Effects of Oxcarbazepine and Levetiracetam on Calcium, Ionized Calcium, and 25-OH Vitamin-D3 Levels in Patients with Epilepsy.

OBJECTIVE: The primary objective of the present study was to further elucidate the effects of oxcarbazepine (OXC) and levetiracetam (LEV) monotherapies on the bone health status of patients with epilepsy. METHODS: This study included 48 patients who attended our epilepsy outpatient clinic, had a diagnosis of epilepsy, and were undergoing either OXC or LEV monotherapy and 42 healthy control subjects. The demographic and clinical features of the patients, including gender, age, onset of disease, daily drug dosage, and duration of disease, were noted. Additionally, the calcium, ionized calcium, and 25-OH vitamin-D3 levels of the participants were prospectively evaluated. RESULTS: The 25-OH vitamin-D3, calcium, and ionized calcium levels of the patients taking OXC were significantly lower than those of the control group. These levels did not significantly differ between the patients taking LEV and the control group, but there was a significant negative relationship between daily drug dose and ionized calcium levels in the LEV patients. CONCLUSION: In the present study, anti-epileptic drugs altered the calcium, ionized calcium, and 25-OH vitamin-D3 levels of epilepsy patients and resulted in bone loss, abnormal mineralization, and fractures. These findings suggest that the calcium, ionized calcium, and 25-OH vitamin-D3 levels of patients with epilepsy should be regularly assessed.

LACK OF ASSOCIATIONS BETWEEN CLU AND PICALM GENE POLYMORPHISMS AND ALZHEIMER'S DISEASE IN A TURKISH POPULATION.

BACKGROUND AND PURPOSE: To investigate the association between the rs11136000 single nucleotide polymorphism (SNP) of the clusterin (CLU) gene, the rs541458 and rs3851179 SNPs of the phosphatidylinositol-binding clathrin assembly protein (PICALM) gene and Alzheimer's disease (AD) in a Turkish population, and to determine whether there are any relationships between the CLU and the PICALM genotypes and behavioral and psychological symptoms of dementia (BPSD) in the Turkish population. METHODS: One-hundred and twelve AD patients and 106 controls were included in this study. BPSD were evaluated by the Behavioral Pathology in Alzheimer's Disease Rating Scale (BEHAVE-AD). SNPs in the CLU and the PICALM gene were genotyped by Real-Time PCR. Genotype distributions were assessed for the groups of patients and controls, for the patient groups with and without each BPSD, and "No BPSD" and "BPSD". RESULTS: The CLU and the PICALM genotypes were similar in the AD and control subjects, and the groups with and without each BPSD. There were also no significant differences between the "No BPSD" and the "BPSD" groups for the PICALM genotypes, but even without a statistical significance, it is notable that none of the "No BPSD" patients had genotype pattern CLU-rs11136000-TT, and the female subjects with genotype pattern CLU-rs11136000-TT had higher mean score of BEHAVE-AD. CONCLUSION: This study claims that investigated SNPs are not genetic risk factors for AD in a Turkish population. In addition, the rs541458 and rs3851179 of PICALM SNPs are not related to development of BPSD, but the rs11136000 of CLU SNP might be related to development of BPSD in AD female Turkish subpopulation.

Effects of Repeated Botulinum Toxin Treatment for Sialorrhea in Patients with Parkinson's Disease.

