[Show abstract][Hide abstract] ABSTRACT: Autonomic dysfunction has frequently been reported in autoimmune encephalitis associated with seizures and there is growing evidence that epilepsy patients may display neuronal autoantibodies (NAAb). The aim of this study was to investigate the frequency of NAAb in epilepsy patients with peri-ictal autonomic findings. Fifty-eight patients (37 women/21 men; average age of 34.2 ± 9.9 years and epilepsy duration of 19.1 ± 9.6 years) who had at least one video-EEG recorded focal or secondary generalized seizure with clear-cut documented peri-ictal autonomic findings, or consistently reported seizures with autonomic semiology, were included. NAAb were tested by RIA or cell based assays. NAAb were present in 17 of 58 (29.3 %) patients. Among seropositive patients, antibodies were directed against N-methyl-D-aspartate receptor (NMDAR) in 5 (29 %), contactin-associated protein-like 2 (CASPR2) in 5 (29 %), uncharacterized voltage gated potassium channel (VGKC)-complex antigens in 3 (18 %), glutamic acid decarboxylase (GAD) in 2 (12 %), glycine receptor (GLYR) in one (6 %) and type A gamma aminobutyric acid receptor (GABAAR) in one patient (6 %). Peri-ictal gastrointestinal manifestations, piloerection, ictal fever, urinary urge, and cough occurred more commonly in the seropositive group. The prevalences of psychotic attacks and status epilepticus were significantly increased in the seropositive group. Seropositivity prevalence in our patient group with peri-ictal autonomic findings is higher than other previously reported epilepsy cohorts. In our study, ictal fever-VGKC-complex antibody and pilomotor seizure-GABAAR antibody associations were documented for the first time. Chronic epilepsy patients with peri-ictal autonomic semiology, history of status epilepticus and psychotic disorder may benefit from autoantibody screening.
Full-text · Article · Jan 2016 · Journal of Neurology
[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.
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.
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.
Full-text · Article · Mar 2014 · Clinical EEG and neuroscience: official journal of the EEG and Clinical Neuroscience Society (ENCS)
[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).
[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.
Full-text · Article · Aug 2013 · Journal of clinical neurophysiology: official publication of the American Electroencephalographic Society
[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.
Full-text · Article · Feb 2013 · Clinical EEG and neuroscience: official journal of the EEG and Clinical Neuroscience Society (ENCS)
[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.
Full-text · Article · Nov 2012 · Epilepsy & Behavior
[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.
Full-text · Article · Dec 2011 · Child s Nervous System
[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.
Full-text · Article · May 2011 · Epilepsy & Behavior
[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.
Full-text · Article · Jan 2009 · Epileptic disorders: international epilepsy journal with videotape
[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.