Sleep architecture changes in the APP23 mouse model manifest at onset of cognitive deficits.

Alzheimer's disease (AD), which accounts for most of the dementia cases, is, aside from cognitive deterioration, often characterized by the presence of non-cognitive symptoms such as activity and sleep disturbances. AD patients typically experience increased sleep fragmentation, excessive daytime sleepiness and night-time insomnia. Here, we sought to investigate the link between sleep architecture, cognition and amyloid pathology in the APP23 amyloidosis mouse model for AD. By means of polysomnographic recordings the sleep-wake cycle of freely-moving APP23 and wild-type (WT) littermates of 3, 6 and 12 months of age was examined. In addition, ambulatory cage activity was assessed by interruption of infrared beams surrounding the home cage. To assess visuo-spatial learning and memory a hidden-platform Morris-type Water Maze (MWM) experiment was performed. We found that sleep architecture is only slightly altered at early stages of pathology, but significantly deteriorates from 12 months of age, when amyloid plaques become diffusely present. APP23 mice of 12 months old had quantitative reductions of NREM and REM sleep and were more awake during the dark phase compared to WT littermates. These findings were confirmed by increased ambulatory cage activity during that phase of the light-dark cycle. No quantitative differences in sleep parameters were observed during the light phase. However, during this light phase, the sleep pattern of APP23 mice was more fragmented from 6 months of age, the point at which also cognitive abilities started to be affected in the MWM. Sleep time also positively correlated with MWM performance. We also found that spectral components in the EEG started to alter at the age of 6 months. To conclude, our results indicate that sleep architectural changes arise around the time the first amyloid plaques start to form and cognitive deterioration becomes apparent. These changes start subtle, but gradually worsen with age, adequately mimicking the clinical condition.

Subcortical vascular cognitive impairment, no dementia: EEG global power independently predicts vascular impairment and brain symmetry index reflects severity of cognitive decline.

BACKGROUND AND PURPOSE: Vascular cognitive impairment, no dementia (vCIND) is a prevalent and potentially preventable disorder. Clinical presentation of the small-vessel subcortical subtype may be insidious, and differential difficulties can arise with mild cognitive impairment. We investigated EEG parameters in subcortical vCIND in comparison with amnestic multidomain mild cognitive impairment to determine the additional diagnostic value of quantitative EEG in this setting. METHODS: Fifty-seven community-residing patients with an uneventful central neurologic history and first presentation of cognitive decline without dementia were included. Neuropsychological test results were correlated with EEG parameters. Predictive values for vCIND and amnestic multidomain mild cognitive impairment were calculated using receiver operating characteristic curves and logistic regression modeling. RESULTS: Vascular cognitive impairment, no dementia and amnestic multidomain mild cognitive impairment differed with regard to the EEG (delta + theta)/(alpha + beta) ratio (DTABR) and pairwise derived brain symmetry index. We found statistically significant correlations between pairwise derived brain symmetry index and immediate verbal memory, immediate global memory, verbal recognition, working memory, and mean memory score in vCIND. Verbal fluency (odds ratio: 1.54, 95% confidence interval: 1.04-2.28, P = 0.033) and (delta + theta)/(alpha + beta) ratio (odds ratio: 2.28, 95% confidence interval: 1.06-4.94, P = 0.036) emerged as independent diagnostic predictors for vCIND with an overall correct classification rate of 95.0%. CONCLUSION: Our data indicate that EEG is of additional value in the differential diagnosis and follow-up of patients presenting with cognitive decline. These findings may have an impact on memory care.

Efficacy of NeuroFlo device in treatment of patients with atrial fibrillation.

Atrial fibrillation (AF) is a well-established independent risk factor for stroke. We examined cerebral blood flow augmentation in the treatment of acute ischemic stroke (AIS) in patients with AF by performing secondary analysis of data from the Safety and Efficacy of NeuroFlo Technology in Ischemic Stroke (SENTIS) trial, a randomized controlled trial evaluating NeuroFlo treatment in stroke patients within 14 hours of symptom onset. We report subgroup analyses of outcomes in SENTIS patients with a history or new diagnosis of AF. Among patients with AF, those treated with NeuroFlo demonstrated significant improvement over those not treated for multiple end points: global efficacy end point (P=.030), modified Rankin Scale (mRS) score 0-2 versus 3-6 (P=.029), and stroke-related mortality (P=.015). There was a significant improvement in global end point for those aged 60 years or older (P=.042) and 80 years or older (P=.017), with a trend toward improvement for age 70 years or older (P=.055), and significant improvement in those who achieved good outcomes (mRS score 0-2 versus 3-6) at age 60 years or older (P=.038), 70 years or older (P=.022), and 80 years or older (P=.008). NeuroFlo treatment in stroke patients with AF resulted in significantly better outcomes compared with nontreated patients with AF. Collateral flow recruitment, maintenance of cerebral blood flow around stroke core, and improvement of penumbral blood flow are potential mechanisms for these improved outcomes. NeuroFlo may represent a valid therapeutic option for patients with AF and AIS, and therefore, future trials of the device are warranted.

