Rana Kurdi

Hippocampal Programmed Cell Death after Status Epilepticus: Evidence for NMDA‐Receptor and Ceramide‐Mediated Mechanisms

Summary:  Purpose: Status epilepticus (SE) can result in acute neuronal injury with subsequent long‐term age‐dependent behavioral and histologic sequelae. To investigate potential mechanisms that may underlie SE‐related neuronal injury, we studied the occurrence of programmed cell death (PCD) in the hippocampus in the kainic acid (KA) model.

Quality of life after surgery for intractable partial epilepsy in children: A cohort study with controls

PURPOSE Investigate if quality of life (QOL) normalizes on long-term follow-up after surgery for partial epilepsy in children. METHODS This is a cohort study with controls in which a consecutive cohort of nineteen 2-14-year-old children who underwent focal resections for intractable partial seizures between 1996 and 2006, were matched with 19 non-surgery intractable partial epilepsy patients, and with 19 healthy subjects. The two epilepsy groups were matched for age, sex, socio-economic status (SES), cognitive level, seizure type, and seizure frequency. The healthy group was matched with the two epilepsy groups for age, sex, SES, and cognitive level. QOL was assessed using the QOLCE (Quality of Life in Childhood Epilepsy Questionnaire). RESULTS In the surgery group (follow-up 3.84+/-2.26 years), 78.9% had Engel class-I versus 21.1% in non-surgery (p=0.01) (follow-up 3.44+/-2.95 years). Surgery patients were similar to healthy subjects in the social, emotional, cognitive, behavioral, and overall QOL (p>0.05) but had lower scores in the total QOL, physical, and health domains (p<0.05). Surgery patients scored better than non-surgery in the behavioral domain and the HASES (Hague Side Effects Scale) score (p<0.05). Non-surgery patients scored worse than healthy in total QOL, physical, behavioral, health, and overall QOL (p<0.05). IQ, HASS (Hague Seizure Severity Scale), and HASES scores were positively associated with total QOL score (p<0.05). Subgroup analysis on seizure-free surgery patients showed that they did not differ from healthy subjects in any of QOL domains (p>0.05, power>0.8). CONCLUSION Our data indicate that epilepsy surgery for partial seizures in children is associated with better QOL as compared to children with intractable epilepsy who are not operated on, and suggest that in those who achieve seizure freedom normal QOL may at least potentially be possible.

Intravenous immunoglobulin therapy in intractable childhood epilepsy: open-label study and review of the literature.

Our aim was to investigate the long term effectiveness of intravenous immunoglobulin (IVIG) against intractable childhood epilepsy in the era of new antiepileptics and to determine the predictors of a favorable response in a prospective open-label add-on study. Of thirty-seven 9.9+/-0.9-year-old patients (11 with partial seizures, 26 with generalized seizures of whom 9 had West syndrome and 17 Lennox-Gastaut syndrome) followed for 15+/-3 months, 43% had a >50% decrease in seizures (including 15% seizure free, 229+/-58 compared with 104+/-3 seizures/month, P=0.035: generalized 246+/-318 to 117+/-200, P=0.025, partial 191+/-437 to 72+/-179, P>0.05; power=0.2). Males were more likely to respond than females (P=0.011, odds ratio=9.3). Review of the literature revealed nine other articles reporting efficacy of IVIG against epileptic seizures. Only one other used statistical methods and, unlike ours, showed only a trend toward seizure frequency reduction without achieving statistical significance, presumably because it was underpowered. These results indicate large-scale controlled studies of IVIG in epilepsy are still needed.

Potential neuroprotective effects of continuous topiramate therapy in the developing brain.

Because antiepileptic drug therapy is usually given chronically with resulting concerns about long-term neurotoxicity, and because short-term topiramate (TPM) therapy has been reported to be neuroprotective against the effects of acute hypoxia, we investigated the long-term effects of continuous TPM therapy during early stages of development. Four groups of rat pups were studied: two sham manipulated normoxia groups and two acute hypoxia groups (at postnatal day [P] 10 down to 4% O(2)), each injected intraperitoneally daily with either vehicle or TPM (30 mg/kg) from P0 to P21. TPM therapy prevented hypoxia-induced long-term (P81) memory impairment (Morris water maze) as well as aggressivity (handling test). The hypoxia group receiving TPM also showed a trend toward reduced CA1 hippocampal cell loss. The aforementioned TPM therapy had no long-term deleterious effects on memory, hyperactivity, or CA1 cell counts in the TPM normoxia group as compared with normal controls.

