Effect of Sleep on Epileptic Discharges in Patients with Idiopathic Generalized Epilepsy.

Background. It is known that sleep and sleep deprivation affect the EEG findings, onset, frequency and semiology of the seizures. Generalized spike and wave discharges were found more common in drowsiness and sleep states, especially in childhood and juvenile absence epilepsy syndromes. Aim. In this study we aimed to show the effects of short sleep on the interictal and ictal discharges of the patients with genetic generalized epileptic seizures and to show the effects of treatment on the discharges during awake and sleep states. Method. 37 patients (29 females and 8 males) with a diagnosis of genetic generalized epilepsy syndrome were included. All the patients were investigated with video-EEG recording during awake, sleep and post sleep states. Epileptic discharges were counted manually. Discharge numbers and their relation with triggers were analyzed to see the difference between different vigilance states. Results. Number of ictal discharges is found to be increased after sleep. There was no difference in the control EEGs, which were taken under treatment. Conclusion. Sleep is a trigger of epileptic discharges in ictal nature, but an effective antiepileptic treatment prevents this effect.

Relation Between ILAE Hippocampal Sclerosis Classification and Clinical Findings in Temporal Lobe Epilepsy.

AIM: To investigate the relationship between clinical features and prognosis of the hippocampal sclerosis (HS) cases and International League Against Epilepsy (ILAE) histopathology classification. MATERIAL AND METHODS: A hundred patients with refractory epilepsy who were operated with the diagnosis of the Mesial Temporal Lobe Epilepsy were included in the study. Socio-demographic characteristics, clinical and family histories, post-operative ILAE and Engel epilepsy scores and diagnostic tests were recorded. At the same time, all of the pathological specimens were classified according to the new semi-quantitative ILAE classification. A significant statistical relationship was investigated between clinical data and HS-ILAE groups. RESULTS: There were 36 male 64 female patients. The mean follow-up period was 6.5 years. 75% of the cases were HS-ILAE type 1, 19% HS-ILAE type 2, 6% were unidentifiable. FCD3A was detected in 3 patients. The HS-ILAE Type 2 ratio was high on the rightsided cases. In addition, HS-ILAE Type 1 ratio was high in patients with early seizure onset and long duration of epilepsy. There was no significant relationship between long-term ILAE and Engel epilepsy outcome scores and HS-ILAE types. CONCLUSION: Resection of mesiotemporal structures in hippocampal sclerosis provides seizure control in at least two-thirds of cases. Histopathological findings may help us understand the epileptogenicity-prognosis of HS. The relationship between ILAE histopathology classification and clinical factors will become more obvious in the future. According to our study, there was a relationship between onset age of epilepsy, epilepsy duration, lesion side and HS-ILAE types. The reinforcement of these relationships with larger series will benefit clinicians.

Evidence of linkage to chromosome 5p13.2-q11.1 in a large inbred family with genetic generalized epilepsy.

The clinical genetics of genetic generalized epilepsy suggests complex inheritance; large pedigrees, with multiple affected individuals, are rare exceptions. We studied a large consanguineous family from Turkey where extensive electroclinical phenotyping revealed a familial phenotype most closely resembling juvenile myoclonic epilepsy. For a subject to be considered affected (n = 14), a diagnostic electroencephalogram was required. Seizure onset ranged between 6 and 19 years (mean = 12 years). Thirteen of 14 experienced myoclonic jerks; in 11, this was associated with eyelid blinking, and in 10 it was interspersed with absences. Generalized tonic-clonic seizures were seen in 11. One individual had generalized tonic-clonic seizures alone. Electroencephalograms demonstrated generalized polyspike and wave discharges that were not associated with photoparoxysmal response. Intellect was normal. Nineteen family members were subsequently chosen for nonparametric multipoint linkage analyses, which identified a 39.5 Mb region on chromosome 5 (P < 0.0001). Iterative analysis, including discovery of a subtly affected individual, narrowed the critical region to 15.4 Mb and possibly to 5.5 Mb. Homozygous versus heterozygous state of the refined 5p13.2-q11.1 haplotype was not associated with phenotypic severity or onset age, suggesting that one versus two pathogenic variants may result in similar phenotypes. Whole exome sequencing (n = 3) failed to detect any rare, protein-coding variants within the highly significant linkage region that includes HCN1 as a promising candidate.

