Gerald Walser

Intravenous lacosamide in status epilepticus and seizure clusters

Status epilepticus (SE) and seizure clusters (SC) represent neurologic emergencies with a case fatality rate up to 34%, depending on cause and comorbidity. As SE becomes more refractory to treatment over time, appropriate medication is important. This study aimed to investigate efficacy and tolerability of intravenous (IV) lacosamide (LCM) in treatment of SC and SE. Data of patients with SE or SC who were treated with IV LCM between December 2009 and February 2011 in two Austrian centers were analyzed retrospectively. Clinical information was extracted from patients’ charts. Forty‐eight patients (26f/22m) aged median 62 years (range 17–95 years) were identified. Thirty‐five percent of patients (17 of 48) had SC and 65% (31 of 48) had SE. SE was nonconvulsive in 10 (32%), convulsive in 11 (36%), and focal in 10 (32%) patients. SE was acute symptomatic in six (20%) and remote symptomatic in 11 (35%) patients. Fourteen (45%) had preexisting epilepsy. Median initial bolus dose was 200 mg (range 200–400 mg) in patients with SE and 200 mg in patients with SC. Maximum infusion rate was 60 mg/min. Cessation was observed in 42 patients (88%). Success rate in patients with SE receiving LCM as first or second drug was 100% (8 of 8), as third drug 81% (11 of 15), and as fourth or later drug 75% (6 of 8). There were no side effects observed except for pruritus and skin rash in two patients. These data support use of IV LCM as a potential alternative to standard antiepileptic drugs for acute treatment of seizure emergency situations, although randomized controlled studies are needed.

Video‐EEG monitoring: Safety and adverse events in 507 consecutive patients

Purpose:  Video–electroencephalography (EEG) monitoring plays a central role in the presurgical evaluation of medically refractory epilepsies and the diagnosis of nonepileptic attack disorders (NEADs). The aim of this study was to analyze safety and adverse events (AEs) during video‐EEG monitoring.

Successful surgical treatment of insular epilepsy with nocturnal hypermotor seizures

Nocturnal hypermotor seizures (NHSs) suggest seizure onset in the frontal lobe. We present a patient with NHSs and insular seizure onset who underwent successful surgical treatment.

Outcome of adult patients with temporal lobe tumours and medically refractory focal epilepsy

SummaryBackground. Tumours are a well-recognized cause of medically intractable epilepsies. Tumours represent the primary pathology in 10%–30% of patients undergoing surgical treatment for chronic epilepsy. This study examines the surgical and epileptological outcome of adults with temporal lobe tumoural epilepsy treated within a comprehensive epilepsy surgery programme. Methods. Between 1999 and 2004, 99 consecutive patients have been operated for intractable temporal lobe epilepsy (TLE). Among these, 14 adult patients exhibited temporal lobe neoplasms associated with TLE. Every patient underwent a comprehensive presurgical evaluation including video-EEG monitoring, MRI, interictal PET scan, ictal SPECT and neuropsychological testing. Surgical strategies were determined in an interdisciplinary seizure conference and tailored to the findings of the presurgical evaluation. All patients were available for follow up at regular intervals after 3, 6, 12 months and yearly thereafter. Epileptological outcome was classified according to Engel [10] and the ILAE (International League Against Epilepsy)/systems [33]. Findings. The surgical procedures performed were temporal lobe resection in 3 patients, extended lesionectomy in 4 and extended lesionectomy with resection of the temporomesial structures in 7. One patient with an astrocytoma grade III underwent a second and third operation for recurrent disease. Histological results: Astrocytoma 5 patients, ganglioglioma/gangliocytoma 5, oligodendroglioma 2, ependymoma 1 and dysembryoplastic neuroepithelial tumour (DNET) 1. Postoperative follow-up was performed after 12–74 months (mean 31). The outcome according to the Engel classification indicated class IA in 9 patients, class IC in 3, and 1 each in classes IIIA and IVA. Epileptological outcome according to the ILAE classification indicated class 1 (12 patients) and class 4 (2 patients). Surgical mortality was zero and mild permanent neurological deficits due to surgery were seen in 2 patients. Postoperatively 3 patients showed a homonymous quadrantanopia. Conclusions. Patients with drug resistant epilepsy and temporal lobe tumours should undergo evaluation in dedicated epilepsy surgery programmes.

