[Show abstract][Hide abstract] ABSTRACT: Background Subacute sclerosing panencephalitis (SSPE) is a late complication of measles infection. Immune dysfunction related to genetic susceptibility has been considered in disease pathogenesis. A functional single nucleotide polymorphism (SNP) of granzyme B gene (GZMB) reported in several pathologies may also be involved in susceptibility to SSPE. Patients and Methods An SNP (rs8192917, G → A, R→Q) was screened in 118 SSPE patients and 221 healthy controls (HC) by polymerase chain reaction-restriction fragment length polymorphism. Frequencies were compared between groups. In vitro production of GZMB was measured in controls with different genotypes. Results The SNP had a minor allele (G) frequency of 0.22 in patients and 0.31 in controls. GG genotype was significantly less frequent in patients (odds ratio, 0.23). G allele carriers produced relatively higher levels of GZMB, when stimulated in vitro. Conclusion These findings implicate possible effect of this genetic polymorphism in susceptibility to SSPE which needs to be confirmed in bigger populations.
[Show abstract][Hide abstract] ABSTRACT: The purpose was to document 4 patients with different epilepsy syndromes, showing electrical status epilepticus during sleep (ESES), without marked cognitive and behavioral regression in the long-term follow-up. The mean age at onset of seizures was 8 years. Absences, myoclonic, focal motor, or generalized tonic - clonic seizures and drop attacks were the prominent seizure types. The neurological examination and neuroimaging findings revealed no abnormality. Focal epileptiform electroencephalographic (EEG) activity was seen in 3 cases, whereas generalized photosensitive epileptic discharges were detected in 1 patient with juvenile myoclonic epilepsy. Neuropsychological evaluations of all cases were within the normal range, and deterioration in mental status was not observed during their mean follow-up duration of 14 years. Our data support the view that ESES can emerge along with different types of childhood epilepsy syndromes, including idiopathic generalized epilepsies, and may not always be a poor prognostic factor.
Clinical EEG and neuroscience: official journal of the EEG and Clinical Neuroscience Society (ENCS) 03/2014; · 1.82 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Neuronal antibodies have been identified in patients with seizures as the main or sole symptom. Our aim was to investigate the prevalence of these autoantibodies in patients with focal epilepsy of unknown cause (FEoUC) and in the group having mesial temporal lobe epilepsy with hippocampal sclerosis (MTLE-HS).
We studied anti-neuronal antibodies of consecutive adult patients diagnosed with FEoUC and MTLE-HS in our epilepsy center. The clinical and laboratory features of antibody-positive patients were compared with those of seronegative patients. The responses to therapy have also been investigated.
Sera from 81 patients with epilepsy were tested. We found antibodies against glycine receptor (GLY-R) in 5 (6.2%), contactin-associated protein 2 (CASPR-2) in 4 (4.9%), N-methyl-d-aspartate receptor (NMDA-R) in 2 (2.5%), and voltage-gated potassium channel (VGKC)-complex in 2 (2.5%) of our patients with epilepsy. Psychotic attacks and nonspecific magnetic resonance imaging (MRI) white matter changes (WMCs) showed significant associations in seropositive patients (p = 0.003 and p = 0.03, respectively). Poor drug-response rates and total seizure counts were also higher in the seropositive patients but without reaching statistical significance. Three seropositive patients with previous epilepsy surgery showed typical histopathologic results for MTLE-HS, but not inflammatory changes. Moreover, some patients harboring these antibodies partly benefited from immunotherapy.
We detected neuronal antibodies in one sixth of patients with focal epilepsy, GLY-R antibodies being the leading one. Psychosis or nonspecific MRI WMCs were frequent in the seropositive group. Our results suggested that relevant antibodies should be screened for a treatment possibility in these groups.
[Show abstract][Hide abstract] ABSTRACT: Mitochondria have an essential role in neuronal excitability and neuronal survival. In addition to energy production, mitochondria also play a crucial role in the maintenance of intracellular calcium homeostasis, generation of reactive oxygen species and mechanisms of cell death. There is a relative paucity of data about the role of mitochondria in epilepsy. Mitochondrial genome analysis is rarely carried out in the investigation of some diseases. In mesial temporal lobe epilepsies (MTLE) cases, genome analysis has never been used previously. The aim of this study is to show mitochondrial dysfunctions using genome analysis in patients with MTLE-hippocampal sclerosis (HS).
