010-3.051, P = 0.029). Baseline IL-6 had the best discriminative capacity, with an area under the receiver operating characteristic curve to predict unfavourable functional outcome of 0.74 (P = 0.031). CONCLUSIONS: Increased baseline levels of NLR, CRP and IL-6 may serve as new predictive markers of worse functional prognosis at 90 days in patients with CVT. No association was found between inflammatory markers and early evolution of brain lesion or venous recanalization.

European Stroke Organization guideline for the diagnosis and treatment of cerebral venous thrombosis - endorsed by the European Academy of Neurology.

BACKGROUND AND PURPOSE: Current guidelines on cerebral venous thrombosis (CVT) diagnosis and management were issued by the European Federation of Neurological Societies in 2010. We aimed to update the previous European Federation of Neurological Societies guidelines using a clearer and evidence-based methodology. METHOD: We followed the Grading of Recommendations, Assessment, Development and Evaluation system, formulating relevant diagnostic and treatment questions, performing systematic reviews and writing recommendations based on the quality of available scientific evidence. RESULTS: We suggest using magnetic resonance or computed tomographic angiography for confirming the diagnosis of CVT and not routinely screening patients with CVT for thrombophilia or cancer. We recommend parenteral anticoagulation in acute CVT and decompressive surgery to prevent death due to brain herniation. We suggest preferentially using low-molecular-weight heparin in the acute phase and not direct oral anticoagulants. We suggest not using steroids and acetazolamide to reduce death or dependency. We suggest using antiepileptics in patients with an early seizure and supratentorial lesions to prevent further early seizures. We could not make recommendations concerning duration of anticoagulation after the acute phase, thrombolysis and/or thrombectomy, therapeutic lumbar puncture, and prevention of remote seizures with antiepileptic drugs. We suggest that, in women who have suffered a previous CVT, contraceptives containing oestrogens should be avoided. We suggest that subsequent pregnancies are safe, but use of prophylactic low-molecular-weight heparin should be considered throughout pregnancy and puerperium. CONCLUSIONS: Multicentre observational and experimental studies are needed to increase the level of evidence supporting recommendations on the diagnosis and management of CVT.

Epilepsia partialis continua after an anterior circulation ischaemic stroke.

BACKGROUND AND PURPOSE: Although cerebrovascular disorders are the main cause of epilepsia partialis continua (EPC) in adulthood, the frequency of EPC after stroke is unknown. The aim was to prospectively ascertain its frequency 1 year after an ischaemic stroke. METHODS: This was a prospective study of consecutive acute anterior circulation ischaemic stroke patients, previously independent, with an admission National Institutes of Health Stroke Scale score ≥4, an acute ischaemic lesion on imaging and no previous epileptic seizures. During admission patients received standardized diagnostic and medical care and were submitted to a neurophysiological evaluation protocol. One year after stroke, patients were re-evaluated by an epilepsy expert neurologist and performed a video-electroencephalogram with electromyography co-registration whenever myoclonus was observed during neurological examination for jerk-locked back averaging analysis (JLBA). EPC was defined as continuously repeated fragments of epileptic seizures, with preserved consciousness, lasting at least 1 h, and representing locally restricted epileptic activity. RESULTS: In all, 151 acute anterior circulation stroke patients were consecutively included and prospectively evaluated, but 23 died in the first year. One year after stroke, from 127 patients alive, 117 (92.1%) underwent clinical and neurophysiological evaluation. In two (1.7%) patients, EPC diagnosis was made both by clinical and electroencephalographic criteria, namely JLBA. Both patients had a history of remote symptomatic seizures and one of them acute symptomatic seizures and non-convulsive status epilepticus criteria during the first 7 days after stroke. CONCLUSIONS: Despite its low frequency, the high stroke incidence makes post-stroke EPC relevant. This study draws attention to this recognizable condition with therapeutic and eventually prognostic implications.

Epileptic manifestations in stroke patients treated with intravenous alteplase.

