Clinical Neuroscience

The methylation status of NKCC1 and KCC2 in the patients with refractory temporal lobe epilepsy

UNAL Yasemin1, KARA Murat2, GENC Fatma3, OZTURK Aslan Dilek1, GÖMCELI Bicer Yasemin3, KAYNAR Taner2, TOSUN Kursad4, KUTLU Gülnihal1

MAY 30, 2019

Clinical Neuroscience - 2019;72(05-06)

DOI: https://doi.org/10.18071/isz.72.0181

Purpose - Methylation is a key epigenetic modification of DNA and regarding its impact on epilepsy, it is argued that “DNA methylation may play an important role in seizure susceptibility and maintenance of the disorder”. DNA methylation status of KCC2 (SCL12A5) and NKCC1 (SCL12A2) associated with refractory temporal lobe epilepsy was investigated in our study. Materials and methods - Thirty-eight patients with temporal lobe epilepsy (TLE) who were diagnosed by video EEG monitoring and 32 healthy control subjects were included in the study. Twenty-three patients in TLE group were men and the remaining 15 were women. Among them, 27 had unilateral temporal focus (9 with right; 18 with left) and 11 patients had bilateral TLE. We analyzed promoter region methylation status of the KCC2 (SCL12A5) and NKCC1 (SCL12A2) genes in the case and control groups. Gene regions of interest were amplified through PCR and sequencing was accomplished with pyro-sequencing. Results - We found a significant relationship between TLE and methylation on the NKCC1. However, there was no association between TLE and methylation on the KCC2 gene. Also, we found no association between right or left and unilateral or bilateral foci of TLE. There was no relationship between TLE and methylation on the NKCC1and KCC2 genes in terms of mesial temporal sclerosis in cranial MRI, head trauma or febrile convulsions. Conclusion - The methylation of NKCC1 can be a mecha­nism of refractory temporal lobe epilepsy. There are limited findings about DNA methylation in TLE. Therefore, further studies with large sample sizes are necessary.

AFFILIATIONS

  1. Department of Neurology, Mugla Sitki Kocman University Faculty of Medicine, Mugla, Turkey
  2. Sitogen Biomedical and Laboratory Systems Industrial Trade Limited Company, Istanbul, Turkey
  3. Department of Neurology, Antalya Research and Training Hospital, Ministry of Health, Antalya, Turkey
  4. Siena College, Loudonville, NY, 12211 USA

COMMENTS

0 comments

Further articles in this publication

Clinical Neuroscience

Hyperhomocysteinemia in female migraineurs of childbearing ages

ALEMDAR Murat, SELEKLER Macit Hamit

Background and purpose - Migraine is a risk factor for ischemic stroke in women of childbearing ages. Previous researches revealed a higher prevalence of hyperhomocysteinemia in migraineurs. Possible differences on the frequencies of hyperhomocysteinemia between migraine with aura and migraine without aura could contribute the established variances in stroke risk between these migraine types. Therefore, we aimed to search if the frequency of hyperhomocysteinemia was different between these subtypes of migraine or not. Methods - We analyzed the findings of serum homocysteine levels in female migraineurs of 16-49 years old who admitted to our outpatient clinic. Results - Homocysteine level was elevated in 13.3% of study population. There were not any significant differences on median serum homocysteine levels between migraine with aura (8.0 mikromol/L) and without aura (8.5 mikromol/L). (p=0.426) The frequencies of hyperhomocysteinemia were also similar (9.1% versus 16.7%, respectively; p=0.373). Correlation analyses did not reveal any linear correlation between ages and homocysteine levels either in group of migraine with aura or in group of migraine without aura (p=0.417 and p=0.647, respectively). Similarly, any linear correlation between disease ages and homocysteine levels either in group of migraine with aura or in group of migraine without aura was not detected (p=0.359 and p=0.849, respectively). Conclusion - The median serum homocysteine levels and the frequencies of hyperhomocysteinemia are similar between migraine with aura and without aura in women of childbearing ages. Therefore, the variances on stroke risk ratios between these types of migraine are probably not originated from the differences of serum homocysteine status.

