Vedat Ali Yürekli

Effects of Antiepileptic Drugs on Antioxidant and Oxidant Molecular Pathways: Focus on Trace Elements

Current reports on trace elements, oxidative stress, and the effect of antiepileptic drugs are poor and controversial. We aimed to review effects of most common used antiepileptics on antioxidant, trace element, calcium ion (Ca2+) influx, and oxidant systems in human and experimental animal models. Observations of lower blood or tissue antioxidant levels in epileptic patients and animals compared to controls in recent publications may commonly support the proposed crucial role of antioxidants in the pathogenesis of epilepsy. Effects of old and new antiepileptics on reactive oxygen species (ROS) production in epilepsy are controversial. The old antiepileptic drugs like valproic acid, phenytoin, and carbamazepine induced ROS overproduction, while new epileptic drugs (e.g., topiramate and zonisamide) induced scavenger effects on over production of ROS in human and animals. Antioxidant trace element levels such as selenium, copper, and zinc were generally low in the blood of epileptic patients, indicating trace element deficiencies in the pathogenesis of epilepsy. Recent papers indicate that selenium with/without topiramate administration in human and animals decreased seizure levels, although antioxidant values were increased. Recent studies also reported that sustained depolarization of mitochondrial membranes, enhanced ROS production and Ca2+ influx may be modulated by topiramate. In conclusion, there is a large number of recent studies about the role of antioxidants or neuroprotectants in clinical and experimental models of epilepsy. New antiepileptic drugs are more prone to restore antioxidant redox systems in brain and neurons.

The clinical significance of the neutrophil-to-lymphocyte ratio in multiple sclerosis

Multiple sclerosis (MS) is one of the main chronic inflammatory diseases of the central nervous system that causes functional disability in young people. The aim of this study was to investigate the neutrophil-to-lymphocyte ratio (NLR) in patients with MS and the relationship between the NLR and the severity of the disease. One hundred and two MS patients (31 patients were in relapse; 71 patients were in remission) and 56 healthy controls were included. Complete blood counts as well as demographic and clinical data from MS patients were evaluated retrospectively. The NLRs were calculated for all participants and were compared; the cut-off value was also determined for the NLR and Expanded Disability Status Scale (EDSS). MS patients had a significantly higher NLR (p < 0.001) than the control group. The NLR levels were significantly higher in patients who were in relapse than patients in remission (p = 0.039). The cut-off value for the NLR to predict an MS diagnosis and activity were determined to be 2.04 and 3.90, respectively. The NLRs were directly correlated with erythrocyte sedimentation rate levels (r = 0.795, p < 0.001). Logistic regression analysis with dichotomous EDSS score showed that a high NLR was an independent predictor of the progression of disability. The NLR may be a biomarker that has simple, quick, inexpensive and reproducible properties in MS to predict patients prognosis.

Modulation of oxidative stress, apoptosis, and calcium entry in leukocytes of patients with multiple sclerosis by Hypericum perforatum

Abstract Objectives Hypericum perfortarum (HP, St Johns wort) is a modulator of Ca2+ entry in neutrophils and it may modulate intracellular free Ca2+ ([Ca2+]i) entry in leukocytes of patients with multiple sclerosis (MS). We investigated effects of HP on oxidative stress, apoptosis, and [Ca2+]i concentrations in serum and leukocytes of patients with MS. Methods Neutrophils of nine newly diagnosed MS patients and nine healthy subjects within four subgroups were used in the study. The first group was a control; the second group was patients with MS. The neutrophils from patient group were incubated non-specific TRPM2 channel blocker (2-APB), voltage-gated calcium channel blockers, verapamil and diltiazem (V + D) with HP before N-formyl-L-methionyl-L-leucyl-L-phenylalanine stimulation, respectively. Results Neutrophil and serum lipid peroxidation, neutrophil apoptosis and [Ca2+]i levels in patients with MS were higher than in control although their levels were decreased by HP, 2-APB, and V + D incubations. The modulator role of V + D in MS and MS + HP groups was higher than in the 2-APB group. Neutrophilic glutathione peroxidase (GSH-Px) and serum vitamin A and E concentrations were lower in the MS group than in control. However, the neutrophil GSH-Px activity was increased by HP incubation. The neutrophil reduced glutathione, serum vitamin C and β-carotene concentrations did not change in control and patients. Discussion We observed that HP-induced protective effects on oxidative stress and [Ca2+]i concentrations by modulating transient receptor potential and voltage gated calcium channel in the patients with MS. Thus, it may provide useful treatment of neutrophil activity in the patients.