BACKGROUND AND PURPOSE: Intravenous alteplase (rtPA) may be associated with seizures and epileptic activity in the electroencephalogram (EEG). The aim of this work was to compare the frequency of seizures and EEG abnormalities between stroke patients treated and not treated with rtPA. METHODS: This was a prospective study of consecutive acute anterior circulation ischaemic stroke patients, with 1-year follow-up. Patients were previously independent, had an admission National Institute of Health Stroke Scale score ≥4, an acute ischaemic lesion and no previous seizures. They received standardized diagnostic and medical care. A video-EEG was performed in 72 h (first EEG); during admission (daily until day 7 and after that if neurological worsening); at discharge and 1 year after stroke. RESULTS: In all, 151 patients (101 treated with rtPA) were included. The frequency of acute and remote symptomatic seizures was not significantly different between rtPA treated and non-treated patients (P = 0.726 and P = 0.748, respectively). Clinical paroxysmal phenomena during rtPA perfusion were observed in five (5%) patients. In the first EEG, rtPA treated patients more often had background diffuse slowing (43.6% vs. 26.0%, P = 0.036). This difference was no longer observed at discharge (24.0% vs. 19.1%, P = 0.517) nor 1 year after (11.8% vs. 10.0%, P = 0.765). No differences were found in the frequency of epileptiform (P = 0.867) or periodic discharges (P = 0.381). CONCLUSIONS: Intravenous alteplase is not associated with an increased risk of clinical or electroencephalographic epileptic phenomena.

Shunting in acute cerebral venous thrombosis: a systematic review.

BACKGROUND AND PURPOSE: The efficacy of cerebrospinal fluid shunting to reduce intracranial hypertension and prevent fatal brain herniation in acute cerebral venous thrombosis (CVT) is unknown. METHOD: From the International Study on Cerebral Vein and Dural Sinus Thrombosis (ISCVT) and a systematic literature review, we retrieved acute CVT patients treated only with shunting (external ventricular drain, ventriculoperitoneal or ventriculojugular shunt). Outcome was classified at 6 months and final follow-up by the modified Rankin Scale (mRS). RESULTS: 15 patients were collected (9 from the ISCVT and 6 from the review) who were treated with a shunt (external ventricular drain in 6 patients, a ventriculoperitoneal shunt in 8 patients or an unspecified type of shunt in another one). Eight patients (53.3%) regained independence (mRS 0-2), while 2 patients (13.3%) were left with a severe handicap (mRS 4-6) and 4 (26.7%) died despite treatment. Five patients with parenchymal lesions were shunted within 48 h from admission deterioration, 4 with an external ventricular drain: 2 (40%) recovered to independence, 2 (40%) had a severe handicap and 1 (20%) died. In contrast, all 3 patients with intracranial hypertension and no parenchymal lesions receiving a ventriculoperitoneal shunt later than 48 h regained independence. CONCLUSION AND IMPLICATIONS: A quarter of acute CVT patients treated with a shunt died, and only half regained independence. With the limitation of the small number of subjects, this review suggests that shunting does not appear to be effective in preventing death from brain herniation in acute CVT. We cannot exclude that shunting may benefit patients with sustained intracranial hypertension and no parenchymal lesions.

Systemic thrombolysis for cerebral venous and dural sinus thrombosis: a systematic review.

