Headache in idiopathic/genetic epilepsy: Cluster analysis in a large cohort.

OBJECTIVE: The link between headache and epilepsy is more prominent in patients with idiopathic/genetic epilepsy (I/GE). We aimed to investigate the prevalence of headache and to cluster patients with regard to their headache and epilepsy features. METHODS: Patients aged 6-40 years, with a definite diagnosis of I/GE, were consecutively enrolled. The patients were interviewed using standardized epilepsy and headache questionnaires, and their headache characteristics were investigated by experts in headache. Demographic and clinical variables were analyzed, and patients were clustered according to their epilepsy and headache characteristics using an unsupervised K-means algorithm. RESULTS: Among 809 patients, 508 (62.8%) reported having any type of headache; 87.4% had interictal headache, and 41.2% had migraine. Cluster analysis revealed two distinct groups for both adults and children/adolescents. In adults, subjects having a family history of headache, ≥5 headache attacks, duration of headache ≥ 24 months, headaches lasting ≥1 h, and visual analog scale scores > 5 were grouped in one cluster, and subjects with juvenile myoclonic epilepsy (JME), myoclonic seizures, and generalized tonic-clonic seizures (GTCS) were clustered in this group (Cluster 1). Self-limited epilepsy with centrotemporal spikes and epilepsy with GTCS alone were clustered in Cluster 2 with the opposite characteristics. For children/adolescents, the same features as in adult Cluster 1 were clustered in a separate group, except for the presence of JME syndrome and GTCS alone as a seizure type. Focal seizures were clustered in another group with the opposite characteristics. In the entire group, the model revealed an additional cluster, including patients with the syndrome of GTCS alone (50.51%), with ≥5 attacks, headache lasting >4 h, and throbbing headache; 65.66% of patients had a family history of headache in this third cluster (n = 99). SIGNIFICANCE: Patients with I/GE can be clustered into distinct groups according to headache features along with seizures. Our findings may help in management and planning for future studies.

Autoimmune encephalitis and paraneoplastic syndromes in Turkey: a multi-centre study.

BACKGROUND: Autoimmune encephalitis (AIE) and paraneoplastic syndromes (PNS) are both rare groups of neurological diseases that are difficult to diagnose. AIM: We aimed to determine the common and distinct aspects of these two aetiologies of encephalitis as well as the characteristics of our patient group. METHODS: We respectively analysed the records of the patients including symptoms, demographic features, neurological examination, cranial-magnetic-resonance-imaging (MRI), electroencephalography (EEG) findings, cerebrospinal fluid results (CSF) findings. Autoimmune/paraneoplastic autoantibodies in blood and/or CSF were all documented. RESULTS: Forty-six patients fulfilled the diagnostic criteria. Thirty-eight of them were diagnosed with AIE, and 8 of them were diagnosed with PNS. The PNS group had higher nonconvulsive status epilepticus than the AIE (2/8 vs 0/38; p=0.027). PNS patients were diagnosed with a malignancy in their follow-ups more than those in the AIE group [4/38 vs 8/8] (p<0.001). When the symptoms of antibody-positive and negative patients were compared in the AIE group, the rates of consciousness/memory problems (13/15 vs 11/23; p=0.020) and speech impairment (8/15 vs 2/23; p=0.004) were significantly higher in patients without antibodies (n: 15) than in antibody-positive patients (n: 23). In antibody-negative groups, the rates of memory problems in neurological examination (13/15 vs 12/23 p=0.028) and temporal findings on electroencephalography were more prominent than antibody-positive groups (1/23 vs 5/15; p=0.027). The number of patients with cerebellar signs was higher in antibody-positive patients (6/23 vs 0/15; p=0.038). CONCLUSION: Although the positivity of autoantibodies is critical in the diagnosis of AIE and PNS, even minor differences in clinical and laboratory findings of patients are helpful in the diagnosis, especially in the autoantibody-negative patients. Comparing the data with other population studies has shown that several inherited and environmental factors may contribute to the pathophysiology of AIE and PNS, as well as clinical and laboratory differences.

Assessment of Patients with Intracerebral Hemorrhage or Hemorrhagic Transformation in the VENOST Study.