A Multicenter Study of 1144 Patients with Cerebral Venous Thrombosis: The VENOST Study

BACKGROUND Based on a number of small observational studies, cerebral venous sinus thrombosis has diverse clinical and imaging features, risk factors, and variable outcome. In a large, multicenter cerebral venous thrombosis (VENOST) study, we sought to more precisely characterize the clinical characteristics of Caucasian patients. METHODS All data for the VENOST study were collected between the years 2000 and 2015 from the clinical follow-up files. Clinical and radiological characteristics, risk factors, and outcomes were compared in terms of age and sex distribution. RESULTS Among 1144 patients 68% were women, and in older age group (>50 years) male patients were more prevalent (16.6% versus 27.8%). The most frequent symptoms were headache (89.4%) and visual field defects (28.9%) in men, and headache (86.1%) and epileptic seizures (26.8%) in women. Gynecological factors comprised the largest group in women, in particular puerperium (18.3%). Prothrombotic conditions (26.4%), mainly methylenetetrahydrofolate reductase mutation (6.3%) and Factor V Leiden mutation (5.1%), were the most common etiologies in both genders. 8.1% of patients had infection-associated and 5.2% had malignancy-related etiology that was significantly higher in men and older age group. Parenchymal involvement constitutively hemorrhagic infarcts, malignancy, and older age was associated with higher Rankin score. Epileptic seizures had no effect on prognosis. CONCLUSIONS Clinical and radiological findings were consistent with previous larger studies but predisposing factors were different with a higher incidence of puerperium. Oral contraceptive use was not a prevalent risk factor in our cohort. Malignancy, older age, and hemorrhagic infarcts had worse outcome.

Topiramate modulates hippocampus NMDA receptors via brain Ca(2+) homeostasis in pentylentetrazol-induced epilepsy of rats.

Background: Increase in neuronal Ca2+, activation of hippocampus N-methyl-D-aspartate receptor (NMDAR) and defects in enzymes such as brain cortex microsomal membrane Ca2+-ATPase (MMCA) are thought to play a role in epilepsy. Topiramate (TOP) is a novel drug with broad antiepileptic effect, and its effect on brain cortex MMCA is not known. We investigated effects of TOP on pentylentetrazol (PTZ)-induced MMCA activity and NMDAR subunits in rat brain. Materials and methods: Thirty-two rats were randomly divided into four equal groups. The first group and second groups were used for the control and PTZ groups, respectively. 50 and 100 mg TOP were administered to rats constituting the third (TOP50) and fourth (TOP100) groups for 7 days, respectively. At the end of 7 days, all groups except the first received a single dose PTZ. Brain and hippocampus samples were taken at 3 hrs after PTZ administration. Results: The microsomal MMCA activity was lower in the PTZ group than in control although the MMCA activities were higher in the treatment group than in PTZ group. Brain cortex total calcium levels, the hippocampus NMDAR 2A and 2B subunit concentrations were higher in the PTZ group than in control although their concentrations were decreased by TOP50 and TOP100 administration. Total brain cortex calcium and hippocampus NMDAR 2A and 2B subunit concentrations were higher in TOP100 group than in TOP50 group. Conclusion: The two doses of TOP modulated MMCA activity, total brain cortex calcium and hippocampus NMDAR 2A and 2B subunit concentrations in the epileptic rats.

Status epilepticus in a 52-year-old woman due to intracranial needle

Intracranial needles are a rare entity. They most commonly present with headache and seizures. The management of such patients is sometimes challenging. We present a 52-year-old woman who was admitted to our hospital with status epilepticus, because of an inracranial needle. There was no history of epileptic seizures and she was asymptomatic until the time of presentation.

The impact of personality on quality of life and disease activity in patients with Behcet’s disease: a pilot study

