Ivana Tyrlíková

Dietary treatment in adults with refractory epilepsy A review

We review adjunctive ketogenic diet (KD) and modified Atkins diet (MAD) treatment of refractory epilepsy in adults. Only a few studies have been published, all open-label. Because of the disparate, uncontrolled nature of the studies, we analyzed all studies individually, without a meta-analysis. Across all studies, 32% of KD-treated and 29% of MAD-treated patients achieved ≥50% seizure reduction, including 9% and 5%, respectively, of patients with >90% seizure frequency reduction. The effect persists long term, but, unlike in children, may not outlast treatment. The 3:1 and 4:1 [fat]:[carbohydrate + protein] ratio KD variants and MAD are similarly effective. The anticonvulsant effect occurs quickly with both diets, within days to weeks. Side effects of both diets are benign and similar. The most serious, hyperlipidemia, reverses with treatment discontinuation. The most common, weight loss, may be advantageous in patients with obesity. Potential barriers to large-scale use of both diets in adults include low rate of diet acceptance and high rates of diet discontinuation. The eligible screened/enrolled subject ratios ranged from 2.9 to 7.2. Fifty-one percent of KD-treated and 42% of MAD-treated patients stopped the diet before study completion. Refusal to participate was due to diet restrictiveness and complexity, which may be greater for KD than MAD. However, long-term adherence is low for both diets. Most patients eventually stop the diet because of culinary and social restrictions. For treatment of refractory status epilepticus, only 14 adult cases of KD treatment have been published, providing insufficient data to allow evaluation. In summary, KD and MAD treatment show modest efficacy, although in some patients the effect is remarkable. The diets are well-tolerated, but often discontinued because of their restrictiveness. In patients willing to try dietary treatment, the effect is seen quickly, giving patients the option whether to continue the treatment.

Long-term levetiracetam treatment in patients with epilepsy: 3-year follow up

Kuba R, Novotná I, Brázdil M, Kočvarová J, Tyrlíková I, Mastík J, Rektor I. Long‐term levetiracetam treatment in patients with epilepsy: 3‐year follow up.
Acta Neurol Scand: 2010: 121: 83–88.
© 2009 The Authors Journal compilation

The role of voxel‐based morphometry in the detection of cortical dysplasia within the temporal pole in patients with intractable mesial temporal lobe epilepsy

Purpose:  To determine whether voxel‐based morphometry (VBM) might contribute to the detection of cortical dysplasia within the temporal pole in patients with mesial temporal lobe epilepsy and hippocampal sclerosis (MTLE/HS).

Lateralized ictal immobility of the upper limb in patients with temporal lobe epilepsy

The primary aim of this study was to establish the incidence and the lateralizing value of ‘lateralized ictal immobility of the upper limb’ (LIL) in patients suffering from temporal lobe epilepsy (TLE), and to describe the connection between LIL and other clinical ictal signs.

Occurrence and lateralizing value of “rare” peri-ictal vegetative symptoms in temporal lobe epilepsy

We retrospectively investigated rare peri-ictal vegetative symptoms (PIVS) in 380 seizures of 97 patients with temporal lobe epilepsy (TLE): 234 seizures of 60 patients with TLE with mesiotemporal sclerosis (TLE/MTS) and 146 seizures of 37 patients with TLE with other lesions (TLE/non-MTS) who were at least 2 years after epilepsy surgery and classified as Engel I. We assessed the following PIVS: peri-ictal cough (pC), peri-ictal water drinking (pWD), peri-ictal vomiting (pV), and peri-ictal spitting (pS). We observed pC in 24.7% of patients and 10% of seizures; pWD in 14.4% of patients and 5.9% of seizures; pV and pS occurred more rarely. Both pWD and pC occurred significantly more often in those with TLE of the non- language-dominant hemisphere. The limited occurrence of pV and pS made it impossible to perform statistical analysis for these symptoms. In patients with TLE, pC and pWD were quite frequent; we observed pV and pS less frequently. Both pC and pWD have a significant lateralizing value in TLE.

Long-term levetiracetam treatment of epilepsy patients : Clinical audit

PURPOSE The long-term efficacy and tolerability of levetiracetam (LEV) was analysed in 218 epilepsy patients. One hundred and ninety-nine patients were treated for at least 6 months. We evaluated LEV efficacy for all types of seizures together, and for simple partial, complex partial and secondary generalized seizures individually. RESULTS A significant decrease in the number of seizures occurred after 6 months of treatment (p<0.001). Mean seizure frequency (irrespective of type) before LEV was 19.2 a month. The mean monthly frequency at 6, 12, 24 and 36 months dropped to 12.7, 10.5, 9.7 and 7.1 seizures a month, respectively. The mean percentage reduction in seizures at these times was 45.7, 52.1, 59.1 and 64.2% and the number of responding patients was 51.3, 54.2, 59.8 and 62.2%. The number of patients completely seizure free was 18.6, 16.7, 15.2 and 16.2%. We found similar results in the last three categories for partial simple, complex and secondary generalized seizures individually. Side effects in 18.3% of patients caused treatment discontinuation in 6.4%. The most frequent were somnolence, moodiness and dizziness. The retention rate at 6, 12, 24 and 36 months was 0.848, 0.72, 0.62 and 0.5, respectively. CONCLUSIONS LEV is effective and well tolerated for long-term treatment of epilepsy.

