Oleuropein Has Modulatory Effects on Systemic Lipopolysaccharide-Induced Neuroinflammation in Male Rats.

BACKGROUND: Neuroinflammation induced by systemic inflammation is a risk factor for developing chronic neurologic disorders. Oleuropein (OLE) has antioxidant and anti-inflammatory properties; however, its effect on systemic inflammation-related neuroinflammation is unknown. OBJECTIVES: This study aimed to determine whether OLE protects against systemic lipopolysaccharide (LPS)-induced neuroinflammation in rats. METHODS: Six-wk-old Wistar rats were randomly assigned to 1 of the following 5 groups: 1) control, 2) OLE-only, 3) LPS + vehicle, 4) OLE+LPS (O-LPS), and 5) a single-dose OLE + LPS (SO-LPS group). OLE 200 mg/kg or saline as a vehicle was administered via gavage for 7 d. On the seventh day, 2.5 mg/kg LPS was intraperitoneally administered. The rats were decapitated after 24 h of LPS treatment, and serum collection and tissue dissection were performed. The study assessed astrocyte and microglial activation using glial fibrillary acidic protein (GFAP) and CD11b immunohistochemistry, nod-like receptor protein-3, interleukin (IL)-1ß, IL-17A, and IL-4 concentrations in prefrontal and hippocampal tissues via enzyme-linked immunosorbent assay, and total antioxidant/oxidant status (TAS/TOS) in serum and tissues via spectrophotometry. RESULTS: In both the O-LPS and SO-LPS groups, LPS-related activation of microglia and astrocytes was suppressed in the cortex and hippocampus (P < 0.001), excluding cortical astrocyte activation, which was suppressed only in the SO-LPS group (P < 0.001). Hippocampal GFAP immunoreactivity and IL-17A concentrations in the dentate gyrus were higher in the OLE group than those in the control group, but LPS-related increases in these concentrations were suppressed in the O-LPS group. The O-LPS group had higher cortical TAS and IL-4 concentrations. CONCLUSIONS: OLE suppressed LPS-related astrocyte and microglial activation in the hippocampus and cortex. The OLE-induced increase in cortical IL-4 concentrations indicates the induction of an anti-inflammatory phenotype of microglia. OLE may also modulate astrocyte and IL-17A functions, which could explain its opposing effects on hippocampal GFAP immunoreactivity and IL-17A concentrations when administered with or without LPS.

Cerebral neoplasm in L-2-hydroxyglutaric aciduria: two different presentations.

BACKGROUND: L-2-hydroxyglutaric aciduria (L2HGA) is a rare neurometabolic disorder characterized by a slowly progressive clinical course, psychomotor and mental retardation, macrocephaly, dysarthria, seizures, and cerebellar and extrapyramidal findings. The diagnosis depends on the presentation of increased levels of L-2-hydroxyglutaric acid in the urine, plasma, and cerebrospinal fluids. Patients with L2HGA have an increased risk for the development of cerebral neoplasms which, though rarely, can be the initial presentation of the disease. Moreover, patients with L2HGA have an increased risk for the development of cerebral neoplasms. CASES PRESENTATION: Although psychomotor and mental retardation, macrocephaly, dysarthria, seizures, and cerebellar and extrapyramidal findings are the most common characteristics of the disease, we present two rare cases admitted with tumoral symptoms. CONCLUSION: Patients with L2HGA have an increased risk for the development of cerebral neoplasms.

An investigation of the ocular toxic effects of levetiracetam therapy in children with epilepsy.

