Gabriella Egeo

Epilepsy with auditory features: A LGI1 gene mutation suggests a loss-of-function mechanism

Autosomal dominant partial epilepsy with auditory features (ADPEAF) is a genetically heterogeneous disorder. Some patients exhibit mutations in the leucine‐rich glioma inactivated (LGI1) gene. In an ADPEAF family, a novel mutation in the Lgi1 signal peptide is predicted to interfere with the protein cell sorting, resulting in altered processing. This finding suggests a loss‐of‐function mechanism for LGI1 gene mutations causing ADPEAF even if other mechanisms cannot be ruled out. Ann Neurol 2003;53:396–399

Familial mesial temporal lobe epilepsy (FMTLE) : a clinical and genetic study of 15 Italian families.

AbstractIntroductionFamilial mesial temporal lobe epilepsy (FMTLE) is characterized by prominent psychic and autonomic seizures, often without hippocampal sclerosis (HS) or a previous history of febrile seizures (FS), and good prognosis. The genetics of this condition is largely unknown.We present the electroclinical and genetic findings of 15 MTLE Italian families.Patients and methodsFMTLE was defined when two or more first-degree relatives had epilepsy suggesting a mesial temporal lobe origin. The occurrence of seizures with auditory auras was considered an exclusion criterion. Patients underwent video-EEG recordings, 1.5-Tesla MRI particularly focused on hippocampal analysis, and neuropsychological evaluation. Genetic study included genotyping and linkage analysis of candidate loci at 4q, 18q, 1q, and 12q as well as screening for LGI1/Epitempin mutations.ResultsMost of the families showed an autosomal dominant inheritance pattern with incomplete penetrance. Fifty-four (32 F) affected individuals were investigated. Twenty-one (38.8 %) individuals experienced early FS. Forty-eight individuals fulfilled the criteria for MTLE. Epigastric/visceral sensation (72.9 %) was the most common type of aura, followed by psychic symptoms (35.4 %), and déjà vu (31.2 %). HS occurred in 13.8% of individuals, three of whom belonged to the same family. Prognosis of epilepsy was generally good. Genetic study failed to show LGI1/Epitempin mutations or significative linkage to the investigated loci.DiscussionFMTLE may be a more common than expected condition, clinically and genetically heterogeneous. Some of the reported families, grouped on the basis of a specific aura, may represent an interesting subgroup on whom to focus future linkage studies.

Video-EEG Study of Psychogenic Nonepileptic Seizures: Differential Characteristics in Patients with and without Epilepsy

Summary:  Purpose: Psychogenic nonepileptic seizures (PNES) are episodes that may resemble epileptic seizures (ES) but are not associated with abnormal electrical discharges in the brain. Video‐EEG recording of a typical episode is considered the best diagnostic tool available. PNES are, however, also documented in patients with epilepsy (PNES/ES). The purpose of this study was to assess this comorbid population, focusing on the differences between patients with PNES/ES and patients with PNES alone.

High prevalence of epilepsy in a village in the Littoral Province of Cameroon

PURPOSE In the Littoral Province of Cameroon, in the Sanaga River Valley, a door-to-door epidemiological study was carried out in order to evaluate the prevalence of epilepsy in a small village located in a geographically isolated area, hyper-endemic for onchocerciasis. It was followed by an electro-clinical evaluation of patients and a case-control study. METHODS The study involved a three-phases design: in phase I, a screening questionnaire was administered, in phase II, the presence of epilepsy was confirmed with electro-clinical evaluation, and in phase III, risk factors for epilepsy, socio-economical factors and life habits were evaluated in patients and two matched controls for the age (+/-1 year) residents in the same village. Endemicity level of onchocerciasis was assessed in the village by measuring the prevalence of nodules in adult males aged >or=20 years (PNAM). RESULTS One hundred eighty-one subjects (100 male and 81 female) were examined (91.9% of the overall population). The crude prevalence rate of active epilepsy was 105 per 1000 pop (CI 95% 60-150) while the age-adjusted prevalence rate was 134.5 cases per 1000 pop (CI 95% 90-178). Seizures were classified as generalized in 10 patients (52.6%) and partial in nine (47.4%). In 17 patients EEG was recorded. Afterward the electro-clinical classification this distribution was inverted: generalized seizures occurred in 35.3% of cases and partial seizures in 64.7% of cases. The PNAM was 62.5%. The surveyed village was classified as hyper-endemic for onchocerciasis. Among risk factors, only positive family history for epilepsy was found (p=0.031). A sample pedigree of a family with 10 epileptic cases (4 included in the epidemiological study) was showed. CONCLUSIONS To our knowledge, this is the first door-to-door study that produce an adjusted prevalence rate on epilepsy in Cameroon. In according to studies done in Tanzania, Liberia, Uganda, and Ethiopia, our results (i.e., the high prevalence rate in a restricted area, the clinical characteristics of epileptic seizures, the positive family history for epilepsy and the type of pedigree of a family with epileptic patients) may be accounted for by the presence of an strong interaction between environmental and genetic factors in some circumscribed areas.

