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A 12-year-old girl was admitted for the evaluation of epilepsy and psychomotor retardation. She was born at term after an uneventful pregnancy. There was no consanguinity. Developmental milestones were delayed and she had been treated for epilepsy since 3months of age. Shewas walking with support and was able to say a few words like “mama” and “dada.” She had dysmorphologic findings including broad nasal tip, frontal bossing, hypertelorism, tongue hamartomas, notching of the teeth (Fig 1), high arched palate, low set ears, and bilateral preaxial polysyndactyly of bilateral feet with bifid hallux. Deep tendon reflexes were hyperactive. Echocardiography, abdominopelvic ultrasonography, and ophthalmologic examinations were normal. Brain magnetic resonance imaging revealed molar tooth sign and vermian agenesis (Fig 2). A diagnosis of Varadi-Papp syndrome (orofaciodigital syndrome type VI) was made based on her clinical and radiologic findings. Genetic analysis of INPP5 E and TMEM216 genes revealed no mutation.

Streptococcus mitis (S. mitis) is a rare cause of meningitis in immunocompetent children. It has been described in patients with neurosurgical procedure, previous spinal anesthesia and immunodeficiency. We report two childhood cases of S. mitis meningitis. The children were previously healthy. One of the patients had poor oral hygiene and the other had a history of sinusitis. Both of them had encephalopathy and signs of meningeal irritation at presentation. Widespread cerebral white matter lesions were found on brain magnetic resonance imaging. The lesions disappeared and encephalopathy recovered with antibiotic and immunomodulatory treatment.

Importance: Knowing the range of symptoms seen in patients with a missense or loss-of-function variant in KCNB1 and how these symptoms correlate with the type of variant will help clinicians with diagnosis and prognosis when treating new patients.Objectives: To investigate the clinical spectrum associated with KCNB1 variants and the genotype-phenotype correlations.Design, Setting, and Participants: This study summarized the clinical and genetic information of patients with a presumed pathogenic variant in KCNB1. Patients were identified in research projects or during clinical testing. Information on patients from previously published articles was collected and authors contacted if feasible. All patients were seen at a clinic at one of the participating institutes because of presumed genetic disorder. They were tested in a clinical setting or included in a research project.Main Outcomes and Measures: The genetic variant and its inheritance and information on the patient's symptoms and characteristics in a predefined format. All variants were identified with massive parallel sequencing and confirmed with Sanger sequencing in the patient. Absence of the variant in the parents could be confirmed with Sanger sequencing in all families except one.Results: Of 26 patients (10 female, 15 male, 1 unknown; mean age at inclusion, 9.8 years; age range, 2-32 years) with developmental delay, 20 (77%) carried a missense variant in the ion channel domain of KCNB1, with a concentration of variants in region S5 to S6. Three variants that led to premature stops were located in the C-terminal and 3 in the ion channel domain. Twenty-one of 25 patients (84%) had seizures, with 9 patients (36%) starting with epileptic spasms between 3 and 18 months of age. All patients had developmental delay, with 17 (65%) experiencing severe developmental delay; 14 (82%) with severe delay had behavioral problems. The developmental delay was milder in 4 of 6 patients with stop variants and in a patient with a variant in the S2 transmembrane element rather than the S4 to S6 region.Conclusions and Relevance: De novo KCNB1 missense variants in the ion channel domain and loss-of-function variants in this domain and the C-terminal likely cause neurodevelopmental disorders with or without seizures. Patients with presumed pathogenic variants in KCNB1 have a variable phenotype. However, the type and position of the variants in the protein are (imperfectly) correlated with the severity of the disorder.

