Effects of cenobamate on cognitive performance of epilepsy patients.

PURPOSE: Cenobamate (CNB) is a new antiseizure medication (ASM) for the treatment of focal epilepsy in adults. While efficacy of CNB was confirmed in controlled clinical trials, its effects on cognition are unclear. Cognitive adverse effects of ASM affect quality of life and retention rate. Therefore, we investigated whether the adjunctive treatment with CNB is associated with changes in cognitive performance. METHOD: Efficacy and tolerability of CNB were investigated in an observational study. Fifty patients with pharmacoresistant focal epilepsy aged 18 to 71 years (Mdn = 37.5 years) were tested before (T0) and after reaching the first target dose of CNB, usually after three months (T1). Cognitive performance was assessed using the EpiTrack©, a change-sensitive screening tool for attention and executive functions. RESULTS: The median CNB dose at T1 was 125 mg/day (range: 50 - 250 mg/day). Most patients received 2-3 concomitant ASMs. Individual test scores remained stable in 72%, significantly improved in 16%, and significantly deteriorated in 12% of the patients from T0 to T1. The total group showed a significant improvement in EpiTrack scores (p < .01). Changes in EpiTrack performance from T0 to T1 occurred independently of CNB dose, changes in the total drug load or reduction in seizure frequency. CONCLUSION: Most of the patients showed stable or improved cognitive performance. Thus, there is preliminary evidence that adjunctive CNB is not associated with an increased risk of cognitive side effects for the majority of patients. These findings need to be confirmed in controlled trials encompassing higher doses.

Diagnostic yield and limitations of in-hospital documentation in patients with epilepsy.

OBJECTIVE: To determine the diagnostic yield of in-hospital video-electroencephalography (EEG) monitoring to document seizures in patients with epilepsy. METHODS: Retrospective analysis of electronic seizure documentation at the University Hospital Freiburg (UKF) and at King's College London (KCL). Statistical assessment of the role of the duration of monitoring, and subanalyses on presurgical patient groups and patients undergoing reduction of antiseizure medication. RESULTS: Of more than 4800 patients with epilepsy undergoing in-hospital recordings at the two institutions since 2005, seizures with documented for 43% (KCL) and 73% (UKF).. Duration of monitoring was highly significantly associated with seizure recordings (p < .0001), and presurgical patients as well as patients with drug reduction had a significantly higher diagnostic yield (p < .0001). Recordings with a duration of >5 days lead to additional new seizure documentation in only less than 10% of patients. SIGNIFICANCE: There is a need for the development of new ambulatory monitoring strategies to document seizures for diagnostic and monitoring purposes for a relevant subgroup of patients with epilepsy in whom in-hospital monitoring fails to document seizures.

Ictal semiology of epileptic seizures with insulo-opercular genesis.

OBJECTIVE: Epileptic seizures with insular genesis are often difficult to distinguish from those originating in the temporal lobe due to their complex and variable semiology. Here, we analyzed differentiating characteristics in the clinical spectrum of insulo-opercular seizures. METHODS: Ictal semiology in patients with a diagnosis of insulo-opercular epilepsy (IOE) based on imaging of epileptogenic lesions or electrophysiological evidence of an insulo-opercular seizure origin was retrospectively analyzed and compared to age-matched controls with mesial temporal lobe epilepsy (MTE). RESULTS: Forty-six IOE and 46 matched MTE patients were included. The most prominent ictal features in IOE were focal motor phenomena in 80.4% of these patients. Somatosensory sensations, version, tonic and clonic features, when present, were more frequent contralateral to the SOZ in MTE patients, while they occurred about equally often ipsilateral and contralateral to the SOZ in IOE patients. Ipsilateral manual automatisms were significantly more frequent in MTE patients than in IOE (p = 0.010). Multivariate analysis correctly identified IOE in 78.3% and MTE in 84.8% using five semiologic features (Chi-square = 53.79 with 5 degrees of freedom, p < 0.0001). A subanalysis comparing patients with purely insular lesions with MTE patients using only the earliest ictal signs showed that somatosensory sensations are significantly more frequent in insular epilepsy (p = 0.010), while automatisms were significantly more frequent in MTE patients (p = 0.06). SIGNIFICANCE: Our study represents the first in-depth analysis of ictal semiology in IOE compared to MTE. Use of these differentiating characteristics can serve for a correct syndrome classification and to steer appropriate diagnostic and local therapeutic procedures.

