Angelo Labate

GABA(B) receptor 1 polymorphism (G1465A) is associated with temporal lobe epilepsy

Background: Dysfunction of γ-aminobutyric acid (GABA) (B) receptors has been implicated in the pathogenesis of temporal lobe epilepsy (TLE). Objective: To evaluate the genetic contribution of cloned human GABA(B) receptors to TLE. Methods: The authors genotyped 141 patients (78 women and 63 men; mean age = 49.1 ± 18.0 years) with nonlesional TLE and 372 age- and sex-matched normal individuals for the known polymorphism G1465A in the human GABA(B) receptor 1 [GABA(B[1])] gene. Results: There was a highly significant overrepresentation of the G1465A heterozygote in patients with TLE compared with controls. The A/G genotype was found in 17% of the 141 patients with TLE and in only 0.5% of the 372 controls (p < 0.0001). The authors also found that patients carrying the A allele had a significantly higher risk (p = 0.003, OR = 6.47, 95% CI = 2.02 to 20.76) of developing drug-resistant TLE. Furthermore, the age at onset of seizures tended to be lower in patients with A/G genotype, but the difference was not significant. Conclusions: The results of this study indicate that the GABA(B[1]) polymorphism (G1465A) confers a highly increased susceptibility to TLE. Moreover, it seems to influence the severity of this common epileptic disorder.

Neuroanatomic correlates of psychogenic nonepileptic seizures: A cortical thickness and VBM study

Purpose:  Psychogenic nonepileptic seizures (PNES) are among the most common clinical manifestations of conversion disorder and consist of paroxysmal behavior that resembles epileptic seizures. Preliminary data from functional neuroimaging studies gave plausible evidence that limbic circuits and sensorimotor cortex might be engaged in conversion disorder. Nonetheless, no advanced magnetic resonance imaging (MRI) studies have focused on patients with PNES.

Hippocampal and thalamic atrophy in mild temporal lobe epilepsy : A VBM study

Background: Patients with temporal lobe epilepsy (TLE) often have mild drug-responsive epilepsy which is frequently associated with MRI detectable mesial temporal sclerosis (MTS), indicating that MTS is not necessarily related to seizure severity. To better define the anatomic substrates associated with TLE, we applied voxel-based morphometry (VBM) analysis to patients with mild TLE. Methods: Optimized VBM was applied to the MRI brain images of 95 consecutive unrelated patients who were diagnosed with mild TLE and to 37 healthy controls. We complemented the investigation by calculating the gray matter volume of regions of interest (ROIs) in the bilateral hippocampus. Standard MRI scans revealed evidence of MTS (pTLE) in 34 patients, and no evidence of MTS in the remaining 61 (nTLE). Results: The VBM analysis provided evidence of a reduction in gray matter volume in the hippocampus and thalami. The gray matter volume reduction in the thalamic and hippocampal networks was significantly more severe in patients with pTLE than in the nTLE or the control groups (at a threshold of FWE-corrected p < 0.05). Patients with nTLE showed the same gray matter abnormalities at an uncorrected statistical threshold (p < 0.001) compared to normal controls. ROI analysis confirmed the ipsilateral hippocampal atrophy that was detected in routine MRI scans. Conclusions: The structural abnormalities seen in patients with mild temporal lobe epilepsy (TLE) demonstrate that a temporo-limbic pathway, which includes the thalamus, plays a major role in the pathogenesis of TLE. It is likely that other factors, especially genetic ones, play a major role in the causation and severity of TLE. GLOSSARY: ANCOVA = analysis of covariance; ANOVA = analysis of variance; FC = febrile convulsion; FWE = family-wise error; GM = gray matter; Hf = hippocampus; MTLE = mesial TLE; MTS = mesial temporal sclerosis; nTLE = patients with TLE without mesial temporal sclerosis; pTLE = patients with TLE with mesial temporal sclerosis; ROI = region of interest; TIV = total intracranial volume; TLE = temporal lobe epilepsy; VBM = voxel-based morphometry; WM = white matter.

MRI evidence of mesial temporal sclerosis in sporadic "benign" temporal lobe epilepsy.

Objective: To determine whether there is MRI-detectable mesial temporal sclerosis (MTS) in patients with sporadic benign temporal lobe epilepsy (BTLE). Methods: Brain MRIs were obtained from 101 consecutive, unrelated patients (51 women; mean age 37.3 ± 17.5 years; range 10 to 83 years) with BTLE, who reported rarely or never having had seizures at the time of long-term (>2 years) follow-up. The mean age at seizure onset was 22.3 ± 17.4 years; the mean duration of epilepsy was 16.4 ± 14.1 years. MRI diagnosis of MTS was based on the occurrence of hippocampal formation atrophy on T1 slices, an increased mesial temporal signal intensity alteration on fluid-attenuated inversion-recovery (FLAIR) or T2 images, or both. Results: Thirty-nine of 101 patients (38.6%) had MRI evidence of unilateral MTS (19/39 left MTS, 20/39 right MTS), which correlated with the epileptiform activity. Hyperintense FLAIR and T2 signal with or without atrophy was observed in 24 of 39 individuals. There was no difference between patients with or without MRI-detected MTS in age at onset and duration of epilepsy. Family history of epilepsy or febrile convulsions (FCs) was more frequent in patients with MRI-detected MTS (36%) as compared with patients with normal MRI (22.7%), but the difference was not significant. Antecedent FCs were more frequent (p = 0.03) in patients with MRI-detected MTS (9/39; 23%) vs those with normal MRI (5/62; 8%). Conclusions: MRI-detected mesial temporal sclerosis is often encountered in patients with sporadic benign temporal lobe epilepsy.