OBJECTIVE: To investigate the potential toxic effects of levetiracetam monotherapy on ocular tissues in cases of pediatric epilepsy using optical coherence tomography (OCT). METHODS: Thirty epileptic children (group 1) receiving levetiracetam monotherapy at a dosage of 20-40 mg/kg/day for at least 1 year with a first diagnosis of epilepsy and 30 age- and gender-matched healthy children (group 2) were included in the study. In addition to a detailed eye examination, peripapillary retinal nerve fiber layer (RNFL) thickness, ganglion cell complex (GCC) thickness, foveal thickness (FT), and central corneal thickness (CCT) were measured in all children by means of spectral domain OCT. The data obtained from the two groups were then subjected to statistical analysis. RESULTS: The mean age of both groups was 12 ± 3.64 years [1-12]. The mean duration of levetiracetam in group 1 was 24.07 ± 12.82 months. Mean RNFL values in groups 1 and 2 were 106.1 ± 10.42 and 104.98 ± 10.04 µm, mean GCC values were 94.72 ± 6.26 and 94.4 ± 6 µm, mean FT values were 240.73 ± 17.94 and 240.77 ± 15.97 µm, and mean CCT values were 555.1 ± 44.88 and 540.97 ± 32.65 µm, respectively. No significant difference was determined between the two groups in terms of any parameter. Best corrected visual acuity values of the subjects in both groups were 10/10, and no color vision or visual field deficit was determined. CONCLUSION: Levetiracetam monotherapy causes no significant function or morphological change in ocular tissues in pediatric epilepsies.

Risk adapted chemoprevention for prostate cancer: an option?

A high disease prevalence, the presentation in older age, a frequently slowly progressing course of disease, and high costs make diagnosis and therapy of prostate cancer a special challenge for urologists. Effective prevention of the disease may help to resolve some of the problems mentioned above. Two randomised, controlled studies prove that effective chemoprevention of prostate cancer is possible using 5-α reductase inhibitors (finasteride, dutasteride) (LoE 1) both in individuals at low and those at high risk developing prostate cancer. Furthermore, there is evidence that other compounds, e.g. selective estrogen receptor modulators (SERMs), non-steroidal anti-inflammatory drugs (NSAIDs) and statins might also be effective. This review investigates potential risks and benefits of chemoprevention including a consideration of health economic aspects. The authors conclude that chemoprevention in a high risk cohort using 5-α reductase inhibitors is a viable option and may even be cost effective. In consequence, the options of chemoprevention in prostate cancer should be further explored in an open and unbiased way.

Lumbar puncture requirement in acute hemiparesis: diagnosis of tuberculous meningitis after hemiparesis in a child.

BACKGROUND: Infections are an important acquired cause of cerebral arteriopathy. Tuberculous (TB) meningitis leading to infectious cerebral vasculopathy is a rare cause of acute hemiparesis. CASE REPORT: A 14-year-old male patient was examined after acute hemiparesis developing within 1 day. Neurological examination revealed total hemiplegia on the left side. Brain MRI findings showed bilateral focal T2-weighted signal hyperintensity in the subcortical and deep white matter regions. There were also areas of restricted diffusion in the right basal ganglia. Although the father had a history of pulmonary TB, the patient had not been given TB prophylaxis because of PPD negativity. At lumbar puncture, opening cerebrospinal fluid (CSF) pressure was 50 cm/H20, CSF protein 66.9 mg/dL, and glucose 54 mg/dL (concurrent blood glucose 93 mg/dL); 170 polymorphonuclear leukocytes per cubic millimeter were present in CSF. Following tests for TB, treatment was started immediately with four anti-TB drugs. TB PCR of CSF and acid-fast bacteria (AFB) staining in gastric aspirate were positive. At clinical follow-up, the patient was able to walk with support at the end of the first month. CONCLUSION: Various infectious agents have been reported as causes of cerebral vasculopathy. TB, which affects a significant number of patients worldwide, should be kept in mind in terms of cerebral vascular complications. Lumbar puncture is essential in order to diagnose TB meningitis.

Optic neuritis in Turkish children and adolescents: A multicenter retrospective study.

