Ekrem Kutluay

Safety and tolerability of oxcarbazepine in elderly patients with epilepsy.

Despite the high incidence of seizures and epilepsy in the elderly, the tolerability and safety of anticonvulsants are rarely evaluated in this patient population. We compared the safety and tolerability of oxcarbazepine in a cohort of 52 patients aged 65 years and older and a group of 1574 adult patients ranging in age between 18 and 64 years. There was no significant difference between the two groups with respect to premature discontinuation due to adverse events. The four most common adverse events experienced by patients in the elderly group, irrespective of their causal relationship to oxcarbazepine, were vomiting (19%), dizziness (17%), nausea (17%), and somnolence (15%). Three patients developed an asymptomatic hyponatremia, with at least one serum sodium level below 125mEq/L. Elderly patients on concomitant natriuretic drugs were significantly more likely to develop serum sodium levels below 135mEq/L. The results indicate that oxcarbazepine is safe to use in elderly patients and that its tolerability in this age group is similar to that of younger adult patients.

Efficacy of Topiramate in Children with Refractory Status Epilepticus

Summary:  Purpose: Status epilepticus (SE) is a life‐threatening medical condition associated with significant morbidity and mortality that requires urgent medical intervention. Although several agents are available to treat SE, they occasionally fail to abort seizure activity. Topiramate (TPM) was anecdotally reported to be effective in adult patients with refractory SE. In this study, we evaluated the efficacy of TPM administered to children with this condition.

Alternating leg muscle activation during sleep and arousals: A new sleep-related motor phenomenon?

We describe a quickly alternating pattern of anterior tibialis activation, recorded during nocturnal polysomnography in 16 patients. Polysomnography, usually for sleep‐disordered breathing, included surface electromyograms over the anterior tibialis of each leg. Cases were identified from approximately 1,500 studies reviewed in the course of standard clinical care. Patients were 12 men and 4 women (mean age, 41 ± 15 years; range, 12–70 years). Brief activation of the anterior tibialis in one leg alternated with similar activation in the other leg. Activations occurred at a frequency of approximately 1 to 2 Hz, each lasted between 0.1 and 0.5 seconds, and sequences of alternating activations usually lasted between several and 20 seconds. The phenomenon occurred in all sleep stages but particularly during arousals. Ten of the 16 patients had periodic leg movements during sleep at a rate ≥ 5.0 per hour, and 12 of the 16 patients were taking antidepressant medication. Alternating leg muscle activation (ALMA) during sleep, at this relatively high frequency, may be a newly described phenomenon. We speculate that ALMA could represent transient facilitation of a spinal central pattern generator for locomotion, perhaps due to serotonergic effects of antidepressant medication.

Sustained Efficacy and Long‐term Safety of Oxcarbazepine: One‐year Open‐label Extension of a Study in Refractory Partial Epilepsy

Summary:  Purpose: To evaluate the long‐term efficacy, tolerability, and safety of oxcarbazepine (OXC) in medically refractory partial epilepsy.

Sporadic Creutzfeldt–Jakob disease presenting with nonconvulsive status epilepticus

Creutzfeldt-Jakob disease (CJD) is a rare prion disease characterized by a spongiform encephalopathy in humans. Although the characteristic triad of myoclonus, dementia, and periodic EEG activity is easy to recognize, unusual manifestations of the disease may be challenging and create a diagnostic dilemma. We report a case of CJD that occurred in a 26-year-old patient who presented with a receptive (Wernickes) aphasia secondary to nonconvulsive status epilepticus.

Seizure semiology and neuroimaging findings in patients with midline spikes.

Summary:  Purpose: Midline epileptiform discharges are rare compared with discharges at other scalp locations. Neuroimaging results and semiologic seizure characteristics of patients with midline spikes are not adequately described. The aim of this study was to describe the neuroimaging findings and detailed seizure semiologies in patients with midline spikes.

Diagnostic and localizing value of ictal SPECT in patients with nonconvulsive status epilepticus

In this study, we evaluate the diagnostic and localizing value of SPECT in three patients with nonconvulsive status epilepticus (NCSE). Our results indicate that ictal/subtraction ictal SPECT is a useful complementary noninvasive diagnostic test in patients with focal NCSE. This is especially the case when the EEG findings are inconclusive and for patients in whom surgical treatment is being considered.

Full neurologic recovery after fulminant thrombotic thrombocytopenic purpura with status epilepticus

Thrombotic thrombocytopenic purpura (TTP) is an ischemic vasculopathy frequently associated with neurological dysfunction including seizures. However, status epilepticus (SE) has rarely been reported in this condition. We report on a 70-year-old woman with fulminant TTP who developed convulsive SE despite high therapeutic serum levels of phenytoin and phenobarbital. Her electroencephalogram (EEG) was characterized by bilateral independent periodic lateralizing epileptiform discharges (BIPLEDs) propagating into clinical and electrographic seizures. She recovered completely after intensive plasmapheresis and treatment with pentobarbital induced coma for 5 days. This case illustrates that aggressive treatment with pentobarbital and plasmapheresis may prevent permanent neurologic deficits when TTP is complicated by SE and that periodic lateralizing epileptiform discharges (PLEDs) in this syndrome can be the manifestation of a reversible ischemic insult.