Long-term seizure outcome in pediatric patients with focal cortical dysplasia undergoing tailored and standard surgical resections.

PURPOSE: Focal cortical dysplasia (FCD) is the major cause of focal intractable epilepsy in childhood. Here we analyze the factors influencing the success of surgical treatment in a large cohort of children with histologically ascertained FCD. METHOD: A retrospective study of the effects of FCD type, surgical intervention, and age at surgery in a pediatric cohort. RESULTS: A total of 113 patients (71 male; mean age at surgery 10.3 years; range 0-18) were analyzed; 45 had undergone lesionectomy, 42 lobectomy, 18 multi-lobectomy, and eight hemispherotomy. Complete seizure control (Engel Ia) was achieved in 56% after two years, 52% at five years, and 50% at last follow-up (18-204 months). Resections were more extensive in younger patients (40% of the surgeries affecting more than one lobe in patients aged nine years or younger vs. 22% in patients older than nine years). While resections were more limited in older children, their long-term outcome tended to be superior (42% seizure freedom in patients aged nine years or younger vs. 56% in patients older than nine years). The outcome in FCD I was not significantly inferior to that in FCD II. CONCLUSIONS: Our data confirm the long-term efficacy of surgery in children with FCD and epilepsy. An earlier age at surgery within this cohort did not predict a better long-term outcome, but it involved less-tailored surgical approaches. The data suggest that in patients with an unclear extent of the dysplastic area, later resections may offer advantages in terms of the precision of surgical-resection planning.

Resultados de la estimulación del nervio vago en pacientes con epilepsia farmacorresistente en un centro de referencia nacional de epilepsia / Results of vagal nerve stimulation in patients with pharmacoresistant epilepsy in a national epilepsy referral centre

Objetivos. Describir los resultados clínicos y complicaciones derivados de la estimulación vagal en pacientes con epilepsia farmacorresistente no tributaria de otras modalidades de tratamiento quirúrgico, desde el primer implante en un centro de referencia nacional. Pacientes y métodos. Se realizó un análisis retrospectivo de los pacientes implantados en nuestro centro y se extrajeron datos relativos a las características basales de su epilepsia y complicaciones derivadas. Resultados. Se incluyeron 32 nuevos implantes en 31 pacientes, con una edad media de 34 años, evolución de enfermedad de 29,3 años, tres fármacos antiepilépticos prequirúrgicos y 4,03 años de seguimiento. Las crisis parciales complejas (71,9%) y criptogénicas (59,4%) fueron el tipo y la etiología de crisis más frecuentes. El 75% no tenía antecedentes quirúrgicos de epilepsia. Un 43,8% presentó mejoría igual o superior al 50%, mayor en las epilepsias parciales complejas (p = 0,22) y la etiología criptogénica. No se halló asociación estadística entre ajustes de medicación y frecuencia de las crisis. Los efectos secundarios encontrados fueron disfonía, ronquera y disfagia transitorias, y una asistolia intraoperatoria recuperada. Se realizó un recambio por ruptura de hardware postraumática. Un paciente con paresia preexistente de cuerda vocal presentó estridor laríngeo que requirió ajuste de intensidad, y se produjo una retirada del sistema por disfunción. En el 84,4%, la tolerancia fue excelente. Conclusiones. Constituye un tratamiento efectivo para mejorar significativamente la frecuencia de crisis de los pacientes farmacorresistentes y con contraindicación para otras modalidades de tratamiento quirúrgico. Se precisan futuros estudios para predecir la respuesta individual de cada paciente, optimizar las indicaciones y mejorar la relación coste/beneficio (AU)

