Reliability of the intracerebral hemorrhage score for predicting outcome in patients with intracerebral hemorrhage using oral anticoagulants.

BACKGROUND AND PURPOSE: The intracerebral hemorrhage (ICH) score is the most widely used and validated prognostic model for estimating 30-day mortality in ICH. However, the score was developed and validated in an ICH population probably not using oral anticoagulants (OACs). The aim of this study was to determine the performance of the ICH score for predicting the 30-day mortality rate in the full range of ICH scores in patients using OACs. METHODS: Data from admitted patients with ICH were collected retrospectively in two Dutch comprehensive stroke centers. The validity of the ICH score was evaluated by assessing both discrimination and calibration in OAC and OAC-naive patient groups. RESULTS: A total of 1752 patients were included of which 462 (26%) patients were on OAC. The 30-day mortality was 54% for the OAC cohort and 34% for the OAC-naive cohort. The 30-day mortality was higher in the OAC cohort for ICH score 1 (33% vs. 12.5%; odds ratio, 3.4; 95% confidence intervals, 1.1-10.4) and ICH score 2 (53% vs. 26%; odds ratio, 3.2; 95% confidence intervals, 1.2-8.2) compared with the predicted mortality rate of the original ICH score. Overall, the discriminative ability of the ICH score was equally good in both cohorts (area under the curve 0.83 vs. 0.87, respectively). CONCLUSIONS: The ICH score underestimated the 30-day mortality rate for lower ICH scores in OAC-ICH. When estimating the prognosis of ICH in patients using OAC, this underestimation of mortality must be taken into account.

European Academy of Neurology and European Stroke Organization consensus statement and practical guidance for pre-hospital management of stroke.

BACKGROUND AND PURPOSE: The reduction of delay between onset and hospital arrival and adequate pre-hospital care of persons with acute stroke are important for improving the chances of a favourable outcome. The objective is to recommend evidence-based practices for the management of patients with suspected stroke in the pre-hospital setting. METHODS: The GRADE (Grading of Recommendations Assessment, Development and Evaluation) methodology was used to define the key clinical questions. An expert panel then reviewed the literature, established the quality of the evidence, and made recommendations. RESULTS: Despite very low quality of evidence educational campaigns to increase the awareness of immediately calling emergency medical services are strongly recommended. Moderate quality evidence was found to support strong recommendations for the training of emergency medical personnel in recognizing the symptoms of a stroke and in implementation of a pre-hospital 'code stroke' including highest priority dispatch, pre-hospital notification and rapid transfer to the closest 'stroke-ready' centre. Insufficient evidence was found to recommend a pre-hospital stroke scale to predict large vessel occlusion. Despite the very low quality of evidence, restoring normoxia in patients with hypoxia is recommended, and blood pressure lowering drugs and treating hyperglycaemia with insulin should be avoided. There is insufficient evidence to recommend the routine use of mobile stroke units delivering intravenous thrombolysis at the scene. Because only feasibility studies have been reported, no recommendations can be provided for pre-hospital telemedicine during ambulance transport. CONCLUSIONS: These guidelines inform on the contemporary approach to patients with suspected stroke in the pre-hospital setting. Further studies, preferably randomized controlled trials, are required to examine the impact of particular interventions on quality parameters and outcome.

Intracranial artery dissection.

The aim of this narrative review is to evaluate the pathogenesis, clinical features, diagnosis, treatment and prognosis of intracranial artery dissection (IAD). IAD is a rare and often unrecognized cause of stroke or subarachnoid haemorrhage (SAH), especially in young adults. Two types of IAD can be identified: a subintimal or subadventitial dissection. It is suggested that a subintimal dissection results in luminal stenosis, thromboembolism and subsequently cerebral ischaemia, whilst a subadventitial IAD could result in the formation of a pseudo-aneurysm and compression on brainstem or cranial nerves. Rupture of such a dissecting aneurysm causes SAH. The exact cause of IAD remains unknown but several factors are associated with its development. Diagnosis is based on clinical presentation and specific features seen on multimodal neuroimaging. The management of IAD depends on the clinical presentation. In the case of cerebral ischaemia, anticoagulants or antiplatelet agents are used, whilst in the case of SAH endovascular treatment is primarily advocated. Prognosis depends on clinical presentation. Presentation with SAH has a worse prognosis.