Neuronal autoantibodies in patients with Rasmussen's encephalitis.

Rasmussen's encephalitis (RE) is a rare disease with unknown pathophysiology. To disclose whether anti-neuronal autoimmunity participates in the aetiology of RE, various neuronal autoantibodies (NAAbs) were investigated in sera of patients with RE and controls. The study included five patients who fulfilled the RE diagnostic criteria (clinical, EEG, and MRI findings) as the patient group, and 50 multiple sclerosis patients and 50 healthy subjects as the control groups. Sera were evaluated for various NAAbs by radioimmunoassay or cell-based assays. All sera were also screened for uncharacterized antibodies to neuronal cell surface or synapse antigens by indirect immunofluorescence using hippocampal cell cultures. The mean age at onset of seizures was 8.3±3.4 years (range: 4-13.5) and mean follow-up time was 11.2±5.4 years (range: 5-19). All patients had unihemispheric atrophy of the cerebral cortex and epilepsia partialis continua. Two of the patients had moderate cognitive impairment, while the others were severely affected, as shown by neuropsychological testing. NAAb positivity was not detected in any of the patients. Immune aetiology is thought to have a role in RE, but the responsible players have not yet been elucidated. Our extensive antibody screening in a small number of patients does not support the presence of antigen-specific anti-neuronal autoimmunity in RE pathophysiology.

Outcome of surgical treatment of hippocampal sclerosis from relatively new epilepsy surgery center.

BACKGROUND: Surgery is apparently superior to prolonged medical therapy in therapy of efficacy and safety for mesial temporal lobe epilepsies. We ­ as a new center ­ presented outcome results and possible outcome predictors of 50 consecutive patients with hippocampal sclerosis underwent resective epilepsy surgery. METHODS: Between 2006 and 2011, fifty patients with intractable mesial temporal lobe epilepsy due to hippocampal sclerosis underwent anterior temporal lobectomy and they were followed-up at least 1 year postoperatively. Detailed neuropsychological tests, video-electroencephalography monitoring and magnetic resonance imaging with epilepsy protocol were obtained for all patients. Standard anteromedial temporal lobectomy was performed. Modified Engel and ILAE classifications were used for seizure outcome. All morbidities were recorded. Demographic variables, diagnostic tests and early postoperative outcome were analyzed for possible predictors of the ultimate seizure outcome. RESULTS: Fifty patients were evaluated. The mean follow-up duration was 47,1 month (range, 12-75 months). The favorable outcome at 1 year was 90% and 82% according to Engel and ILAE classifications respectively. These rates were almost same at the end of follow-up period (92% and 82% respectively). The completely seizure free rate at one year was 80% and decreased to 68% at the end of the follow-up. There was no mortality. Morbidity rate was 10% and none of them was permanent. Triple concordance of the noninvasive tests (neuropsychological tests, video- electroencephalography monitoring and magnetic resonance imaging) and favorable seizure outcome at the first year were predictors of the ultimate seizure outcome (P=0.01 and P=0.04 respectively). CONCLUSIONS: Our findings demonstrated that anteromedial temporal lobectomy is a safe and effective treatment method in well-chosen patients with hippocampal sclerosis. This surgical procedure can be performed with a low rate of morbidity even in relatively new epilepsy surgery center.

Transcranial direct current stimulation improves seizure control in patients with Rasmussen encephalitis.