BACKGROUND: Various etiologies may underlie optic neuritis, including autoantibody-mediated disorders described in the last decade. We re-examined demographic, clinical, laboratory features and prognostic factors in pediatric patients with autoimmune optic neuritis according to current knowledge. METHODS: Cases of pediatric ON from 27 centers in Türkiye diagnosed between 2009 and 2022 were included for retrospective evaluation. RESULTS: The study included 279 patients, 174 females and 105 males, with a female-to-male ratio of 1.65. The average age at onset was 12.8 ± 3.4 years, and mean follow-up, 2.1 years (range: 1-12.1 years). Patients <10 years old were grouped as "prepubertal" and those ≥10 years old as "others". The diagnoses made at the end of follow-up were multiple sclerosis associated optic neuritis (n = 90, 32.3 %), single isolated optic neuritis (n = 86, 31 %), clinically isolated syndrome (n = 41, 14.7 %), myelin oligodendrocyte glycoprotein antibody associated optic neuritis (n = 22, 7.9 %), and relapsing isolated optic neuritis (n = 18, 6.5 %). Predominant diagnoses were myelin oligodendrocyte glycoprotein antibody associated optic neuritis and acute disseminated encephalomyelitis associated optic neuritis in the prepubertal group and multiple sclerosis associated optic neuritis in the older group. Recurrences were observed in 67 (24 %) patients, including 28 with multiple sclerosis associated optic neuritis, 18 with relapsing isolated optic neuritis, 11 with myelin oligodendrocyte glycoprotein antibody associated optic neuritis, 8 with aquaporin-4 antibody related optic neuritis, and 2 with chronic relapsing inflammatory optic neuropathy. Recurrences were more common among female patients. Findings supporting the diagnosis of multiple sclerosis included age of onset ≥ 10 years (OR=1.24, p = 0.027), the presence of cranial MRI lesions (OR=26.92, p<0.001), and oligoclonal bands (OR=9.7, p = 0.001). Treatment in the acute phase consisted of intravenous pulse methylprednisolone (n = 46, 16.5 %), pulse methylprednisolone with an oral taper (n = 212, 76 %), and combinations of pulse methylprednisolone, plasmapheresis, or intravenous immunoglobulin (n = 21, 7.5 %). Outcome at 12 months was satisfactory, with 247 out of 279 patients (88.5 %) demonstrating complete recovery. Thirty-two patients exhibited incomplete recovery and further combination treatments were applied. Specifically, patients with relapsing isolated optic neuritis and aquaporin-4 antibody related optic neuritis displayed a less favorable prognosis. CONCLUSION: Our results suggest optic neuritis is frequently bilateral in prepubertal and unilateral in peri­ or postpubertal patients. Age of onset 10 or older, presence of oligoclonal bands, and brain MRI findings reliably predict the development of multiple sclerosis. The risk of developing multiple sclerosis increases mostly during the second and third years of follow-up. Relapsing isolated optic neuritis remains a separate group where the pathogenesis and outcome remain unclear. Investigation of predisposing and diagnostic biomarkers and long follow-up could help to define this group.

An Investigation of Changing Attitudes and Behaviors and Problematic Internet Use in Children Aged 8 to 17 Years During the COVID-19 Pandemic.

PURPOSE: To examine the effects of the COVID-19 pandemic on the lifestyle, habits, and behavioral differences in children, and their changing internet use habits. METHODS: The research was planned as a cross-sectional study involving 4892 children aged 8 to 17 years attending schools in the city center of Trabzon, Turkey. Children's daily living activities, social habits, mood and temperament changes, and internet use were investigated before and during the pandemic. In terms of problematic internet use, internet addiction rates were evaluated using the validated Turkish-language version of the Parent-Child Internet Addiction Scale (PCIAT-20). RESULTS: The children's mean age was 13 ± 2.45 years, and 17.1% (n = 837) exhibited problematic internet use features on the PCIAT-20. Problematic internet use was higher in boys and in children older than 13 years. The presence of COVID-19 infection among members of the household, quarantine measures, attending private schools, the mother's occupation, the time spent by the mother and father on their mobile phones, and high parental education levels were associated with a high level of internet addiction. Families also described significant changes in their children's temperament and character compared with the pre-pandemic period. CONCLUSION: The prevalence of problematic internet use increased during the COVID-19 pandemic compared with previous studies from Turkey. Children were also more introverted, irritable, and pessimistic during the pandemic.

An investigation of the effects of chronic zonisamide, sultiam, lacosamide, clobazam, and rufinamide anti-seizure medications on foliculogenesis in ovarian tissue in prepubertal non-epileptic rats.