BACKGROUND: The use of thrombolytics is frequently considered in patients with cerebral venous and dural sinus thrombosis (CVT) who deteriorate despite anticoagulant therapy. PURPOSE: To collect all the published information about the use of systemic thrombolysis in CVT in order to assess its efficacy and safety. METHODS: We performed a PubMed search, checked all reference lists of studies found and used data from the International Study on Cerebral Vein and Dural Sinus Thrombosis (ISCVT). Outcome was classified at the last available follow-up by the modified Rankin Scale (mRS). The cases were stratified according to variables that might influence outcome. RESULTS: A total of 16 reports (26 patients, 2 from the ISCVT and 24 from the systematic review of the literature) were included. No randomized clinical trial was found. Seven patients presented with isolated intracranial hypertension syndrome (26.9%), 17 with encephalopathy (65.4%) and 2 were comatose (7.7%). The superior sagittal sinus was the one most often affected (n = 21; 80.8%), and there was thrombosis of the deep cerebral venous system in 5 patients (19.2%). Urokinase was the thrombolytic agent most frequently administered (n = 19; 73.1%), whereas streptokinase and recombinant tissue plasminogen activator were used in 2 cases each (7.7%). Intracranial hemorrhages occurred in 3 cases (11.5%). Extracranial hemorrhages occurred in 5 cases (19.2%), and overall there were 3 cases of serious bleeding (11.5%), including 2 deaths (7.7%). Partial or complete recanalization was verified in most patients (n = 16; 61.5%). The survival rate was 92.3% (24/26 patients). At the last available follow-up, 22/25 patients regained independency (mRS scores 0-2; 88%), 2/25 died (mRS score 6; 8%) and 1/25 was severely dependent (mRS scores 3-5; 4%). CONCLUSIONS: In all, 88% of the CVT patients treated with systemic thrombolysis regained their independency, but 2 deaths associated with intracranial hemorrhage occurred. The mortality rate and disability at the last available follow-up were similar to those found in 2 previous systematic reviews concerning the use of thrombolytics in CVT. Due to the small sample size and lack of controls, the efficacy of systemic thrombolysis in acute CVT cannot be assessed from the published information. Concerning safety, a nonnegligible proportion of bleedings was reported.

Central nervous system vasculitis associated with hepatitis C virus infection: a brain MRI-supported diagnosis.

BACKGROUND: The Hepatitis C virus (HCV) infection is associated with various extrahepatic manifestations, being the Central Nervous System (CNS) rarely involved. CASE REPORT: We report a case of a 54 year-old black man with arterial hypertension who presented with progressively worsening headaches, apathy, somnolence and left hemiparesis. Brain MRI showed an acute ischemic lesion in the left anterior cerebral artery (ACA) and an old ischemic infarct in the right ACA territory. Brain MRI with gadolinium revealed mural thickening and contrast enhancement of the A1 and A2 segments of the ACAs, of the middle and distal basilar artery and of the P1 segment of the left posterior cerebral artery, suggesting active vasculitis. Digital angiography confirmed those irregularities and stenosis. Laboratory evaluation revealed ESR (73 mm/h), transaminase elevation, elevated HCV viral load genotype 2, positive IGRA, negative cryoglobulins, CSF protein elevation with oligoclonal bands (mirror pattern) and no pleocytosis; investigation excluded other infectious causes. Pegylated interferon alpha-2a and ribavirin, corticotherapy and tuberculosis prophylaxis were started with clinical and imagiological improvement. CONCLUSION: The typical inflammation signs of the vascular wall demonstrated by the gadolinium-enhanced MRI strengthened the hypothesis of CNS vasculitis. The association with HCV infection is rare but should be investigated once specific therapeutic is required.

Safety of lumbar puncture in patients with cerebral venous thrombosis.

