The genetic and epidemiological features of hereditary ataxias have been reported in several populations; however, Turkey is still unexplored. Due to high consanguinity, recessive ataxias are more common in Turkey than in Western European populations.

Autoimmune encephalitis should be excluded in unexplained encephalitis. A significant portion of autoimmune encephalitis in childhood is anti- NMDA encephalitis. However, neuroimaging and routine diagnostic tests are inadequate, diagnosis sholud be confirmed by the demonstration of autoantibodies. The treatment may be delay in this process. Extreme delta brush waves are unique electroencephalography pattern, seen in some of Anti-NMDA encephalitis, useful for early diagnosis. Extreme delta brush activity is associated with prolonged hospitalization and illness. Despite of these, the specificity and sensitivity of this pattern is not-known clearly. We present a five years old boy with the loss of consciousness, involuntary movements, intermittant generalized tonic clonic seizures and extreme delta brush activity in electroencephalography.

Glutaric aciduria Type 1 (GA-I) is a rare inherited metabolic disease, deficiency of glutaryl-CoA dehydrogenase results in accumulation of the putatively neurotoxic metabolites glutaric and 3-hydroxyglutaric acid (GA, 3-OH-GA) in body tissues, particularly within the brain. Here we presented a 3-year-old girl with hypotonia and dystonia diagnosed with GA-I although the repeated analysis of the carnitine profile and organic acid analyses were normal. The patient has motor, mental retardation, hypotonia. Her weight standard deviation score (SDS) was -1.86 SDS, height SDS was -0.55 SDS, head circumference SDS was -1.01. The physical examination was normal except severe hypotonia. Spot blood carnitine profile, blood amino acid, urine organic acid, lactic acid and pyruvic acid were normal in repeated analysis. Dystonia and spastic tetraparesis developed on her follow-up. Cranial magnetic resonance imaging revealed bilateral cortical atrophy and bilateral striatal and caudate nucleus T2 flair hyperintensities. In GCDH gene analysis p.Y123C (c.368A > G)/p.L340F (c.368A > G) mutation was found. There was no history of encephalopathy. The patient treated with levodopa and trihexyphenidyl and lysine-restricted diet. In the presence of bilateral striatal involvement and cortical atrophy and dystonia, GA-I should be kept in mind. Blood carnitine profile and urine organic acid analyses may not be consistent. It is important to evaluate the cases for genetic investigation.

Objective To provide an overview of clinical and MRI characteristics of the different variants of the leukodystrophy megalencephalic leukoencephalopathy with subcortical cysts (MLC) and identify possible differentiating features. Methods We performed an international multi-institutional, cross-sectional observational study of the clinical and MRI characteristics in patients with genetically confirmed MLC. Clinical information was obtained by questionnaires for physicians and retrospective chart review. Results We included 204 patients with classic MLC, 187 of whom had recessive mutations in MLC1 (MLC1 variant) and 17 in GLIALCAM (MLC2A variant) and 38 patients with remitting MLC caused by dominant GLIALCAM mutations (MLC2B variant). We observed a relatively wide variability in neurologic disability among patients with classic MLC. No clinical differences could be identified between patients with MLC1 and MLC2A. Patients with MLC2B invariably had a milder phenotype with preservation of motor function, while intellectual disability and autism were relatively frequent. Systematic MRI review revealed no MRI features that distinguish between MLC1 and MLC2A. Radiologic improvement was observed in all patients with MLC2B and also in 2 patients with MLC1. In MRIs obtained in the early disease stage, absence of signal abnormalities of the posterior limb of the internal capsule and cerebellar white matter and presence of only rarefied subcortical white matter instead of true subcortical cysts were suggestive of MLC2B. Conclusion Clinical and MRI features did not distinguish between classic MLC with MLC1 or GLIALCAM mutations. Absence of signal abnormalities of the internal capsule and cerebellar white matter are MRI findings that point to the remitting phenotype.

