Serap Saygi

Frontal lobe partial seizures and psychogenic seizures Comparison of clinical and ictal characteristics

Of all partial seizures, those of frontal lobe origin (FLPS) are most bizarre and are often mistaken for psychogenic seizures (PS). The reverse can also be true. To clarify the confusing clinical presentation of these different seizure types, we compared the clinical ictal characteristics of 63 FLPS in 11 patients with 29 PS in 12 patients. Patients with PS had significantly later age at onset and longer ictal duration. There was no statistically significant difference between the two groups with respect to history of psychiatric disorder, ictal pelvic thrusting, rocking of body, side-to-side head movements, or rapid postictal recovery, all of which previously have been reported as characteristic features of PS. Turning to a prone position during the seizure occurred only in FLPS. Nocturnal occurrence, short ictal duration, younger age at onset, stereotyped patterns of movements, and MRI and EEG abnormality suggested FLPS.

Lafora disease due to EPM2B mutations A clinical and genetic study

Objective: To study EPM2B gene mutations and genotype-phenotype correlations in patients with Lafora disease. Methods: The authors performed a clinical and mutational analysis of 25 patients, from 23 families, diagnosed with Lafora disease who had not shown mutations in the EPM2A gene. Results: The authors identified 18 mutations in EPM2B, including 12 novel mutations: 4 nonsense mutations (R265X, C26X, W219X, and E67X), a 6-base pair (bp) microdeletion resulting in a two amino acid deletion (V294_K295del), a 4-bp insertion resulting in a frameshift mutation (S339fs12), and 6 missense mutations (D308A, I198N, C68Y, E67Q, P264H, and D233A). In our data set of 77 families with Lafora disease, 54 (70.1%) tested probands have mutations in EPM2A, 21 (27.3%) in EPM2B, and 2 (2.6%) have no mutations in either gene. The course of the disease was longer in patients with EPM2B mutations vs patients with EPM2A mutations. Conclusions: Genetic allelic heterogeneity is present in Lafora disease associated with mutations in EPM2B. Patients with mutations in EPM2A and EPM2B express similar clinical manifestation, although patients with EPM2B-associated Lafora disease seem to have a slightly milder clinical course. The lack of mutations in EPM2A and EPM2B in two families could be because of the presence of mutations in noncoding, nontested regions or the existence of an additional gene associated with Lafora disease.

Recessive LAMC3 mutations cause malformations of occipital cortical development

The biological basis for regional and inter-species differences in cerebral cortical morphology is poorly understood. We focused on consanguineous Turkish families with a single affected member with complex bilateral occipital cortical gyration abnormalities. By using whole-exome sequencing, we initially identified a homozygous 2-bp deletion in LAMC3, the laminin γ3 gene, leading to an immediate premature termination codon. In two other affected individuals with nearly identical phenotypes, we identified a homozygous nonsense mutation and a compound heterozygous mutation. In human but not mouse fetal brain, LAMC3 is enriched in postmitotic cortical plate neurons, localizing primarily to the somatodendritic compartment. LAMC3 expression peaks between late gestation and late infancy, paralleling the expression of molecules that are important in dendritogenesis and synapse formation. The discovery of the molecular basis of this unusual occipital malformation furthers our understanding of the complex biology underlying the formation of cortical gyrations.

Psychiatric morbidity, quality of life, and disability in mesial temporal lobe epilepsy patients before and after anterior temporal lobectomy