Pre-stroke use of beta-blockers does not affect ischaemic stroke severity and outcome.

BACKGROUND AND PURPOSE: It is unclear whether pre-stroke beta-blockers use may influence stroke outcome. This study evaluates the independent effect of pre-stroke use of beta-blockers on ischaemic stroke severity and 3 months functional outcome. METHODS: Pre-stroke use of beta-blockers was investigated in 1375 ischaemic stroke patients who had been included in two placebo-controlled trials with lubeluzole. Stroke severity was assessed by either the National Institute of Health Stroke Scale (NIHSS) or the European Stroke Scale (ESS). A modified Rankin scale (mRS) score of >3 at 3 months was used as measure for the poor functional outcome. RESULTS: Two hundred and sixty four patients were on beta-blockers prior to stroke onset, and 105 patients continued treatment after their stroke. Pretreatment with beta-blockers did not influence baseline stroke severity. There was no difference in stroke severity between nonusers and those on either a selective beta(1)-blocker or a non-selective beta-blocker. The likelihood of a poor outcome at 3 months was not influenced by pre-stroke beta-blocker use or beta-blocker use before and continued after stroke onset. CONCLUSIONS: Pre-stroke use of beta-blockers does not appear to influence stroke severity and functional outcome at 3 months.

tPA treatment for acute ischaemic stroke in patients with leukoaraiosis.

BACKGROUND AND PURPOSE: Whether leukoaraiosis on baseline CT is associated with an increased risk of symptomatic intracerebral haemorrhage (sICH) or poor outcome following tissue plasminogen activator (tPA) treatment for acute ischaemic stroke is still a matter of debate. OBJECTIVE: To investigate the relationship between the presence and severity of leukoaraiosis on baseline CT and the risk of sICH and functional outcome after tPA treatment for acute ischaemic stroke. METHODS: A single-center observational cohort study with a retrospective analysis on consecutive patients with ischaemic stroke treated with tPA in the period 2002-2008. Outcome measures were the occurrence of sICH and functional outcome at 3 months. RESULTS: Of the 400 patients, 24% had leukoaraiosis on their baseline CT. Eleven patients (11%) with leukoaraiosis versus thirteen (4%) patients without leukoaraiosis had a sICH [odds ratio (OR) 2.85 95%-CI 1.23-6.60, P = 0.02]. Multivariate analysis showed a non-significant trend towards an association of leukoaraiosis and sICH (OR 1.9, 95%-CI 0.78-4.68, P = 0.16). Leukoaraiosis was independently associated with poor functional outcome (OR 2.39, 95%-CI 1.21-4.72, P = 0.01). No difference was observed in the outcome measures amongst patients with moderate or severe leukoaraiosis. CONCLUSION: Our study demonstrates that patients treated with tPA and leukoaraiosis on their baseline CT are at greater risk of sICH and have a worse functional outcome compared to patients without leukoaraiosis. It is important to note that these results should not lead to exclusion of patients with leukoaraiosis for tPA treatment.

Statin use and functional outcome after tissue plasminogen activator treatment in acute ischaemic stroke.