Rasmussen encephalitis is associated with severe seizures that are unresponsive to antiepileptic drugs, as well as immunosuppressants. Transcranial direct current stimulation (t-DCS) is a non-invasive and safe method tried mostly for focal epilepsies with different aetiologies. To date, there is only one published study with two case reports describing the effect of t-DCS in Rasmussen encephalitis. Our aim was to investigate the effect of t-DCS on seizures in Rasmussen encephalitis and to clarify its safety. Five patients (mean age: 19; three females), diagnosed with Rasmussen encephalitis were included in this study. Patients received first cathodal, then anodal (2 mA for 30 minutes on three consecutive days for non-sham stimulations), and finally sham stimulation with two-month intervals, respectively. Three patients received classic (DC) cathodal t-DCS whereas two patients received cathodal stimulation with amplitude modulation at 12 Hz. Afterwards, all patients received anodal stimulation with amplitude modulation at 12 Hz. In the last part of the trial, sham stimulation (a 60-second stimulation with gradually decreasing amplitude to zero in the last 15 seconds) was applied to three patients. Maximum current density was 571 mA/m2 using 70 mm x 50 mm wet sponge electrodes with 2-mA maximum, current controlled stimulator, and maximum charge density was 1028 C/m2 for a 30-minute stimulation period. After cathodal stimulation, all but one patient had a greater than 50% decrease in seizure frequency. Two patients who received modulated cathodal t-DCS had better results. The longest positive effect lasted for one month. A second trial with modulated anodal stimulation and a third with sham stimulation were not effective. No adverse effect was reported with all types of stimulations. Both classic and modulated cathodal t-DCS may be suitable alternative methods for improving seizure outcome in Rasmussen encephalitis patients.

Are There Any Specific EEG Findings in Autoimmune Epilepsies?

This study evaluated the EEG findings of patients whose seizures were associated with a possible autoimmune etiology. Our aim was to find clues to distinguish patients with antineuronal antibodies (Ab) through EEG studies. We reviewed our database and identified antineuronal Ab positive epilepsy patients with or without autoimmune encephalitis. These patients had Abs to N-methyl-d-aspartate receptor (NMDAR) (n = 5), glycine receptor (GLY-R) (n = 5), contactin-associated protein-like 2 (CASPR-2) (n = 4), uncharacterized voltage-gated potassium channel complex (VGKC) antigens (n = 2), glutamic acid decarboxylase (GAD) (n = 2), Hu (n = 1), and amphiphysin (n = 1). The control group consisted of 21 seronegative epilepsy or encephalopathy patients with similar clinical features. EEG findings were compared between the groups in a blindfolded design. We did not find any significant difference in EEG findings between antineuronal Ab positive epilepsy patients and seronegative control group. It was remarkable that four seropositive but none of the seronegative patients presented with nonconvulsive status epilepticus (NCSE) or focal motor status epilepticus. Continuous theta and delta rhythms were observed in 5 (71%) seropositive patients with autoimmune encephalitis and 2 (25%) seronegative patients. Eight (40 %) seropositive patients showed a frontal intermittent rhythmic delta activity (FIRDA) pattern as opposed to 5 (24%) seronegative patients. Two patients with NMDAR Ab positivity showed rhythmic delta waves superimposed with beta frequency activity resembling "delta brush" pattern. EEG seems as a limited diagnostic tool in differentiating epilepsy and/or encephalopathy patients with a possible autoimmune etiology from those without. However, antineuronal Abs associated with encephalitis should be considered in the etiology of status epilepticus forms. A possible autoimmune etiology for seizures may be considered in the presence of continuous slow waves, FIRDA, and delta brush pattern in the EEG.

Rasmussen encephalitis and comorbid autoimmune diseases: A window into disease mechanism?

OBJECTIVE: To describe a potential association between comorbid autoimmune disease and Rasmussen encephalitis (RE) and discuss potential insights into underlying RE pathogenesis. METHODS: We report a case series of 4 patients with RE in whom a comorbid autoimmune disease was subsequently diagnosed and review the literature on possible common susceptibility factors. RESULTS: In 4 patients who presented with typical clinical features of RE, a comorbid autoimmune disease was subsequently diagnosed: Hashimoto thyroiditis, ulcerative colitis, Crohn disease, and systemic lupus erythematosus. We discuss the possible common predisposing factors. CONCLUSIONS: The association of RE, a rare entity, with a comorbid autoimmune disease raises the possibility of shared mechanisms of susceptibility, including common immunogenetic and/or environmental risk factors.

Calcium channel antibodies in patients with absence epilepsy.