Considerable interest has been focused on the psychiatric complications of medically refractory temporal lobe epilepsy (TLE) before and after epilepsy surgery. The aim of the present study was to evaluate the psychiatric status, quality of life, and level of disability in medically refractory mesial temporal lobe epilepsy (MTLE) patients, a homogenous subgroup of patients with TLE, before and after anterior temporal lobectomy (ATL). The study population consisted of 22 patients with medically refractory MTLE who were candidates for ATL. Patients were examined before surgery as well as in the third and sixth months of the postoperative period. Psychiatric diagnosis was determined by using SCID-I. To rate the severity of psychiatric disorders, BPRS, HDRS, and HARS were employed on each visit. WHO-DAS-II and WHOQOL-BREF were used to determine the level of disability and quality of life. Preoperatively, six patients had a psychiatric diagnosis. Three months after surgery, six of the patients had psychiatric diagnoses. Five of these six patients had not been previously diagnosed. There was no significant difference between preoperative and postoperative follow-up evaluations in terms of HDRS, HARS, and BPRS ratings. With respect to the total scores and domains of WHO-DAS-II, the change in pre- and postoperative evaluations was statistically significant only for the social life attendance domain. There was no significant difference in the mean scores on the WHOQOL-BREF domains or on the first question about general evaluation of quality of life. For the second question on the level of satisfaction with health, the difference between the three ratings was statistically significant. Preoperative and postoperative rates of psychiatric disorders in our sample were low. While social phobia was frequently seen preoperatively, the postoperative period was spearheaded by major depressive disorder. The decrease in disability in attendance to social life and improvement in the quality of health were in concordance with the literature, indicating the positive results of surgical treatment of epilepsy on quality of life. This study suggests that surgical intervention might be one of the causes of postoperative psychiatric disorders in patients with MTLE.

Generalised periodic epileptiform discharges: clinical features, neuroradiological evaluation and prognosis in 37 adult patients

Generalised periodic epileptiform discharges (GPEDs) are very rare patterns and are classified as periodic short-interval diffuse discharges (PSIDDs), periodic long-interval diffuse discharges (PLIDDs) and suppression-burst patterns according to the interval between the discharges. In this study we analysed the demographics, history of the seizures during the current illness, mental status, diagnosis, metabolic abnormalities, neuroimaging studies and prognosis of 37 adult patients who had GPEDs in their EEGs. Ages ranged from 17 to 82 years (mean 45 years). There were 19 males and 18 females. The most common aetiology of GPEDs was metabolic and/or infectious disease which was established in 22 patients (59.5%). Other aetiologies included subacute sclerosing panencephalitis (SSPE) in 11 patients (29.7%) and Creutzfeld-Jakob disease (CJD) in 4 patients (10.8%). We showed that structural lesions were found in most of the patients with GPEDs, but concurrent metabolic abnormalities and/or infectious diseases were also detected. Consciousness was impaired and clinical conditions were poor in various degrees in all of the patients when GPEDs were seen. Relatively little is known regarding the mechanism of GPEDs. When GPEDs are seen in EEG, the patient should carefully be checked for metabolic abnormalities and/or infectious diseases and intracranial lesions. GPEDs may be helpful in the determination of prognosis, showing the poor prognosis especially in cases when suppression-burst pattern is seen.

Differentiation of temporal lobe ictal behavior associated with hippocampal sclerosis and tumors of temporal lobe.

Summary: Ictal behavioral characteristics may reflect seizure spread patterns and provide a clue to seizure onset location, between or within specific cerebral lobes. Sequential symptomatology might therefore distinguish patients with hippocampal sclerosis from patients with temporal lobe tumors. To determine ictal behavioral differences in patients of these groups, we analyzed 145 seizures of 33 patients with hippocampal sclerosis (group I) and 79 seizures of 22 patients with temporal lobe tumors (group 11). First appearance of a variety of ictal behavioral characteristics was determined in three phases (first 5 s, 5–60 s, and from 60 s to mental clearing) for patients in both groups. Ipsilateral hand automatisms were significantly more frequent in the first 60 s in group I (p < 0.005). Onset of contralateral head turning was observed in the first 5 s only in group Il (p < 0.05). First appearance of leg automatisms in group I and of oral automatisms in group Il were very rare in phase 2 (p < 0.01, p < 0.005). Time of onset of other ictal behavioral characteristics and duration of seizures were not statistically different between the two groups. Ictal behavioral characteristics varied among and within patients and patient groups, but certain behavioral characteristics were helpful in differentiating these two groups of temporal lobe epilepsy (TLE) patients.