BACKGROUND: Preliminary findings suggest that statins may have a neuroprotective effect in patients with acute ischaemic stroke. This study investigated whether patients on prior statin therapy and treated with tissue plasminogen activator (tPA) for acute ischaemic stroke have a better functional outcome than statin-naïve patients. METHODS: In a prospective observational cohort study of 476 acute ischaemic stroke patients treated with tPA we investigated the relationship between prior statin use and functional outcome at 3 months, the occurrence of symptomatic intracerebral haemorrhage (SICH) and early in-hospital mortality. Ischaemic stroke subtypes were defined according to the TOAST classification. Favourable outcome was defined as a modified Rankin Scale score < or =2. RESULTS: Of the 476 patients included, 98 (20.6%) used a statin at stroke presentation. In the entire cohort, 45.6% of patients had a favourable outcome with no difference between patients with or without statin therapy (45.9 vs. 45.5%, p = 0.94). In the multivariable analysis, statin use was not associated with favourable outcome (OR = 1.1, 95% CI = 0.6-1.9, p = 0.87). In none of the different stroke subtype groups was statin use associated with favourable outcome. Finally, statin use was not an independent risk factor of SICH or of early in-hospital mortality. CONCLUSION: Prior statin therapy in patients with acute ischaemic stroke treated with tPA is not associated with a more favourable outcome, and this is independent of stroke subtype.

Two cases with postural axial tremor: Consider a genetic origin.

We present two cases with postural axial tremor predominantly involving the head, trunk, and shoulders. In the first patient, the postural tremor occurred in multiple attacks a day lasting approximately 10 min. The second patient developed a progressive tremor of his head and arms, worsened during sitting and standing. Electrophysiological supported the postural axial tremor in both patients with a varying 3-10 Hz tremor frequency between different muscles and within the same muscles at different times. Postural axial tremor is a rare and complex movement disorder. The majority of cases are caused by acquired cerebellar pathology. However, isolated cases with underlying genetic disorders are described in literature. Here, we illustrate how to differentiate paroxysmal axial tremor from other axial hyperkinetic movement disorders and extend the genetic heterogeneity of this intriguing movement disorder phenotype.

Pharmacokinetics of moxifloxacin in cerebrospinal fluid and plasma in patients with tuberculous meningitis.

Moxifloxacin cerebrospinal fluid (CSF) penetration was evaluated by obtaining full plasma and CSF time concentration curves for 4 patients with tuberculous meningitis. The geometric mean ratio of the areas under the curve for CSF to plasma were 0.82 (range, 0.70-0.94) at 400 mg once per day and 0.71 (0.58-0.84) at 800 mg once per day.

Early seizures and cerebral oedema after trivial head trauma associated with the CACNA1A S218L mutation.

OBJECTIVE: To study the clinical spectrum of CACNA1A S218L mutation carriers with special attention to "early seizures and cerebral oedema after trivial head trauma (ESCEATHT)", a combination of symptoms which resembles the "juvenile head trauma syndrome". PATIENTS AND METHODS: In two patients with ESCEATHT all exons of CACNA1A were sequenced. Both patients also had hemiplegic migraine and ataxia. Subsequently, we screened the literature for S218L mutation carriers. RESULTS: In both patients, a de novo S218L mutation in the CACNA1A gene was found. In addition, we identified 11 CACNA1A S218L carriers from the literature. Of these 13 S218L mutation carriers, 12 (92%) had ataxia or cerebellar symptoms and nine (69%) had hemiplegic migraine that could be triggered by trivial head trauma. Three mutation carriers had the complete ESCEATHT phenotype. Seven (54%) had seizures (four had early post-traumatic seizures) and five (38%) had oedema as detected by MRI/CT. CONCLUSIONS: The CACNA1A S218L mutation is associated with familial hemiplegic migraine, ataxia and/or ESCEATHT. A minority of S218L mutation carriers have the complete ESCEATHT phenotype but a high percentage of patients had one or more ESCEATHT symptoms. As the S218L mutation enhances the propensity for cortical spreading depression (CSD), we postulate a role for CSD not only in hemiplegic migraine but also in early seizures and cerebral oedema after trivial head trauma. As this combination of symptoms is part of the unexplained "juvenile head trauma syndrome", a similar molecular mechanism may underlie this disorder.

Development and validation of a predictive outcome score of cerebral venous thrombosis.