Autoimmunity has aroused interest in the last years as a contributory mechanism of epilepsy, especially in epilepsies with unknown cause or therapy resistance. Since the relationship of absence epilepsy (AE) with calcium channels is well established, we aimed to investigate related antibodies in patients diagnosed with AE. Consecutive patients with typical absence seizures having either childhood absence epilepsy (CAE) or juvenile absence epilepsy (JAE) with generalized spike and wave discharges on electroencephalography (EEG) were included after their consent. The patients were diagnosed according to the International League Against Epilepsy (ILAE) 2010 criteria. Antibodies against P-Q type voltage gated calcium channels (VGCC) and T-type VGCC subunit Cav3.2 (encoded by the CACNA1H gene) were investigated by RIA and ELISA, respectively. We searched for these antibodies in 32 patients with AE and 53 patients with focal epilepsy of unknown cause (FEOUC) as the disease control group; furthermore, 30 healthy persons served as the healthy controls. Eleven patients (34.3%) with AE had CAE and the remaining patients had JAE. Only a 47-year-old female FEOUC patient, who also had systemic lupus erythematosus with normal MRI scans showed antibodies against P-Q type VGCC, whereas no antibody positivity could be found in other FEOUC and AE patients and healthy controls. Our results might suggest that calcium channel antibodies do not play an important role in the pathophysiology of AE. Further studies with larger groups of other epileptic syndromes are needed to confirm our results.

Rasmussen's encephalitis and Behcet's disease: autoimmune disorders in first degree relatives.

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.

An unspecified clinical syndrome in mentally retarded patients with bilateral mesial temporal sclerosis.

PURPOSE: The association of febrile convulsions and mesial temporal sclerosis (MTS) is a well-known phenomenon. However, the effects of mental retardation on febrile convulsions and MTS have not been investigated previously. The aim of this study is to investigate the relation of mental retardation to febrile convulsions especially as febrile status epilepticus and MTS. METHODS: We describe three patients who have bilateral mesial temporal sclerosis with mental retardation and a history of febrile status epilepticus (FSE), and have clinically typical mesial temporal lobe epilepsy (MTLE). RESULTS: The FRSB and neuropsychology test revealed executive dysfunction in patients whose bilateral MTS had a benign course, which was unexpected. CONCLUSIONS: Febrile status epilepticus might have a role in the development of their mental retardation. This study also pointed out that MTS might have subtypes as a result of our attempts at distinguishing patients with MTS.

Microsurgery in the removal of a large cerebral hydatid cyst: technical case report.

OBJECTIVE: Surgery is presently the mainstay in the treatment of cerebral hydatid cysts, but removal without perforation of the cyst wall is critical. The Dowling-Orlando technique has been the main surgical choice for the intact removal of intracranial hydatid cysts. Dowling described his technique in 1929, well before the introduction of the microscope in neurosurgery. Using the operating microscope has not been reported in the removal of a large hydatid cyst. CLINICAL PRESENTATION: The case of a 16-year-old male with a large, right parieto-occipital hydatid cyst is presented. INTERVENTION: In this case, surgery was greatly aided by the use of the microscope in the initial stage of the removal of the cyst. Cyst extraction during the delivery process was continued without the aid of the microscope. The cyst was successfully removed intact. CONCLUSION: The use of the magnification during the early part of the surgery of a hydatid cyst is extremely helpful because, at a crucial stage of the procedure, it prevents inadvertent damage of the very thin cyst wall and allows development of the critical surgical plane.

The role of periventricular nodular heterotopia in epileptogenesis.

A temporal resection in patients with periventricular nodular heterotopia (PNH) and intractable focal seizures yields poor results. To define the role of heterotopic grey matter tissue in epileptogenesis and to improve outcome, we performed stereoencephalography (SEEG) recordings in eight patients with uni- or bilateral PNH and intractable focal epilepsy. The SEEG studies aimed to evaluate the most epileptogenic areas and included the allo- and neocortex and at least one nodule of grey matter. Interictal spiking activity was found in ectopic grey matter in three patients, in the cortex overlying the nodules in five and in the mesial temporal structures in all. At least one heterotopion was involved at seizure onset in six patients, synchronous with the overlying neocortex or ipsilateral hippocampus. Two patients had their seizures originating in the mesial temporal structures only. Six patients had surgery and the resected areas included the seizure onset, with follow-up from 1 to 8 years. An amygdalo-hippocampectomy was performed in two (Engel class Id and III), an amygdalo-hippocampectomy plus removal of an adjacent heterotopion in two (class Ia), and a resection of two contiguous nodules plus a small rim of overlying occipital cortex in one patient (class Id). One patient with bilateral PNH had three adjacent nodules resected and an ipsilateral amygdalo-hippocampectomy resulting in a reduction of the number of seizures by 25-50%. The best predictor of surgical outcome is the presence of a focal epileptic generator; this generator may or may not include the PNH. Invasive recording is required in patients with PNH; it improves localization and is the key to better outcome.