We aimed to determine the morphological and histological effects of zonisamide, sultiam, lacosamide, clobazam, and rufinamide on ovarian folliculogenesis in rats. Sixty female Wistar rats were divided into six experimental groups as control, zonisamide, sultiam, lacosamide, clobazam, and rufinamide groups; control solution and drugs were administered by gavage for 90 days. The number of healthy follicles in the control group was significantly higher than in the anti-medication groups (p < 0.001), and the number of corpus luteum was significantly lower (p < 0.001). There was a significant difference in the number of TUNEL positive apoptotic follicles between the control and drug groups (p < 0.001). With EGF, IGF-1, and GDF-9 staining, a very strong immunoreaction was observed in the ovarian multilaminar primary follicle granulosa cells and oocytes in the control group compared to the drug group (p < 0.001). Long-term anti-seizure medication with zonisamide, sultiam, lacosamide, clobazam, and rufinamide from prepubertal to adulthood causes apoptosis and disruption of folliculogenesis in the ovarian follicles of nonepileptic rats.

The effectiveness and tolerability of clobazam in the pediatric population: Adjunctive therapy and monotherapy in a large-cohort multicenter study.

OBJECTIVE: To evaluate the effectiveness and tolerability of clobazam therapy in the pediatric population in terms of seizure semiology, epileptic syndromes, and etiological subgroups. METHODS: A retrospective cohort study was conducted consisting of 1710 epileptic children from eight centers in seven geographic regions of Turkey. The initial efficacy of clobazam therapy was evaluated after three months of treatment. The long-term effectiveness of the drug, overall seizure outcomes, and overall therapeutic outcomes were evaluated during 12 months of therapy. RESULTS: Analysis of initial efficacy after the first three months of clobazam therapy showed that 320 (18.7 %) patients were seizure-free, 683 (39.9 %) had > 50 % seizure reductions, and 297 (17.4 %) had < 50 % seizure reductions. A positive response (seizure-free and >50 % seizure reduction) was determined for focal-onset (62.3 %) seizures, epileptic spasms (61.5 %), and generalized onset seisures (57.4). The highest positive response rate among the epileptic syndromes was for self-limited epilepsy with centrotemporal spikes (SeLECTS). The highest negative response rate was for developmental and/or epileptic encephalopathies (DEEs). Magnetic resonance imaging (MRI) revealed a structural etiological diagnosis in 25.8 % of the cohort. A higher positive response rate was observed at MRI in patients with sequelae lesions than in those with congenital lesions. The seizure recurrence rate was higher in the patient group with epilepsy with genetic and metabolic causes, in individuals with more than one seizure type, and in those using three or more antiseizure drugs. CONCLUSIONS: This cohort study provides additional evidence that clobazam is an effective and well-tolerable drug with a high seizure-free rate (18.7 %), a significant seizure reduction rate (57.3 %), and with excellent overall therapeutic outcomes with a low seizure relapse rate and considerable reversible benefits in the pediatric population.

Effect of Multileaf Collimator Leaf Position Error Determined by Picket Fence Test on Gamma Index Value in Patient-Specific Quality Assurance of Volumetric-Modulated Arc Therapy Plans.

Aim The correlation between the MLC QA (IBA Dosimetry, Germany) results of the picket fence test created with intentional errors and the patient's quality assurance (QA) evaluation was investigated to assess the impact of multileaf collimator (MLC) positioning error on patient QA. Materials and methods The picket fence, including error-free and intentional MLC errors, defined in Bank In, Bank Out, and Bank Both were analyzed using MLC QA. The QA of 15 plans consisting of stereotactic radiosurgery (SRS), stereotactic body radiotherapy (SBRT), and conventionally fractionated volumetric-modulated arc therapy (VMAT) acquired with electronic portal imaging devices (EPID) was evaluated in the presence of error-free and MLC errors. The QA of plans were analyzed with 2%/2 mm and 3%/3 mm criteria. Results The passing rates of the picket fence test were 97%, 92%, 91%, and 87% for error-free and intentional errors. The criterion of 3%/3 mm wasn't able to detect an MLC error for either SRS/SBRT or conventionally fractionated VMAT. The criterion of 2%/2mm was more sensitive to detect MLC error for the conventionally fractionated VMAT than SRS/SBRT. While only two of SBRT plans had <90%, four of conventionally fractionated VMAT plans had a <90% passing rate. Conclusion We found that the systematic MLC positioning errors defined with picket fence have a smaller but measurable impact on SRS/SBRT than the VMAT plan for a conventionally fractionated and relatively complex plan such as head and neck and endometrium cases.

Turkish version of Brief Ataxia Rating Scale.