Mutations in the genes encoding voltage-gated sodium channels cause a variety of epilepsy syndromes, with most of the mutations occurring in SCN1A gene. It is one of the most well-researched epilepsy genes. The SCN1A gene, which seems to be a relevant regulator of excitability of the CNS, is implicated in various epilepsy phenotypes through various genetic mechanisms ranging from common variants to rare monogenic variants. It is known that SCN1A gene is tightly linked to severe myoclonic epilepsy of infancy (SMEI). However, its phenotypic spectrum is expanding. Here, we report clinical and genetic findings of 10 patients with SCN1A mutations where two of them were found to have novel mutations. Our findings support understanding and updating knowledge on the correlation between phenotype distribution and location and type of mutations in SCN1A-related disorders.

Objectives To reveal the contribution of MRI and diffusion-weighted imaging (DWI) to the diagnosis of mitochondrial encephalopathy (ME) and to evaluate the parenchymal changes associated with this disease in the involved parenchymal areas using the apparent diffusion coefficient (ADC) parameter. Methods Ten patients who had undergone MRI and DWI analysis with a pre-diagnosis of neurometabolic disease, and who were subsequently diagnosed with ME in laboratory and/or genetic studies, were included in our study. ADC values were compared with a control group composed of 20 patients of similar age with normal brains. Evaluations involved measurements made in 20 different areas determined on the ADC map. The dominance or contribution of ADC coefficient measurements to the conventional sequences was compared with the controls. Results In the first examination, an increase in both diffusion and ADC values was detected in six cases and diffusion restriction and a decrease in ADC values in three patients. While an increase in both diffusion and ADC values was demonstrated in four cases, there was diffusion restriction and a decrease in ADC values in three cases in the control examinations. Conclusions DWI provides information that complements conventional MRI sequences in the diagnosis of ME.

Friedreich ataksi otozomal resesif geçişli nörodejeneratif bir hastalık olup kalıtsal ataksilerin en sık nedenidir. Hastaların %95’inde kromozom 9q13 üzerinde bulunan FRDA geninin birinci intronunda GAA trinukleotid tekrar artışı mevcuttur. Bu durum demir homeostazında önemli bir role sahip olan frataksin proteininin düzeyinde azalışa yol açar. Friedreich ataksi hastalığının patogenezinden mitokondrilerde demir birikimi ve bunun neden olduğu spesifik mitokondriyal enzim eksiklikleri, oksidatif strese artmış duyarlılık ve serbest radikal aracılı hücre ölümü sorumludur. Günümüzde hastalığın etkin bir tedavisi yoktur, ancak antioksidan tedaviler özellikle kardiyak tutulumda umut vaat etmektedir. Friedreich ataksili olguların erken tanınması ve işlevsel kısıtlılıkların zamanında belirlenmesi rehabilitasyon, semptomatik tedavi ve genetik danışma açısından önemlidir. Bu yazıda homozigot GAA artışına sahip beş hastanın klinik özellikleri sunulmakta ve ilerleyici ataksi ile başvuran hastalarda ayırıcı tanıda Friedreich ataksinin düşünülmesinin gerekliliğini vurgulamaktır. Friedreich ataxia is an autosomal recessive neurodegenerative disease, which is the most common cause of inherited ataxias. About 95% of the patients demonstrate an expansion of a GAA trinucleotide repeat in intron 1 of the FRDA gene on chromosome 9q13. This leads to reduced levels of frataxin which has an important role in iron homeostasis. Friedreich ataxia is the result of accumulation of iron in mitochondria leading to excess production of free radicals, defects in specific mitochondrial enzymes, enhanced sensitivity to oxidative stress, and eventually free- radical mediated cell death. Currently there is no effective therapy for the disease, but antioxidant therapy has shown promise especially in cardiac involvement. Early identification of individuals with Friedreich ataxia and precise characterization of impairments and functional limitations gain importance as symptomatic treatment, rehabilitation and genetic counseling are considered. Here, we present the clinical findings of five cases with Friedreich ataxia who had homozygous GAA trinucleotide expansion and emphasize that Friedreich ataxia should be considered in the differential diagnosis of cases who present with progressive ataxia.