Adjunctive clinical trials in epilepsy: is a placebo arm necessary?

One of the fundamental questions that needs to be answered when evaluating an investigational drug in randomized clinical trials is whether the study drug demonstrated efficacy for the condition under evaluation. For patients with epilepsy, clinical trials are initially conducted to assess the efficacy of the investigational agent when administered as adjunctive therapy. This design is derived from ethical concerns that argue against exposing patients with epilepsy to a study drug as monotherapy without some evidence of efficacy. Once efficacy is demonstrated in adjunctive clinical trials, the study drug can be subsequently evaluated in monotherapy trials. The design of add-on clinical trials in patients with localization-related epilepsy has been relatively uniform. Eligible patients are those with medically refractory partial-onset seizures and experiencing a minimum number of monthly seizures (typically four or more seizures/month), while maintaining constant doses of one to three antiepileptic drugs (AEDs). Following a prospective baseline phase of approximately 8 weeks, patients still satisfying the entry criteria and with the required number of seizures are randomized in a doubleblind fashion to add-on treatment with the study drug (at one or multiple daily doses) or to add-on placebo in addition to constant doses of their baseline AEDs. The double-blind period, which consists of a titration and a maintenance phase, typically lasts 12–16 weeks. The primary efficacy variable is the change in seizure frequency during the double-blind period compared to baseline between the study drug and the placebo. A relatively large number of such trials were conducted over the past 15 years and were successful in demonstrating the efficacy of a number of newer AEDs, including felbamate, gabapentin, lamotrigine, topiramate, tiagabine, levetiracetam, oxcarbazepine, and vigabatrin. The availability of such a number of trials of relatively consistent design allows for the opportunity to reconsider if a placebo arm is actually needed in adjunctive clinical trials for patients with medically refractory localization-related epilepsy or whether placebo can be established as a historical control. An argument could be made that a placebo arm in such trials would not be needed if one of two requirements were satisfied. The first would be a ‘‘consistent’’ finding of a negligible placebo effect (e.g., a minimal reduction of seizure frequency of 5% or less for the placebo arm) across clinical trials of similar designs. The other would be a ‘‘homogeneous’’ treatment effect for patients randomized to placebo. For instance, if the placebo response were repeatedly found to be within a limited range (e.g., a 15–20% reduction in seizure frequency across clinical trials), the calculated 95% confidence interval would fall within a narrow range and could be therefore used as a historical control. In such a scenario, patients could be randomized to multiple doses of the study drug (since allocation to only one arm could introduce investigator bias) and the efficacy of the study drug could be compared to that of the historical placebo response. In a recent issue of Epilepsy & Behavior, Burneo et al. evaluated the placebo effect in randomized, placebocontrolled, adjunctive clinical trials conducted in patients with medically refractory localization-related epilepsy and included in the Cochrane Database of Systematic Reviews [1]. The placebo effect was assessed with one efficacy variable, namely the 50% responder rate (patients with a 50% or better improvement in seizure frequency compared to baseline). Based on the results, the authors state ‘‘the effects in the placebo arms appear quite homogenous across trials and meta-analyses.’’ The authors based that conclusion on the observation that ‘‘the response to placebo was similar across meta-analyses’’ ranging from 9.3 to 16.6%. This is an Epilepsy & Behavior 4 (2003) 4–5

Personality and Mood Changes in a Teenager

Publisher Summary This chapter examines the case of a teenager diagnosed with nonconvulsive status epilepticus of frontal lobe origin. The 17-year-old womans medical illness started in February 2000 when she was diagnosed with a left frontal abscess complicating a pansinusitis. She underwent a left frontal craniotomy with an evacuation of the left frontal brain abscess and her sinuses. Perioperatively, she was treated with antibiotics and put on phenytoin prophylaxis for 3 weeks. She was admitted to the hospital for an evaluation. During the 3 days of monitoring, her awake EEG revealed well-modulated posterior 8–9 Hz activity, a left frontal breach rhythm, continuous slowing over the left frontal region, and intermittent bifrontal spikewave activity, which occurred occasionally in bursts of up to 5 s; in addition, a total of five electrographic partial seizures without clinical accompaniment were recorded. On the insistence of the patient and her mother, she was discharged home the next day on levetiracetam 1500 mg/day and divalproex 1250 mg/day. A brain magnetic resonance imaging scan showed an area of encephalomalacia in the left frontal lobe at the site of her known previous abscess. On the combination of levetiracetam 3000 mg/day and divalproex 1500 mg/day she was seizure-free on prolonged EEG monitoring and her personality returned to baseline. The interesting feature of this case was the dissociation between the electrographic findings and the clinical manifestations. Status epilepticus is a medical emergency that requires immediate and aggressive treatment in order to prevent mortality or significant morbidity. Nonconvulsive status epilepticus is usually suspected when there is a sudden and persistent change in mental status or behavior and confirmed by EEG.