Investigation of HSV-1, HSV-2, CMV, HHV-6 and HHV-8 DNA by real-time PCR in surgical resection materials of epilepsy patients with mesial temporal lobe sclerosis

OBJECTIVE The objective of this study is to investigate the presence of viral DNAs of HSV-1, HSV-2, HHV-6, HHV-8, and CMV in hippocampus of the patients with mesial temporal lobe epilepsy (MTLE) syndrome. METHODS Pathological specimens were obtained from 33 patients with MTLE undergone temporal lobectomy with amygdalo-hippocampectomy due to intractable seizures. Autopsy materials from the hippocampus of 7 patients without neurological disease were used as controls. The data was also correlated with the clinical history of patients including febrile convulsions, age, and history of CNS infections. Real-time polymerase chain reaction method was performed for detection of DNAs of these viruses. RESULTS HHV-6, HSV-1 and HHV-8 were detected in the hippocampus of 3, 2 and 1 patients with MTLE respectively. None of the hippocampus of patients with MTLE was positive for DNA of HSV-2 and/or CMV. Three patients with positive HHV-6 DNAs had febrile convulsions and family history for epilepsy. None of our control specimens showed PCR positivity to any of the 5 tested viruses. CONCLUSIONS Our study is the first to report the presence of HHV-8 viral genome in the brain tissue of patient with MTLE. Viral DNAs were detected in a total of 18% of the patients in this study; we can conclude that activity of the latent virus in patients with hippocampal sclerosis should be more extensively studied to establish its role in active infection.

Serial analysis of gene expression in the hippocampus of patients with mesial temporal lobe epilepsy

Hippocampal sclerosis constitutes the most frequent neuropathological finding in patients with medically intractable mesial temporal lobe epilepsy. Serial analysis of gene expression was used to get a global view of the gene profile in human hippocampus in control condition and in epileptic condition associated with hippocampal sclerosis. Libraries were generated from control hippocampus, obtained by rapid autopsy, and from hippocampal surgical specimens of patients with mesial temporal lobe epilepsy and the classical pattern of hippocampal sclerosis. More than 50,000 tags were analyzed (28,282, control hippocampus; 25,953, hippocampal sclerosis) resulting in 9206 (control hippocampus) and 9599 (hippocampal sclerosis) unique tags (genes), each representing a specific mRNA transcript. Comparison of the two libraries resulted in the identification of 143 transcripts that were differentially expressed. These genes belong to a variety of functional classes, including basic metabolism, transcription regulation, protein synthesis and degradation, signal transduction, structural proteins, regeneration and synaptic plasticity and genes of unknown identity of function. The database generated by this study provides an extensive inventory of genes expressed in human control hippocampus, identifies new high-abundant genes associated with altered hippocampal morphology in patients with mesial temporal lobe epilepsy and serves as a reference for future studies aimed at detecting hippocampal transcriptional responses under various pathological conditions.

Is the Cell Death in Mesial Temporal Sclerosis Apoptotic

Summary:  Purpose: Mesial temporal sclerosis (MTS) is characterized by neuronal loss in the hippocampus. Studies on experimental models and patients with intractable epilepsy suggest that apoptosis may be involved in neuronal death induced by recurrent seizures.

Prognosis of patients with mesial temporal lobe epilepsy due to hippocampal sclerosis

PURPOSE Hippocampal sclerosis (HS) is the most common pathology in mesial temporal lobe epilepsy (MTLE). There are a few reports concerning prognosis in patients with MTLE-HS treated medically. The study was carried out to determine the clinical risk factors affecting prognosis. METHODS We enrolled 287 patients with MTLE-HS treated medically. Gender, age at onset of epilepsy, history of trauma, infection, febrile convulsion, status epilepticus, mental retardation, handedness, consanguinity, side of hippocampal sclerosis, additional extrahippocampal temporal lesion, aura, seizures types, antiepileptic drugs, psychiatric disturbances and seizure frequency were noted. All patients were divided into three groups. Group I: patients seizure-free during follow up, Group II: patients with improved seizure control whose seizure frequency had decreased >50% after the treatment, and Group III: patients with poor seizure control whose seizure frequency had no change or increased. Each clinical feature was also compared among three subgroups statistically. RESULTS Early age of seizure onset [Group II-III (p=0.000) and Group I-III (p=0.0004)], age of head trauma [Group II-III (p=0.04)], the presence of mental retardation (p=0.04) and female sex (p=0.03) were risk factors for poor prognosis. However, the other parameters did not affect prognosis. CONCLUSION Recognizing bad prognostic features such as the presence of mental retardation, early age of seizure onset, age of head trauma and female gender may help physicians to identify risk groups with MTLE-HS and drug resistance seizures for epilepsy surgery.