Tekin H, Tekgül H, Yılmaz S, Arslangiray D, Reyhan H, Serdaroğlu G, Gökben S. Prevalence and severity of malnutrition in pediatric neurology outpatients with respect to underlying diagnosis and co-morbid nutrition and feeding related problems. Turk J Pediatr 2018; 60: 709-717. This study aimed to determine prevalence and severity of malnutrition with respect to underlying diagnosis and co-morbid nutrition and feeding related problems in pediatric neurology outpatients. A total of 1,057 pediatric neurology outpatients (7.2±5.4 years, 56.9% males) were included. Data on patient demographics, neurological diagnosis, anthropometrics and Nutritional Questionnaire (NQ) for co-morbid feeding difficulties and nutritional problems were recorded. Epilepsy (45.2%) was the most common diagnosis, while prevalence of acute malnutrition was 17.7%. Nutritional support resulted in a significant decrease in the percentage of malnourished patients (from 17.1% to 6.7%, p˂0.001) and significant improvement in weight for height scores (increased to 81.42±8.17, p=0.045). In NQ-10 item assessment, at least one item was positive in 66.0% (gastrointestinal in 54.3%) of acutely malnourished patients, more commonly in severe acute malnutrition. NQ 4- item set of `red flags` revealed that prolonged meal time, meal time stressful to child or parent, lack of weight gain not just weight loss and cough during feeding were evident in 45.2%, 46.8%, 36.7% and 14.8% of patients with acute malnutrition, respectively; and more common in patients with severe malnutrition. NQ 4-item set of `red flags` was associated with high sensitivity (95%) and specificity (88%) in detection of malnutrition. In conclusion, our findings in a cohort of pediatric neurology outpatients revealed that 17.1% of overall patients were acutely malnourished along with higher prevalence of malnutrition in underlying diagnosis of cerebral palsy and higher likelihood of nutritional problems and feeding difficulties in severe malnutrition. Given the association of 6-month nutritional support with improved anthropometrics and decreased percentage of malnourished patients, our findings indicate that increased awareness of nutritional status and nutritional support is essential for the care of neurologically impaired children with potential benefit of identifying early feeding/swallowing related signs of malnutrition.

Sturge-Weber syndrome (SWS) is a neurogenetic disease with an incidence of 1 in 20.000-50.000 live births. The less common form, which can be difficult to diagnose and only involves leptomeningeal angioma, has been defined as Type III SWS. A 5.5-month-old male patient with normal neuromotor development presented with right sided partial seizures, which had been occurring frequently for the previous two days and could not be controlled. A cranial magnetic resonance imaging showed pathological contrasts in the cortical regions involving the left hemisphere and in the leptomeningeal structures. We aim to present the case of an infant with SWS, which unlike the classical form was unidentifiable in physical examination and diagnosed using imaging methods.

Today rapidly increasing obesity causes significant morbidity and mortality. Gastric by-pass is frequently used for the treatment of morbid obesity, which cannot be controlled with diet and exercise. Although this treatment modality achieves rapid success, it also has several complications such as nutritional deficiency and its clinical results. We aimed to present a patient with polyneuropathy after having undergone gastric by-pass surgery for morbid obesity.

Objective: Cases with cerebral palsy (CP) followed in Child Neurology Outpatient Clinic between 2008-2015 years were evaluated retrospectively. Group 1 (n:116) and Group 2(n:118) were consisted of CP cases without and with epilepsy respectively. Clinical, laboratory findings of two groups were compared to each other. Methods: Statistical analyses were performed by using SPSS programme. P value less than 0.05 was considered as statistically significant. Results: There was no significant difference between two groups in terms of gender, gestationel age, birth type, birth weight, risk factors for CP development (pre/peri/postnatal), length of NICU stay and the need for mechanical ventilation. (p>0.05). Cases were evaluated in according to SCPE definitions and subtypes in spastic group were also defined depending on Sweedish classification. These factors outlined below were found to be significant for epilepsy development in CP cases: * History of neonatal convulsion *The presence of focal clonic or generalized tonic neonatal seizures *Abnormal base rhtyhm on neonatal EEG (generalized low amplitude, amplitude asymmetry or absence of maturational properties in according to postconceptional age) *Discharge of the case from NICU with at least one antiepileptic drug * Presence of bilateral spastic (tetraplegic) CP * Abnormal paroxysmal activity on EEG obtained at the 6 months of age * Having of abnormal cranial MRI findings (cerebral atrophy, hydrocephaly, cortical dysplasia and cerebral malformations) *Having microcephaly, visual problems and mental retardation. Conclusion: CP cases having one or more these risk factors should be monitored closely in regard to epilepsy.