INTRODUCTION: Cerebral venous and sinus thrombosis (CVST) may lead to cerebral edema and increased intracranial pressure; besides, ischemic or hemorrhagic lesions may develop. Intracerebral hemorrhages occur in approximately one-third of CVST patients. We assessed and compared the findings of the cerebral hemorrhage (CH) group and the CVST group. MATERIALS AND METHODS: In the VENOST study, medical records of 1,193 patients with CVST, aged over 18 years, were obtained from 35 national stroke centers. Demographic characteristics, clinical symptoms, signs at the admission, radiological findings, etiologic factors, acute and maintenance treatment, and outcome results were reported. The number of involved sinuses or veins, localizations of thrombus, and lesions on CT and MRI scans were recorded. RESULTS: CH was detected in the brain imaging of 241 (21.1%) patients, as hemorrhagic infarction in 198 patients and intracerebral hemorrhage in 43 patients. Gynecologic causes comprised the largest percentage (41.7%) of etiology and risk factors in the CVST group. In the CH group, headache associated with other neurological symptoms was more frequent. These neurological symptoms were epileptic seizures (46.9%), nausea and/or vomiting (36.5%), altered consciousness (36.5%), and focal neurological deficits (33.6%). mRS was ≥3 in 23.1% of the patients in the CH group. DISCUSSION AND CONCLUSION: CVST, an important cause of stroke in the young, should be monitored closely if the patients have additional symptoms of headache, multiple sinus involvement, and CH. Older age and parenchymal lesion, either hemorrhagic infarction or intracerebral hemorrhage, imply poor outcome.

A Case of Seronegative Limbic Encephalitis with Multiple Sclerosis: A Possible Overlapping Syndrome.

BACKGROUND Autoimmune encephalitis might coexist in patients with autoimmune demyelinating disorders. CASE REPORT We report on a case of a 45-year-old female multiple sclerosis (MS) patient presenting with acute onset short-term memory loss, altered mental status, inflammatory cerebrospinal fluid (CSF) findings and an MRI lesion on the left temporal lobe. An extensive panel for neuronal autoantibodies proved negative. Neuropsychological symptoms gave a prompt response to immunotherapy but nevertheless control MRI showed left hippocampal atrophy. CONCLUSIONS Several recent reports of concurrent emergence of autoimmune encephalitis and MS suggest a common mechanism for these disorders. Since autoimmune encephalitis and MS share certain common CSF and neuroimaging findings, an increased understanding of overlapping autoimmune brain disorders is required to avoid misdiagnosis especially in antibody negative autoimmune encephalitis cases.

Limbic Encephalitis Associated with Sjögren's Syndrome: Report of Three Cases.

Sjögren's syndrome (SS) may be complicated by neurological manifestations. We herein report three women (age range 26-60 years old) who all presented with limbic encephalitis (LE) as the predominant clinical feature 3 months to 15 years after the diagnosis of SS. The 26-year-old patient also developed acute motor axonal neuropathy one week after autoimmune encephalitis. All three patients showed contrast-enhanced MRI lesions and inflammatory cerebrospinal fluid findings, while not displaying any anti-neuronal antibodies and showing a remarkable response to immunotherapy. SS is often overlooked when the symptoms are mild. Therefore, in LE cases with no identifiable cause, serological screening for rheumatologic disorders is recommended.

Frequency of left atrial dilatation in ischemic stroke.

OBJECTIVE: The study aimed to evaluate the frequency of left atrial dilatation in cases of first-ever acute ischemic stroke with or without atrial fibrillation in a cohort of patients hospitalized for ischemic stroke. METHODS: Files of 120 patients admitted to our hospital with the diagnosis of acute ischemic stroke were investigated. All patients had at least one brain imaging. Etiology of stroke was categorized according to Trial of Org 10172 in Acute Stroke Treatment (TOAST) classification. Transthoracic and/or transoesophageal echocardiography was used to measure left atrium size. Optimal cut-off value of left atrial diameter was determined as 4 cm. SPSS 11.5 was used for statistical analyses. RESULTS: In 40% of the patients, left atrial dilatation was detected. Nineteen patients with left atrial dilatation had atrial fibrillation, which was statistically significant (p<0.05). Ninety-four (30.8%) patients with no atrial fibrillation had left atrial dilatation. In the TOAST classification trial, as a statistically significant finding, left atrial dilatation was detected 68.9% of the patients with cardioembolic infarcts. The most frequently encountered risk factor in patients was hypertension. CONCLUSION: Left atrial dilatation is an important marker for cerebrovascular diseases, and if accompanied by atrial fibrillation becomes even more significant.

Prognostic role of mean platelet volume and platelet count in ischemic and hemorrhagic stroke.

