Rishi Sheorajpanday

Middelheim Fabry Study (MiFaS): a retrospective Belgian study on the prevalence of Fabry disease in young patients with cryptogenic stroke.

OBJECTIVE To assess the prevalence of Fabry disease in young patients with cryptogenic stroke. PATIENTS AND METHODS We retrospectively assessed the prevalence of Fabry disease in patients aged 16-60 years that were admitted to ZNA Middelheim Hospital from January 1, 2000 to December 31, 2004 for cryptogenic stroke. We screened for Fabry disease by measurement of alpha-galactosidase A and beta-glucuronidase activity on blood spot. In all patients with abnormal enzymatic activity and in all female patients with low normal values, genetic sequencing of the alpha-GAL-gene was performed. RESULTS In a population of 103 young patients with cryptogenic stroke that met the in- and exclusion criteria, we were unable to identify any patient with Fabry disease. CONCLUSION Based on the results of alpha-galactosidase A and beta-glucuronidase activity, genetic sequencing and the low prevalence of clinical signs and symptoms of Fabry disease in this population, we believe that the true prevalence of Fabry disease in patients with cryptogenic stroke may be less than currently accepted in literature.

Quantitative EEG in ischemic stroke : Correlation with functional status after 6 months

OBJECTIVE Stroke is a major cause of adult-onset disability and dependency. We investigated whether EEG parameters are of prognostic value for functional outcome 6 months after ischemic stroke. METHODS One-hundred and ten patients presenting with acute ischemic stroke and persistent neurological deficits at EEG recording were incrementally included. Clinical characteristics, volume of ischemia and EEG parameters were correlated with functional outcome assessed with the modified Rankin Scale (mRS) score. Predictive values for disability, dependency and death were calculated using receiver operating characteristic (ROC) curves and logistic regression modeling. RESULTS The EEG pairwise derived Brain Symmetry Index (pdBSI) and (delta+theta)/(alpha+beta) ratio (DTABR) were significantly correlated with the modified Rankin Scale (mRS) score at month 6 (Spearman ρ=0.46 and ρ=0.47, respectively, p<0.0005 for both). NIHSS (OR 1.15, 95% CI 1.04-1.27, p=0.005) and pdBSI (OR 4.07, 95% CI 1.32-12.58, p=0.015) were independently associated with disability 6 months after stroke. Dependency was independently indicated by NIHSS (OR 1.22, 95% CI 1.09-1.37, p<0.0005) and DTABR (OR 2.25, 95% CI 1.16-4.37, p=0.016). Six month mortality was independently indicated by age at stroke onset (OR 1.18, 95% CI 1.05-1.32, p=0.007), NIHSS (OR 1.11, 95% CI 1.03-1.21, p=0.009) and DTABR (OR 2.04, 95% CI 1.08-3.85, p=0.028). CONCLUSIONS EEG in the subacute setting of ischemic stroke may be of prognostic value for disability, dependency and death after 6 months. SIGNIFICANCE Early prognostication of functional outcome after stroke is relevant to efficient rehabilitation management to enhance recovery and minimize long-term disability.

Reproducibility and clinical relevance of quantitative EEG parameters in cerebral ischemia: A basic approach

OBJECTIVE To investigate reproducibility and clinical relevance of quantitative EEG parameters in ischemic cerebrovascular disease. METHODS EEG was recorded in 31 patients suffering from subacute ischemic cerebrovascular disease. Ten age-matched control subjects were included as a reference group. Intra-recording, intrarater and interrater reproducibility was calculated for standard EEG measures and for a pair wise derived Brain Symmetry Index (pdBSI). Correlations between EEG parameters, clinical status and volume of ischemia on diffusion weighted imaging (DWI) were calculated. RESULTS pdBSI was sensitive to asymmetry in the amplitude and frequency domain in a random white noise model and in a simulated sinusoidal model. Minimal Cronbach alpha for intra-recording, intra- and inter-rater reproducibility ranged between 0.95 and 0.99 for standard spectral parameters and between 0.96 and 0.99 for pdBSI. We found a significant difference in pdBSI between stroke patients and control or TIA (p=0.0003). pdBSI correlated significantly with NIH stroke scale at admission and DWI volume across different levels of stroke probability (Spearmans rho=0.64-0.70 and 0.79-0.84, respectively, p<0.00001 for both). CONCLUSIONS pdBSI displays high multilevel reproducibility and reliably discriminates between stroke and TIA patients or control subjects, and correlates significantly with clinical and radiological status. SIGNIFICANCE Based on this methodological analysis, reliable EEG parameters can be evaluated in a general stroke population for clinically relevant state and outcome measures.