We investigated the genetic background of early-onset epileptic encephalopathy (EE) using targeted next generation sequencing analysis. Thirty sporadic or familial cases associated with early-onset EE were included. An early-onset EE gene panel including sixteen genes (ARX, CDKL5, CNTNAP2, FOLR1, FOXG1, LAMC3, MBD5, MECP2, NTNG1, PCDH19, PNKP, SCN1A, SCN1B, SCN2A, STXBP1, KCNQ2) was constituted. Nine definite and three potential causal mutations in 30 cases (40 %) were identified. All mutations presented heterozygously except one. Five mutations had been previously detected (SCN1A c.842C > T (p.P281L), SCN1A c.4907G > C (p.A1636P), PCDH19 c.1091dupC (p.Y366LfsX10), CNTNAP2 c.416A > G (p.N139S), MBD5 c.3595G > A(p.Y1199R) while other seven were novel (SCN1A c.4907G > C (p.A1636P), SCN2A c.4633A > G (p.M1545 V), CDKL5 c.197_198delCT (p.L67QfsX23), FOXG1 c.*6C > T, KCNQ2 c.560c > A (p.S187Y), KCNQ2 c.835G > A (p.G279S), STXBP1 c.1105G > T (p.E369X)). Eight of 12 mutations were de novo. While the overall mutation detection rate was found 40 %, this ratio was 55.5 % (10 out of 18) and 16.6 % (2 out of 12) in patients born to nonconsanguineous parents and consanguineous parents, respectively. In conclusion, a selected gene panel approach including mainly de novo and channel-encoding genes will result in the detection of variants in isolated patients and support the channelopathy theory underlying epilepsy, while consanguineous families will remain less diagnosed. Targeted next generation sequencing approach is an efficient diagnostic tool in the detection of the genetic basis of early-onset EE.

Biotinidase deficiency is characterized by severe neurological manifestations as hypotonia, lethargy, ataxia, hearing loss, seizures and developmental retardation in its classical form. Late-onset biotinidase deficiency presents distinctly from the classical form such as limb weakness and vision problems. A 14-year-old boy presented with progressive vision loss and upper limb weakness. The patient was initiated steroid therapy with a preliminary diagnosis of neuromyelitis optica spectrum disorder due to the craniospinal imaging findings demonstrating optic nerve, brainstem and longitudinally extensive spinal cord involvement. Although the patient exhibited partial clinical improvement after pulse steroid therapy, craniocervical imaging performed one month after the initiation of steroid therapy did not show any regression. The CSF IgG index was <0.8 (normal: <0.8), oligoclonal band and aquaporin-4 antibodies were negative. Metabolic investigations revealed a low biotinidase enzyme activity 8% (0.58 nmoL/min/mL; normal range: 4.4 to 12). Genetic testing showed c.98-104delinsTCC and p.V457 M mutations in biotinidase (BTD) gene. At the third month of biotin replacement therapy, control craniospinal MRI demonstrated a complete regression of the lesions. The muscle strength of the case returned to normal. His visual acuity was 7/10 in the left eye and 9/10 in the right. The late-onset form of the biotinidase deficiency should be kept in mind in all patients with myelopathy with or without vision loss, particularly in those with inadequate response to steroid therapy. The family screening is important to identify asymptomatic individuals and timely treatment.