Clinical Neuroscience

Mid-term oral isotretinoin therapy causes a predominantly sensory demyelinating neuropathy

ALTUN Yasar, INAN Esra

Aim - The purpose of this prospective study was to investigate whether mid-term treatment with oral isotretinoin may impact peripheral nerve function. Methods - In this study, we included 28 patients with no apparent neurological or neurophysiological findings. The patients received treatment with oral isotretinoin for papulopustular or nodulocystic acne. The patients with normal findings in the first examination were given 1 mg/kg/day oral isotretinoin. Neurological examinations and electroneurographic studies were performed before and 6 months after the onset of isotretinoin treatment. Results - Clinical examinations and electroneurographic evaluations prior to treatment revealed no abnormalities in any of the patients. However, 20 patients (72%) displayed one or more abnormal values in the tested parameters after treatment. Although the mean amplitudes of compound muscle action potential of the ulnar and median nerves did not vary, significant decreases were observed in the mean sensory conduction velocities of median, ulnar, sural, medial plantar, medial dorsal cutaneous, and dorsal sural nerves 6 months after the onset of treatment. Conclusion - Systemic use of isotretinoin may cause electroneurographic changes. Probable electroneurographic alterations may be detected at a much earlier period via dorsal sural nerve tracing when electrophysiological methods used in routine clinical practice cannot detect these changes.

Clinical Neuroscience

The prevalence of sarcopenia and dynapenia according to stage among Alzheimer-type dementia patients

YAZAR Tamer, YAZAR Olgun Hülya

Aim - In this study, the aim was to identify the prevalence of sarcopenia and dynapenia according to disease stage among Alzheimer-type dementia (AD) patients and collect data to suggest precautions related to reducing the disease load. Method - The study was completed with 127 patients separated into stages according to Clinical Dementia Rating Scale (CDR) criteria and 279 healthy volunteers aged 18-39 years and 70-80 years abiding by the exclusion criteria who agreed to participate in the research. Our prospective and cross-sectional study applied the CDR and mini mental test (MMSE) to patients with disorder in more than one cognitive area and possible AD diagnosis according to NINCDS-ADRDA (National Institute of Neurological and Communicative Disorders and Stroke-Alzheimer’s Disease and Related Disorders Association) diagnostic criteria. The patient and control groups had skeletal muscle mass index (SMMI), muscle strength and physical performance assessed with sarcopenia diagnosis according to European Working Group on Sarcopenia in Older People (EWGSOP) diagnostic criteria. Results - In our study, in parallel with the increase in disease stage of AD patients, the prevalence of sarcopenia (led by severe sarcopenia) and dynapenia was higher compared to a control group of similar age. Conclusion - In chronic, progressive diseases, like AD, identification of changes in parameters, like muscle mass and strength and reductions in physical performance in the early period, is important for identification and to take precautions in the initial stages considering the limitations of the preventive effects of treatment applied after diagnosis of AD.

Clinical Neuroscience

[The effect of bevacizumab monotherapy on progression free survival in recurrent glioblastoma]

CZIGLÉCZKI Gábor, SINKÓ Dániel, BENKŐ Zsolt, BAGÓ Attila, FEDORCSÁK Imre, SIPOS László

[Introduction, the aim of study - Glioblastoma, WHO grade IV is the most frequent primary malignant brain tumor in adults. There are few articles and result about the efficacy of bevacizumab monotherapy. The aim of our paper is to examine the effect of bevacizumab therapy on progression free and overall survival in an extended database of recurrent glioblastoma patients. Patients and methods - In our retrospective study, patients with recurrent glioblastoma treated with bevacizumab had been collected. All of our patients received first line chemo-irradiation according the Stupp protocol treatment. The histological diagnosis was primary or secondary glioblastoma in every patient. The prognostic features of primary and secondary glioblastomas were statistically analyzed. Results - Eighty-six patients were selected into the retrospective analysis. The histological diagnosis was primary glioblastoma in 65 patients (75.6%) and secondary glioblastoma in 21 patients (24.4%). The mean follow up period was 36.5 months. The mean second progression free survival beside bevacizumab therapy was 6.59 months and the mean overall survival was 24.55 months. In secunder glioblastoma cases, the mean second progression free survival was 6.16 months and the mean overall survival was 91.94 months. Conclusion - The bevacizumab therapy is a safe option in recurrent glioblastoma patients. Bevacizumab therapy has a positive effect both on progression free and overall survival and our results confirm the findings in the literature. There is no statistically significant difference in the second progression free survival between glioblastoma subtypes.]