Autosomal dominant lateral temporal epilepsy: Absence of mutations in ADAM22 and Kv1 channel genes encoding LGI1-associated proteins.

Mutations in the LGI1 gene are linked to autosomal dominant lateral temporal epilepsy (ADTLE) in about half of the families tested, suggesting that ADLTE is genetically heterogeneous. Recently, the Lgi1 protein has been found associated with different protein complexes and two distinct molecular mechanisms possibly underlying ADLTE have been hypothesized: the one recognizes Lgi1 as a novel subunit of the presynaptic Kv1 potassium channel implicated in the regulation of channel inactivation, the other suggests that Lgi1 acts as a ligand that selectively binds to the postsynaptic receptor ADAM22, thereby regulating the glutamate-AMPA neurotransmission. Both mechanisms imply that LGI1 mutations result in alteration of synaptic currents, though of different types. Since their protein products have been found associated with Lgi1, the Kv1 channel subunit genes KCNA1, KCNA4, and KCNAB1 and ADAM22 can be considered strong candidates for ADLTE. We sequenced their coding exons and flanking splice sites in the probands of 9 carefully ascertained ADLTE families negative for LGI1 mutations. We failed to detect any mutation segregating with the disease, but identified several previously unreported polymorphisms. An association study of four non-synonymous variants (three found in ADAM22, one in KCNA4) in a population of 104 non-familial lateral temporal epilepsy cases did not show any modification of susceptibility to this disorder. Altogether, our results suggest that neither ADAM22 nor any of the three Kv1 channel genes are major causative genes for ADLTE.

Drug resistant ADLTE and recurrent partial status epilepticus with dysphasic features in a family with a novel LGI1mutation: electroclinical, genetic, and EEG/fMRI findings.

Purpose:  We characterized a family with autosomal dominant lateral temporal epilepsy (ADLTE) whose proband presented uncommon electroclinical findings such as drug‐resistant seizures and recurrent episodes of status epilepticus with dysphasic features.

Ictal epileptic headache as “subtle” symptom in generalized idiopathic epilepsy

Epilepsy and migraine are common neurologic chronic disorders with episodic manifestations characterized by recurrent attacks and a return to baseline conditions between attacks. Epilepsy and migraine are frequently observed in comorbidity, with the occurrence of one disorder increasing the probability of the other: Migraine occurs in about one‐fourth of patients with epilepsy, whereas epilepsy is present in 8–15% of patients with migraine. The link between headache and seizures is controversial and multifactorial. In epilepsy, headache can be seen as a preictal, ictal, or postictal phenomenon. In this report, we describe a case of a 37‐year‐old patient, affected by both drug‐resistant generalized idiopathic epilepsy and headache, who displayed the sudden onset of a headache attack referred during a 24‐h electroencephalography (EEG). The EEG tracing during this event revealed the activation of subcontinuous epileptic activity consisting of generalized spike‐wave discharges (GSWDs) and generalized polyspike and wave discharges (GPSWDs) that persisted for 60 min, that is, until the disappearance of the headache. The case we describe appears to be original in that it represents one of the few EEG‐documented ictal epileptic headaches in generalized idiopathic epilepsy.

A case-control study on excessive daytime sleepiness in chronic migraine

BACKGROUND Excessive daytime sleepiness is a major clinical and health concern that can have varied and sometimes harmful consequences. Findings from uncontrolled studies suggest a high prevalence in patients with chronic migraine. METHODS In a case-control study, we compared frequency data for excessive daytime sleepiness in 100 patients with chronic migraine and 100 healthy controls paired for sex and age, and assessed risk factors including lifestyle, sleep quality, anxiety, depression, concomitant disease and medications. RESULTS The frequency of excessive daytime sleepiness was higher in migraineurs (especially in those with medication overuse) than in controls (20% versus 6%; odds ratio 3.92, 95% CI 1.5-10.22), but was lower than previously reported and correlated with poor quality sleep and anxiolytic and antidepressant use. CONCLUSIONS Again confirming that disability in chronic migraine is multifactorial in origin, excessive daytime sleepiness, especially in migraineurs who overuse medications, adds to the multiple factors known to impair social and working function. Patients with chronic migraine might benefit from diagnostic interviews focussing also on sleep problems and from targeted psychoactive drug prescribing.

Low penetrance of autosomal dominant lateral temporal epilepsy in Italian families without LGI1 mutations.

In relatively small series, autosomal dominant lateral temporal epilepsy (ADLTE) has been associated with leucine‐rich, glioma‐inactivated 1 (LGI1) mutations in about 50% of the families, this genetic heterogeneity being probably caused by differences in the clinical characteristics of the families. In this article we report the overall clinical and genetic spectrum of ADLTE in Italy with the aim to provide new insight into its nosology and genetic basis.

Cerebral transverse sinus morphology as detected by MR venography in patients with chronic migraine.

Objective.— To clarify the frequency and characteristics of altered transverse sinus morphology in a series of consecutive patients with chronic migraine.