Impact of catechol-O-methyltransferase Val108/158 Met genotype on hippocampal and prefrontal gray matter volume

A variation in catechol-O-methyltransferase (COMT) gene (Val108/158Met) affects the physiological response of hippocampal–prefrontal circuits, predicts variation in human memory and is associated with increased risk for psychiatric disorders. Using optimized voxel-based morphometry we studied the effect of this functional polymorphism on the anatomy of the hippocampus, and the prefrontal cortex. Fifty-seven healthy participants were investigated (nine had Met/Met, 30 Val/Met, and 14 Val/Val). Voxel-based morphometry showed that individuals who are homozygous for the Val–COMT allele had greater gray matter volume of the prefrontal cortex bilaterally, whereas Met–COMT carriers were associated with increased tissue volume of the hippocampus bilaterally. This study provides evidence that the Val108/158Met polymorphism of the COMT gene might be responsible for individual variation in the human brain morphology.

Silent Celiac Disease in Patients with Childhood Localization-Related Epilepsies

Summary:  Purpose: To evaluate how many patients with a clinical picture of idiopathic childhood localization‐related epilepsies may also have silent celiac disease (CD). This will help determine whether investigation for CD should be restricted to those patients with childhood partial epilepsy with occipital paroxysms (CPEO) or should be extended to all patients with childhood partial epilepsy (CPE) regardless of seizure type and electroencephalographic (EEG) paroxysms.

Two Novel SCN1A Missense Mutations in Generalized Epilepsy with Febrile Seizures Plus

) for muta-tions in SCN1A, SCN1B, and GABRG2 genes (1–3).Probands were ascertained from the clinical practice inthree epilepsy centers in southern Italy. Detailed familypedigrees were constructed, including maternal and pa-ternal lines extending as far back as possible. In the ninefamilies, we investigated 110 members of whom 37 indi-viduals were determined to be affected. Most patients hadfebrile seizures (FSs) or FS plus (FS

Benign mesial temporal lobe epilepsy

Benign mesial temporal lobe epilepsy (bMTLE), which is defined as at least 24 months of seizure freedom with or without antiepileptic medication, has probably been under-recognized because of a literature bias toward refractory epilepsy cases. Seizure onset in bMTLE tends to be in adolescence or adulthood, and patients frequently have a family history of febrile seizures and epilepsy. Long-term seizure freedom is observed with or without antiepileptic medication. On brain MRI, nearly 40% of patients with long-standing bMTLE show evidence of hippocampal sclerosis, a feature usually associated with refractory temporal lobe epilepsy. Prospective studies are needed to determine the features that allow prediction of a benign course, and to clarify the significance of hippocampal MRI changes.

The parkin gene is not involved in late-onset Parkinson’s disease

Mutations in the parkin gene have been reported in patients with early onset PD. The authors investigated the parkin gene in 118 patients who had an onset of PD after age 45 years: 95 subjects were sporadic patients and 23 subjects were from 18 families with a probable autosomal recessive inheritance. No pathogenetic mutations in the parkin gene were detected either in familial or in sporadic patients. Moreover, no differences were found between patients and 100 age-matched normal controls in the allele and genotype frequencies of four exonic parkin polymorphisms.

Cerebral venous thrombosis and isolated intracranial hypertension without papilledema in CDH

BackgroundThere is evidence that patients with chronic daily headache (CDH) may have isolated intracranial hypertension without papilledema (IHWOP). Recent studies have emphasized that isolated IH may be due to cerebral venous thrombosis (CVT). ObjectiveTo detect the occurrence of CVT in patients with CDH. MethodsThe authors investigated the occurrence of CVT in 114 consecutive patients with CDH by using MR venography (MRV). A portion of these patients underwent a lumbar puncture (LP) to measure CSF pressure. MRV and LP were also performed in 28 age-matched control subjects. ResultsIn all the control subjects, both MRV and CSF pressure were normal. One hundred three of the 114 patients with CDH had normal MRV. Twenty-seven (Group 1) of these 103 patients underwent LP, and all of them had normal CSF pressure. Eleven (9.6%) of the 114 patients with CDH had CVT of one or both transverse sinuses. Six of these 11 patients had flowing abnormalities of one transverse sinus (Group 2), whereas the remaining five patients showed involvement of both transverse sinuses (Group 3). The CSF pressure of Group 2 was higher than that of either Group 1 or the control subjects, and one of the six patients showed isolated IHWOP. Patients of Group 3 displayed the highest CSF pressure, and four of five had isolated IHWOP. The headache profiles of patients with CDH and CVT did not differ from those of patients with CDH but normal MRV. ConclusionsCVT, as detected by MRV, occurred in 9.6% of patients who presented with CDH. Almost half of the patients with CVT had isolated IHWOP. These results suggest that MRV may be a useful tool for selecting patients with CDH who should have LP to exclude isolated IHWOP.