Aim. To describe clinical results and complications derived from vagal nerve stimulation therapy in drug resistant epileptic patients unsuitable for other surgical treatments, since the first implant in an epilepsy national referral centre. Patients and methods. A retrospective analysis of the patients implanted in our centre was held. Data related to baseline characteristics of their epilepsy and therapy complications was collected. Results. 32 new implants in 31 patients are included, mean age of 34 years, 29.3 years of disease evolution, three antiepileptic drugs at surgery and a postoperative follow-up of 4.03 years. Complex partial seizures types (71.9%) and cryptogenic aetiology (59.4%) were the most frequent. 75% of patients hadn’t history of previous epilepsy surgery. 43.8% of patients had a seizure frequency improvement above 50%, with a better response in patients with complex partial seizures (p = 0.22) and cryptogenic aetiology. None statistical significance was found between antiepileptic drugs and seizure frequency. Dysphonia, hoarseness and dysphagia, mostly transient, were the side effects registered. There was an asystole during surgery, completely recovered. One device was replaced due to hardware rupture after a seizure related trauma, one had to be adjusted due to a previous vocal cord paresis, and one dysfunctioning device was removed. In 84.4% the tolerance was excellent. Conclusions. Vagal nerve stimulation is an effective treatment for significant seizure frequency improvement of resistant patients untreatable with other medical or surgical treatments. Further studies are needed to predict the individual response of each patient to therapy and optimizing indications, therefore contributing to cost/benefit optimization (AU)

Total Cerebral Blood Flow in Patients with Cardioembolic Stroke: Is It Clinically Meaningful?

Chronic hypoperfusion may hinder the washout of emboli coming from the heart and facilitate the formation of intra-cavitary thrombi. We investigated whether a decreased total cerebral blood flow (tCBF) resulted in recurrence of stroke and other vascular events in consecutive patients with cardioembolic stroke. We excluded patients with extra-cranial carotid or vertebral stenosis. The recorded tCBF was the sum of blood flow in both the carotid and vertebral extra-cranial arteries as measured with ultrasonography. Patients were followed up to assess stroke recurrence, vascular events and mortality. We also recorded demographic data, vascular risk factors, treatment data, echocardiographic variables and the C congestive heart failure history H Hypertension history A Age D Diabetes S Sex S2 Stroke/TIA/Thromboembolism history Vasc Vascular Disease history (CHA2DS2-VASc) score. We studied 79 patients (age 77.9 ± 8.4 y). Mean tCBF was 65.5 ± 15.7 mL/100 g/min. Cox regression analysis found that CHA2 DS2-VASc score and ejection fraction were associated with tCBF. After a mean follow-up of 22 ± 8.5 mo, 7.6% of patients experienced a recurrent stroke, 12.7% experienced a vascular event and 21.5% of patients died. Clinical outcomes were not predicted by tCBF.

Cerebral amyloid angiopathy-related atraumatic convexal subarachnoid hemorrhage: an ARIA before the tsunami.

Atraumatic convexal subarachnoid hemorrhage (cSAH) in elderly patients is a rare entity that has been associated with cerebral amyloid angiopathy (CAA) and intracerebral hematomas (ICH). To characterize this entity and to study these associations, 22 patients over 60 with cSAH were included in a multicenter ambispective cohort study. Clinical data, magnetic resonance imaging (MRI) studies, APOE genotyping, and cerebrospinal fluid (CSF) biomarkers were evaluated. Results were compared with data from healthy controls (HC), non-cSAH CAA patients (CAAo), and Alzheimer disease patients. Convexal subarachnoid hemorrhage presented with transient sensory or motor symptoms. At follow-up (median 30.7 months), 5 patients had died, 6 survivors showed functional disability (modified Rankins Scale (mRS)>2), and 12 cognitive impairment. Four patients had prior ICH and six had an ICH during follow-up. CSF-Aß40 and Aß42 levels were lower in cSAH and CAAo compared with HC. Convexal subarachnoid hemorrhage presented an APOE-ɛ2 overrepresentation and CAAo had an APOE-ɛ4 overrepresentation. On MRI, all patients fulfilled CAA-modified Boston criteria and 9 showed cortical ischemia in the surrounding cortex or the vicinity of superficial siderosis. The neuropathologic study, available in one patient, showed severe CAA and advanced Alzheimer-type pathology. Convexal subarachnoid hemorrhage in the elderly is associated with cognitive impairment and lobar ICH occurrence. Our findings support the existence of an underlying CAA pathology.