BACKGROUND AND PURPOSE: Lumbar puncture (LP) may precipitate cerebral venous thrombosis (CVT), but it is unclear if LP is deleterious in patients with CVT. We aimed to assess the safety of LP in the International Study on Cerebral Veins and Dural Sinus Thrombosis prospective cohort. METHODS: In 624 patients with CVT, we compared the prognosis of patients submitted or not to LP. The primary outcome was 'death or dependency at 6 months', as evaluated by the modified Rankin Scale (mRS; mRS = 3-6, with adjustment for variables associated with poor prognosis); secondary outcomes were: 'worsening after admission'; 'acute death'; and 'complete recovery at 6 months' (mRS = 0-1). We analyzed the same outcomes in subgroups of patients with brain lesions on the admission computer tomography/magnetic resonance imaging. RESULTS: LP was performed in 224 patients (35.9%). There was no difference in frequency of 'death or dependency at 6 months' between patients with or without LP [13.4% vs. 14.4%; odds ratio (OR) = 0.9, 95% confidence interval (CI) 0.6-1.5; P = 0.739]. LP was not associated with 'worsening after hospitalization' [21.5% vs. 23.5%; OR = 0.9, 95% CI 0.6-1.3; P = 0.577], 'acute death' [3.6% vs. 3.3%; OR = 1.1, 95% CI 0.5-2.7; P = 0.844] or 'complete recovery' [79.9% vs. 76.6%; OR = 1.2, 95% CI 0.8-1.7; P = 0.484]. In the subgroups of patients with brain lesions, the prognoses were not different between patients submitted or not to LP. CONCLUSION: LP was not associated with the functional outcome of patients with CVT, suggesting that LP was not harmful in these patients. These results should not be generalized to patients with large brain lesions and risk of herniation where LP is contraindicated.

Time course of NT-proBNP levels after acute ischemic stroke.

BACKGROUND: Studies suggest that N-terminal-pro-brain natriuretic peptide (NT-proBNP) can be a biomarker of cardioembolic stroke. However, the best time to measure it after stroke is unknown. We studied the time course of NT-proBNP in patients with ischemic stroke. METHODS: Consecutive acute ischemic stroke patients were admitted over 10 months to a Stroke Unit. Stroke type was classified according to TOAST. Blood samples were drawn within 24, 48, and 72 hours after stroke. Friedman test was used to compare NT-proBNP values across the 3 times in all, cardioembolic and non-cardioembolic stroke patients. Post hoc analysis with Wilcoxon signed-rank tests was conducted with a Bonferroni correction. Mann-Whitney test was used to compare median values of NT-proBNP between cardioembolic and non-cardioembolic stroke patients. ROC curves were drawn to determine NT-proBNP accuracy to diagnose cardioembolic stroke at 24, 48, and 72 hours after stroke onset. RESULTS: One hundred and one patients were included (29 cardioembolic) with a mean age of 64.5±12.3 years. NT-proBNP values for cardioembolic stroke were significantly higher (P < 0.001) than for non-cardioembolic stroke in the 3 time points. NT-proBNP was highest in the first 24-48 h after ischemic stroke and decreased significantly 72 h after stroke onset. The area under the curve for the three time points was similar. CONCLUSION: NT-proBNP levels were highest in the first 2 days after ischemic stroke and declined significantly thereafter. However, the area under the curve for the three time points was similar. The first 72 hours after ischemic stroke have a similar diagnostic accuracy to diagnose cardioembolic stroke.

Diagnostic difficulties in the classification of transient neurological attacks.

BACKGROUND: It is frequently difficult to distinguish transient ischaemic attacks (TIA) from other transient (<24 h) neurological attacks (TNA). We aimed to classify patients with TNA and identify the most frequent problems in establishing a diagnosis. METHODS: Analysis of a consecutive cohort of patients referred to a TIA Clinic during 5 years. TNA were classified as TIA, mimic and difficult to classify/possible TIA. Reasons limiting classification were listed and grouped. RESULTS: Four hundred and fifty-eight patients were included. Diagnoses were as follows: TIA-259 (56.6%), mimic-90 (19.7%) and difficult to classify/possible TIA-109 (23.8%). Amongst the 109 patients, main difficulties in the differential diagnosis were between TIA and seizure, psychiatric disturbance, peripheral vertigo, pre-syncope and metabolic condition. The reasons contributing for classification difficulties were as follows: atypical symptoms (49 patients), paucity of details in symptoms description (24 patients), presence of focal symptoms accompanying psychiatric symptoms (anxiety or panic) (12 patients), restraints formulated by current criteria of TIA and migraine (16 patients), previous neurological deficit (eight patients). CONCLUSION: This systematic study identified distinct groups of reasons limiting the diagnosis of TNA. Different clinical approaches should be applied according to specific reasons for classification difficulty. These strategies may help to clarify the aetiology of transient neurological symptoms and improve TIA diagnosis.

