Discriminant analysis using MRI asymmetry indices and cognitive scores of women with temporal lobe epilepsy or schizophrenia.

PURPOSE: This study aims to assess the diagnostic power of brain asymmetry indices and neuropsychological tests for differentiating mesial temporal lobe epilepsy (MTLE) and schizophrenia (SCZ). METHODS: We studied a total of 39 women including 13 MTLE, 13 SCZ, and 13 healthy individuals (HC). A neuropsychological test battery (NPT) was administered and scored by an experienced neuropsychologist, and NeuroQuant (CorTechs Labs Inc., San Diego, California) software was used to calculate brain asymmetry indices (ASI) for 71 different anatomical regions of all participants based on their 3D T1 MR imaging scans. RESULTS: Asymmetry indices measured from 10 regions showed statistically significant differences between the three groups. In this study, a multi-class linear discriminant analysis (LDA) model was built based on a total of fifteen variables composed of the most five significantly informative NPT scores and ten significant asymmetry indices, and the model achieved an accuracy of 87.2%. In pairwise classification, the accuracy for distinguishing MTLE from either SCZ or HC was 94.8%, while the accuracy for distinguishing SCZ from either MTLE or HC was 92.3%. CONCLUSION: The ability to differentiate MTLE from SCZ using neuroradiological and neuropsychological biomarkers, even within a limited patient cohort, could make a substantial contribution to research in larger patient groups using different machine learning techniques.

Encephalocraniocutaneous Lipomatosis: Haberland Syndrome.

BACKGROUND Encephalocraniocutaneous lipomatosis (ECCL) was first announced as a new type of ectomesodermal dysgenesis in 1970 by Haberland and Perou. ECCL was first described in 1970, and approximately 60 cases have been reported since then. The classic triad of ECCL are skin, ocular, and central nervous system involvement, including conditions such as unilateral porencephalic cyst, ipsilateral lipomatous hamartoma of the scalp-eyelids-eye globe, cortical atrophy, cranial asymmetry, developmental delay, seizures, mental retardation, and spasticity of the contralateral limbs. The dermatological hallmark is a hairless fatty tissue nevus of the scalp called nevus psiloliparus. CASE REPORT An 11-year-old right-handed boy, born at full term, was referred to our clinic. His family had no consanguinity or history of neurocutaneous disease. The patient's physical examination revealed a large hairless lesion on the right frontoparietal scalp called nevus psiloliparus. Beginning from the birth, a dermolipoma (an uncommon benign tumor) was reported to have occurred on the conjunctiva, mostly ipsilateral in his right eye and present on the ipsilateral side of the neurological abnormalities shown on magnetic resonance imaging and computed tomography. The patient had muscle weakness in left upper and lower extremities. He had a mild form of mental retardation. CONCLUSIONS There is no specific treatment for ECCL. Management of ECCL is usually symptomatic. Surgical correction of a cutaneous lesion can be performed for cosmetic improvement. An early diagnosis of ECCL allows for early symptom treatment and improved patient quality of life.

Up-to-date Critical Review of the Classification of Epilepsies and Epileptic Seizures.

The classification of epileptic seizures and epilepsies is a subject of interest in various medical disciplines (such as neurology, pediatric neurology, molecular biology and genetics, neurosurgery, pharmacology, radiology, histopathology), and each of them requires a different approach in their practice. In last 15 years, enormous amount of debate in which irrelevant to actual level of knowledge, were ongoing in the literature. Epilepsy classification is a fundamental tool that impacts not only daily clinical practice but also research era and education. The current lack of consensus in this field causes a serious obstacle in patient management, student and resident education, and information sharing among different scientific interest groups. The comparison of different classification proposals by means of positive and negative aspects is beyond the scope of discussion in this article; therefore, I will try to give a brief summary of our current level of understanding. Main issues regarding the classifications proposal are as follows: Concepts of epileptic seizure/epilepsy/syndromeFocal & generalized epilepsy conceptIdiopathic, genetic, cryptogenic, and symptomatic (structural/metabolic) concepts.

Brain malformations associated with Knobloch syndrome--review of literature, expanding clinical spectrum, and identification of novel mutations.