Palliative temporal resection for the treatment of intractable bioccipital epilepsy.

RATIONALE: Temporal resection is usually ineffective in patients with occipital seizures. However, when seizures are unilateral occipital resections are now, occasionally, considered. When bilateral seizures and visual field defects exist, occipital resection can not be carried out. When predominantly lateralized, temporal seizure onset can be shown in such patients, palliative temporal resection may be justified. METHODS: We report two patients with medically refractory, bilateral occipital lobe seizures. Clinical and electrophysiological patterns suggested consistent spread of the ictal discharge to temporal lobe structures. Long-term EEG video monitoring was followed by stereoelectroencephalography (SEEG) to assess involvement of temporal and occipital regions symmetrically. RESULTS: Both patients had non-lateralized, elementary visual aura followed by loss of contact, automatisms, frequent falls and occasionally secondary generalization. Brain MR imaging revealed bilateral parieto-occipital ischemic lesions without concomitant temporal volumetric abnormalities. They had bilateral or unilateral visual field defects. Scalp EEGs showed bilateral temporal or temporo-parieto-occipital interictal and ictal epileptic abnormalities. Intracranial SEEG recordings confirmed the presence of multifocal, temporo-occipital epileptic abnormalities. In both however, disabling seizures originated in, or rapidly spread to the right hippocampus. Since occipital resections were inadvisable, both patients underwent selective, right amygdalohippocampectomy. Seizures continued in both (two-year follow-up), but were much less severe, not associated with falling or secondary generalization, not followed by fatigue or headache and with faster recovery. CONCLUSION: When occipital resection is inadvisable because of bilateral or diffuse visual problems, palliative temporal resection may be considered in patients with lesional, bilateral occipital lobe epilepsy, and rapid seizure spread to mesial temporal structures. (Published with videosequences).

[Clinical and magnetic resonance imaging findings in patients with surgically treated mesial temporal sclerosis]. / Cerrahi uygulanan mezial temporal skleroz olgularinda klinik ve MRG bulgular.

PURPOSE: Mesial temporal sclerosis (MTS) is one of the leading causes of medically intractable complex partial seizures. Magnetic resonance imaging (MRI) and clinical findings in seventeen patients who had surgery for medically intractable mesial temporal lobe epilepsy (MTLE) are presented in this report. MATERIALS AND METHODS: 17 patients (9 females and 8 males) aged 19-35 years with clinically and electrophysiologically proven MTLE have been included in the study. Age at seizure onset was six months to 17 years, frequency of seizures 4-20 times/month, and duration of medical treatment 10-28 years with no response. MRI and volumetry of the mesial temporal structures were performed in all patients. RESULTS: On preoperative MRI and volumetry, pathologic signal, loss of internal structures and atrophy were present in the right hippocampus in twelve cases and left hippocampus in five. The hippocampal head and body were involved in ten cases and all three parts in seven. The Wada test was performed in three cases showing that memory and speech functions were controlled by the noninvolved side. All patients underwent surgery. The histopathological examination result was MTS in all cases. In the postoperative follow up period of one to 24 months, 12 patients were assessed as class I and II, and seven as III according to the Engel Classification. CONCLUSION: MRI and volumetry are among the most important tools in the preoperative diagnosis of MTS. All patients have benefited from surgery, verifying the preoperative clinical and MR imaging diagnosis. Interpretation of MR findings is important in determining surgical candidates and success of surgery in MTS, which is a major cause of medically intractable temporal epilepsy.