BACKGROUND AND PURPOSE: Cerebral venous thrombosis (CVT) is a rare disease with a variable outcome. The aim of this study was to develop and validate a predictive outcome score for CVT patients. METHODS: The score was based on the 8 predictive variables of poor outcome (modified Rankin Scale score>2) from the International Study on Cerebral Vein and Dural Sinus Thrombosis: age >37, male, mental status disorder, coma, intracranial hemorrhage, deep CVT, CNS infection, and malignancy. To assign a weighted index (WI), the natural logarithm of the hazard ratio of each variable was calculated, multiplied by 10 and rounded to the nearest integer. The individual score of each patient was the sum of the WI. The validation sample consisted of a retrospective single center cohort of 90 CVT patients. RESULTS: Sixteen patients (18%) had a poor outcome. The predictive score had an area under the receiver operating characteristic curve of 0.81 (95% CI 0.71-0.90). The cut-off score with the maximum sum of sensitivity and specificity was a score> or =14 with sensitivity of 88% (81%-95%) and specificity of 70% (61%-79%). The predictive value of a score<14 for good outcome was 96% (92%-100%), whereas the predictive value of a score> or =14 for poor outcome was 39% (29%-49%). CONCLUSIONS: This relatively simple predictive outcome score may be useful in CVT patients. A cut-off score of 14 reliably predicts good outcome, but is less accurate in predicting poor outcome.

Does smoking influence outcome after intravenous thrombolysis for acute ischaemic stroke?

BACKGROUND AND PURPOSE: It remains uncertain whether current smoking influences outcome in patients with acute ischaemic stroke. OBJECTIVES: To evaluate the effect of current smoking in routinely tissue plasminogen activator (tPA)-treated stroke patients on the 3-month functional outcome and the occurrence of symptomatic intracerebral hemorrhage (ICH). METHODS: We analyzed data from a single stroke care unit registry of 345 consecutive patients with ischaemic stroke, treated with tPA. Logistic regression models were used to assess if smoking was independently associated with 3-months good outcome defined as a modified Rankin Scale score of < or =2, and the occurrence of symptomatic ICH. RESULTS: In the multivariable models, smoking was not associated with a good outcome or a decreased risk of symptomatic ICH. CONCLUSION: Current smoking did not affect functional outcome at 3 months or the risk of symptomatic ICH in patients routinely treated with tPA for ischaemic stroke.

Utility of the stroke-thrombolytic predictive instrument.

OBJECTIVE: The goal of this study was to evaluate the utility of the stroke thrombolytic predictive instrument (s-TPI) in predicting clinical outcome in patients with acute ischaemic stroke treated with intravenous tissue plasminogen activator (t-PA). METHODS: The study assessed the external validity of the s-TPI in 301 consecutive stroke patients treated with intravenous t-PA. Clinical outcome was measured with the modified Rankin scale (mRs) at 3 months. The study used the s-TPI to calculate probabilities of a good outcome (mRs 0-1) and a poor outcome (mRs 5-6). We compared these probabilities with the observed outcome using receiver-operator characteristics (ROC) curves and calibration curves. Subgroup analyses for different onset-to-treatment time windows were performed. RESULTS: According to the s-TPI, the mean predicted probability of a good and a poor outcome in the validation cohort were 0.45 and 0.17. The area under the ROC curves were 0.80 (4.5-hour time window), 0.82 (3-hour time window) and 0.77 (3-4.5 hours time window) for predicting good outcome, and 0.78 (4.5 hours), 0.80 (3 hours) and 0.74 (3-4.5 hours) for predicting poor outcome. Calibration curves revealed a slight overestimation of probabilities of a good outcome and underestimation of probabilities of a poor outcome. CONCLUSIONS: The s-TPI appears to be reasonably valid for predicting outcome after t-PA treatment in daily practice, although a slight overestimation of a good and underestimation of a poor outcome was observed.

Lipid profile, statin use, and outcome after intravenous thrombolysis for acute ischaemic stroke.