Evaluation of lactate as a marker of metabolic stress and cause of secondary damage in acute ischemic stroke or TIA

BACKGROUND Accumulation of lactate in ischemic regions has been documented in acute stroke. We evaluated the relation between lactate levels in blood and cerebrospinal fluid (CSF) and ischemic stroke evolution and outcome. METHODS Lactate was measured in blood of 187 acute ischemic stroke and TIA patients at admission, 24 h, 72 h and 7 days after stroke onset. In a subpopulation of 85 stroke patients and in 51 controls, lactate was measured in CSF. Stroke evolution was evaluated by change in the NIHSS score within the first 72 h and by occurrence of progressing stroke. At 3 months after stroke, outcome was assessed on the basis of mortality rate and the modified Rankin Scale. RESULTS We found no relation between lactate levels in blood and stroke evolution or outcome. Lactate in CSF was higher in stroke patients than in controls and correlated with stroke evolution and outcome. Multivariate regression analyses showed that CSF lactate levels, age and stroke severity are independent predictors for stroke evolution and outcome. CONCLUSIONS Lactate levels in CSF, but not in blood, are a reliable marker for metabolic crisis in acute ischemic stroke and correlate with the stroke evolution in the subacute phase and with long-term outcome.

Decrease in uric acid in acute ischemic stroke correlates with stroke severity, evolution and outcome.

Abstract Background: Although uric acid (UA) is one of the most important antioxidants in plasma and appears to be neuroprotective in animal models, results from human studies are controversial. In this study, we investigated the kinetics of serum UA concentrations in the acute, subacute and chronic phase of ischemic stroke and its relation with initial stroke severity, stroke evolution in the subacute phase and long-term stroke outcome. Methods: Serum concentrations of UA were measured in 199 stroke patients at admission (median, 2.8 h after stroke onset), at 24 h, 72 h, day 7, month 1 and month 3 after onset of stroke. We evaluated the relationship between changes in UA concentrations and (a) stroke severity [patients with transient ischemic attack (TIA) vs. stroke patients, National Institutes of Health Stroke Scale (NIHSS) score at admission], (b) stroke evolution (stroke progression, infarct volume at 72 h), and (c) stroke outcome [modified Rankin scale (mRS) score at month 3, mortality]. Results: UA concentrations decreased significantly during the first 7 days after stroke onset before returning to baseline (p<0.001). Mean plasma UA concentrations decreased from 336.66±113.01 μmol/L at admission to 300.37±110.04 μmol/L at day 7 (p<0.001) in patients with stroke, but did not change significantly in patients with TIA. Changes in UA concentrations from admission to day 7 (ΔUAday 7) correlated with the NIHSS score (ρ=0.32; p<0.001), stroke progression (ρ=0.29; p=0.001), infarct volume (ρ=0.37; p<0.001), mRS score (ρ=0.28; p=0.001) and mortality (p=0.010). Conclusions: Decreases in UA during the first week after onset of stroke correlates with more severe stroke, unfavorable stroke evolution, and poor long-term stroke outcome. Clin Chem Lab Med 2010;48:383–90.

The decrease in procarboxypeptidase U (TAFI) concentration in acute ischemic stroke correlates with stroke severity, evolution and outcome

See also Willemse JL, Brouns R, Heylen E, De Deyn PP, Hendriks DF. Carboxypeptidase U (TAFIa) activity is induced in vivo in ischemic stroke patients receiving thrombolytic therapy. J Thromb Haemost 2008; 6: 200–2.

Epileptic fits and epilepsy in the elderly: General reflections, specific issues and therapeutic implications

Seizures and epilepsy are commonly encountered in the elderly. Diagnosis is not always straightforward as reliable history is often difficult to obtain and EEG findings can be non-specific. When to treat and how may be difficult choices as adequate studies in elderly are rather scarce. Treatment should be based on careful assessment and comparison of risk/benefit profiles of various anti-epileptic drugs (AEDs) in this specific elderly population. Since most AEDs are effective in terms of seizure control in the elderly, the choice of treatment is often determined by tolerability, pharmacokinetic profile and drug interactions of AEDs. As recently introduced AEDs have a better safety profile compared to older agents it seems logical to initiate treatment in the frail elderly patient with those more modern AEDs. In this review some distinctive clinical features of epilepsy in the elderly are discussed in three sections (general issues, special issues and selected treatment options with special reference to medicinal treatment).

