Daniela Passarelli

Autosomal Dominant Lateral Temporal Epilepsy: Clinical Spectrum, New Epitempin Mutations, and Genetic Heterogeneity in Seven European Families

Summary:  Purpose: To describe the clinical and genetic findings of seven additional pedigrees with autosomal dominant lateral temporal epilepsy (ADLTE).

Transcranial magnetic stimulation in partial epilepsy: drug-induced changes of motor excitability

Single‐pulse transcranial magnetic stimulation (s‐TMS) with recording of motor evoked potentials (MEPs) from thenar muscles of both hands was performed on 84 patients with cryptogenic partial epilepsy and 50 healthy controls. We analyzed the cortical latency (CL), central conduction time (CCT), and threshold intensity (TI) required to elicit liminal MEPs at rest. In the patients, CL and CCT were normal, but TI was significantly higher than in the controls. Of the 84 patients, 65 were taking one or more antiepileptic drugs and 19 were untreated. The untreated patients had a significantly lower TI than the treated patients. In the treated patients, the TI increase paralleled the number of drugs taken. Additionally, in 2 subgroups of patients undergoing major modifications of antiepileptic treatment, TI dropped after partial withdrawl of medication and increased following the commencement of therapy. The results suggest that anticonvulsants depress the excitability of human motor pathways in epileptic subjects.

Electroclinical features of idiopathic generalised epilepsy with persisting absences in adult life.

OBJECTIVES: To describe the electroclinical features of typical absences persisting in adult life. METHODS: Twelve adult patients (aged 21 to 56 years) with idiopathic generalised epilepsy featuring typical absences as the prominent clinical feature were studied. All patients underwent a full clinical and neurophysiological investigation including ictal documentation of seizures. RESULTS: Neurological examination and neuroradiological investigations were normal in all cases. Clinical findings included a median age at onset of absences of 14 (range 4-32) years, almost constant tonic-clonic seizures (in 83% of patients), frequent episodes of absence status (in 33% of patients), and associated cognitive or psychiatric disturbances. Interictal EEG findings showed normal background activity, generalised paroxysms of spike waves or polyspike waves, and inconstant focal spikes (in five patients); runs of polyspikes were seen during non-REM sleep. Ictal EEG findings showed generalised spike waves at 3 Hz, sometimes preceded by multiple spikes, or more complex EEG patterns with sequences of polyspikes intermingled with spike waves or polyspike waves, showing discharge fragmentation or variation of intradischarge frequency. CONCLUSION: The results of the present study show that absences persisting in adult life may show particular clinical and EEG patterns, distinct from those in childhood or adolescence.

Autosomal dominant partial epilepsy with auditory features: description of a new family.

Summary: Purpose: To report the clinical and genetic study of a new family with autosomal dominant partial epilepsy with auditory features (ADPEAF).

An educational campaign toward epilepsy among Italian primary school teachers 1. Survey on knowledge and attitudes

A questionnaire survey was undertaken to assess the impact of a nationwide educational campaign about epilepsy on the knowledge and attitudes toward the disease among Italian primary school teachers. Five hundred and eighty-two teachers participated. All interviewees were aware of the existence of epilepsy, and most of them had direct experience with the disease. Answers about frequency, causes, outcome, and response to treatments were variable and not correlated with age, residency, and years of experience. Teachers had positive attitudes toward epilepsy, except for the idea that driving and sports can be safe for people with epilepsy. Epilepsy and its treatment were considered a source of learning disability and social disadvantages. Several teachers declared themselves being unable to help a child having seizures. Calling an ambulance was a frequent action. Knowledge and attitudes toward epilepsy are improved compared with those reported in our previous studies. Although this may be a positive reflection of the increasing knowledge and the greater availability of information on epilepsy, there are still areas of uncertainty and incorrect behaviors.