AIM: Our aim was to perform the Turkish-language adaptation of a practical ataxia rating scale for children. METHODS: The Brief Ataxia Rating Scale was subjected to cultural adaptation following receipt of the requisite permissions. Thirty-six children aged 4-18 years followed-up with a diagnosis of ataxia were included in the study. Evaluation of each child was recorded on video. The video recordings were scored independently by nine observers (four physiotherapists, one pediatric neurologist, and four pediatricians). Intra-rater reliability was tested by the same video images being scored twice, at 15-day intervals, by a pediatric neurologist. Intraclass correlation coefficients were used for inter-rater and intra-rater reliability. The Scale for the Assessment and Rating of Ataxia was used for concurrent validity. RESULTS: Good to excellent reliability was determined among the nine observers in terms of total scores with the intraclass correlation coefficient among the nine observers (intraclass correlation coefficient = 0.926; 95% CI: 0.885-0.956). Intra-rater reliability analysis results exhibited strong reliability in terms of scores elicited at two-week intervals (intraclass correlation coefficient = 0.967; 95% CI: 0.890-0.987, r = 0.97, p < 0.001). At concurrent validity analysis, a strong relation was determined between total Scale of the Assessment and Rating of Ataxia score and total Brief Ataxia Rating Scale score (r = 0.942, p < 0.001). CONCLUSION: The Turkish-language adaptation of the Brief Ataxia Rating Scale is reliable and valid for application in children.Implications for RehabilitationThis study shows the reliability and validity of the Turkish language adaptation of brief ataxia rating scale in children.The scale being both practical and easily applicable to ataxic children will contribute to broadening its use in the pediatric age group in particular.

Assessment of low-density lipoprotein oxidation, paraoxonase activity, and arterial distensibility in epileptic children who were treated with anti-epileptic drugs.

OBJECTIVE: Studies show that anti-epileptic drugs increase oxidative stress. Thus, low-density lipoprotein oxidation increases and atherogenesis is induced. Paraoxonase-associated high-density lipoprotein protects low-density lipoprotein and high-density lipoprotein oxidation. The effects of anti-epileptic drugs on paraoxonase activity has not been investigated yet. The aim of this study is to investigate the effect of anti-epileptic drugs on paraoxonase activity, lipid profiles, folat, vitamin B12, homocysteine, thyroid hormones, apolipoprotein A-1, total anti-oxidant capacity, malondialdehyd, nitric oxide, and oxidised low-density lipoprotein. The association with carotid-femoral pulse wave velocity and current biochemical parameters had been searched for assessing the effects of anti-epileptic drugs on the vascular system. PATIENTS AND METHODS: We recruited 59 epileptic patients treated with anti-epileptic drugs and 23 controls (group IV) at least 6 months ago. The epileptic group was divided into three groups by receiving anti-epileptic drugs as follows: group I: carbamazepine, group II: valproic acid, and group III: carbamazepine and valproic acid. Arterial distensibility was assessed with the Complior device. RESULTS: There was no difference between the current biochemical parameters in epileptic children. Serum-free T4 was decreased, when compared with group IV. Thyroid-stimulating hormone was increased in group II, compared with group IV. The carotid-femoral pulse wave velocity was increased in group III, compared with group IV. The carotid-femoral pulse wave velocity was correlated with thyroid-stimulating hormone and valproic acid levels. CONCLUSIONS: Anti-epileptic drugs may induce atherogenesis by affecting the thyroid hormones. According to the current data, the effects of thyroid hormones on vascular system may be independent of other biochemical markers. Epileptic patients using anti-epileptic drugs must be followed closely for arterial stiffness, and also for the development and progression of atherosclerosis.

Increased Hemoglobin and Plateletcrit Levels Indicating Hemoconcentration in Pediatric Patients with Migraine.