Spontaneous abortion and the prophylactic effect of folic acid supplementation in epileptic women undergoing antiepileptic therapy

BackgroundAntiepileptic drugs (AEDs) like phenytoin (PHE), carbamazepine (CBZ), barbiturates and valproic acid (VPA) interfere with folic acid absorption and metabolism, which in turn can be the cause of adverse pregnancy outcome.ObjectiveTo study the prophylactic effect of folic acid supplementation with regard to spontaneous abortion and preterm delivery (fetal demise after week 20 of gestational age) in pregnant women receiving AED therapy, as well as benefits of most common dosage and preconceptional commencement.MethodsProspective examination of 104 patients, registered in EURAP from 1999–2004 at a single center and a retrospective analysis of data from our epilepsy databank completed with medical records and patients interviews of the Department of Neurology of Innsbruck University Hospital from 1971 to 1999.Results388 pregnancies in 244 patients were analyzed. Pregnancies with folic acid supplementation showed significant reduction of spontaneous abortion. With regard to monotherapies, in the group of women taking VPA, supplementation of folic acid had significant benefit. Other examined monotherapies (CBZ, PHE, and PB) known to interfere with folic acid showed no significant results.ConclusionsThis study confirms the prophylactic effect of folic acid supplementation on spontaneous abortion. For AED therapy, folic acid supplementation should be part of the therapy of every pregnant epileptic woman, especially for those treated with VPA.

Genital Automatisms: A Video‐EEG Study in Patients with Medically Refractory Seizures

Summary:  Purpose: Genital automatisms (GAs) are rare clinical phenomena during or after epileptic seizures. They are defined as repeated fondling, grabbing, or scratching of the genitals. The anatomic correlates of GAs have been discussed controversially. The aim of this investigation was to assess the localizing and lateralizing value of GAs.

Hippocampal abnormalities in malformations of cortical development: MRI study.

Objectives: Hippocampal abnormalities may coexist with malformations of cortical development (MCD). This cross-sectional MRI study aimed at categorizing hippocampal abnormalities in a large group of MCD and comparing MCD patients with (group W) and without (group W/O) hippocampal abnormalities. Methods: Hippocampal anatomy, rotation, size, internal structure, and MRI signal alterations were assessed visually by 3 independent raters in patients with MCD and epilepsy. Four types of hippocampal abnormalities were examined in 220 patients (116 women, mean age 31 ± 16.6, range 2-76 years): partially infolded/hypoplastic hippocampus (HH), hippocampal sclerosis (HS), malrotated hippocampus (MH), and enlarged hippocampus (EH). The commonest MCD in the cohort were focal cortical dysplasia (27%), polymicrogyria (PMG) (21%), developmental tumors (15%), and periventricular nodular heterotopia (PNH) (14%). Results: Hippocampal abnormalities were seen in 69/220 (31%) patients: HH in 34/69 (49%); HS in 18/69 (26%); MH in 15/69 (22%); and EH in 2/69 (3%). PNH (21/30 [70%]) and PMG (22/47 [47%]) were most commonly associated with hippocampal abnormalities. Compared to the W/O group, patients in the W group had a higher rate of learning disability (W 41/69 [59%] vs W/O 56/151 [37%]; p = 0.003) and delayed developmental milestones (W 36/69 [52%] vs W/O 53/151 [35%]; p = 0.025); groups did not differ otherwise with regard to clinical presentation. HH was associated with symptomatic generalized epilepsies (11/34 [32%]) and high rate of learning disability (27/34 [79%]), neurologic deficits (25/34 [73%]), and delayed developmental milestones (23/34 [68%]). Conclusions: About a third of patients with malformations of cortical development had hippocampal abnormalities. Patients with hypoplastic hippocampus had the most severe clinical phenotype.

