Use of intravenous brivaracetam in status epilepticus: A multicenter registry.

OBJECTIVE: The pharmacokinetics of brivaracetam (BRV), added to its effectiveness observed in animal models of status epilepticus (SE), makes this drug attractive for use in emergency situations. Our objective was to evaluate the use of intravenous BRV in a multicenter study. METHODS: A retrospective multicenter registry of SE cases treated with BRV was created. These patients were evaluated between January and December 2018 at seven hospitals in Spain. Demographic variables, SE characteristics, concomitant drugs, loading doses, and response to treatment were collected. RESULTS: Forty-three patients were registered. The mean age was 56 ± 23.1 years, 51.2% were male, 29 had previous epilepsy, 24 (55.8%) had prominent motor symptoms, and 19 had nonconvulsive symptoms. Regarding the etiology, 19 (44.2%) were considered acute symptomatic, 16 (17.2%) remote symptomatic, four (9.3%) progressive symptomatic, and four (9.3%) cryptogenic. Regarding concomitant antiepileptic drugs (AEDs), 17 had previously received levetiracetam (LEV). In 14 patients, BRV was used early (first or second AED). The median loading dose was 100 mg (range = 50-400), and the weight-adjusted dose was 1.8 mg/kg (range = 0.4-7.3). BRV was effective in 54% (n = 23), and a response was observed in <6 hours in 13 patients. We observed a tendency for it to be more effective when administered earlier (P = 0.09), but there were no differences regarding SE type and the concomitant use of LEV. In those with the fastest responses, we observed that both the total administered dose (300 mg vs 100 mg, P = 0.008) and the weight-adjusted dose (3.85 mg vs 1.43 mg, P = 0.006) were significantly higher. The receiver operating characteristic curve showed that the best cutoff point for a faster response was 1.82 mg/kg. SIGNIFICANCE: BRV is useful for the treatment of SE, even when patients are already being treated with LEV. The response rate seems higher when it is administered earlier and at higher doses (>1.82 mg/kg).

Intracranial EEG potentials estimated from MEG sources: A new approach to correlate MEG and iEEG data in epilepsy.

Detection of epileptic spikes in MagnetoEncephaloGraphy (MEG) requires synchronized neuronal activity over a minimum of 4cm2. We previously validated the Maximum Entropy on the Mean (MEM) as a source localization able to recover the spatial extent of the epileptic spike generators. The purpose of this study was to evaluate quantitatively, using intracranial EEG (iEEG), the spatial extent recovered from MEG sources by estimating iEEG potentials generated by these MEG sources. We evaluated five patients with focal epilepsy who had a pre-operative MEG acquisition and iEEG with MRI-compatible electrodes. Individual MEG epileptic spikes were localized along the cortical surface segmented from a pre-operative MRI, which was co-registered with the MRI obtained with iEEG electrodes in place for identification of iEEG contacts. An iEEG forward model estimated the influence of every dipolar source of the cortical surface on each iEEG contact. This iEEG forward model was applied to MEG sources to estimate iEEG potentials that would have been generated by these sources. MEG-estimated iEEG potentials were compared with measured iEEG potentials using four source localization methods: two variants of MEM and two standard methods equivalent to minimum norm and LORETA estimates. Our results demonstrated an excellent MEG/iEEG correspondence in the presumed focus for four out of five patients. In one patient, the deep generator identified in iEEG could not be localized in MEG. MEG-estimated iEEG potentials is a promising method to evaluate which MEG sources could be retrieved and validated with iEEG data, providing accurate results especially when applied to MEM localizations. Hum Brain Mapp 37:1661-1683, 2016. © 2016 Wiley Periodicals, Inc.

Antithyroid antibodies as a potential marker of autoimmune-mediated late onset temporal lobe epilepsy.