Update on subarachnoid haemorrhage.

Subarachnoid haemorrhage (SAH) is less frequent than ischaemic stroke or intracerebral haemorrhage, but has a high public health relevance because it can affect young and middle-age adults, has considerable mortality and morbidity, it is treatable and preventable. SAH is traditionally a topic for neurosurgeons. However as endovascular interventions are becoming effective alternatives to surgical treatment, SAH should turn out to be of interest to neurologists, in particular to those devoted to stroke, emergency and neurointensive care. Despite stable incidence, the mortality of SAH has decreased in the last two decades due to better neurosurgical techniques and neurocritical care and to advances in interventional neuroradiological procedures. We review the recent advances in the clinical and diagnostic aspects of SAH and in the genetics of intracranial aneurysms. A systematic review of the treatment of SAH and grading of the available evidence is included.

Headache in acute stroke. A prospective study in the first 8 days.

We aimed to describe and classify headaches associated with acute stroke, by interviewing patients consecutively admitted to a stroke unit using a validated headache questionnaire and the International Classification of Headache Disorders of the International Headache Society (IHS). One hundred and twenty-four patients (61% ischaemic and 39% haemorrhagic stroke) reported headache. Headaches started mostly on the day of stroke, were more often continuous, pressure-type, bilateral and located in the anterior region, were increased by movement and by cough and lasted for a mean of 3.8 days. Tension-type was the most frequent type of headache. Eleven per cent of headaches could not be classified using the criteria of the IHS. Previous primary headache was documented in 71 patients. The presence of nausea/vomiting due to acute stroke can confound headache classification using the IHS criteria. In up to half of the patients, headache seems to be a reactivation of previous primary headache.

Complications of cerebral vein and sinus thrombosis.

Thrombosis of the dural sinus and encephalic veins (CVT) is an infrequent condition accounting for less than 1% of all strokes. Several recent prospective series, in particular the large International Study on Cerebral Vein and Dural Sinus Thrombosis cohort, definitely have shown a more benign prognosis compared with that of arterial strokes: CVT has an acute case fatality of less than 5%, and almost 80% of patients recover without sequelae. However, patients surviving the acute phase of CVT are at risk of a number of complications such as recurrence of any thrombotic events in about 7%, recurrence of CVT in about 2-12%, seizures in 5 to 32%, visual loss due to optic atrophy in percentages that range from less than 1 to 5%, presence of dural fistula (there are no data available about exact frequency) and neuropsychological and neuropsychiatric sequelae characterized by aphasia, abulia and depression. However, there is only little information on the long-term neuropsychological outcome. Studies investigating professional status, cognitive performance, depressive symptoms and quality of life evidenced depression and anxiety in 2/3 of CVT patients despite an apparent good recovery in 87% of these patients. Thus, patients should be encouraged to return to previous occupations and hobbies and reassured about the very low risk of recurrence.

Interobserver agreement in the magnetic resonance location of cerebral vein and dural sinus thrombosis.

The interobserver variation in the magnetic resonance (MR) location of cerebral vein and dural sinus thrombosis (CVT) has not been previously reported. Four independent observers rated a convenience sample of 40 MR/MR angiographies to assess whether or not each dural sinus and major cerebral veins were occluded. Interobserver reliability was measured using kappa statistics. Interobserver agreement was comparable between the six pairs of raters. Agreement was excellent for thrombosis of the deep cerebral venous system (kappa = 1.00), cerebellar veins (kappa = 1.00), superior sagittal sinus (kappa range: 0.82-1) and right jugular vein (kappa range: 0.84-0.95); good to excellent for the right transverse/sigmoid sinus (kappa range: 0.75-0.90) and the left jugular vein (kappa range: 0.65-0.85); moderate to excellent for the left lateral sinus (kappa range: 0.59-0.78) and the straight sinus (kappa range: 0.59-0.92); poor to good for the cortical veins (kappa range: 0.02-0.65). Agreement between observers varies with the location of CVT. It is good or excellent for most of the occluded sinus and veins, except for the cortical veins. This study suggests that information on the location of CVT can be reliably collected and used in multicentre studies.