INTRODUCTION: To evaluate the efficacy and adverse effects of repeated onabotulinumtoxinA (BoNT-A) treatment in patients suffering from Parkinson's disease (PD) with sialorrhea. METHODS: A retrospective analysis of 16 patients with sialorrhea treated with BoNT-A at our movement disorders outpatient clinic was conducted from February 2009 to September 2013. A patient with adult cerebral palsy and a patient with PD who received only a single application were excluded. BoNT-A was injected into the parotid glands without ultrasound guidance. Pre-treatment sialorrhea severity was quantified according to the Drooling Frequency and Severity Scale (DFSS). The efficacy was evaluated four weeks after BoNT-A injections using DFSS and according to the subjective assessment of the patients and/or caregivers. RESULTS: The mean age of the patients was 70.00±9.82 years and the mean follow-up duration was 18.78±10.37 months. Totally, 37 applications were performed. The mean BoNT-A total dose was 34.35±6.41 units. The mean scores of DFSS before and after injections were 7.00±1.03 and 3.21±0.89, respectively (p<0.001). Efficacy was 100%, and the mean experienced sialorrhea improvement was 71.78±12.95%. We found a significant difference between the first and last application in the mean duration of efficacy (17.28±9.21 weeks and 18.03±9.02 weeks, respectively, p=0.001). We did not observe side effects in this study group. CONCLUSION: Repeated injections of BoNT-A are safe and effective in treating sialorrhea in patients with PD. Based on our results, it seems that there is a maintenance of efficacy after a three-year period and an increase in the mean duration of efficacy with the number of injections. Further prospective clinical studies with larger number of patients and more longer duration of follow-up are needed to confirm our results.

Forehead sympathetic skin responses in determining autonomic involvement in Parkinson's disease.

OBJECTIVE: The purpose of this study was to evaluate forehead sympathetic skin response (SSR) and demonstrate any differences with extremity SSR in determining autonomic nervous system (ANS) involvement in patients with Parkinson's disease (PD). METHODS: Twenty early stage, 20 advanced stage idiopathic PD patients and 20 healthy controls participated in this study. SSR of forehead, hands and feet, heart rate variability (HRV), orthostatic intolerance, QT intervals and dysautonomic symptoms were evaluated. RESULTS: Absent forehead SSR was determined unilaterally in 4, bilaterally in 7 early stage patients, and unilaterally in 4, bilaterally in 8 advanced stage PD patients; there was significant difference between early and advanced stage PD and control groups in terms of the lack of SSR (p=0.000). Absent extremity SSR was determined in at least 1 extremity of 3 advanced stage PD patients, and none of the early stage PD patients. No difference was noted in HRV at rest between early and advanced stage PD and control groups (p=0.218); but HRV at deep breathing was lower in both early and advanced PD patients compared to controls (p=0.014, p=0.002, respectively). CONCLUSION: Forehead SSR is more sensitive in determining ANS dysfunction not only in late but also in early stage of PD. SIGNIFICANCE: With further supportive research, forehead SSR might be used as a simple diagnostic electrophysiological test in the early diagnosis of ANS dysfunction enabling proper treatment and increasing the quality of life of PD patients.

A rare paroxysmal movement disorder: mixed type of paroxysmal dyskinesia.

Paroxysmal dyskinesias are rare, heterogeneous group of disorders characterised by recurrent attacks of involuntary movements. The four classic categories of paroxysmal dyskinesias are kinesigenic, nonkinesigenic, exercise-induced and hypnogenic. There are some patients that do not fit in these four groups of paroxysmal dyskinesia and are termed as "mixed type". We describe a 13-year-old girl who had features of both paroxysmal kinesigenic dyskinesia and paroxysmal nonkinesigenic dyskinesia that was misdiagnosed as refractory epilepsy. She improved substantially with a combination of carbamazepine and clonazepame. It is important to recognize the clinical presentation of paroxysmal dyskinesias and distinguish these movement disorders from other disorders, such as psychogenic disorders and epilepsia, for deciding the treatment and prognosis of the patients. This case highlights the importance of the recognition of a rare paroxysmal movement disorders.

Clinical Characteristics and Response to Long-Term Botulinum Toxin Type A Therapy in Patients with Cervical Dystonia at a Neurology Clinic.