Sir, We read with great interest, the article by Zollo et al. (2017) presenting the first cases with functional molecular analysis of PRUNE1-related microcephaly with neurodevelopmental impairment. PRUNE1 was first described by Karaca et al. (2015) as a candidate disease-causing gene for neurodevelopmental impairment with microcephaly. Mutations in PRUNE1 were identified in families of various ethnic backgrounds with autosomal recessive neurodevelopmental and neurodegenerative disorder that includes primary microcephaly and profound global developmental delay (Karaca et al., 2015; Zollo et al., 2017). We report an additional affected individual with congenital hypotonia, secondary microcephaly, global developmental delay and respiratory insufficiency from a healthy consanguineous Turkish family. Hereby, we confirm the pathogenicity of recessive PRUNE1 mutations, but also underline the type of microcephaly that has developed after birth, progressed in 2 years and presented as a secondary microcephaly. Informed consent for next-generation sequencing and photos of the affected individual were obtained from the parents and the affected individual under NeurOmics consortium regulations. The 3-year-old male was followed since birth because of neonatal generalized hypotonia, knee contractures and hip dislocation. He was born uneventfully via caesarean section due to breech presentation. His birth weight was 3750 g (75th percentile), height was 50 cm (50th percentile) and head circumference was 36 cm (75th percentile). He was able to smile and make eye contact at 2 months of age, but these abilities were gradually lost. After frequent admissions to the intensive care unit due to pneumonia, he developed respiratory insufficiency at 8 months of age, and has been mechanically ventilated since then (Fig. 1A–E). First focal motor seizures started at 2 months of age and flexor spasms occurred shortly thereafter. Cranial MRI scans at 14 months of age revealed cerebral and cerebellar atrophy with delayed myelination and inferior vermis hypoplasia (Fig. 1G–I). Electromyography findings were compatible with neurogenic involvement. At 38 months of age, he was unable to hold his head, had general muscle weakness and hypotonia along with spasticity and clonus at lower extremities, secondary microcephaly with a head circumference of 48.0 cm ( 2 standard deviations) (Fig. 1F), brachycephaly, large ears, optic atrophy, severe kyphoscoliosis and flexion contractures. He required permanent mechanical ventilation through tracheostomy and feeding via nasogastric tube (Fig. 1). Trio-whole genome sequencing (trio-WGS) was performed, which revealed a homozygous frameshift variant, c.874_875insA (p.H292Qfs*3), in PRUNE1 (prune exopolyphosphatase 1, NM_021222.2) as the primary candidate mutation (Fig. 1J–K). The consanguinity of the parents and the parental status were confirmed by allele sharing doi:10.1093/brain/awx197 BRAIN 2017: 140; 1–4 | e61

Congenital myasthenic syndromes are clinically and genetically heterogeneous disorders of neuromuscular transmission. Most are treatable, but certain subtypes worsen with cholinesterase inhibitors. This underlines the importance of genetic diagnosis. Here, the authors report on cases with genetically proven congenital myasthenic syndromes from Turkey. The authors retrospectively reviewed their experience of all patients with congenital myasthenic syndromes, referred over a 5-year period (2011-2016) to the Child Neurology Department of Dokuz Eylül University, Izmir, Turkey. In addition, PubMed was searched for published cases of genetically proven congenital myasthenic syndromes originating from Turkey. In total, the authors identified 43 (8 new patients, 35 recently published patients) cases. Defects in the acetylcholine receptor (n = 15; 35%) were the most common type, followed by synaptic basal-lamina associated (n = 14; 33%) and presynaptic syndromes (n = 10; 23%). The authors had only 3 cases (7%) who had defects in endplate development. One patient had mutation GFPT1 gene (n = 1; 2%). Knowledge on congenital myasthenic syndromes and related genes in Turkey will lead to prompt diagnosis and treatment of these rare neuromuscular disorders.

The objective of this study is to evaluate neurologic problems caused by nutritional vitamin B12 deficiency in infancy. Twenty-four cases between 2 and 18 months of age with neurologic symptoms and/or signs and diagnosed as nutritional vitamin B12 deficiency were analyzed. The most common symptoms were developmental retardation, afebrile seizures, and involuntary movements. The mean vitamin B12 levels were lower in patients with both neurologic and extraneurologic involvement when compared to those with only neurologic symptoms. All of the cases were treated with vitamin B12. In patients with severe deficiencies, involuntary movements were observed during vitamin B12 treatment using cyanocobalamin form. At the 1-year follow-up, all but 3 patients were considered neurodevelopmentally normal. The 3 patients that did not fully recover, on admission, had the lowest vitamin B12 levels. It is of great importance to prevent, diagnose, and treat vitamin B12 deficiency promptly to prevent the long-term neurologic problems.