BACKGROUND: Low cholesterol levels have been associated with an increased risk of haemorrhagic stroke. This study investigated whether lipid levels or prior statin use influence outcome in patients with acute ischaemic stroke treated with IV thrombolysis. METHODS: The relation between admission lipid levels or statin use and both the development of symptomatic intracerebral haemorrhage (sICH) and 3-months functional outcome was assessed in a prospective hospital-based stroke registry comprising 252 patients treated with IV tissue plasminogen activator (tPA). The fasting status of the patients was unknown. Favourable outcome at 3 months was defined as a modified Rankin scale score

[Treatment of acute ischemic stroke with intravenous thrombolysis: extension of the time window should not delay initiation of treatment]. / Behandeling van het acute herseninfarct met intraveneuze trombolyse: meer tijd, maar geen minuut te verliezen.

In the European Cooperative Acute Stroke Study 3 (ECASS3), the efficacy of intravenous thrombolysis between 3 and 4.5 hours following onset of ischaemic stroke was investigated. Compared to the placebo group, patients treated with intravenous alteplase had a better functional outcome after 3 months (odds ratio 1.34, 95% confidence interval 1.02-1.76). The risk of symptomatic intracerebral haemorrhage was higher in the alteplase group (2.4% versus 0.3%). The time window for intravenous alteplase can be safely extended to 4.5 hours, but efforts should be made to start treatment as soon as possible, since the effectiveness ofalteplase decreases over time.

Measuring disability in stroke: relationship between the modified Rankin scale and the Barthel index.

BACKGROUND AND PURPOSE: The effectiveness of therapeutic interventions in acute stroke trials is traditionally measured with the modified Rankin scale (mRs) and the Barthel index (BI). The mRs is a global disability scale divided into six steps from total independence to total dependence. The BI assesses ten basal activities of daily living, of which eight assess level of dependence (bathing, grooming, using stairs, dressing, feeding, toilet use, transfers and walking). The aim of this study was to investigate the relationship between the mRs and the total scores and item-scores of the BI. METHODS: During a period of 3 months mRs and BI scores were collected from two multicentre randomised, placebo-controlled trials with lubeluzole (515 and 519 patients). In each patient we compared the mRs grades with the total BI score and the scores on the ten subitems. RESULTS: For both trials there was extensive overlap of BI scores between mRs grades and a wide range in BI scores among patients with mRs grades 3 and 4. We also found discrepancies between the BI item-scores and mRs grades. About 40% of patients with mRs grades 1 (able to carry out all usual activities) and 2 (able to look after own affairs without assistance) were not independent on at least one activity of the BI. In both studies, about 30% of the patients needed help or supervision for walking, although they were classified as mRs 3 (requiring some help but able to walk without assistance). CONCLUSIONS: Investigators in stroke trials use the mRs as a subjective global disability scale, and they do not strictly take into account limitations in performing specific basal activities of daily living, as assessed by the BI, to assign mRs grades.

Pitfalls in the diagnosis of reversible cerebral vasoconstriction syndrome and primary angiitis of the central nervous system.

A case of a 51-year-old woman with reversible cerebral vasoconstriction syndrome (RCVS) without an associative cause is reported. Initially the diagnosis primary angiitis of the central nervous system (PACNS) was considered. Both diagnosis are rare and can mimic each other. Distinction between both can be difficult, but is necessary because of different treatment options. Clinical features and diagnostic assessments to distinguish RCVS from PACNS and the potential pitfalls are discussed.

Safety of routine IV thrombolysis between 3 and 4.5 h after ischemic stroke.