Quantitative EEG in ischemic stroke: Correlation with infarct volume and functional status in posterior circulation and lacunar syndromes

OBJECTIVE The significant impact of stroke on health care results in an unmet need for efficient stroke care in resources limited environments. Practical, inexpensive and easy to obtain predictive EEG parameters have been suggested in anterior circulation syndromes. We investigated whether EEG parameters are of additional predictive value with regard to lesion volume and short-term functional outcome in lacunar (LACS) and posterior circulation (POCS) syndromes of presumed ischemic origin. METHODS Sixty (60) patients presenting with LACS or POCS were incrementally included. EEG parameters were correlated with volume of ischemia and functional status. Predictive values for definite stroke and unfavourable outcome were calculated using receiver operating characteristic (ROC) curves and logistic regression modelling. RESULTS The pairwise derived brain symmetry index (pdBSI) emerged as independent predictor for definite stroke in patients presenting with LACS and POCS (odds ratio (OR) 2.69, 95% confidence interval (CI) 1.24-5.82, p=0.012) and in patients with a National Institutes of Health Stroke Scale (NIHSS) score of 0 at EEG recording (OR 7.67, 95% CI 1.24-47.32, p=0.026). In ROC analysis, the (delta+theta)/(alpha+beta) ratio (DTABR) predicted unfavourable outcome at day 7 with an accuracy of 83% in LACS but not in POCS. In logistic regression, unfavourable outcome in LACS was predicted by nominal NIHSS with marginal significance (OR 1.84, 95% CI 1.00-3.37, p=0.05), while in categorical modelling, DTABR>2.4 displayed a statistically significant ominous odd ratio of 13.00 (95% CI 1.11-152.35, p=0.041) with identical predicted and observed values. CONCLUSIONS EEG may be of additional value by confirming or excluding definite stroke after resolution of symptoms in lacunar and posterior circulation syndromes of presumed ischemic origin and prognosticating short-term functional status in lacunar syndrome. SIGNIFICANCE These findings may have an impact on stroke care.

Carboxypeptidase U (TAFIa) decreases the efficacy of thrombolytic therapy in ischemic stroke patients

INTRODUCTION Thrombolytic therapy improves clinical outcome in patients with acute ischemic stroke but is compromised by symptomatic intracranial hemorrhage and an unpredictable therapeutic response. In vitro and in vivo data suggest that activation of procarboxypeptidase U (proCPU) inhibits fibrinolysis. AIMS To investigate whether the extent of proCPU activation is related to efficacy and safety of thrombolytic therapy in ischemic stroke patients. METHODS In twelve patients with ischemic stroke who were treated with intravenous (n=7) or intra-arterial (n=5) thrombolysis, venous blood samples were taken at different time points before, during and after thrombolytic therapy. ProCPU and carboxypeptidase U (CPU, TAFIa) plasma concentrations were determined by HPLC. The maximal CPU activity (CPU(max)) and the percentage of proCPU consumption during thrombolytic therapy were calculated. The efficacy and safety of the thrombolytic therapy were assessed by evolution of the clinical deficit, recanalisation, final infarct volume, thrombolysis-induced intracranial hemorrhage and mortality. RESULTS No correlations between CPU(max) or proCPU consumption and patient or stroke characteristics were found. However, CPU(max) is associated with evolution of the clinical deficit and achieved recanalisation. ProCPU consumption is related to the risk of intracranial hemorrhage, mortality and final infarct volume. CONCLUSIONS Irrespective of patient and stroke characteristics, CPU(max) and proCPU consumption during thrombolytic treatment for ischemic stroke are parameters for therapeutic efficacy and safety. Further evaluation of the clinical applicability of these parameters and further investigation of the potential role for CPU inhibitors as adjunctive therapeutics during thrombolytic treatment may be of value.

Additional value of quantitative EEG in acute anterior circulation syndrome of presumed ischemic origin.

OBJECTIVE The clinical course of acute stroke can be highly variable and for effective management outcome prediction needs to be refined. We investigated whether EEG parameters are of additional diagnostic and prognostic value in the early phase of acute ischemic anterior circulation stroke. METHODS Ninety-four patients presenting with acute anterior circulation syndrome (ACS) of presumed ischemic origin were incrementally included. Clinical characteristics were correlated with volume of ischemia and EEG parameters. Predictive values for definite stroke, early neurological deterioration, spontaneous early neurological improvement and death within 1 week after ACS were calculated using ROC curves and logistic regression modelling. RESULTS In patients with normal or near normal NIHSS score of 0 or 1, the pairwise derived brain symmetry index (pdBSI) was an independent predictor for definite stroke displaying an overall accuracy of 80%. Early neurological deterioration was independently predicted by pdBSI with a correct classification rate of 95%. In ROC analysis, death was predicted by pdBSI with overall accuracy of 97%. Spontaneous neurological improvement was independently predicted by the delta+theta/alpha+beta - ratio with overall accuracy of 75%. Small-vessel stroke was independently predicted by pdBSI with a correct classification rate of 92%. CONCLUSIONS EEG may be of prognostic value for spontaneous neurological improvement, early neurological deterioration and death in the acute setting of acute anterior circulation syndrome of presumed ischemic origin. SIGNIFICANCE These findings may have an impact on stroke care.