44 patients with MTLE-HS and 86 matched healthy unrelated controls were included in this study. The patients were divided into four groups according to their clinical presentation as the following: Group 1 consist of patients with intractable epilepsy who refused operation; Group 2 of operated seizure free patients; Group 3 of operated patients with seizures; and Group 4 unoperated seizure free patients with or without antiepileptic drugs. Blood samples were used to isolate DNA. Parallel tagged sequencing was employed to allow pyrosequencing of 130 samples. Complete mtDNA is amplified in two overlapping fragments (11 and 9kb). The PCR amplicons were pooled in equimolar ratios. Titanium kits were used to produce shotgun libraries according to the manufacturer's protocol.
The average coverage in total was 130±30 and an average of 2365127 bases and 337bp fragment length was received from all samples. The mean mtDNA heteroplasmy in patients was 26.35±12.3 and in controls 25.03±9.34. Three mutations had prominently high significance in patient samples. The most significantly associated variation was located in the MT-ATP-8 gene (8502 A>T, Asn46Ile) whereas the other two were in the MT-ND4 (11994 C>T, Thr412Ile) and MT-ND5 (13231 A>C, Lys299Gln) genes.
We have observed that three mutations were significantly related to the presence of epilepsy. These mutations were found at the 8502, 11994, and 13231bp of mtDNA, which resulted in amino acid changes at the MT-ATP-8, MT-ND4 and MT-ND5 genes. Finding mutations can lead us to knowing more about the pathophysiology of the MTLE disease.
[Show abstract][Hide abstract] ABSTRACT: The purpose of this study was to analyze electrophysiological properties of four main stages of ictal patterns of patients with operated temporal lobe epilepsy related to hippocampal sclerosis.
We included 48 patients with temporal lobe epilepsy-hippocampal sclerosis. Seizures were classified according to their electrophysiological properties and surgical outcomes as seizure-free and not seizure-free. The EEGs with artifacts at the beginning were analyzed separately.
The most frequent type of ictal onset patterns was rhythmic theta/alpha activity, which was correlated to seizure-free group, whereas "switch of lateralization" and "bitemporal asynchrony" correlated to not seizure-free group. When bilateral independent ictal propagation patterns emerged, seizures tended to predict the side of epileptogenic zone wrongly. As a later significant pattern, rhythmic theta/alpha activity lateralized the focus correctly. Seizure termination was significantly concordant with hippocampal sclerosis lateralization in the seizure-free group.
Ictal onset pattern with rhythmic theta/alpha activity correlates well with seizure freedom. Morphology of later significant patterns was more important in determining the lateralization reliability than time of appearance. The EEGs with short artifacts at the beginning are seen to be valuable in presurgical evaluation. Lateralization of ictal termination ipsilateral to MRI indicates good prognosis after surgery. Scalp EEG monitoring helps predict epileptogenic zones and postsurgical outcomes.
Journal of clinical neurophysiology: official publication of the American Electroencephalographic Society 08/2013; 30(4):329-38. · 1.47 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Hippocampal sclerosis is the most common lesion in patients with mesial temporal lobe epilepsy. Recently, there has been growing evidence on the involvement of mitochondria also in sporadic forms of epilepsy. In addition, it has been increasingly argued that mitochondrial dysfunction has an important role in epileptogenesis and seizure generation in temporal lobe epilepsy. Although mtDNA polymorphisms have been identified as potential risk factors for neurological diseases, the link between homoplasmy and heteroplasmy within tissues is not clear. We investigated whether mitochondrial DNA (mtDNA) polymorphisms are involved in a case report of a patient with mesial temporal lobe epilepsy-hippocampal sclerosis (MTLE-HS).
We report the whole genome mtDNA deep sequencing results and clinical features of a 36-year-old woman with MTLE-HS. We used pyrosequencing technology to sequence a whole mitochondrial genome isolated from six different regions of her brain and blood. To assess the possible role of mitochondrial DNA variations in affected tissues, we compared all specimens from different regions of the hippocampus and blood.