BACKGROUND: The administration of tissue plasminogen activator (t-PA) has been proven effective for ischemic stroke within 3 h after onset. A pooled-analysis of six trials showed that intravenous t-PA still improves outcome when given between 3 to 4.5 h after stroke onset. On the basis of this pooled analysis, t-PA was also routinely offered to our patients between 3-4.5 h. We report the safety and clinical features of this group together with the features of the group given t-PA within 3 h. METHODS: Prospectively patient characteristics, stroke severity, stroke subtype, incidence of symptomatic intracerebral hemorrhage (SICH), in-hospital mortality, and 3-months modified Rankin Scale scores (mRS) were registered. Data was analyzed separately for patients treated within 3 h (early group) and those treated between 3-4.5 h (late group). RESULTS: Among 176 patients who underwent intravenous thrombolysis, 101 were treated in the early group and 75 in the late group. Six (5.9%; 95% CI 2.8%-12.3%) patients in the early group and 4 (5.3%; 95% CI 2.2%-12.9%) in the late group developed SICH (p=1.0). In the early group 13 (12.9%; 95% CI 7.7%-20.8%) patients died within 7 days after admission, compared to 5 (6.7%; 95% CI 3.0%-14.7%) in the late group (p=0.179). In the early group 44 (43.6%; 95% CI 43.3%-53.3%) were independent (mRS< or =2) at three months, compared to 36 (48.0%; 95% CI 37.0%-59.1%) in the late group (p=0.559). CONCLUSION: Our data show no trend of decreased safety of thrombolysis beyond 3 h. Due to a small sample size a harmful effect cannot be excluded but seems unlikely.

[Effectiveness of endarterectomy for symptomatic stenosis of the internal carotid artery; more risk factors important than only the severity of the stenosis]. / Effectiviteit van endarteriëctomie voor symptomatische stenose van de A. carotis; meer factoren belangrijk dan alleen de ernst van de stenose.

Carotid endarterectomy prevents ischaemic stroke in patients who have suffered either a transient ischaemic attack (TIA) or a non-disabling ischaemic stroke and are also diagnosed with severe stenosis of the internal carotid artery (ICA). In order to prevent the occurrence ofa single stroke, 6 patients with a symptomatic 70 to 99% ICA stenosis will have to be operated upon. A meta-analysis of individual patient data from 3 randomised trials shows that the decision whether to advise endarterectomy to an individual patient should not be based solely on the degree of the ICA stenosis, but also on the time interval between symptoms and surgery, the type and severity of symptoms and the plaque morphology. In general, endarterectomy is more effective in men than in women, it is very effective in the elderly, and it is even more effective when performed within two weeks of the symptoms occurring. A decision scheme has been set up enabling one to predict the absolute risk of an ipsilateral stroke in the next 5 years in individual patients who have symptomatic ICA stenosis. This is based on 5 factors: sex, age, the most severe symptom in the last 6 months (stroke, TIA, or ischaemic retinopathy), the number of weeks since the last incident and the morphological characteristics of the plaque.

Adverse events associated with the use of cervical spine manipulation or mobilization and patient characteristics: A systematic review.

Cervical spinal manipulation (CSM) and cervical mobilization are frequently used in patients with neck pain and headache. Pre-manipulative cervical instability and arterial integrity tests appear to be unreliable in identifying patients at risk for adverse events. It would be valuable if patients at risk could be identified by specific characteristics during the preliminary screening. Objective was to identify characteristics of 1) patients, 2) practitioners, 3) treatment process and 4) adverse events (AE) occurring after CSM or cervical mobilization. A systematic search was performed in PubMed, Embase, CINAHL, Web-of-science, AMED, and ICL (Index Chiropractic Literature) up to December 2014. Of the initial 1043 studies, 144 studies were included, containing 227 cases. 117 cases described male patients with a mean age of 45 (SD 12) and a mean age of 39 (SD 11) for females. Most patients were treated by chiropractors (66%). Manipulation was reported in 95% of the cases, and neck pain was the most frequent indication. Cervical arterial dissection (CAD) was reported in 57% (P = 0.21) of the cases and 45.8% had immediate onset symptoms. The overall distribution of gender for CAD is 55% (n = 71) for female and therefore opposite of the total AE. Patient characteristics were described poorly. No clear patient profile, related to the risk of AE after CSM, could be extracted. However, women seem more at risk for CAD. There seems to be under-reporting of cases. Further research should focus on a more uniform and complete registration of AE using standardized terminology.