INTRODUCTION: To determine the demographic and clinical characteristics and response to botulinum toxin type A (BoNT-A) therapy in patients with cervical dystonia (CD). METHOD: A retrospective analysis of the detailed medical records of the patients with CD, followed up at our Botulinum Toxin Outpatient Clinic from 1998 to 2012, was performed. The treatment data were compared between the patients with primary CD and those with secondary CD; between patients receiving BoNT-A treatment for more than 5 years and less than five years, and between first applications and last applications. RESULTS: Fifty-seven patients (56.15% women) with CD were included in this study. The mean age was 41.01±13.42 years, the mean age at symptom onset was 32.93±15.45 years, and the mean dystonia duration was 8.10±8.5 years. The interval between onset of symptom and first BoNT-A treatment was 5.94±9.06 years, the duration of BoNT-A treatment was 36.13±29.17 months, and the number of applications was 8.48±6.23 in 45 patients with CD who were under treatment with BoNT-A for more than 1 year and had received at least three injections before. There was no difference between the patients with primary and secondary CD in terms of treatment results. The injection interval of the patients receiving BoNT-A treatment for more than 5 years and less than 5 years was 18.37±5.10 and 14.43±2.36 weeks, respectively (p=.001). There were no differences in the other treatment values. The mean doses were 559.00±147.60 vs. 681.66±188.09 units (p=.0001), the durations of improvement were 11.82±2.71 vs. 13.00±4.00 weeks (p=.014), the response scores were 2.71±.3 vs. 3.02±.5 (p=.002), the response ratings were 64.66%±16.18 vs. 71.22%±17.29 (p=.001), and the numbers of muscles applied were 3.15±1.16 vs. 3.51±0.99 (p=.012) in the first and last applications, respectively. CONCLUSION: There were no differences between the response of the patients with primary and secondary CD. Our results showed a statistically significant increase in the mean dose of BoNT-A, the response rating, the number of muscles applied, the duration of improvement, and the injection interval over time.

Assessment of structural and functional visual outcomes in relapsing remitting multiple sclerosis with visual evoked potentials and optical coherence tomography.

The purpose of this study is to consider the clinical utility of optical coherence tomography (OCT) and find a correlation with VEP. Effects of different disease modifying treatments (DMT) were further evaluated by measuring OCT parameters and whether a correlation exists between the RNFL thickness, disease duration and expanded disability status scale (EDSS) were also assessed. 13 patients were on interferon beta-1a (IFN), 14 patients were receiving glatiramer acetate (GA), 19 patients were not being treated with any DMT and 21 healthy controls were included the study. During OCT examination, retinal nerve fiber layer (RNFL) and ganglion cell complex (GCC) thickness was found to be lower in all MS groups but macular volume (MV) was lower only in GA group than controls. Although, P100 latencies were longer than controls in all MS groups, there was no statistically significant difference between IFN and w/o DMT groups. Patients with ON history, P100 latencies were found significantly longer than those without ON. VEP amplitudes were found lower with ON history patients than those without ON, however this was not statistically significant. EDSS strongly correlated with P100 latency, RNLF, GCC but no correlation was observed with VEP amplitude and MV. Our results show that RNFL, GCC and MV were all decreased in MS patients with or without DMT comparing to controls and it is more prominent in eyes with ON. Further follow-up studies are warranted to understand the pathophysiology of CNS axonal degeneration and involvement of optic nerves.

Cortical excitability in juvenile myoclonic epileptic patients and their asymptomatic siblings: a transcranial magnetic stimulation study.

In this study, we aimed to evaluate motor cortical excitability changes in patients with juvenile myoclonic epilepsy (JME) and their asymptomatic siblings (AS) using single-pulse transcranial magnetic stimulation (spTMS). 21 patients with JME and their 21 AS were compared to 20 healthy controls. All of JME patients were receiving antiepileptic therapy and their seizures were well controlled. Firstly, standard EEG examinations and then TMS studies were performed. Resting motor threshold (RMT), motor evoked potential (MEP) amplitudes, the durations of central motor conduction time (CMCT) and cortical silent period (CSP) were measured. After TMS studies, EEG recordings were repeated in an hour to evaluate any effect of TMS study on EEG. There were no significant differences between the first and second EEG recordings. No seizures were recorded during and after the TMS study. RMT was found higher in JME patients than AS and normal controls. There were no significant differences between cortical MEP amplitudes and MEP amplitude/CMAP (compound muscle action potential) amplitude ratio in all three groups. CMCT duration was shorter in JME patients than AS. CSP durations of JME patients were found to be longer than controls. In AS, CSP durations were also found to be longer than controls but this difference was not found statistically significant. Our results suggested that although high MT may be related to antiepileptic therapy, the prolongation of CSP duration may reflect impairment of supraspinal and/or intracortical inhibitory mechanism in JME. To eliminate the drug effect, further studies are needed in newly diagnosed JME patients without medication and large series of their asymptomatic siblings.