EEG in silent small vessel disease: sLORETA mapping reveals cortical sources of vascular cognitive impairment no dementia in the default mode network.

INTRODUCTION: Vascular cognitive impairment, no dementia (vCIND) is a prevalent and potentially preventable disorder. Clinical presof the small vessel subcortical subtype may be insidious and difficult to diagnose in the initial stage. We investigated electroencephalographic sources of subcortical vCIND in comparison to amnesic multidomain mild cognitive impairment (amdMCI) to determine the additional diagnostic value of quantitative electroencephalograhy (EEG) in this setting. METHODS: Fifty-seven community residing patients with an uneventful central neurological history and first presentation of cognitive decline without dementia were included, 35 patients were diagnosed with vCIND and 22 with amdMCI. A cognitive control group, deliberately recruited from a cerebrovascular impaired cohort, consisted of cognitively healthy participants who experienced a fully recovered first ever transient ischemic attack (TIA) without clinical or magnetic resonance imaging evidence of stroke. From standard EEGs, the differences in standardized low-resolution brain electromagnetic tomography (sLORETA) sources were determined for the discrete frequency ranges 1-4 (delta), 4-8 (theta), 8-10.5 (alpha1), 10.5-13 (alpha2), 13-22 (beta1), and 22-30 (beta2) Hz. RESULTS: In vCIND, a statistically significant decrease in parietooccipital alpha1 relative power current density compared with TIA and mild cognitive impairment patients was found. There was a significant decrease in frontal and parietooccipital beta1 relative power current density in vCIND compared with TIA patients. A significant increase in (pre) frontal delta relative power current density in vCIND compared with amdMCI was found as well. In amdMCI, delta relative power current density was significantly increased in the core limbic system. DISCUSSION: Cortical sources of abnormal EEG activity in regions implicated in the default mode network are revealed by sLORETA at an early stage in vascular cognitive impairment. Mapping of parietooccipital alpha1, frontoparietooccipital beta1 and (pre) frontal delta loci in vCIND may reflect early executive and visuospatial dysfunction in this cohort. Standard EEG with sLORETA mapping might be an additional, noninvasive, and cost-effective tool in the diagnostic workup of patients presenting with a cognitive decline.

Phenotypical characterization of α-galactosidase A gene mutations identified in a large Fabry disease screening program in stroke in the young.

OBJECTIVE: In the Belgian Fabry Study (BeFaS), the prevalence of Fabry disease was assessed in 1000 young patients presenting with stroke, unexplained white matter lesions or vertebrobasilar dolichoectasia. The results of the BeFaS suggested that Fabry disease may play a role in up to 1% of young patients presenting with cerebrovascular disease. However, the clinical relevance was unclear in all cases. We report on detailed phenotyping in subjects identified with α-galactosidase A (α-Gal A) enzyme deficiency or GLA mutations identified in the BeFaS (n=10), and on the results of family screening in this population. METHODS: Family screening was performed to identify additional mutation carriers. Biochemical and/or clinical evaluation of all subjects (BeFaS index patients and relatives carrying a GLA mutation) was performed. RESULTS: Genetic family screening revealed 18 additional GLA mutation carriers. Bloodspot α-Gal A enzyme activity was normal in all GLA mutation carriers, even in 2 males with the p.A143T mutation. Plasma Gb3 and lyso-Gb3 levels were normal in all subjects. Elevated Gb3 in urine was detected in 2 subjects. Some classic clinical signs of Fabry disease, like angiokeratoma or cornea verticillata, could not be detected in our population. Cardiac symptoms of Fabry disease were found in 6 out of 10 p.A143T carriers. No signs of cerebrovascular disease were found in the relatives with a GLA mutation. CONCLUSIONS: We could not identify mutations causing the classical clinical phenotype of Fabry disease in our cerebrovascular disease population. Enzyme activity analysis in bloodspots and plasma may fail to identify late-onset variants of Fabry disease. We recommend genetic testing when an atypical, late-onset variant of Fabry disease is suspected in a male cerebrovascular disease patient. However, this may lead to the identification of non-disease causing or controversial genetic variants.

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.

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.

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.

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

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 micromol/L at admission to 300.37 +/- 110.04 micromol/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 (DeltaUA(day 7)) correlated with the NIHSS score (rho = 0.32; p < 0.001), stroke progression (rho = 0.29; p = 0.001), infarct volume (rho = 0.37; p < 0.001), mRS score (rho = 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.