Brivaracetam for the treatment of epilepsy

ABSTRACT Introduction: Approximately one third of patients with epilepsy fail to respond to existing medications. Levetiracetam is an effective antiepileptic drug (AED) postulated to act by binding to synaptic vesicle protein 2A. Brivaracetam is a novel high affinity SV2A ligand with approximately 20-fold higher affinity for SV2A protein than levetiracetam. It is at an advanced stage of clinical development for treatment of epilepsy. Areas covered: This article reviews animal data, pharmacokinetics, and phase 1-3 data of Brivaracetam treatment of epilepsy. Brivaracetam has broad-spectrum anticonvulsant activity in animal models. Expert Opinion: Phase 1 studies indicated that single oral doses of 5-800 mg and repeated oral doses of up to 600 mg were well tolerated and showed favorable pharmacokinetic profile. Phase 2 studies indicated good safety and tolerability of brivaracetam in the dose range of 5-150 mg/day and provided proof of concept for efficacy in treating refractory partial onset seizures. Efficacy and safety have been evaluated in 4 phase 3 studies with dose range of 5-200 mg which have demonstrated efficacy in the range of 100-200 mg/day dose and, in most studies, also with 50 mg/day dose, and good safety and tolerability profile across 5-200 mg doses in adjunctive treatment of refractory partial onset seizures.

Secondary generalization in seizures of temporal lobe origin: Ictal EEG pattern in a stereo-EEG study

OBJECTIVE We tested the hypothesis that secondary generalized seizures (SGS) are not truly generalized and may involve selective regions. METHODS The spread from focal to generalized seizures in temporal lobe epilepsy (TLE) was studied in 20 SGS recorded via stereo-EEG (SEEG) in 15 candidates for surgery. Electrodes were assigned to fronto-orbital, prefrontal, and temporal cortex, cingulate, hippocampus, and amygdala. The onset of SGS was ascertained by behavioral analysis of the video recordings. EEG recordings were evaluated using the rating scale developed by Blumenfeld [Blumenfeld H, Rivera M, McNally KA, Davis K, Spencer DD, Spencer SS. Ictal neocortical slowing in temporal lobe epilepsy. Neurology 2004;63:1015-21]. The seizure rating in each region was compared with the rating in the hippocampus. RESULTS Ranking significantly differed in the cingulate and fronto-orbital cortex; there was a trend toward significance in the prefrontal cortex. In these regions, slow activity dominated. CONCLUSION The onset of secondary generalization, when the head, face and all limbs are involved, does not implicate global cortical involvement.

Prevention of epilepsy: Should we be avoiding clinical trials?

Epilepsy prevention is one of the great unmet needs in epilepsy. Approximately 15% of all epilepsy is caused by an acute acquired CNS insult such as traumatic brain injury (TBI), stroke or encephalitis. There is a latent period between the insult and epilepsy onset that presents an opportunity to intervene with preventive treatment that is unique in neurology. Yet no phase 3 epilepsy prevention studies, and only 2 phase 2 studies have been initiated in the last 16years. Current prevailing opinion is that the research community is not ready for clinical preventive epilepsy studies, and that animal models should first be refined and biomarkers of epileptogenesis and of epilepsy discovered before clinical studies are embarked upon. We review data to suggest that there is basis to do epilepsy prevention studies now with the current knowledge and available drugs, and that those studies are feasible with currently available tools. We suggest that a different approach is needed from the past in order to maximize chances of success, minimize the cost, and set up platform for future preventive treatment development. That approach should include close coordination of preclinical and clinical development programs in a combined PTE prevention strategy, consideration of polytherapy, and simultaneous, combined clinical development of preventive treatment and of biomarker discovery. We argue that the currently favored approach of eschewing clinical studies until biomarkers are available will delay the discovery of epilepsy prevention treatment by at least 10 years and significantly increase the cost of such discovery.

Peri-ictal bed leaving in temporal lobe epilepsy: Incidence and lateralizing value

We analyzed peri-ictal bed leaving (PBL) symptoms in 105 patients with temporal lobe epilepsy (TLE). All patients were classified as Engel I at the 2-year follow-up visit. Histopathological examination revealed hippocampal sclerosis (TLE-HS) in 64 patients and other lesions in 38 patients (TLE-other); 3 patients had no lesions. We reviewed 412 seizures. PBL was defined as lateralized leaving of the bed occurring during the seizure or up to 3 minutes after the end of the seizure. PBL was observed in 28 of 105 patients (26.7%), and in 45 of 412 seizures (10.9%). PBL occurred more frequently in patients with TLE-HS than in patients with TLE-other (32.8% vs 17.1%, P=0.058). PBL was ipsilateral to the seizure onset in 71.4% of patients and 71.2% of seizures (P=0.012 and P<0.001). In patients with TLE-HS, PBL was ipsilateral to seizure onset in 76.2% of patients and 81.2% of seizures (P=0.008 and P<0.001). In patients with TLE-other, PBL was ipsilateral to seizure onset in 42.8% of patients and 46.1% of seizures. There were no differences in the incidence and lateralizing value between patients with right-sided and those with left-sided TLE. PBL is a relatively frequent peri-ictal sign in patients with TLE. The side of PBL in patients with TLE-HS lateralizes the seizure onset to the ipsilateral temporal lobe.