BACKGROUND: Knobloch syndrome is a rare, autosomal recessive, developmental disorder characterized by stereotyped ocular abnormalities with or without occipital skull deformities (encephalocele, bone defects, and cutis aplasia). Although there is clear heterogeneity in clinical presentation, central nervous system malformations, aside from the characteristic encephalocele, have not typically been considered a component of the disease phenotype. METHODS: Four patients originally presented for genetic evaluation of symptomatic structural brain malformations. Whole-genome genotyping, whole-exome sequencing, and confirmatory Sanger sequencing were performed. Using immunohistochemical analysis, we investigated the protein expression pattern of COL18A1 in the mid-fetal and adult human cerebral cortex and then analyzed the spatial and temporal changes in the expression pattern of COL18A1 during human cortical development using the Human Brain Transcriptome database. RESULTS: We identified two novel homozygous deleterious frame-shift mutations in the COL18A1 gene. On further investigation of these patients and their families, we found that many exhibited certain characteristics of Knobloch syndrome, including pronounced ocular defects. Our data strongly support an important role for COL18A1 in brain development, and this report contributes to an enhanced characterization of the brain malformations that can result from deficiencies of collagen XVIII. CONCLUSIONS: This case series highlights the diagnostic power and clinical utility of whole-exome sequencing technology-allowing clinicians and physician scientists to better understand the pathophysiology and presentations of rare diseases. We suggest that patients who are clinically diagnosed with Knobloch syndrome and/or found to have COL18A1 mutations via genetic screening should be investigated for potential structural brain abnormalities even in the absence of an encephalocele.

State of the Art Approach to the Classification of Epileptic Seizures and Epilepsies.

In the light of the latest knowledge acquired from clinical and laboratory research dealing with genetic, molecular biology and neuroimaging, existing classifications were successively revised by the International League Against Epilepsy (ILAE) in 2001, 2006, and 2010. In the latest classification established in 2010, proposals articulated radical changes in terms of concepts and definitions of the previously published classifications and put forward new classifications for epileptic seizures, epilepsies and electroclinical syndromes. This review refers to the changes of the new classification with their reasons and criticisms.

Interleukin-1ß secretion in hippocampal sclerosis patients with mesial temporal lobe epilepsy.

Mesial temporal lobe epilepsy with hippocampal sclerosis (MTLE-HS) is a common medically intractable epilepsy syndrome. Although pathogenesis of HS still remains highly controversial, genetics may play a role as a predisposing factor. Previous evidence in a Japanese population revealed that the homozygotes for allele T at position -511 of the interleukin (IL)-1ß gene promoter region (IL-1ß-511 T/T) confers susceptibility to the development of HS. However, whether this polymorphism has an effect on IL-1ß levels in MTLEHS patients was not demonstrated. This study aimed to analyze the distribution of this particular polymorphism in a group of Turkish HS patients and correlate the polymorphism with IL-1ß secretion from the lymphocytes, thus revealing a functional role for IL-1ß in the etiopathogenesis of HS. A single base pair polymorphism at position -511 in the promoter region of the IL-1ß gene was analyzed. The spontaneous and 1 ng/mL lipopolysaccharidestimulated production of IL-1ß by peripheral blood mononuclear cells after 4 and 24 h of incubation were measured by ELISA method. The heterozygous type (-511 C/T) was the most common genotype. There was no difference in frequency of allele -511 T between patients and controls. Analysis of IL-1ß levels, genotype and allele distributions showed no significant difference among the groups (P>0.05). Nevertheless, it was seen that patients who carry a T allele at position -511 of the IL-1ß gene had increased IL-1ß levels. T-allele carriage may be important. Only IL-1ß secretion from the lymphocytes has been assessed in this study. Considering the importance of IL-1ß in the etiopathogenesis of HS, further studies are needed to evaluate locally produced IL-1ß levels.

Efficacy, tolerability, and side effects of oxcarbazepine monotherapy: a prospective study in adult and elderly patients with newly diagnosed partial epilepsy.