BACKGROUND: To evaluate clinical, genetic, and radiologic features of our patients with muscle-eye-brain disease. METHODS: The data of patients who were diagnosed with muscle-eye-brain disease from a cohort of patients with congenital muscular dystrophy in the Division of Pediatric Neurology of Dokuz Eylul University School of Medicine and Gaziantep Children’s Hospital between 2005 and 2013 were analyzed retrospectively. RESULTS: From a cohort of 34 patients with congenital muscular dystrophy, 12 patients from 10 families were diagnosed with muscle-eyebrain disease. The mean age of the patients was 9 � 5.5 years (2-19 years). Mean serum creatine kinase value was 2485.80 � 1308.54 IU/L (700-4267 IU/L). All patients presented with muscular hypotonia at birth followed by varying degrees of spasticity and exaggerated deep tendon reflexes in later stages of life. Three patients were able to walk. The most common ophthalmologic and radiologic abnormalities were cataracts, retinal detachment, periventricular white matter abnormalities, ventriculomegaly, pontocerebellar hypoplasia, and multiple cerebellar cysts. All of the patients had mutations in the POMGNT1 gene. The most common mutation detected in 66% of patients was c.1814 G > A (p.R605H). Two novel mutations were identified. CONCLUSIONS: We suggest that muscle-eye-brain disease is a relatively common muscular dystrophy in Turkey. It should be suspected in patients with muscular hypotonia, increased creatine kinase, and structural eye and brain abnormalities. The c.1814 G > A mutation in exon 21 of the POMGNT1 gene is apparently a common mutation in the Turkish population. Individuals with this mutation show classical features of muscle-eye-brain disease, but others may exhibit a milder phenotype and retain the ability to walk independently. Congenital muscular dystrophy patients from Turkey carrying the clinical and radiologic features of muscle-eye-brain disease should be evaluated for mutations in POMGNT1 gene.

Dravet syndrome is a rare epileptic encephalopathy characterized by frequent seizures beginning in the first year of life and behavioral disorders. Mutations in the sodium channel α1 subunit gene are the main cause of this disease. We report two patients with refractory seizures and psychomotor retardation in whom the final diagnosis was Dravet syndrome with confirmed mutations in the sodium channel α1 subunit gene. The mutation identified in the second patient was a novel frame shift mutation, which resulted from the deletion of five nucleotides in exon 24.

The aim of this study was to characterize the etiology, course and prognosis in children admitted to a pediatric intensive care unit (PICU) of Gaziantep Children's Hospital for impaired state of consciousness. Three hundred and eighty cases were evaluated. Convulsions (44%; n=170) were the leading cause of the impaired state of consciousness followed by poisonings, envenomation, infection, metabolic disease, electrical injury, hepatic encephalopathy, intracranial hemorrhage, brain tumor, and drowning. The diagnosis was definite in 95% (n=359) and probable in 5% (n=21) of cases. Twenty-seven (7%) patients died with impaired state of consciousness. We suggest that defining the causes of impaired state of consciousness in a specific region will help physicians to evaluate the patients faster and in a more systemic manner. Since most of the causes seem to be preventable, appropriate education programs and policies should be provided for improving sanitation and socioeconomic conditions.

Fibromuscular dysplasia is a rare, idiopathic and nonatheromatous disease. It is rarely encountered as a cause of stroke in children. We report a nine-year-old girl with stroke in whom extensive fibromuscular dysplasia of intracranial vessels was established. She also had familial combined hyperlipidemia as an additional risk factor. This case suggests that additional risk factors like hyperlipidemia in cases with fibromuscular dystrophy may facilitate the occurrence of stroke at early ages.