Familial epilepsy and developmental dysphasia: Description of an Italian pedigree with autosomal dominant inheritance and screening of candidate loci

PURPOSE To describe a familial epileptic condition combining a peculiar electro-clinical pattern with developmental language dysfunction in a large Italian kindred. METHODS We studied the clinical and neurophysiological features of a 4-generation family with 10 affected members (3 deceased). We also analysed in 7 affected and 7 healthy members microsatellite markers for 51 candidate loci for epilepsy, including 42 loci containing ion channel genes expressed in the brain, as well as the SPCH1 and SRPX2 loci. RESULTS Five of the seven living affected members (aged 20-58 years) had the full phenotype (seizures, EEG epileptiform abnormalities and dysphasia). The language dysfunction was the first symptom, becoming evident since the period of language development and mainly consisting of phonemic and syntactic paraphasias, difficulty of expression and reduced verbal fluency. The seizures had their onset between 2 and 23 years and were reported as epileptic falls (4) associated or not with myoclonic features, absences (3), tonic-clonic (1) and complex partial seizures (1). The seizures were easily controlled by antiepileptic treatment in all patients except one. In the five patients with a good response of seizures to treatment, the EEG tracings showed the coexistence of focal and generalized epileptiform abnormalities; in the refractory patient the interictal EEG demonstrated bilateral asynchronous fronto-temporal paroxysms with left predominance and ictal SEEG recording suggested a multifocal origin of the discharges. MRI of the brain was normal in all patients. Linkage analysis provided negative LOD scores for all the investigated loci. CONCLUSION We have described a novel familial pattern of epilepsy and developmental dysphasia which is not genetically linked to epilepsy or speech disorder loci, as documented by a candidate-gene linkage approach.

Single-blind, placebo-controlled dose-modification study of vigabatrin in refractory epileptic patients

Thirty patients with drug-resistant epileptic seizures received vigabatrin as add-on treatment in a single-blind, placebo-controlled dose-modification study. After a 3-month baseline period (1 month run-in, 2 months placebo), the patients were given vigabatrin (2 g/day, fixed dose) for 2 months, followed by a 2- to 6-month dose-titration period to achieve the individual optimal dose. Mean monthly seizure frequency significantly decreased from 29.5 seizures during the placebo period to 12.2 while taking vigabatrin, 2 g daily fixed-dose, and to 8.7 during titration phase with vigabatrin, 3 g daily, on average. Sixteen (53%) patients experienced a 50% or greater reduction in seizure frequency compared with placebo, and 3 (10%) patients reported a relevant improvement in seizure severity and duration while on vigabatrin, 3 g daily; therefore, 19 (63%) patients were allowed to continue the treatment on a long-term basis. Adverse effects, mostly drowsiness and weight gain, occurred particularly at the highest vigabatrin dose, although also in any case of mild severity. Serum phenytoin and phenobarbital levels significantly decreased during vigabatrin treatment. These results suggest that vigabatrin in a dose of 2–3 g daily is an effective and safe antiepileptic drug.

Long-term follow-up study of vigabatrin in the treatment of refractory epilepsy

Abstract Thirty adult patients with drug-resistant partial epilepsy who had responded favorably to add-on vigabatrin under placebo-controlled conditions were maintained on long-term treatment with the drug. Twenty patients are still in the trial with a follow-up ranging from 26 to 70 months (median, 60). Ten patients were withdrawn from the study after having received the drug for 4–14 months (median, 9) because of seizure breakthrough (n = 7) and other reasons (n = 3). Overall, the initially favorable therapeutic response was generally maintained during the long-term treatment. Side effects were minor, the most frequent being a moderate gain in body weight. Plasma concentrations of phenytoin were significantly reduced during vigabatrin treatment. Our findings suggest that vigabatrin retains its anticonvulsant efficacy in about two-thirds of the patients after a 5-year follow-up period. Tolerability is also good during long-term treatment.

Mutations in MICAL-1cause autosomal-dominant lateral temporal epilepsy: MICAL-1 Mutations in ADLTE

Autosomal‐dominant lateral temporal epilepsy (ADLTE) is a genetic focal epilepsy characterized by auditory symptoms. Two genes, LGI1 and RELN, encoding secreted proteins, are implicated in the etiology of ADLTE, but half of the affected families remain genetically unsolved, and the underlying molecular mechanisms are yet to be clarified. We aimed to identify additional genes causing ADLTE to better understand the genetic basis and molecular pathway underlying this epileptic disorder.