The aim of this study is to assess the seizure and developmental outcome and to determine the prognostic factors affecting the outcome of West syndrome in an etiologically well-defined large cohort. Demographic features, treatment modalities, etiology, seizure and developmental outcome of 216 cases with West syndrome were recorded retrospectively. Ten prognostic factors possibly affecting the outcome of West syndrome including (1) gender, (2) age at the onset (3) presence of seizures prior to spasms, (4) presence of asymmetric spasm, (5) presence of abnormal neurological signs, (6) treatment lag, (7) etiology, (8) drug chosen as the initial treatment, (9) response to initial treatment regardless of the kind, (10) development of other seizure types after spasms were evaluated in terms of seizure and developmental outcome. Twelve percent of the cases were developmentally normal at the end of 2-year follow-up. Ongoing seizures requiring antiepileptic drug medication at the last follow-up were noted in 90 % of the cases. Hypoxia (29 %), metabolic disorders (11 %), infectious diseases (9 %) and cerebral developmental disorders (8 %) were the most frequent etiological factors. Five of the ten prognostic factors (presence of seizures prior to spasms, presence of abnormal neurological signs, response to initial treatment regardless of the kind, etiology and development of other seizure types after spasms) were found to be statistically significant prognostic factors predicting the outcome. In conclusion, West syndrome is still a catastrophic epileptic encephalopathy. Preventable causes still constitute a substantial portion of the etiological causes of West syndrome. Therefore, the prevention of avoidable causes is at least as important as the treatment.

Landau-Kleffner syndrome (LKS) is acquired aphasia circumstance with loss of gained language ability and epilepti form electroencephalography or clinical seizure described first in 1957 by Landau and Kleffner. Expressive aphasia starts commonly among children of 3 to 8 age group and verbal auditor agnosia are other clinical features of LKS. Patients have difficulty in understanding what they are being told and respond to visual as well as auditory arousals. Seizure is seen in 70% of the cases. Patients with LKS usually develop normally, but it has been reported that about 13% of the cases had speech ability problem previously. Due to resemblance of symptomatology, causals such as audition loss, deafness, psychiatric disorders, progressive encephalopathy, "Childhood Rolandic Epilepsy" should be considered as differential diagnoses of LKS. We have briefly discussed the clinical progress of an 8-year-old male child who was followed with prediagnosis of major depression by child psychiatry department because of agression, relationship problems with his friends and regression in his speech. His behavior problems and absence of seizures had delayed obtaining an EEG in the early period. Seizures started two years after the behavior problems and loss of speech. Thus, we suggest that if a child with normal language development starts to regress, Landau-Kleffner syndrome must be considered in the differential diagnosis even in the absence of epileptic seizures.

Cyclin-dependent kinase-like 5 gene-related epileptic encephalopathy is gradually becoming better known in child neurology practice. The related gene mutations cause early infantile epileptic encephalopathy characterized by intractable epilepsy, severe mental retardation and, later, the development of Rett syndrome-like features. Herein, we report the first two Turkish cases of cyclin-dependent kinase-like 5 gene-related epileptic encephalopathy with novel mutations in exon 8, which is located in the catalytic domain of the gene.

BACKGROUND:Ictal urinary urge is a rare autonomic symptom usually lateralizing to the non-dominant hemisphere and localizing to the temporal lobe.CASE REPORT:A 12-year-old boy was referred with desire to void and contraction of the left arm. The history of the case revealed tickling and an unpleasant rising feeling in the stomach and sense of fear lasting for 1 year. He had been evaluated and treated several times with the diagnosis of gastroesophageal reflux and cystitis. His cranial MRI displayed an intra-axial mass formation on the right temporal lobe. Pathological findings were consistent with a low-grade glial mass.CONCLUSION:Ictal urinary urge has a considerable value both for localization and lateralization of seizures.

Neurobrucellosis is an uncommon complication of pediatric brucellosis. Direct invasion of the central nervous system occurs in about 5% of the cases of Brucella melitensis infection. Meningitis or meningoencephalitis are the most common manifestations. Neurobrucellosis may rarely affect second, third, sixth, seventh and the eighth cranial nerves. Peripheral nerve involvement is also rarely seen in pediatric neurobrucellosis. Here we reported is a twelve years old girl presented with bilateral peripheral facial nerve palsy and peripheral neuropathy. This case is an unusual presentation of neurobrucellosis in pediatric population. Our report emphasizes that neurobrucellosis should be kept in mind in the cases with atypical neurologic manifestations in endemic regions.