INTRODUCTION: Fluid intake was reported to reduce migraine attacks. This may be due to its effect on hemoconcentration. Hemoconcentration may manifest itself by increasing in the hemoglobin and platelet-related values. This study aimed to reveal hemoconcentration by evaluating complete blood cell counts in attack-free periods of pediatric patients with migraine. MATERIALS AND METHODS: Consecutive children with migraine (n = 70) and tension-type headache (TTH) (n = 65) were compared with the control groups. Control 1 (n = 70) and control 2 (n = 60) groups consisted of age- and gender-matched patients, respectively. Control 2 group patients had gastrointestinal symptoms leading to fluid loss, which may have caused hemoconcentration. To evaluate hemoglobin and platelets together, the M1-value was created by multiplying hemoglobin level by plateletcrit. RESULTS: The M1-value was higher in the migraine group than in control 1 and TTH groups (P = 0.017 and 0.034) and the hemoglobin and hematocrit levels were also higher in the migraine group than in control 2 group (P = 0.013 and 0.012). Female patients with migraine had higher hemoglobin levels as compared to the female patients in control group 1 (P = 0.041). Male patients with migraine had higher M1-values than the male patients in control group 1 (P = 0.034). In the subgroup of migraine with aura (n = 10), folic acid was significantly lower than the other patients with migraine (P = 0.02). CONCLUSION: This study suggests that migraine may be accompanied with hemoconcentration in children.

HMGB-1, TLR4, IL-1R1, TNF-α, and IL-1ß: novel epilepsy markers?

The purpose of this study was to compare HMGB-1, TLR4, IL-1ß, IL-1R1, and TNF-α levels in patients with mild and severe epilepsy with those in a healthy control group. Children aged 4-17 years, diagnosed with epilepsy for at least three years and with no progressive neurological disease, metabolic disease or infection, were selected for the study. The severe epilepsy group consisted of 28 children with at least one episode a week despite receiving three or more antiepileptic drugs. The mild epilepsy group consisted of 29 children with no seizures in the previous year, receiving only one antiepileptic drug, while 27 healthy children were selected as the control group. HMGB-1, TLR4, IL-1R1, TNF-α and IL-1ß levels were investigated in these three groups. The MRI findings and clinical characteristics of the patients in the epilepsy group were also compared with these markers. HMGB-1, TLR4, TNF-α, and IL-1ß levels in the severe epilepsy group were higher than in the control group and the mild epilepsy group (p<0.05), and were higher in the mild epilepsy group than in the control group (p<0.05). IL-1R1 was also higher in the severe epilepsy group than in the control group (p<0.05). In this first report to identity a possible correlation between HMGB-1, TLR4, IL-1ß, IL-1R1, and TNF-α levels and severity of epilepsy, our data demonstrates that the serum level of these cytokines is higher in cases of drug-refractory epilepsy.

Reduced cerebrospinal fluid levels of interleukin-10 in children with febrile seizures.

PURPOSE: The exact etiology of febrile seizures (FS) is still unclear. However, it is thought that cytokine network activation may have a causative role. Therefore, this study aimed to evaluate the levels of interleukin-12 (IL-12) as a proinflammatory cytokine, interleukin-10 (IL-10) as an anti-inflammatory cytokine, and interferon-ß (IFN-ß), a marker of toll-like receptor-3 activation as a host response to viruses. These cytokine levels were analyzed in the cerebrospinal fluid (CSF) of children after a FS. METHODS: With the approval of the Human Research Ethics Committee, 76 patients with FS, who underwent lumbar puncture (LP) for the exclusion of central nervous system (CNS) infection, and who didn't have CSF pleocytosis, were included in the study. The control group consisted of 10 patients with similar ages, with an acute febrile illness and who required LP to exclude CNS infection. The analyses were made by the enzyme-linked immunoassay method. RESULTS: Age, gender distribution and CSF IL-12 and IFN- ß levels did not differ, but CSF IL-10 levels were significantly lower in the FS group as compared to the control group (0.78 ± 4.5 pg/ml, versus 27 ± 29 pg/ml, p < 0.0001). CONCLUSION: The low-level of CSF IL-10, considering its anti-inflammatory properties, may play a role in the etiopathogenesis of FS.

White Matter Evaluation in Multiple Sclerosis Through Magnetic Resonance Kurtosis Imaging.

OBJECTIVES: To investigate diffusional changes in multiple sclerosis (MS) plaques and non-Gaussian behavior of water diffusion by using diffusional kurtosis imaging (DKI). METHODS: 31 MS patients and 21 controls underwent MRI on a 3T scanner. Mean kurtosis (MK) parametric maps were computed. Region of interest (ROI) was delineated as white matter (WM) in controls and MS plaques and WM in patients. RESULTS: There was no significance of WM kurtosis and skewness parameters among MS group and control group patients p=0.213 and p=0.390, respectively. In MS patients, kurtosis, skewness, maximum intensity, minimum intensity, and median intensity values of WM, Plaque 1, Plaque 2, and Plague 3 were significantly higher at p<0.0001 for all.  Conclusions: DKI may provide more extensive characterization of lesions and WM and may be a sensitive indicator of tissue damage and microstructural change in patients with MS in addition to conventional diffusional evaluations.

