In this study, we aimed to assess sleep function in patients with recent-onset familial Creutzfeldt-Jakob disease (fCJD). The largest cluster of fCJD patients is found in Jews of Libyan origin, linked to the prion protein gene (PRNP) E200K mutation. The high index of suspicion in these patients often leads to early diagnosis, with complaints of insomnia being a very common presenting symptom of the disease. The study included 10 fCJD patients diagnosed by clinical manifestations, magnetic resonance imaging (MRI) scan of the brain, elevated tau protein in the cerebrospinal fluid (CSF) and positive PRNP E200K mutation. Standard polysomnography was performed after a brief interview confirming the presence of sleep disturbances. All patients showed a pathological sleep pattern according to all scoring evaluation settings. The sleep stages were characterized by (i) disappearance of sleep spindles; (ii) outbursts of periodic sharp waves and shallowing of sleep consisting in increased Stage 2 and wake periods during the night, as well as decrease of slow-wave sleep and rapid eye movement (REM) sleep. Recordings of respiratory functions reported irregular breathing with central and obstructive apnea and hypopnea. The typical hypotonia occurring during the night and atonia during REM sleep were replaced by hyperactive sleep consisting of multiple jerks, movements and parasomnia (mainly talking) throughout the night. In conclusion, we report unique pathological sleep patterns in early fCJD associated with the E200K mutation. Specific respiratory disturbances and lack of atonia could possibly serve as new, early diagnostic tools in the disease.

BACKGROUND:Although seizures (other than myoclonus) are frequently reported in Creutzfeldt-Jakob disease (CJD), their frequency, clinical manifestations, and effect on the disease course is unknown.OBJECTIVES:To characterize the frequency of seizures in E200K familial and sporadic CJD, to describe its semiology, EEG and MRI findings.METHODS:In this retrospective study, we reviewed all patients with CJD who were seen in the Sheba Medical Center between the years 2003-2012 and underwent clinical evaluation, genetic testing, EEG and MRI studies. The diagnosis of seizures was carried out based on documentation of episodes consistent with seizures or episode of unresponsiveness correlated with ictal activity in EEG.RESULTS:Sixty-four probable patients with CJD were included in the study, 57 (89%) with E200K familial (fCJD) and 7 (11%) with sporadic (sCJD). Seizures occurred in 8 patients: 3 of 7 (43%) in patients with sCJD compared to 5/57 (9%) in patients with E200K fCJD (P = 0.04, chi-square test). Two of E200K fCJD patients with seizures had other non-prion etiologies for seizures (brain metastasis, known history of temporal lobe epilepsy which started 44 years before the diagnosis of CJD). Seizures occurred late in the course of the disease with an average of 12 days between the onset of seizures and death.CONCLUSION:Seizures in E200K fCJD were infrequent and occurred late in the disease course. This difference suggests that E200K fCJD represents a separate subtype of the disease with distinct clinical characteristics.

BACKGROUND:Non-convulsive status epilepticus (NCSE) indicates a change in the mental state with no motor manifestations, being a clinical expression of prolonged epileptiform activity. In contrast to convulsive status epilepticus (CSE), no unified treatment recommendations have been proposed so far. We were interested to review the clinical and encephalographic characteristics in hospitalized patients with NCSE and CSE and compare their treatment and outcome.PATIENTS AND METHODS:The electroencephalographic recording records of adult patients with electrographic status epilepticus were retrieved. Patients' clinical records were then analyzed.RESULTS:Fifty-three patients with CSE and 25 patients with NCSE were identified. Background diseases, neuroimaging findings and complications were similar in CSE and NCSE. Anoxia was a more frequent etiological factor only for myoclonic SE. Patients with CSE presented more often with coma. The number of drugs used for treatment was similar, but anesthetics drugs were administered more frequently in patients with CSE. The 30-day mortality rate was higher in myoclonic SE and generalized tonic-clonic SE, but the outcome on discharge in terms of survival and recovery was comparable between CSE and NCSE.CONCLUSIONS:The results of the present study show that the clinical parameters of NCSE in acutely ill patients do not substantially differ from those of patients with CSE. Moreover, despite more severe mental changes and the need for more anesthetic drugs for treatment of CSE, the final outcome did not differ between both groups. This might indicate that NCSE in acutely ill patients should be regarded as seriously as CSE.