Clinical Neuroscience

Somatosensory amplification absorption contribute to electrosensitivity

KÖTELES Ferenc, SIMOR Péter, SZEMERSZKY Renáta

Background - Two trait-like characteristics, somatosensory amplification and absorption, have been associated with symptom reports and idiopathic environmental intolerances in past research. Purpose - As the two constructs are not connected with each other, their independent contribution to symptom reports and electromagnetic hypersensitivity, as well as their interaction can be expected. Methods - On-line questionnaire. Patients - 506 college students completed an on-line questionnaire assessing absorption, somatosensory amplification, negative affect, somatic symptoms, and electromagnetic hypersensitivity. Results - Somatosensory amplification (β = 0.170, p < 0.001) and absorption (β = 0.128, p < 0.001) independently contributed to somatic symptoms after controlling for gender and negative affect (R2 = 0.347, p < 0.001). Similarly, somatosensory amplification (OR = 1.082, p < 0.05) and absorption (OR = 1.079, p < 0.01) independently contributed to electromagnetic hypersensitivity after controlling for somatic symptoms, gender, and negative affect (Nagelkerke R2 = 0.134, p < 0.001). However, no interaction effects were found. Discussion - Somatosensory amplification and absorption independently contribute to symptom reports and electromagnetic hypersensitivity. Conclusion - The findings suggest that psychological mechanisms underlying symptom reports and electromagnetic hypersensitivity might be heterogeneous.

All articles in the issue

Related contents

Clinical Neuroscience

[PREDICTIVE FACTORS OF TEMPORAL LOBE SURGERY]

KELEMEN Anna, RÁSONYI György, SZŰCS Anna, FABÓ Dániel, HALÁSZ Péter

[The most effective type of epilepsy surgery in adults is temporal lobe epilepsy (TLE) surgery. Three quarter of the patients become seizure free, however the remaining patients experience seizures after resection. In our study we analyzed retrospectively the possible electro-clinical, neuroimaging and surgery-related outcome predictors in 94 adult patients who had anterior temporal lobectomy (ATL) from the material of Epilepsy Centre of the National Institute of Psychiatry and Neurology, Budapest since the beginning of the surgery program in 1989 until 2001. Three outcome endpoints were chosen: the seizure status at the last visit, the longest seizure free period and the time to the first non-acute postoperative seizure. The predictors were assessed by multivariate and Cox regression methods. After one year of surgery 72% of the patients were seizure free, after two years 67% and after five years 59%. Factors predicting favorable outcome in TLE surgery were: typical temporomesial aura, strictly unilateral interictal anterotemporal spikes, unilateral ictal onset, slow contralateral propagation, hippocampal sclerosis (HS) as etiology. Factors predicting poor outcome in TLE surgery were: increase in seizure frequency in the last two preoperative years, presence of preoperative psychiatric disturbances, ictal contralateral propagation, MRI lesion distant from the surgery site, incongruency of data of preoperative investigations, postoperative sequels and non-HS type MR residuum.]

Clinical Neuroscience

[LATE CONTRALATERAL EPILEPTOGENESIS AFTER INCOMPLETE SURGERY IN TEMPORAL LOBE EPILEPSY FOLLOWED ACROSS 18 YEARS]

HALÁSZ Péter, JANSZKY József, KELEMEN Anna, BARSI Péter, RÁSONYI György

[Objectives - To present evidence of changes in seizure semiology suggesting late contralateral epileptogenesis after incomplete surgery in a patient with temporal lobe epilepsy. Methods - The presently 36 year old female patient was followed across 18 years by clinical observation and EEG, and video-EEG monitored before and 18 years after surgery. Results - The patient had complex partial seizures defined by video-EEG which started from the right temporal lobe with an ictal spread to the contralateral (left) temporal lobe. After right amygdalo-hippocampectomy she did not become seizure free. Years after surgery a new type of seizure emerged. Video-EEG monitoring 18 yrs after surgery revealed two seizure types. One started in the right temporal region clinically resembling to the earlier seizures. The new seizure type showed left sided electroclinical pattern. The postoperative MRI detected bilateral hippocampal sclerosis. Side specific memory tasks revealed bilateral hippocampal dysfunctions with subdominant (right) side predominance. Conclusions - The well documented evolution from unilateral to bilateral seizures suggests late contralateral epileptogenesis in which the persisting seizure spread from the primary epileptogenic side and/or the earlier silent contralateral hippocampal sclerosis (HS) may play role. This case show that progressive changes with bilateral involvement may occur during the course of chronic temporal lobe epilepsy.]

Clinical Neuroscience

[How do temporal lobe seizures changeby age?]

FOGARASI András

[Seizure semiology describes different - motor, sensory, autonomic, etc. - aspects of epileptic seizures. Several semiological studies showed already that different epilepsies - especially temporal lobe epilepsy - contain age-dependent features. In our researches, we tried to assess these subjective aspects with as objective methods as possible. We gave a comprehensive (preictal, ictal, and postictal) description of seizure semiology in patients fulfilling the gold standard criteria of semiological studies: being seizure free after temporal lobe resections. Our studies based on a large population, assess epileptic features at different levels of brain maturation. They help to understand why certain semiological axes show special characteristics at different ages. In this review, I summarize the most important results of our seizure semiology studies in temporal lobe epilepsy.]