BACKGROUND: Mean platelet volume (MPV) is an indicator of platelet function or reactivity. Platelets play an important role in the pathophysiology of ischemic stroke but the effect of platelet count (PC) and dysfunction in the pathogenesis of hemorrhagic stroke is poorly understood. We have investigated the possibility of MPV and PC being an independent risk factor of ischemic and haemorrhagic stroke and their effect on prognosis. METHODS: We prospectively studied 692 patients with either ischemic or hemorrhagic stroke and compared them with 208 control subjects with similar risk factors, but without evidence of vascular events. The association of MPV and PC with cause, localization, and size of the infarct or hemorrhage was examined. Prognosis was determined by Glasgow Outcome Scale. By multivariate logistic regression analysis, the influence of MPV and PC on stroke subtype and prognosis was determined. RESULTS: MPV and PC were observed as independent risk factors for ischemic stroke (P = .007, odds ratio [OR] = 0.866; P = .000, OR = 0.996; 95% confidence interval [CI], respectively). There was a negative and significant correlation between PC and hemorrhagic stroke (P = .001), but no association was found with MPV (P > .05). MPV and PC were not statistically significant related to etiological subgroups, localization, and size of the infarct or hemorrhage (P > .05). Ischemic group MPV (P = .013, OR = 1.02, 95% CI) and hemorrhagic group PC were in correlation with worse outcome (P = .001, OR = 1.004, 95% CI). CONCLUSION: MPV, may be an early and important predictor for the prognosis of ischemic stroke, whereas for hemorrhagic stroke PC has a role for outcome.

The role of neutrophils and interleukin-8 in acute ischemic stroke.

OBJECTIVE: To investigate the crucial role of interleukin 8 (IL-8) as an inflammatory marker in infarct evolution, and course of the disease. METHODS: The study included 76 patients that were admitted to Haydarpasa Numune Training and Research Hospital, Istanbul, Turkey between September 2001 and June 2002 with an initial diagnosis of acute ischemic stroke, and 28 control subjects with a corresponding mean age. The serum IL-8 levels obtained within 24 hours of the stroke were assessed by the enzyme-linked immunoabsorbent assay method. The patients were divided into 4 groups according to the extent, and localization of the ischemic lesions. Prognosis was evaluated by modified Rankin Scale. RESULTS: In comparison between patients and control groups, there was a statistically significant difference in (p<0.001) IL-8, and neutrophil (net) levels (p=0.000). The serum IL-8 levels were associated with the extent of the lesion (p<0.01). Though the serum IL-8 levels were significantly higher in the dependent group (p<0.05), there was no significant difference between net levels, and prognosis (p>0.05). There was also no significant difference according to age, gender, and etiology between IL-8 and net levels. CONCLUSION: The high serum IL-8 levels are associated with prognosis. The development of new neuroprotective treatments aimed to prevent neutrophil-mediated-inflammation induced by IL-8 is critical in the treatment of stroke, and prevention of clinical worsening.

Tumor necrosis factor alpha serum levels and inflammatory response in acute ischemic stroke.

OBJECTIVE: To assess the implication of tumor necrosis factor alpha (TNF-alpha) and interleukine-6 (IL-6) in acute ischemic stroke and to correlate this with lesion size, vascular risk factors, and neurological impairment. METHODS: We included 70 patients consecutively admitted to the Department of 1st Neurology, Haydarpasa Numune Educational and Research Hospital, Istanbul, Turkey, between September 2001 and April 2002, with first-ever ischemic cerebral infarction within the first 24 hours from onset. The TNF-alpha, IL-6, fibrinogen, C-reactive protein, erythrocyte sedimentation rate (ESR) and leukocytes were determined in plasma on admission. Neurological impairment was evaluated with the modified Rankin Scale. RESULTS: We found higher baseline levels of TNF-alpha and IL-6 in the plasma of patients with acute ischemic stroke and neurological impairment in comparison to control subjects. In the large infarct group, TNF-alpha, IL-6, low-density lipoprotein-cholesterol and fibrinogen were found significantly higher compared to the small infarct group. While an association between TNF-alpha and IL-6 values and lesion size were determined, no relation was found between localization and etiology. The TNF-alpha level was found to be in positive correlation with IL-6, fibrinogen, and ESR. The IL-6 level was found to be in positive correlation with ESR fibrinogen, and leukocytes. CONCLUSION: Inflammatory findings are associated with the early stage of ischemic stroke. The TNF-alpha and IL-6 were also higher in patients with clinical worsening. The release of proinflammatory cytokines after focal cerebral ischemia indicates a step leading to tissue necrosis or reflects the amount of ischemic brain injury, since the higher concentrations of TNF-alpha and IL-6 are found in patients with large infarctions.

Ischemic stroke in the vertebrobasilar system. Risk factors, etiology, and localization.