OBJECTIVES:To determine the response rate of patients with juvenile myoclonic epilepsy (JME) to lamotrigine (LTG) and identify predictive factors for treatment response.MATERIAL AND METHODS:Medical records of 62 patients with JME were reviewed for demographic, clinical, and EEG parameters. We determined clinical response to LTG and compared LTG responders with non-responders.RESULTS:There were 35 LTG responders (56%) and 27 non-responders (44%). JME patients without generalized tonic clonic seizures (GTCS) responded better to LTG (P = 0.04). Valproic acid (VPA) failure because of adverse events rather than lack of efficacy (P = 0.069) and delay in diagnosis (P = 0.07) showed a tendency toward good response to LTG.CONCLUSIONS:LTG should be considered a drug of first choice for JME patients without GTCS. LTG as second-line treatment after VPA failure seems more appropriate for those patients whose reason for VPA failure is poor tolerability rather than lack of efficacy.

PURPOSE:To compare subclinical balance dysfunction in patients with various epilepsy syndromes with apparently healthy subjects. METHODS:Twenty-seven patients with localization-related epilepsy (LRE), 19 with primary generalized epilepsy (PGE), who had no subjective complaints of impaired balance and no abnormal neurologic findings on examination, and 22 apparently healthy subjects, underwent static posturography using the Posture Scale Analyzer (PSA) system. RESULTS:Sway index was higher in patients compared to healthy subjects in all tests, significant for single leg stance (p=0.005). Patients with PGE had a higher sway index compared to patients with LRE in six of the tests, also significant for single leg stance (p=0.027). This difference was not affected by the type of AED treatment or disease duration. CONCLUSION:Posturography can improve balance function assessment in patients with epilepsy, demonstrate subclinical impairment in seemingly asymptomatic patients, and further characterize balance deficits in different epilepsy syndromes.

Objective. To assess the frequency of epilepsy in primary and secondary antiphospholipid syndrome (APS); to analyze the clinical and laboratory features characterizing those with epilepsy in a cohort of 538 patients with APS; and to find associated features that would suggest risk factors for epilepsy in APS.Methods. We analyzed the clinical features of patients with APS who had epilepsy and compared them to the clinical features of non-epileptic APS patients.Results. Of 538 APS patients, 46 (8.6%) had epilepsy. Epilepsy was more prevalent among APS secondary to systemic lupus erythematosus (SLE) compared to primary APS (13.7% vs 6%; p < 0.05). The patients with epilepsy had a higher prevalence of central nervous system (CNS) manifestations including focal ischemic events (strokes or transient ischemic events, 54.3% vs 24.6%; p < 0.0001) and amaurosis fugax (15.2% vs 4.9%; p < 0.05). APS patients with epilepsy had a higher frequency of valvular pathology (30.4% vs 14.6%; p < 0.01), thrombocytopenia (43.5% vs 25%; p < 0.05), and livedo reticularis (26.1% vs 11.5%; p < 0.01). The multivariate logistic regression analysis found CNS thromboembolic events as the most significant factor associated with epilepsy, with an odds ratio (OR) of 4.05 (95% confidence interval, CI: 2.05-8), followed by SLE (OR 1.4, 95% CI 1.2-4.7), and valvular vegetations (OR 2.87, 95% CI 1-8.27).Conclusion. Epilepsy is common in APS and most of the risk seems to be linked to vascular disease as manifested by extensive CNS involvement, valvulopathy, and livedo reticularis and to the presence of SLE. These factors,, however, explain only part of the increased occurrence of epilepsy in APS and other causes such as direct immune interaction in the brain should be investigated.