Carlo Di Bonaventura

Diffusion-weighted magnetic resonance imaging in patients with partial status epilepticus

Purpose:  Diffusion‐weighted magnetic resonance imaging (DWI) is used to detect changes in the distribution of water molecules in regions affected by various pathologies. Like other conditions, ictal epileptic activity, such as status epilepticus (SE), can cause regional vasogenic/cytotoxic edema that reflects hemodynamic and metabolic changes. This study describes the electroclinical and neuroimaging findings in 10 patients with partial SE whose DWI evaluation disclosed periictal changes related to sustained epileptic activity.

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

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.

Effects of levetiracetam on EEG abnormalities in juvenile myoclonic epilepsy

Purpose: A multicenter, prospective, long‐term, open‐label study to evaluate the effects of levetiracetam on electroencephalogram (EEG) abnormalities and photoparoxysmal response (PPR) of patients affected by juvenile myoclonic epilepsy (JME).

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.

A pilot trial of levetiracetam in eyelid myoclonia with absences (Jeavons syndrome)

Objective: Eyelid myoclonia with absences (EMA) or Jeavons syndrome characterized by eyelid myoclonia (EM) (with or without absences), eye closure‐induced EEG paroxysms, and photosensitivity. We conducted an open‐label trial of levetiracetam in EMA.

Heterozygous Reelin Mutations Cause Autosomal-Dominant Lateral Temporal Epilepsy

Autosomal-dominant lateral temporal epilepsy (ADLTE) is a genetic epilepsy syndrome clinically characterized by focal seizures with prominent auditory symptoms. ADLTE is genetically heterogeneous, and mutations in LGI1 account for fewer than 50% of affected families. Here, we report the identification of causal mutations in reelin (RELN) in seven ADLTE-affected families without LGI1 mutations. We initially investigated 13 ADLTE-affected families by performing SNP-array linkage analysis and whole-exome sequencing and identified three heterozygous missense mutations co-segregating with the syndrome. Subsequent analysis of 15 small ADLTE-affected families revealed four additional missense mutations. 3D modeling predicted that all mutations have structural effects on protein-domain folding. Overall, RELN mutations occurred in 7/40 (17.5%) ADLTE-affected families. RELN encodes a secreted protein, Reelin, which has important functions in both the developing and adult brain and is also found in the blood serum. We show that ADLTE-related mutations significantly decrease serum levels of Reelin, suggesting an inhibitory effect of mutations on protein secretion. We also show that Reelin and LGI1 co-localize in a subset of rat brain neurons, supporting an involvement of both proteins in a common molecular pathway underlying ADLTE. Homozygous RELN mutations are known to cause lissencephaly with cerebellar hypoplasia. Our findings extend the spectrum of neurological disorders associated with RELN mutations and establish a link between RELN and LGI1, which play key regulatory roles in both the developing and adult brain.

The visual system in eyelid myoclonia with absences.

To investigate the functional and structural brain correlates of eyelid myoclonus and absence seizures triggered by eye closure (eye closure sensitivity [ECS]).

EEG/fMRI Study of Ictal and Interictal Epileptic Activity: Methodological Issues and Future Perspectives in Clinical Practice

Summary:  Purpose: Electroencephalography/functional magnetic resonance imaging (EEG/fMRI) has been proposed recently as a tool to study electrophysiological activity and, consequently, detect brain regions activated during epileptiform EEG abnormalities. The purpose of the study was to review our two‐year experience with studying ictal and interictal activities in patients with epilepsy.

Benign adult familial myoclonic epilepsy (BAFME): evidence of an extended founder haplotype on chromosome 2p11.1-q12.2 in five Italian families

Benign adult familial myoclonic epilepsy (BAFME or FAME) is an autosomal dominant condition, characterized by shivering-like tremors of cortical origin, myoclonus, and epilepsy. Linkage to chromosomes 2p11.1-q12.2 and 8q23.1-q24.11 has been reported in Japanese and Italian families, respectively. We aimed to determine whether a common founder haplotype was shared by five BAFME families from southern Italy and attempted preliminary genotype–phenotype correlation analyses. Five Italian BAFME families were identified. One family has not been previously reported. DNA from 53 affected individuals was genotyped with highly polymorphic microsatellite markers spanning chromosomes 2p11.1-q12.2 and 8q23.1-q24.11. Multipoint linkage analysis was performed using LINKMAP 5.1 software assuming an autosomal dominant trait with 0.99 penetrance and frequency of 0.001. Significant linkage was found on chromosome 2p11.1-q12.2 and a maximum cumulative lod score of 18.5 was found for markers D2S2161 and D2S388. The haplotype “5332” of adjacent markers D2S388, D2S2216, D2S113, and D2S2175 segregates with the disease in all families indicating that the same mutation inherited from a common ancestor segregates in these families. Preliminary genotype–phenotype showed that patients carrying the disease haplotype show minor clinical differences, suggesting that expressivity of the founder mutation is not markedly influenced by other factors. The identification of causative mutations in BAFME requires an extensive and collaborative screening effort.