Effect of therapy on motor cortical excitability in Parkinson's disease.

OBJECTIVE: To assess the impact of the disease stage and therapy on motor cortical excitability in Parkinson's disease (PD). METHODS: Twenty newly diagnosed and medication-free, early stage patients, 20 late stage patients under antiparkinsonian therapy and 20 normal healthy controls were included. Motor threshold (MT), amplitudes of motor evoked potential (MEP), motor evoked potential amplitude/compound muscle action potential amplitude (MEP/CMAP) ratio, central motor conduction time (CMCT) and cortical silent period (CSP) were measured by stimulation of the motor cortex using a 13.5 cm circular coil and recordings from abductor digiti minimi muscle. Following the first study protocol, early stage patients were given therapy and the same protocol was repeated three months later. RESULTS: Motor threshold was lower; and the MEP/CMAP ratio was higher in early and late stage patients than normals. In early stage patients after proper therapy, the MTs became higher than before therapy, but still remained lower than normals. In late stage patients, the CMCTs were shorter than the early stage patients before therapy and normals, but there was no difference between the early stage patients and normals. In early stage patients after therapy, the CMCT became longer than before therapy and this difference was significant in both late stage patients and normals. Although more prominent in late stage patients, the CSP duration in both PD groups was found shorter than normals. In early stage patients, after therapy, the CSP durations became significantly longer compared with before therapy. CONCLUSION: These findings suggest that the motor cortical excitability increases in PD because of the impairment of the corticomotoneuronal inhibitory system.

Clinical effectiveness of quetiapine in children and adolescents with Tourette's syndrome : a retrospective case-note survey.

BACKGROUND AND OBJECTIVE: Tourette's syndrome is a relatively common biological genetic disorder with a broad spectrum of neurobehavioural manifestations. Unfortunately, treatment of the condition is often unsatisfactory and all available drugs are associated with potential adverse effects. We therefore aimed to investigate the efficacy of quetiapine, a newer atypical antipsychotic, in the treatment of children and adolescents with Tourette's syndrome. METHODS: This was a retrospective study carried out in outpatient clinics. Twelve patients aged 8-18 years with Tourette's syndrome (diagnosed according to Diagnostic and Statistical Manual IV criteria) who were receiving quetiapine therapy and had no diagnosis of epilepsy, major depression or psychotic disorder, were included in the study. The main outcome measure was the Yale Global Tic Severity Scale (YGTSS) score. RESULTS: The initial dose of quetiapine was 25 mg/day, but the mean dose was increased to 114.6 +/- 51.6 mg/day and 175.0 +/- 116.8 mg/day at the fourth and eighth weeks of treatment, respectively. The YGTSS score, which was 21.6 +/- 4.0 at baseline, showed significant decreases at 4 and 8 weeks (reducing to 7.5 +/- 7.4 and 5.6 +/- 8.1, respectively; p < 0.003). Routine laboratory parameters and serum prolactin level were all normal and did not change throughout treatment. Mild but significant increases in both bodyweight and body mass index at 4 and 8 weeks compared with baseline were observed. CONCLUSION: Other than causing mild weight gain, quetiapine appears to be an effective, safe and well tolerated drug in children and adolescents with Tourette's syndrome.

Motor and occipital cortex excitability in migraine patients.

OBJECTIVE: We evaluated motor and occipital cortex excitability in migraine patients using transcranial magnetic stimulation. METHODS: In this study, we included 15 migraine patients with aura (MwA), 15 patients without aura (MwoA) between attacks, and 31 normal healthy controls. Motor thresholds at rest, amplitudes of motor evoked potentials, central motor conduction time and cortical silent period were measured by stimulation of the motor cortex by using 13.5 cm circular coil and recording from abductor digiti minimi muscle. Additionally, phosphene production and the threshold of phosphene production was determined by stimulation of the visual cortex with the same coil. RESULTS: No significant differences were observed between the groups with respect to the motor thresholds, Motor evoked potential max/compound muscle action potential max (MEPmax/Mmax) amplitudes, central motor conduction times and duration of cortical silent period. Although not statistically significant, the proportion of the migraineurs with phosphene generation (90%) was found to be higher than that of normal controls (71%). Phosphene threshold levels in migraine patients, however, were significantly lower than those of the controls with MwA patients having the lowest levels. CONCLUSION: Our findings indicate that the occipital cortex, but not the motor cortex, is hyperexcitable in migraine patients.