Thrombolysis for cerebral vein and dural sinus thrombosis.

BACKGROUND: Treatment of cerebral sinus thrombosis with thrombolytics has been reported in cases with a deteriorating clinical course despite anticoagulant therapy. The rationale of this treatment is to promote rapid recanalisation of the occluded sinus. OBJECTIVES: To review the available evidence on the efficacy and safety of thrombolysis in confirmed cerebral sinus thrombosis. SEARCH STRATEGY: We searched the Cochrane Stroke Group trials register (March 2003), the Cochrane Central Register of Controlled Trials (The Cochrane Library, Issue 1, 2003), MEDLINE (1966 to March 2003), EMBASE (1980 to March 2003), and reference lists of all relevant publications. SELECTION CRITERIA: We aimed to analyse separately unconfounded randomised controlled trials comparing thrombolytic agent with placebo, or thrombolytic agent with antithrombotic therapy, or thrombolytic agent and antithrombotic with antithrombotic alone, in patients with dural sinus thrombosis (confirmed by MR venography, intra-arterial venography or CT venography). DATA COLLECTION AND ANALYSIS: Two groups of reviewers independently applied the inclusion criteria. MAIN RESULTS: No randomised controlled trials were found. REVIEWER'S CONCLUSIONS: There is currently no available evidence from randomised controlled trials regarding the efficacy or safety of thrombolytic therapy in dural sinus thrombosis. A randomised controlled trial is justified to test this therapy especially in patients predicted to have a poor prognosis.

Cognitive and emotional consequences of perimesencephalic subarachnoid hemorrhage.

Little is known about the long-term cognitive-functional outcome of patients with perimesencephalic subarachnoid haemorrhage (PM SAH). We investigated the neurological, cognitive and emotional consequences of perimesencephalic subarachnoid haemorrhage in eighteen PM SAH patients admitted between November 1990 and July 1997 to the Neurology/Neurosurgery services of a University Hospital. The follow-up study consisted of a face-to-face interview, a neurological examination, an headache questionnaire, a neuropsychological evaluation (Mini-Mental State and a complementary battery to assess specific cognitive domains), the Hamilton Depression Rating Scale (HDRS) and the Blessed Dementia Scale. Thirteen patients performed below the 10th percentile in at least one cognitive domain. Six patients scored more than 12 points on the HDRS. Mini-Mental State and HDRS scores were moderately correlated (r = 0.55). Only three patients left their previous occupation. Minor cognitive deficits and high scores on a depression scale were frequent findings in this cohort of PM SAH patients. Reassurance and treatment of depressive symptoms could be important to improve the long-term outcome of PM SAH patients.

Vascular risk factors for perimesencephalic nonaneurysmal subarachnoid hemorrhage.

No data have been published on the role of vascular risk factors for perimesencephalic nonaneurysmal subarachnoid hemorrhage (PMSAH). In a case-control study we compared the prevalence of vascular risk factors in 40 consecutive patients who suffered a perimesencephalic subarachnoid hemorrhage with that in two controls groups: (a) 120 subjects registered with a general practitioner (GP: matched at a 3:1 ratio for age and sex) and (b) 81 proxies of patients of a hospital outpatient clinic. A conditional multivariate logistic regression model was performed taking into account the matched design. Hypertension was more frequent among PMSAH patients than among the two control group subjects for men and women. Among women, smoking was more common in PMSAH than in the GP control group. The conditional multivariate logistic regression model confirmed that hypertension was an independent risk factor for PMSAH (P = 0.036) Hypertension is a preventable risk factor of PMSAH.