BACKGROUND The aim of this study was to examine the personality characteristics of patients with Behcets Disease (BD) using the Temperament and Character Inventory (TCI) compared with healthy control subjects and to investigate the relationship between the temperament and character properties and quality of life, disease activity, depression and anxiety in Behcets patients. METHODS A total of 46 BD patients and 40 healthy subjects were included in the study. All patients and controls were determined using the TCI, Structured Clinical Interview for Diagnostic and Statistical Manual of Mental Disorders Clinical Version for Axis I disorders (SCID-CV), Beck Depression Inventory (BDI), Beck Anxiety Inventory (BAI), Quality of life (QOL) Instrument for Skin Disorders and Behcet Disease Current Activity Form (BDCAF). RESULTS BD patients demonstrated significantly lower Reward Dependence than healthy controls. Among the subscales; Explarotory Excitability, Shyness with Strangers, Attachment, Spiritual Acceptance were lower and Self-Acceptance was higher in patients compared to control subjects. Decreased quality of life and increased disease activity of the patients were correlated with increased anxiety and depression. Responsibility, Self-Forgetfulness and Transpersonal Identification were associated with quality of life while Responsibility was the major factor effecting QOL. Disease activity was not found related with TCI properties. CONCLUSION Temperament and Character traits of BD patients were different from healthy group that might be due to many factors like genetics, biological or socio-cultural differences. BD patients were demonstrated as materialistic, self-contained, self-confident, cold, detached, and reserved although they are not shy. Considering the different personality traits of BD patients in psychotherapeutic approaches, may have a positive impact on QOL and comorbid major depressive disorder.

Behçet’s disease as a causative factor of cerebral venous sinus thrombosis: subgroup analysis of data from the VENOST study

OBJECTIVE This study was performed to determine the rate of cerebral venous sinus thrombosis (CVST) among cases of Behçets disease (BD) included in a multicentre study of cerebral venous sinus thrombosis (VENOST). METHODS VENOST was a retrospective and prospective national multicentre observational study that included 1144 patients with CVST. The patients were classified according to aetiologic factors, time of CVST symptom onset, sinus involvement, treatment approach and prognosis. RESULTS BD was shown to be a causative factor of CVST in 108 (9.4%) of 1144 patients. The mean age of patients in the BD group was 35.27 years and 68.5% were men, whereas in the non-BD CVST group, the mean age was 40.57 years and 28.3% were men (P < 0.001). Among the aetiologic factors for patients aged 18-36 years, BD was predominant for men, and puerperium was predominant for women. The onset of symptoms in the BD group was consistent with the subacute form. The transverse sinuses were the most common sites of thrombosis, followed by the superior sagittal sinuses. The most common symptom was headache (96.2%), followed by visual field defects (38%). CONCLUSIONS BD was found in 9.4% of patients in our VENOST series. Patients with BD were younger and showed a male predominance. The functional outcome of CVST in patients with BD was good; only 12% of patients presenting with cranial nerve involvement and altered consciousness at the beginning had a poor outcome (modified Rankin Score ⩾2).

Vertebral Artery Dolichoectasia with Fusiform Aneursym Presented By Internuclear Ophthalmoplegia: A Case Report

Dolichoectasia is a term used to describe marked widening, tortuosity and elongation of an artery. Intracranial vertebral and basilar arteries are most commonly involved. Vertebrobasilar dolichoectasia is usually asymptomatic. Cranial nerve compression and cerebral ischemia findings are frequently seen in symptomatic patients. However, vertebrobasilar artery dolichoectasia with internuclear ophthalmoplegia (INO) clinical presentation has not been reported in literature yet. In our case, we report of a 67 year old female who had symptoms of diplopia, left abducens palsy and headache with no prior medical or family history of cerebrovascular disease. She has been presented with INO due to left vertebrobasilar dolichoectasia. Atypical presentation of INO is rare and vertebral artery dolichoectasia as the underlying aetiology, like in our case is even rarer and has not been seen in literature so far.

Refractive Errors in Patients with Migraine Headache

ABSTRACT Purpose: To evaluate refractive errors in patients with migraine headache and to compare with healthy subjects. Materials and Methods: This prospective case-control study includes patients with migraine and age- and sex-matched healthy subjects. Clinical and demographic characteristics of the patients were noted. Detailed ophthalmological examinations were performed containing spherical refractive error, astigmatic refractive error, spherical equivalent (SE), anisometropia, best-corrected visual acuity, intraocular pressure, slit lamp biomicroscopy, fundus examination, axial length, anterior chamber depth, and central corneal thickness. Spectacle use in migraine and control groups was compared. Also, the relationship between refractive components and migraine headache variables was investigated. Results: Seventy-seven migraine patients with mean age of 33.27 ± 8.84 years and 71 healthy subjects with mean age of 31.15 ± 10.45 years were enrolled (p = 0.18). The migraine patients had higher degrees of astigmatic refractive error, SE, and anisometropia when compared with the control subjects (p = 0.01, p = 0.03, p = 0.02, respectively). Conclusion: Migraine patients may have higher degrees of astigmatism, SE, and anisometropia. Therefore, they should have ophthalmological examinations regularly to ensure that their refractive errors are appropriately corrected.