Electrophysiological evaluation of peripheral and autonomic involvement in leprosy.

OBJECTIVE: Motor and sensory nerve conductions, F responses, sympathetic skin responses and R-R interval variations (RRIV) were studied to determine the type of peripheral neuropathy among patients with leprosy. METHODS: Twenty-nine consecutive patients with leprosy (25 male, 4 female) hospitalized in the "Istanbul Leprosy Hospital" between January - December, 1999 were included in this study. Ten patients had borderline lepromatous leprosy, and 19 had lepromatous leprosy. None of the patients studied had the tuberculoid form. The mean age was 55 +/- 12 years. The control group consisted of 30 (26 male, 4 female) healthy volunteers (mean age: 58.1 +/- 7.8 years). All subjects included in the study underwent neurological examination and electrophysiological evaluation. Standard procedures were performed for evaluating sensory and motor conduction studies. Motor studies were carried out on both left and right median, ulnar, tibial and common peroneal nerves while median, ulnar, sural and superficial peroneal nerves were examined for sensory studies. Sympathetic skin response recordings on both hands and RRIV recordings on precordial region were done in order to evaluate the autonomic involvement. RESULTS: The lower extremity was found to be more severely affected than the upper, and sensory impairment predominated over motor. Of 58 upper limbs examined, no sympathetic skin responses was recorded in 46 (79.3%). Compared with the controls, the RRIVs of the leprosy patients were found to be reduced during both resting and deep forced hyperventilation. CONCLUSION: Our results indicate that leprosy causes a predominantly axonal polyneuropathy that is more severe in the lower extremities. Sensory nerve damage is accompanied by autonomic involvement.

A study on awareness and attitude of teachers on epilepsy in Istanbul.

Epilepsy is a disease frequently seen among school children. Children having seizures may bother their teachers, who do not receive specific training about epilepsy during their education. Moreover, teachers feel desperate not knowing how to handle the situation. In a series of seminars it was our aim both to investigate and to improve the present awareness, knowledge, and attitude of elementary school teachers about epilepsy in Istanbul. In the pre- and post-seminar tests teachers who attended the seminar on a voluntary basis, were asked 29 questions. There were 346 male and female participants aged (mean +/- S.D.) 32.19 +/- 7.25. 69.3% of the participating teachers had either read or heard about epilepsy, while 71.9% had seen someone having a seizure and 59.4% knew someone with epilepsy. Although they had some prior misconceptions, like considering epilepsy a contagious (2.3%) or a psychological disease (17.8%), the teachers' knowledge and awareness improved after the seminar due to their special interest in the subject. Consequently, their negative attitude toward the participation of people with epilepsy in sports and social activities diminished post seminar. However, it should be noted that further education not only of teachers but also of family members is always required.

Cognitive function in juvenile myoclonic epilepsy.

In this study, we examined 35 patients with juvenile myoclonic epilepsy (JME) and 35 healthy volunteers. We used tests of cognitive performance (mini mental state examination, verbal and visual memory, visuospatial, frontal function, attention). In the JME group, we examined age, sex, family history, education level, age of seizure onset, seizure types, characteristics of EEG, duration of the therapy, drug dose and level, and verbal IQ level. Additionally, patients initially diagnosed as JME and patients who were initially under inappropriate drug therapy because of misdiagnosis were compared. As a result, we found statistically significant differences between JME patients and the control group with respect to verbal and visual memory. Furthermore, JME patients had impaired frontal and visuospatial function compared with the control group. We detected negative effects of younger age, family history, and absence seizures on cognitive function in JME patients.