In total, 35 homoplasmic and 18 heteroplasmic variations have been detected in 6 different regions of the hippocampus and in blood samples. While the samples did not display any difference in homoplasmic variations, it has been shown that hippocampus regions contain more heteroplasmic variations than blood. The number of heteroplasmic variations was highest in the CA2 region of the brain and accumulated in ND2, ND4 and ND5 genes. Also, dentate and subiculum regions of the hippocampus had similar heteroplasmic variation profiles.
We present a new rare example of parallel mutation at 16223 position. Our case suggests that defects in mitochondrial function might be underlying the pathogenesis of seizures in temporal lobe epilepsy.
[Show abstract][Hide abstract] ABSTRACT: We present the characteristics of eating epilepsy (EE), which is an underrecognized and complex form of reflex epilepsy. The files of 8996 patients with epilepsy were investigated retrospectively and only 6 cases (0.067%) were found. Four males and 2 females, aged 20 to 63 years, had focal seizures, mostly with dyscognitive and experiential aura triggered by eating, as well as spontaneous seizures. All had an initial precipitating event for seizures (such as head/birth trauma or encephalitis). In 4 patients, the seizures were induced in the middle of the meal or even closely after the end. In the remaining 2 cases the seizures were at the beginning of the meal, suggesting 2 different mechanisms. Two patients had normal magnetic resonance imaging (MRI), whereas the others had heterogeneous findings. The interictal electroencephalographs (EEGs) showed frequent spikes over a large area on the left temporal region in 5 and over the right temporal area in 1 case. We recorded eating-related seizures originating from the left temporal region in 3 cases. Positron-emission tomography (PET) investigations were concordant with the EEG foci in 2 patients. All but 1 had a therapy-resistant course. Our study suggested that EE is extremely rare and occurred many years after an initial precipitating event for seizures. These focal seizures, starting mostly with experiential/dyscognitive aura, usually originated from the left temporal region, had mostly a therapy-resistant course, and were triggered by different mechanisms during eating with a long latency in most of the cases.
Clinical EEG and neuroscience: official journal of the EEG and Clinical Neuroscience Society (ENCS) 02/2013; · 1.82 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Some patients with idiopathic/genetic generalized epilepsy (IGE) experience visual aura, which can confuse the diagnosis. We sought to determine the frequency and characteristics of visual auras in IGE patients. Among the 176 IGE patients, 4 men and 7 women reported visual auras (mean age - 24years). Syndromic diagnoses were juvenile myoclonic epilepsy in four, eyelid myoclonia with absences (EMA) in three, juvenile absence epilepsy in three, and other in one. Visual auras consisted of flashing lights, macropsia, illusional movements, and blindness. Eyelid myoclonia with absences was significantly more common in the group with visual aura (3 of 11 patients vs. 8 of 165 IGE patients; P=0.02). Furthermore, photosensitivity was found significantly more common in IGE patients with visual aura (90% vs 46% of the total IGE patients) (P=0.004). In conclusion, the visual auras do not exclude a diagnosis of IGE. The presence of visual aura in the EMA syndrome is also remarkable.
[Show abstract][Hide abstract] ABSTRACT: The typical clinical presentation of subacute sclerosing panencephalitis (SSPE) includes behavioral and intellectual changes followed by myoclonia. However, there are a considerable number of SSPE cases which present with distinct clinical features that can lead to a diagnostic difficulty. In this report, we summarize the clinical features of patients with SSPE who have uncommon presentations or features of the disease or coexisting medical conditions which may lead to diagnostic difficulties.
We studied 173 patients, all under the age of 17. Patients were included in the study group according to following criteria: onset of the disease before age 2 years, seizures occurring before the onset of myoclonia and/or behavioral symptoms, extrapyramidal or cerebellar signs and ocular manifestations as initial presenting symptoms, fulminant course including coma or death within 6 months. Additionally, patients with onset of SSPE at the setting of a known neurological disorder are defined as another group in the study.
Out of 173 patients with SSPE who were followed in two neurology centers, 31 (17.9%) met our criteria.
We found a relative high frequency of these clinical features. Our findings suggest that clinicians should be aware of this clinical characteristics and rule out the disease in cases were other common causes have been excluded, especially in countries with insufficient measles immunization.