OBJECTIVE: To investigate and determine the clinical findings, lesions, risk factors, and variety of etiology in Turkish patients suffering from vertebrobasilar ischemia. METHODS: The clinical, radiological, and prognostic features of patients with ischemic stroke in the vertebrobasilar system (VBS) are not homogeneous. The mechanism, localization, and severity of the vascular lesions and the presence of coexisting vascular risk factors influence the prognosis. The study included 134 patients with ischemic strokes in the VBS that were evaluated according to age, gender, clinical findings, risk factors, lesion localization, echocardiography, Doppler sonography, and cervical magnetic resonance angiography at Haydarpasa Numune Education and Research Hospital, Istanbul, Turkey between 1998-2002. RESULTS: Hypertension, heart disease, smoking, diabetes mellitus, and hyperlipidemia were the most commonly observed risk factors. While infratentorial involvement was seen at a higher ratio (75.4%), acute multi-infarcts appearing simultaneously were mostly localized in the thalamus and the brain stem (18.7%). Large and small vessel disease incidences have been found in 32.8% and 20.1% of the patients. Cardioembolism with an incidence rate of 41.8% was the most frequent etiological cause in VBS ischemia. No significant meaning has been developed with age and gender as compared to the relationship between localization and etiological subgroups. CONCLUSION: The most common risk factors were hypertension and cardiac diseases, and the most common localization of the infarcts was the infratentorial region. The cerebellum was seen as the most coexisting localization with all multiple infarcts. Cardioembolism accounted for the largest etiological group in all localizations and in multiple infarcts.

Silent brain infarction in patients with rheumatic mitral stenosis.

Silent brain infarction (SBI) is defined as asymptomatic infarction areas detected in computerized tomography (CT) scans in patients without a history of stroke. The incidence of SBI is increased in CT or magnetic resonance imaging in patients with carotid stenosis and with atrial fibrillation (AF), but its relation with rheumatic mitral stenosis (MS), another major source of emboli, is uncertain. The aim of this study was to investigate the incidence of SBI in patients with MS. Fifty-three patients with MS (44 females and 9 males; range 25-52 years; mean age 38 +/- 7 years) diagnosed by transthoracic echocardiography (TTE) were enrolled in the study. Mitral valve calcification, left atrium (LA) dimension, and the presence of associating mitral regurgitation on TTE were recorded. Electrocardiographic evaluation was done for rhythm analysis and neurologic examination was performed prior to cerebral CT. Carotid artery Doppler examination was carried out in patients with SBI to exclude carotid artery lesions. Patients with a history of hypertension, diabetes mellitus, anticoagulant drug usage, presence of thrombus in LA, left ventricular segmental or systolic dysfunction, or other valve diseases were excluded from the study. The incidence of SBI was found to be 24.5% in patients with MS (47% cortical, 53% lacunar). SBI was observed to be significantly high in patients with LA dimension > 4 cm or in patients with AF (p < 0.05). The SBI incidence was markedly higher if AF was found with enlarged LA when compared with patients having sinus rhythm and small LA (p < 0.01). When moderate to severe mitral regurgitation was associated with MS, the SBI incidence was found to be lower (p < 0.05). Although SBI was higher in patients with MVA < 1.5 cm2, it was not statistically significant (p > 0.05). No significant correlation was found between calcific and noncalcific valves for SBI (p > 0.05). Our data suggest that SBI may be expected in about 1/4 of patients with MS. The presence of LA enlargement and AF increase the incidence of SBI in patients with MS, whereas the presence of moderate to severe mitral regurgitation decreases the incidence of SBI.

Relation of lipid and lipoprotein(a) to ischaemic stroke.

The relationship of lipids and Lp(a) to ischemic stroke hasn't been established yet. Our aim was to determine lipid profile and vascular risk factors in stroke patients and compare them with control subjects. Seventy-nine consecutive patients with ischemic stroke were analyzed by total cholesterol, HDL-C, LDL-C, triglyceride, Lp(a) and doppler ultrasonography and vascular risk factors were recorded. Thirty control subjects of same ages were compared with the patient group. Lp(a) and lipids were correlated with stroke subtype and carotid atherosclerosis. There was no statistical significance between patients and control subjects related to total cholesterol, triglyceride, HDL-C, LDL-C and Lp(a) (P>0.05). Atherotrombotic and lacunar strokes didn't show any difference correlated with lipids and Lp(a). Hypertension and diabetes mellitus were important risk factors with (OR=4.50, 95% CI=1.25-16.22) and (OR=4.43, 95% CI=1.79-10.93) respectively. These results were statistically significant (P<0.05). Total cholesterol (308.67+/-85.82) and Lp(a) (32.10+/-17.30) values showed statistical significance (P<0.05) in patients with marked stenosis when compared with patients of normal doppler ultrasonography. Hypertension and diabetes mellitus were found as independent risk factors for ischemic stroke. Lipids and Lp(a) were not independent for atherotrombotic and lacunar stroke. Lp(a) concentration and carotid atherosclerosis in ultrasonography were associated significantly.