Functional imaging of semantic memory predicts postoperative episodic memory functions in chronic temporal lobe epilepsy

Medial temporal (MTL) structures have crucial functions in episodic (EM), but also in semantic memory (SM) processing. Preoperative functional magnetic resonance imaging (fMRI) activity within the MTL is increasingly used to predict post-surgical memory capacities. Based on the hypothesis that EM and SM memory functions are both hosted by the MTL the present study wanted to explore the relationship between SM related activations in the MTL as assessed before and the capacity of EM functions after surgery. Patients with chronic unilateral left (n=14) and right (n=12) temporal lobe epilepsy (TLE) performed a standard word list learning test pre- and postoperatively, and a fMRI procedure before the operation using a semantic decision task. SM processing caused significant bilateral MTL activations in both patient groups. While right TLE patients showed asymmetry of fMRI activation with more activation in the left MTL, left TLE patients had almost equal activation in both MTL regions. Contrasting left TLE versus right TLE patients revealed greater activity within the right MTL, whereas no significant difference was observed for the reverse contrast. Greater effect size in the MTL region ipsilateral to the seizure focus was significantly and positively correlated with preoperative EM abilities. Greater effect size in the contralateral MTL was correlated with better postoperative verbal EM, especially in left TLE patients. These results suggest that functional imaging of SM tasks may be useful to predict postoperative verbal memory in TLE. They also advocate a common neuroanatomical basis for SM and EM processes in the MTL.

Seizure outcome in 175 patients with juvenile myoclonic epilepsy – A long-term observational study

INTRODUCTION Juvenile myoclonic epilepsy (JME) is a genetic generalized epilepsy syndrome. Under appropriate antiepileptic drugs (AED) up to 85% of patients become seizure-free, but many may have a relapse after AED withdrawal. METHODS We retrospectively studied 242 patients with JME at the Department of Neurology, Medical University Innsbruck, Austria (1975-2006). We analyzed age at seizure onset, age at last follow up, seizure types, photosensitivity, seizure outcome and neuroimaging findings; inclusion criterion was a medical treatment period of >2 years; exclusion criteria were traumatic or infectious brain injury before the onset of JME and/or gross structural pathology on neuroimaging. RESULTS We identified 175 patients (111 women) with a median age at seizure onset of 15 years, (range 3-46) and a median age at follow-up (FU) of 38 years (range 14-87; median FU 8 years, range 2-38). Fourteen percent showed (24/175) photosensitivity on routine EEG. Seizure outcome: 62% (109/175) were seizure-free of myoclonic seizures (MS), generalized tonic clonic seizures (GTCS) and absence seizures (AS) for >1 year, and 53% (94/175) for >2 years, including 16 patients (9%) without AEDs. Thirty-one percent (54/175) were seizure-free between 2 and 5 years, 15% (26/175) between 6 and 10, and 8% (14/175) >10 years; 38% (66/175) were not seizure-free. Not seizure-free patients had more often MS, AS and GTCS within the first year of epilepsy than those who were seizure-free at last FU (11% vs. 3%, Chi(2)=4.679, df=1, p=0.043). Seizure-free patients had more often MS and GTCS as last seizure types in the year before becoming seizure-free (37% vs. 15%, p=0.003), whereas in not seizure-free group MS only and GTCS only persisted. CONCLUSIONS JME does not always need lifelong treatment, as a substantial minority of patients remain seizure-free without AEDs. AS, MS and GTCS at onset of the disease are indicators of poor long-term seizure control.

Hippocampal formation involvement in a language-activation task in patients with mesial temporal lobe epilepsy

Summary:  Purpose: The study aims to explore the contribution of the hippocampal formation to the retained language‐comprehension network in patients with unilateral mesial temporal lobe epilepsy (TLE).