Child s Nervous System 12/2011; 27(12):2041-4. · 1.24 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Our aim was to investigate the clinical features and sleep characteristics of patients with pure sleep-related seizures.
Patients with pure sleep epilepsy were prospectively enrolled and their clinical, EEG, and MRI findings investigated. The Medical Outcomes Study Sleep Scale (MOS-SS) was administered after receiving consent.
Thirty-nine of 1401 consecutive patients (2.7%) with pure sleep-related seizures were included. Of these, 30 (76.9%) had epilepsy of unknown cause and 7 had epilepsy with known structural etiologies. Twenty-seven patients reported less than one seizure per month and 19 had been seizure free for at least 1 year. Thirty-four patients participated in our MOS-SS study. Comparison of sleep problems between those with epilepsy and healthy controls and between the subgroups with frequent and rare seizures did not reveal significant differences.
Patients with pure sleep seizures had mostly undetermined etiology usually with a good prognosis, and this rare condition did not seem to affect their sleep quality.
[Show abstract][Hide abstract] ABSTRACT: We report a patient with adolescent-onset, Rasmussen's encephalitis, presenting with intractable focal seizures, mild hemiparesis, cognitive impairment, dystonia, and severe hemiballism. His father had Behcet's disease, considered to be an autoimmune disorder. Recent reports have directly implicated the role of cytotoxic T lymphocytes in the pathogenesis of both Rasmussen's encephalitis and Behcet's disease. The occurrence of Behcet's disease and Rasmussen's encephalitis in the same family suggests involvement of common genetic factors such as HLA haplotypes in both autoimmune disorders. It is possible that members of this family are genetically susceptible to developing autoimmune conditions that have been precipitated by separate environmental triggers.
Epileptic disorders: international epilepsy journal with videotape 01/2009; 10(4):319-24. · 1.17 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Our aim was to assess the long-term follow-up of juvenile myoclonic epilepsy (JME), with an emphasis on the course of the myoclonic seizures.
We enrolled 48 patients with JME (29 F, 19 M; aged 39.9 +/- 9.5 years) followed up for a mean of 19.6 +/- 5.7 years. The remission for 5 years and relapses were evaluated for all seizure types and the changes in severity/frequency of myoclonia were systematically questioned. The clinical and EEG features, antiepileptic drug (AED) treatment regimen, and systemic and psychiatric comorbid diseases were evaluated.
We found a benign course in 66.6% whereas 16.7% had pseudo-resistance due to problems in treatment or lifestyle. The true-resistant course observed in the remaining 16.7% was significantly associated with psychiatric disorders and the presence of thyroid diseases. In 54.2% of the patients, myoclonia were in remission for a mean duration of 8.4 +/- 7.7 years, after an average age of 32.9 +/- 9.6. Of these patients, 6 were on a lower dose of AED in comparison to the dosage needed to control the seizures in the beginning, and 5 patients had stopped AED treatment. None of the latter 11 patients except one relapsed during the follow-up. Furthermore, 21 other patients (43.8%) described substantial alleviation after age 31.3 +/- 8.4 in the severity of myoclonia.
Although a great majority of the patients with juvenile myoclonic epilepsy had continuing seizures after a follow-up of 20 years, almost all had either 5-year remission or a substantial alleviation of the myoclonic seizures.
[Show abstract][Hide abstract] ABSTRACT: Cerebral cavernous malformations (CCM) are vascular malformations causing seizures and cerebral hemorrhages. They occur in sporadic and familial forms. Familial cases are associated with a high frequency of multiple lesions, which are less frequently associated with sporadic cases.
We report a 46-year-old woman presenting with epilepsy with multiple cerebral cavernomatosis on MRI. Because she had had a previous liver transplantation operation, and received immunosuppressants, she was not advised to have a brain operation. However, she had to be operated as a result of a bleeding in one of her cerebral cavernomas. The histologic diagnosis was cavernoma. She has been seizure free after the operation with levetiracetam therapy for the last 17 months. She had no positive family history for both epilepsy and cavernomatosis.