Programmed cell death in the lithium pilocarpine model: Evidence for NMDA receptor and ceramide-mediated mechanisms

Ceramide is known to induce programmed cell death (PCD) in neural and non-neural tissues and to increase after kainic acid (KA) status epilepticus (SE). Ceramide increases have been shown to depend on NMDA receptor activation in the KA model, but these changes have not been studied in the lithium pilocarpine (LiPC) model. Thus, the purpose of this study was to determine if hippocampal ceramide levels increase after LiPC induced SE and if NMDA receptor blockade prevents PCD and any such ceramide increases. We found that LiPC induced SE resulted in ceramide increases and DNA fragmentation in the hippocampus of adult, P21, and P7 rats. The administration of MK-801, the NMDA receptor antagonist, in adults, 15min prior to pilocarpine, prevented ceramide increases, and DNA fragmentation.

Effects of creatine and cyclocreatine supplementation on kainate induced injury in pre-pubescent rats

Purpose: To investigate if energy precursor supplementation is neuroprotective in two neuroexcitotoxicity models; the kainate and the kainate followed by chronic phenobarbital models. Methods: Rats in experiment 1 received 1% creatine or cyclocreatine chow from age (P) 21–65 days, underwent kainate induced status epilepticus on P35 and were compared, as adults, to kainate alone rats and to normal controls. Rats in experiment 2 received 1% creatine chow (P21–P85), underwent kainate status epilepticus on P35, received daily phenobarbital (or saline) injections (P36–P85) and were compared, as adults, to kainate, kainate-phenobarbital and to normal control rats that received regular chow. Results: In experiment 1, the cyclocreatine-kainate group had increased emotionality and visuospatial learning deficits on the handling and watermaze tests as compared to all other groups. Creatine supplementation did not have any effects. In experiment 2, creatine supplementation did not prevent spontaneous recurrent seizures, aggressivity on the handling test or hippocampal histologic injury. Conclusion: Energy precursor supplementation in the doses used did not have neuroprotective effects in the kainate or kainate-phenobarbital models in pre-pubescent rats.

Epilepsy surgery in a developing country (Lebanon): ten years experience and predictors of outcome

We present our 10-year experience and preoperative predictors of outcome in 93 adults and children who underwent epilepsy surgery at the American University of Beirut. Presurgical evaluation included video-EEG monitoring, MRI, neuropsychological assessment with invasive monitoring, and other tests (PET, SPECT, Wada). Surgeries included temporal (54%), extratemporal (22%), and multilobar resections (13%), hemispherectomy (4%), vagal nerve stimulation (6%), and corpus callosotomy (1%). Mesial temporal sclerosiswas the mostcommonaetiology (37%). After resective surgery, 70% had Engel class I, 9% class II, 14% class III, and 7% class IV. The number of antiepileptic drugs before surgery was the only preoperative factor associated with Engel class I (p=0.005). Despite the presence of financial and philanthropic aid, many patients could not be operated on for financial reasons. We conclude that advanced epilepsy presurgical workups, surgical procedures, and favourable outcomes, comparable to those of developed countries, are achievable in developing countries, but that issues of financial coverage remain to be addressed.

Epilepsy surgery in a developing country (Lebanon)

We present our 10-year experience and preoperative predictors of outcome in 93 adults and children who underwent epilepsy surgery at the American University of Beirut. Presurgical evaluation included video-EEG monitoring, MRI, neuropsychological assessment with invasive monitoring, and other tests (PET, SPECT, Wada). Surgeries included temporal (54%), extratemporal (22%), and multilobar resections (13%), hemispherectomy (4%), vagal nerve stimulation (6%), and corpus callosotomy (1%). Mesial temporal sclerosiswas the mostcommonaetiology (37%). After resective surgery, 70% had Engel class I, 9% class II, 14% class III, and 7% class IV. The number of antiepileptic drugs before surgery was the only preoperative factor associated with Engel class I (p=0.005). Despite the presence of financial and philanthropic aid, many patients could not be operated on for financial reasons. We conclude that advanced epilepsy presurgical workups, surgical procedures, and favourable outcomes, comparable to those of developed countries, are achievable in developing countries, but that issues of financial coverage remain to be addressed.

Landau kleffner syndrome

INTRODUCTION: The Landau Kleffner syndrome (SLK) is associated with paroxystic alterations of the electroencephalogram which are intensified during sleep, with acquired aphasia and epilepsy, in 75 83% of the cases. The syndrome is associated with other features, such as personality disorders presenting as autistic behaviour, cognitive regression and in some cases, motor dysfunction. The epileptic activity appears to be responsible for the disorder. Treatment with anti epileptic drugs is ineffective in many cases, although there may be periods of spontaneous improvement, or there may be permanent sequelas of language. Design. A systematic revision of one case. CASE REPORT: A five year old boy with no previous clinical history had, at the age of four years, presented with behaviour changes and aphasia, accompanied by paroxystic changes on the EEG and nocturnal polysomnogram. On cranial CT there was a mid line cyst. He had had no seizures. Treatment. Treatment with carbamazepine led to clinical improvement in behaviour, reduction in the paroxysms and appearance of sleep spindles, but little effect on the degree of aphasia. CONCLUSIONS: The case described is a variant of SLK, with no epileptic seizures, some improvement on carbamazepine and a mid line cyst.