UNLABELLED: In one third of patients with epilepsy starting in adulthood the aetiology remains undetermined. Some patients with late onset temporal lobe epilepsy (TLE) together with memory decline have elevated antithyroid antibodies. PURPOSE: To compare the prevalence of antithyroid antibodies (aTR-ab) in adult onset temporal lobe epilepsy (TLE) patients with known and unknown TLE aetiology (N=42). Moreover, the sera of these patients was also assayed for antinuclear antibodies (ANA), anticardiolipin antibodies (ACL), anti glutamic acid decarboxylase antibodies (GAD) and antiglidadin antibodies. RESULTS: Positive aTR-ab in the sera of patients with unknown aetiology was 11/23 (47.8%) vs. 1/19 (4.3%) in the group with known aetiology (p=0.005). In 9/11 (81%) a pre-existing autoimmune disease was confirmed. Nine (81%) were women and five (45%) had memory impairment. There were 5/11 (45%) pharmacoresistant patients, and corticosteroid treatment was initiated in 3/5 with cognitive and seizure improvement. The results of other immunological tests were only remarkable for antiGAD antibodies with 3/11 (27%) positive patients, but this subgroup does not have any significant clinical differential feature. CONCLUSIONS: Late-onset TLE with positive aTR-ab tends to be middle-aged women with nonpharmacoresistant cryptogenic epilepsy plus cognitive decline and other associated autoimmune diseases. It could be advisable to test aTR-ab in TLE patients with an unknown aetiology, in order to improve diagnosis and resulting treatment.

Hyperexcitability of the facial nerve in tuberculous meningitis.

INTRODUCTION: Facial myokymias (FM) are continuous, involuntary, undulating movements of the facial muscles associated with spontaneous electromyographic activity, such as fasciculations and myokymic discharges. They may occur in healthy individuals, or be secondary to multiple sclerosis, posterior fossa tumors, or an inflammatory process. PATIENT AND RESULTS: We describe the case of a 31-year-old man who presented with headache, vomiting, low fever, and disorientation. Cerebrospinal fluid findings included low glucose and high protein content and lymphocyte pleocytosis, with positive culture for Myobacterium tuberculosis. The patient was diagnosed with tuberculous meningitis. Magnetic resonance imaging showed high contrast enhancement in the basal meninges and a left frontal tuberculoma. Over the course of the disease, he experienced FM and persistent, involuntary contraction of the facial muscles. The electromyogram recorded myokymic discharges. DISCUSSION: Tuberculous meningitis is a rare cause of FM. The presence of myokymic discharges on electromyography verified the peripheral origin of facial nerve hyperexcitability in this case, in contrast to persistent contraction of the facial muscles, which has a central origin. The phenomena were transitory and only positive symptoms were observed, with no facial nerve injury. CONCLUSION: Tuberculous meningitis is a rare cause of facial nerve hyperexcitability, which can have a peripheral, nuclear, or supranuclear origin.

Efficacy of intravenous levetiracetam as an add-on treatment in status epilepticus: a multicentric observational study.

INTRODUCTION: Treatment of status epilepticus (SE) has not changed in the last few decades, benzodiazepines plus phenytoin being the most common first line treatment. Intravenous levetiracetam (ivLEV) is a new antiepileptic drug with interesting properties for SE. MATERIAL AND METHODS: Efficacy and effectiveness of ivLEV in SE were assessed in an observational, multicentric and retrospective study. Efficacy was defined as cessation of seizures in the 24h subsequent to starting ivLEV, with no need of any further antiepileptic drug. All patients were treated following the standard protocol (benzodiazepines plus phenytoin or valproate). ivLEV was used as add-on therapy, except in those cases with contraindication for the standard protocol, when it was administered earlier. RESULTS: 40 patients were included, 57% men, with a mean age of 63 years. The most common type of SE was partial convulsive (90%). ivLEV was effective in approximately half of the patients (57.5%), in a mean time of 14.4h. ivLEV was used as add-on treatment in 26 patients (after benzodiazepines plus phenytoin, valproate or both) with an efficacy of 46.1%, and as early treatment (pretreatment with benzodiazepines or nothing) in 14 patients with an efficacy of 78.5% (p 0.048). Adverse events were observed in 15% of patients. CONCLUSIONS: ivLEV was an effective antiepileptic drug for SE, but its efficacy depends on the timing of its administration, being more effective when used as early treatment, and less effective as add-on treatment.

Refractory nonconvulsive status epilepticus in Creutzfeldt-Jakob disease.

Creutzfeldt-Jakob disease (CJD) is a rare human transmissible spongiform subacute encephalopathy. The most common clinical manifestations of CJD include rapidly progressive dementia, behavioural changes, cerebellar dysfunction and myoclonus. Other seizure types are rare and nonconvulsive status epilepticus (SE) is exceptional. We report a case of a 44-year-old man who presented a psychotic episode followed by akinetic mutism and refractory nonconvulsive SE. The final diagnosis was CJD. Continuous video-EEG monitoring revealed the ictal pattern of nonconvulsive SE to be periodic sharp wave complexes characteristic of CJD. [Published with video sequences].