When multiple cerebral cavernomatosis are identified in a patient, a detailed neurologic family history should be sought despite the possibility of its being a sporadic case. Our main intention is to present a patient who is surgically controversial and to point out the importance of genetic heredity.
The Neurologist 02/2008; 14(1):46-9. · 1.48 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: The presence of anti-ganglioside (GM1) or anti-glutamic acid decarboxylase (GAD) antibodies has been reported in association with therapy-resistant epilepsy mostly of focal origin. Our aim was to detect GM1 and GAD autoantibodies in patients with juvenile myoclonic epilepsy (JME) and to evaluate their association with rarely encountered therapy-resistant cases in this idiopathic generalised epilepsy syndrome.
Ninety-six consecutive JME patients and 25 healthy normal control subjects were included to the study. We investigated anti-GM1 and anti-GAD antibodies with enzyme-linked immunosorbent assay (ELISA) and radioimmunoassay (RIA), respectively.
We found anti-GM1 antibodies in one of 96 (1.04%) JME patients and in one out of 25 (4%) healthy controls, without reaching a significant difference between the titres. Anti-GAD antibodies were detected in 5.8% of the patients and in 4% of the healthy controls. Both antibodies did not have any association with therapy-resistant cases and with any other relevant parameters.
The results of our pilot study suggested that anti-GM1 and anti-GAD antibodies are rare and they did not associate with therapy-resistance and other parameters in JME syndrome.
[Show abstract][Hide abstract] ABSTRACT: 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.
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.
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.
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.
[Show abstract][Hide abstract] ABSTRACT: This study is a field study with cross-section and case control conducted in the Kucukcekmece Region of Istanbul between June 1999 and February 2000. Four hundred and ninety three dwellings selected by a simple random sampling method were visited. From a population of 2187, 58 people, after filling in a questionnaire were suspected to have epilepsy. Following an interview, neurological examination and an electroencephalogram (EEG) 17 were diagnosed as having epilepsy. Lifetime epilepsy prevalence was 0.8%. 41.2% of the 17 epilepsy cases had partial epilepsy ( n= 7), 47.0% had generalized (n = 8) and in 11.8% seizures could not be classified ( n= 2). The risk factors for epilepsy in the control group ( n= 125) from the same region and those with epilepsy were investigated by means of logistic regression analyses. Educational status (odds ratio : 1.82, 95% confidence interval : 1.13-2.94; P= 0.01), profession (OR : 0.76, 95% CI : 0.60-0.97; P= 0.03), history of epilepsy in the family (OR : 0.67, 95% CI : 0.47-0.94; P= 0.02) were determined to be correlated with epilepsy. The results have drawn attention to the fact that individuals should be informed about epilepsy.
[Show abstract][Hide abstract] ABSTRACT: Our aim is to outline the clinical and electroencephalographic (EEG) features of patients with hot water epilepsy (HWE), a rare and unique form of reflex epilepsy.
Twenty-one patients with HWE, seen in our clinic until 1999, were studied. Male outnumbered female subjects in a ratio of 3:1. The age at the onset of seizures ranged from 19 months to 27 years (mean age at onset, 12 years).
The main factors precipitating seizures were bathing with hot water and/or pouring water over the head. Six patients reported self-induction, either by increasing the heat or the amount of water and/or recalling earlier bathing experiences. Nine patients expressed feeling pleasure during the seizures. Twenty patients had partial seizures, eight of whom also had secondarily generalized seizures. One patient had apparent generalized seizures only. Spontaneous seizures were present in 62% of the cases. Interictal epileptogenic abnormalities were documented in the EEGs of eight patients; the other eight had normal EEGs. The major sites of epileptogenic activity were over the unilateral temporal regions (in 40% of patients). Neuroimaging studies available for 12 patients (four cranial computed tomography and eight cranial magnetic resonance imaging scans) revealed normal findings. Seizure control in patients who were followed up was achieved by reducing the temperature or the duration of the bath or shower; several of the patients required medication.
The major findings of this study are that HWE has a male preponderance, can be self-induced, is often done for pleasure, has complex triggering factors, and shows temporally located abnormalities in the EEGs. Although HWE is generally known to be self-limited, antiepileptic drug treatment may sometimes be necessary to control seizures. Hot water epilepsy should be classified separately among the epileptic syndromes.