Vitamin D protects against hippocampal apoptosis related with seizures induced by kainic acid and pentylenetetrazol in rats.

OBJECTIVES: The hippocampus is susceptible to damage in patients with epilepsy and in animals with seizures caused by excitotoxic agents. The effect of vitamin D on hippocampal apoptosis related with seizures has not been reported. However, epileptic patients have an increased risk of hypovitaminosis D which is most likely due to the effects of antiepileptic drugs. Therefore, in this study, it was aimed to evaluate the effects of vitamin D on hippocampal apoptosis related with seizures by using pentylenetetrazol (PTZ) and kainic acid (KA) in rats. METHODS: Male Sprague Dawley rats, aged 5.5 weeks, were randomly divided into six groups: control, vitamin D, PTZ, KA, PTZ + vitamin D and KA + vitamin D groups. The groups that received vitamin D were given 500 IU/kg of vitamin D daily for two weeks in addition to a standard diet. At the end of this period, PTZ and KA were applied to trigger seizures in the rats in the seizure groups. 24 h after the administration of PTZ and KA, the rats were decapitated. In the hippocampal region, apoptosis was assessed by TUNEL and brain-derived neurotrophic factor (BDNF), Bax, caspase-3 and c-fos activation were evaluated by immunohistochemical method. RESULTS: BDNF level increased while c-fos, Bax and caspase-3 levels decreased (p < 0.0001, in all) in the hippocampal neurons of the groups that were pre-treated with vitamin D before the administration of PTZ and KA, in comparison with the PTZ and KA groups. Vitamin D significantly decreased the number of apoptotic cells in these rats in comparison with the PTZ and KA groups (p < 0.0001). CONCLUSION: This study indicates that vitamin D has neuroprotective effects on hippocampal apoptosis induced by PTZ and KA in rats. With this study it is suggested that keeping vitamin D levels within normal limits may be beneficial for patients with epilepsy, especially children.

Are diagnostic magnetic resonance patterns life-saving in children with biotin-thiamine-responsive basal ganglia disease?

BACKGROUND: Biotin-thiamine responsive basal ganglia disease (BTBGD) is an autosomal recessive disorder caused by mutations in the SLC19A3 gene and characterized by recurrent sub-acute episodes of encephalopathy that typically starts in early childhood. This study describes characteristic clinical and magnetic resonance imaging (MRI) findings of six cases of BTBGD diagnosed with newly identified mutations and genetically confirmed, with very early and different presentations compared to cases in the previous literature. METHODS: Six patients referred from different centers with similar clinical findings were diagnosed with BTBGD with newly identified mutations in the SLC19A3 gene. Two novel mutations in the SLC19A3 gene were identified in two patients at whole exome sequencing analysis. The clinical characteristics, responses to treatment, and electroencephalography (EEG) and MRI findings of these patients were examined. The other four patients presented with similar clinical and cranial MRI findings. These patients were therefore started on high-dose biotin and thiamine therapy, and mutation analysis concerning the SLC19A3 gene was performed. Responses to treatment, clinical courses, EEG findings and follow-up MRI were recorded for all these patients. RESULTS: Age at onset of symptoms ranged from 1 to 3 months. The first symptoms were generally persistent crying and restlessness. Seizures occurred in five of the six patients. Cranial magnetic resonance imaging revealed involvement in the basal ganglia, brain stem, and the parietal and frontal regions in general. The first two patients were siblings, and both exhibited a novel mutation of the SLC19A3 gene. The third and fourth patients were also siblings and also exhibited a similar novel mutation of the SLC19A3 gene. The fifth and sixth patients were not related, and a newly identified mutation was detected in both these subjects. Three novel mutations were thus detected in six patients. CONCLUSION: BTBGD is a progressive disease that can lead to severe disability and death. Early diagnosis of treatable diseases such as BTBGD is important in order to prevent long-term complications and disability.