OBJECTIVE: The aim of the study described here was to investigate the efficacy, tolerability, and side effects of oxcarbazepine (OXC) monotherapy in newly diagnosed, previously untreated adult and elderly patients with partial epilepsy. METHODS: We prospectively analyzed and recorded the efficacy, tolerability, and side effects of OXC monotherapy. The results were analyzed on the basis of etiologic classifications and age distributions. Remission was defined as seizure freedom for at least 1 year. RESULTS: A total of 147 patients were evaluated in a single center for a median of 18 months (range: 14-36 months). Overall, 92 patients (62.6%) were seizure free for at least 12 months and 55 of them (37.4%) were unresponsive despite treatment with the maximum tolerable dose of OXC. There was a significant difference in the outcomes of patients with cryptogenic (75% remission) and symptomatic (51.9% remission) epilepsy (P=0.004). Patients with cerebral tumors did worse than the remainder of the patients in the symptomatic group (36.7% remission) (P=0.03). Results were favorable for the elderly; 14 patients (73.6%) in the elderly subgroup became seizure free for at least 1 year, and the remission was achieved with low to moderate doses (approximately 900 mg/day). Overall, 13 patients (8.8%) discontinued OXC due to intolerable side effects. Side effects leading to discontinuation were: Stevens-Johnson syndrome (n=2, 1.4%); fatigue and drowsiness (n=2, 1.4%); dizziness, nausea, and vomiting with normal laboratory tests (n=2, 1.4%); dizziness, nausea, and vomiting with serum Na levels <130 mEq/L (n=5, 3.4%); and elevated serum gamma-glutamyl transferase levels (GGT>200mg/dL) (n=1, 0.7%). OXC proved to be a tolerable drug for the elderly; only one patient experienced symptomatic hyponatremia with mild symptoms and responded well to fluid restriction, which did not lead to discontinuation of OXC. CONCLUSION: Although the limitations of our study include its open-label design, the results suggest that OXC monotherapy may be regarded as an effective first-line monotherapy option for adult and elderly patients with partial epilepsy, but has low efficacy in patients with cerebral tumors.

Epilepsia partialis continua in a patient with Behçet's disease.

Behçet's disease (BD) is a multisystemic, recurrent, inflammatory disorder of unknown aetiology. Neurological involvement is characterised either by primary parenchymal lesions or secondary to major vascular involvement. Seizures are rarely seen in BD and their occurrence can be related to seizure provoking factors or exacerbation of the disease. We experienced a case of neuro-BD presenting with subacutely developing mental and behavioral changes, followed by left dominant tetraparesis with bilateral pyramidal signs, fever and left hand focal motor seizures with elementery clonic motor signs which later evolved into right hand epilepsia partialis continua (EPC) of Kojevnikov. The seizures were very resistant to antiepileptic drugs and 8 months after neurological involvement the patient died. The EPC evolving after neurological involvement is associated with high mortality rate.

Withdrawal of antiepileptic drugs in adult patients free of seizures for 4 years: a prospective study.

We aimed to assess the relapse rate of epilepsy, prospectively attributable to antiepileptic drug (AED) withdrawal in seizure-free patients and to determine the risk factors for seizure recurrence. Seventy-nine patients with epilepsy who were seizure-free for at least 4 years were enrolled into the study. The AEDs were tapered by one-sixth every 2 months. The EEG and clinical examination were performed at the beginning; at each visit during discontinuation and 2, 6, 12, 24, and 36 months after the complete drug withdrawal. For each patient, records were obtained of the main demographic and clinical variables. A total of 49 patients completed the discontinuation programme. Twenty-eight patients (57%) relapsed while 21 of those (42.8%) did not suffer a relapse at the end of the study period. In patients discontinuing treatment, the probability of relapse was 21.4% during the tapering period (especially in the last months), 28.6% at 1 month, 14.3% at 3 months, 3.6% at 6 months, 7.1% at 12 months, 17.8% at 24 months, and 7.1% at 36 months. The age at onset of epilepsy and the duration of active disease were found to affect the risk of relapse. Although drug withdrawal could be considered in adult patients free of seizures for 4 years, the final decision should be tailored to the patient's clinical, emotional, and socio-cultural profile.

Comparison of classifications of seizures: a preliminary study with 28 participants and 48 seizures.