Clinical and biochemical diagnosis of small-vessel disease in acute ischemic stroke.

BACKGROUND AND PURPOSE: Both from clinical and research standpoints, it may be highly relevant to differentiate between small-artery and large-artery infarction in the acute phase of ischemic stroke. We conducted a study on the added value of two D-dimer assays over clinical assessment for diagnosis of lacunar infarction. METHODS: Clinical evaluation using the Oxfordshire Community Stroke Project (OCSP) classification and measurement of plasma D-dimer levels by the VIDAS D-dimer test (VIDAS) and the Triage Stroke Panel (TSP) were performed in 128 patients with ischemic stroke presenting within 9 h after onset of symptoms. The stroke subtype was defined as small-artery or large-artery infarction based on the TOAST classification. RESULTS: The overall accuracy for diagnosing of acute lacunar stroke using the OCSP classification, VIDAS (cut point for D-dimer 445 ng/mL) or TSP (cut point 300 ng/mL) was 89%, 88% and 87% respectively (P<0.001). The conjunctive use of the OCSP classification and VIDAS or TSP improved the accuracy to 97% and 98% respectively (P<0.001). The kappa coefficient for agreement between the two assays was acceptable (kappa, 0.64). These results were reproducible in subgroups of patients presenting within 4.5 h and within 6 h after onset of stroke symptoms. CONCLUSIONS: Diagnosis of acute lacunar infarction can reliably be made, based on the conjunctive use of clinical evaluation and measurement of D-dimer levels either by a standard assay or by a bedside testing kit.

Clinical, biochemical and neuroimaging parameters after thrombolytic therapy predict long-term stroke outcome.

INTRODUCTION: We investigated the predictive value of standard neurological evaluation, a commercially available biomarker assay and neuroimaging in the subacute phase for outcome after thrombolytic therapy in ischemic stroke. METHODS: Thirty-four consecutive ischemic stroke patients were evaluated by means of the NIH Stroke Scale (NIHSS(72)), the Triage(R) Stroke Panel (MMX(72)) and standardized infarct volumetry at 72 h after treatment with intravenous recombinant tissue plasminogen activator or intra-arterial urokinase. Outcome was assessed by the modified Rankin Scale (mRS) at 3 months after the stroke. RESULTS: NIHSS(72), MMX(72) and infarct volume correlated significantly with the mRS score at month 3 and emerged as independent outcome predictors from logistic regression analysis. NIHSS(72) is the best predictor for outcome, but its accuracy increases by 9 and 6% when combined with MMX(72) and infarct volumetry, respectively. The combined use of NIHSS(72) and MMX(72) allows long-term outcome prediction with 97% accuracy, which is not further improved by infarct volumetry. CONCLUSIONS: Routine clinical evaluation, bedside testing of biochemical markers by the Triage Stroke Panel and infarct volumetry on neuroimaging at 72 h after thrombolytic therapy are predictors for long-term outcome of ischemic stroke patients. Clinical assessment is the most reliable parameter for outcome prediction, but its predictive value is substantially improved when combined with the biomarker panel.

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 (Spearman's 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.

Dimethylarginine levels in cerebrospinal fluid of hyperacute ischemic stroke patients are associated with stroke severity.

We hypothesise that asymmetric and symmetric dimethylarginine (ADMA, SDMA) are released in cerebrospinal fluid (CSF) due to ischemia-induced proteolysis and that CSF dimethylarginines are related to stroke severity. ADMA and SDMA were measured in CSF of 88 patients with ischemic stroke or TIA within 24 h after stroke onset (mean 8.6 h) and in 24 controls. Stroke severity was assessed by the National Institutes of Health Stroke Scale (NIHSS) score at admission. Outcome was evaluated by institutionalization due to stroke and the modified Rankin scale. Dimethylarginine levels were higher in patients with stroke than in TIA patients, who had higher levels than controls and correlated with the NIHSS. Logistic regression analysis confirmed that dimethylarginines were independently associated with stroke severity. The SDMA/ADMA ratio did not differ significantly between controls and stroke patients. CSF dimethylarginine levels are increased in hyperacute ischemic stroke and are associated with stroke severity.

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.

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.

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).

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.

Small cell lung carcinoma presenting as collapsin response-mediating protein (CRMP) -5 paraneoplastic optic neuropathy.

A 77-year-old woman presenting with progressive visual loss in both eyes was found to have small cell lung cancer. Assay for collapsin response-mediating protein (CRMP) -5 was positive suggesting a paraneoplastic optic neuropathy (PON). During treatment of the small cell lung cancer, the patient died of pneumonia and autopsy disclosed neuropathologic abnormalities consistent with PON. This is only the second case of CRMP-5-confirmed PON to report neuropathologic findings.