Faculty Bibliography

Vigabatrin (VGB) is a structural analogue of the inhibitory neurotransmitter gamma-amino butyric acid (GABA), which produces its antiepileptic effect by irreversibly inhibiting the degradative enzyme GABA-transaminase. This produces an increase in central nervous system (CNS) GABA levels. VGB is among the few antiepileptic drugs (AEDs) that was synthesized with a specific targeted mechanism in mind and was subsequently demonstrated to function by that mechanism. Tiagabine, a GABA reuptake blocker, is the only other 'designer drug' among the currently available AEDs. Therefore, VGB is among the few AEDs for which the mechanism of action is well understood. Recently, safety issues have been raised with regard to the use of vigabatrin. This article reviews the mechanism of action, pharmacokinetics, safety, and efficacy of VGB

The advent of numerous new options in epilepsy drag therapy over the last 5 years is enabling a more flexible and individualized approach to patients with seizures and, in many cases, reducing troublesome side effects associated with the more standard anticonvulsants. This article profiles the five most recently approved antiepileptic drugs (felbamate, gabapentin, lamotrigine, topiramate, and tiagabine) and two investigational agents that may soon he approved (vigabatrin and zonisamide), and also briefly discusses new formulations of several older anticonvulsants. No clear differences in efficacy have emerged among the new agents. Although one drug may be clearly superior in an individual patient, accurate prediction of individual response is not possible. Thus, patients with epilepsy should have access to all new antiepileptic drugs. $$:

PURPOSE: The syndrome of temporal lobe epilepsy has been described in great detail. Here we focus specifically on the clinical manifestations of seizures originating in the hippocampus and surrounding mesial temporal structures. METHODS: Seizure origin was confirmed in 67 cases by depth EEG recording and surgical cure after mesial temporal resection. RESULTS: Among nonlateralized manifestations, we commonly found oral automatisms, pupillary dilatation, impaired consciousness, and generalized rigidity. Appendicular automatisms were often ipsilateral to the seizure focus, whereas dystonia and postictal hemiparesis were usually contralateral. Head deviation, when it occurred early in the seizure, was an ipsilateral finding, but was contralateral to the seizure focus when it occurred late. Clear ictal speech and quick recovery were found when seizures originated in the non-language-dominant hemisphere, but postictal aphasia and prolonged recovery time were characteristic of seizure origin in the language-dominant hemisphere. CONCLUSIONS: These signs help to define the mesial temporal lobe epilepsy (MTLE) syndrome and often provide information as to the side of seizure origin

PURPOSE: The objective of this prospective study was to compare the usefulness of a sleep-deprived electroencephalogram (EEG) versus a computer-assisted 16-channel ambulatory EEG in patients with historical information consistent with epilepsy but with a normal or non-diagnostic initial routine EEG. METHODS: A total of 46 patients had both a 30-60 min sleep-deprived EEG and a computer-assisted ambulatory 24 h EEG. Each EEG was assigned a number and reviewed independently by two board-certified electroencephalographers for the presence of interictal epileptiform discharges and seizures. RESULTS: Both the sleep-deprived EEG and ambulatory EEG improved detection of epileptiform discharges by a similar amount (24% versus 33%); however, the ambulatory EEG detected seizures in 7/46 (15%) patients, and in three patients the seizures were solely detected by the computer. CONCLUSIONS: we conclude that the computer-assisted ambulatory EEG offers greater benefit than a sleep-deprived recording because in addition to detecting interictal epileptiform discharges, it may also capture seizures. The discovery of unsuspected seizures can significantly impact clinical management

Lennox-Gastaut syndrome (LGS) is a complex epilepsy of childhood characterised by an EEG demonstrating slow spike and wave complexes, multiple seizure types and cognitive impairment. Control of seizures is difficult, and the effectiveness of established anticonvulsants is often disappointing. In the past few years, many new medications have been introduced for the treatment of partial epilepsy in adults, Emerging evidence suggests that some of these agents are also useful in LGS. Felbamate has been shown to be effective in a large controlled clinical trial, although its use is limited by life-threatening idiosyncratic reactions. Lamotrigine and topiramate have recently been shown in prospective controlled trials to be beneficial and well tolerated in patients with LGS, Vigabatrin appears to be particularly useful in children with underlying tuberous sclerosis. Novel neuroprotective strategies may be tested in the near future, The ketogenic diet has empirical efficacy in some children with intractable seizures. Vagal nerve stimulation is currently being tested in LGS, and preliminary data are encouraging, Anterior callosotomy may provide an improved quality of life in children with frequent 'drop attacks'. These pharmacological and nonpharmacological approaches to the treatment of LGS offer new hope to patients and their families. $$:

Seizures are commonly encountered in patients who do not have epilepsy. Factors that may provoke such seizures include organ failure, electrolyte imbalance, medication and medication withdrawal, and hypersensitive encephalopathy. There is usually one underlying cause, which may be reversible in some patients. A full assessment should be done to rule out primary neurological disease. Treatment of seizures in medically ill patients is aimed at correction of the underlying cause with appropriate short-term anticonvulsant medication. Phenytoin is ineffective in the management of seizures secondary to alcohol withdrawal, and in those due to theophylline or isoniazid toxicity. Control of blood pressure is important in patients with renal failure and seizures. Non-convulsive status epilepticus should be considered in any patient with confusion or coma of unclear cause, and electroencephalography should be done at the earliest opportunity. Most ill patients with secondary seizures do not have epilepsy, and this should be explained to patients and their families. Only those patients with recurrent seizures and uncorrectable predisposing factors need long-term treatment with anticonvulsant medication

OBJECTIVE: To determine the feasibility of using functional magnetic resonance imaging (fMRI) to detect asymmetries in the lateralization of memory activation in patients with temporal lobe epilepsy (TLE). BACKGROUND: Assessment of mesial temporal lobe function is a critical aspect of the preoperative evaluation for epilepsy surgery, both for predicting postoperative memory deficits and for seizure lateralization. fMRI offers several potential advantages over the current gold standard, intracarotid amobarbital testing (IAT). fMRI has already been successfully applied to language lateralization in TLE. METHODS: fMRI was carried out in eight normal subjects and 10 consecutively recruited patients with TLE undergoing preoperative evaluation for epilepsy surgery. A complex visual scene encoding task known to activate mesial temporal structures was used during fMRI. Asymmetry ratios for mesial temporal activation were calculated, using regions of interest defined in normals. Patient findings were compared with the results of IAT performed as part of routine clinical evaluation. RESULTS: Task activation was nearly symmetric in normal subjects, whereas in patients with TLE, significant asymmetries were observed. In all nine patients in whom the IAT result was interpretable, memory asymmetry by fMRI concurred with the findings of IAT including two patients with paradoxical IAT memory lateralization ipsilateral to seizure focus. CONCLUSIONS: fMRI can be used to detect asymmetries in memory activation in patients with TLE. Because fMRI studies are noninvasive and provide excellent spatial resolution for functional activation, these preliminary results suggest a promising role for fMRI in improving the preoperative evaluation for epilepsy surgery