PURPOSE: Our aim was to compare three available seizure classifications (SCs), namely, the international classification of epileptic seizures published in 1981 (ICES; Epilepsia 1981;22:489-50); the semiological seizure classification (SSC) by H. Luders, J. Acharya, C. Baumgartner, et al. (Epilepsia 1998;39:1006-13; Acta Neurol Scand 1999;99:137-41); and the proposal of a new diagnostic scheme for seizures (PDSS) by J. Engel, Jr. (Epilepsia 2001;42:796-803) published in 2001. The three SCs were compared with respect to diagnostic success rates, usefulness, and consistency by a large group of neurologists in this preliminary study. METHODS: After a training period, 28 blindfed participants with different levels of experience with epilepsy classified videos or written descriptions of 48 randomly selected seizures according to the three SCs. Definite diagnoses of the seizures were established based on all clinical, ictal/interictal EEG, and MRI data. All the participants answered a questionnaire concerning their preferences for SCs after the study. RESULTS: The overall diagnostic success rates were 81.4% for ICES, 80.5% for PDSS, and 87.5%, for SSC. Various parameters concerning experience with epilepsy affected success rates positively, without reaching statistical significance, whereas experience with epilepsy surgery appeared to be a parameter significantly affecting the success rate in all SCs. In reliability analysis, Cronbach's alpha was 0.94 for ICES, 0.88 for PDSS, and 0.70 for SSC, all showing good agreement in the group. Nineteen reviewers chose SSC, eight chose ICES, and one chose PDSS as their preference in the questionnaire, completed after the end of the study. CONCLUSION: The results of this preliminary study demonstrate that with proper training, physicians treating epilepsy patients can handle new SCs, and emphasize the need for revision of the current classification.

Cortical silent period in a patient with focal epilepsy and Parry-Romberg syndrome.

Progressive facial hemiatrophy (PFH), Parry-Romberg syndrome, is a rare disorder frequently associated with epilepsy. We describe a 28-year-old man who had PFH and partial epilepsy that was easily controlled with antiepileptic drugs. In accordance with this patient's benign course of seizures, the cortical silent period was prolonged in the symptomatic hemisphere. This finding may represent compensatory interictal mechanisms in epilepsy.

Effect of long-term swimming exercise on zinc, magnesium, and copper distribution in aged rats.

Trace element content of different tissues might be altered by both age and exercise training. We aimed to determine the effects of a 1-yr swimming protocol (60 min/d, 5 day/wk) on tissue levels and the distribution of zinc (Zn), magnesium (Mg), and copper (Cu) in aging rats. Three groups were formed: sedentary and trained old groups and a young control group. Tissue Zn, Mg, and Cu concentrations were measured in the kidney, heart, liver, lungs, and gastrocnemius and soleus muscles. Kidney zinc concentration significantly decreased in the sedentary old group compared to the young control group (p<0.01) and was significantly higher in the trained old group compared to the sedentary old group (p<0.01), whereas Zn levels in the soleus muscle significantly increased in the sedentary old group in comparison to young controls (p<0.05). Tissue Mg concentrations remained unchanged. The sedentary old group exhibited a significant decrease in kidney Cu concentration compared to the young control group (p<0.01). Although kidney Cu levels also decreased in trained old rats in comparison to young controls (p<0.05), they were significantly higher than in sedentary old rats (p<0.01). The decrease in kidney Zn and Cu content as a result of aging was partly prevented by long-term swimming exercise.

Changes in somatosensory evoked potentials, lipid peroxidation, and antioxidant enzymes in experimental diabetes: effect of sulfur dioxide.

The effect of sulfur dioxide (SO2) on brain antioxidant status, lipid peroxidation, and somatosensory evoked potentials (SEPs) was investigated in diabetic rats. A total of 40 rats were divided into 4 equal groups: control (C), SO2 + C (SO2), diabetic (D), and SO2 + D (DSO2). Experimental diabetes mellitus was induced by i.v. injection of alloxan at a dose of 50 mg/kg body weight. Ten ppm SO2 was administered to the rats in the sulfur dioxide groups (SO2 and DSO2) in an exposure chamber. Exposure occurred 1 hr/day, 7 days/wk, for 6 wk; control rats were exposed to filtered air during the same time periods. Although SO2 exposure markedly increased copper, zinc Superoxide dismutase activity, it significantly decreased glutathione peroxidase activity in both the diabetic and nondiabetic groups, compared with the C group. Brain catalase activity was unaltered; however, brain thiobarbituric acid reactive substances (TBARS) were elevated in all experimental groups with respect to the C group. SEP components P1, N1, P2, and N2 were significantly increased in all experimental groups, compared with the C group, and these components were also prolonged in the DSO2 group with respect to the other groups. The authors' findings suggest that exposure to SO2, because it increases lipid peroxidation, can change antioxidant enzyme activities and affect SEP components in diabetic rats.