Streptococcus mitis, an important member of viridans streptococci, is found in the normal flora of the oropharynx, gastrointestinal tract, female genital tract and skin. Although it is of low pathogenicity and virulence, it may cause serious infections in immunocompromised patients. Meningitis caused by S.mitis has been described in patients with previous spinal anesthesia, neurosurgical procedure, malignancy, bacterial endocarditis with neurological complications and alcoholics, but it is rare in patients who are previously healthy. In this report, a rare case of meningoencephalitis caused by S.mitis developed in a previously healthy child has been presented. A previously healthy eight-year-old girl who presented with fever, altered state of consciousness, and headache was hospitalized in intensive care unit with the diagnosis of meningitis. Past history revealed that she was treated with amoxicillin-clavulanate for acute sinusitis ten days before her admission. Whole blood count revealed the followings: hemoglobin 13 g/dl, white blood cell count 18.6 x 109/L (90% neutrophils), platelet count 200 x 109/L and 150 leucocytes were detected on cerebrospinal fluid (CSF) examination. Protein and glucose levels of CSF were 80 mg/dl and 40 mg/dl (concomitant blood glucose 100 mg/dl), respectively. Brain magnetic resonance imaging (MRI) revealed widespread white matter lesions, and alpha-hemolytic streptococci were grown in CSF culture. The isolate was identified as S.mitis with conventional methods, and also confirmed by VITEK2 (bioMerieux, France) and API 20 STREP (bioMerieux, France) systems. Isolate was found susceptible to penicillin, erythromycin, clindamycin, tetracycline, cefotaxime, vancomycin and chloramphenicol. Regarding the etiology, echocardiography revealed no vegetation nor valve pathology, and peripheral blood smear showed no abnormality. Immunoglobulin and complement levels were within normal limits. Ongoing inflammation in maxillary sinuses detected in brain MRI suggested that meningitis could be related to previous sinus infection. After 14 days of ceftriaxone treatment, the patient was discharged from the hospital with cure. The aim of this case presentation was to emphasize that S.mitis may cause meningitis and white matter lesions in previously healthy children with concomitant sinusitis.

Ring chromosome 21 syndrome is a rare clinical condition. Most of the patients have a recognizable phenotype and multisystem involvement is described. Structural neurologic anomalies have also been described, but waddling gait due to lower motor neuron involvement has not been previously reported in association with ring 21.

The most common cause of recurrent rhabdomyolysis in childhood is inherited metabolic disorders. Carnitine palmitoyl transferase II (CPT II) deficiency is a lipidosis and is a common cause of inherited recurrent myoglobinuria. The disease is inherited in autosomal recessive trait, and the clinical phenotype ranges from a severe and multisystemic infantile form to a milder muscle form, which is characterized with rhabdomyolysis and myoglobinuria. Exercise, infection, fasting, and cold are the most important triggering factors of rhabdomyolysis in CPT II deficiency. The severity of attacks is highly variable and some of these attacks may be complicated by acute renal failure. We report a case of a 13-year-old girl with recurrent rhabdomyolysis due to CPT II deficiency whose last attack was complicated by acute renal failure.

Centronuclear myopathies (CNM) describe a group of rare muscle diseases typically presenting an abnormal positioning of nuclei in muscle fibers. To date, three genes are known to be associated to a classical CNM phenotype. The X-linked neonatal form (XLCNM) is due to mutations in MTM1 and involves a severe and generalized muscle weakness at birth. The autosomal dominant form results from DNM2 mutations and has been described with early childhood and adult onset (ADCNM). Autosomal recessive centronuclear myopathy (ARCNM) is less characterized and has recently been associated to mutations in BIN1, encoding amphiphysin 2. Here we present the first clinical description of intrafamilal variability in two first-degree cousins with a novel BIN1 stop mutation. In addition to skeletal muscle defects, both patients have mild mental retardation and the more severely affected male also displays abnormal ventilation and cardiac arrhythmia, thus expanding the phenotypic spectrum of BIN1-related CNM to non skeletal muscle defects. We provide an up-to-date review of all previous cases with ARCNM and BIN1 mutations.

Megalencephalic leukoencephalopathy with subcortical cysts is a rare leukodystrophy that is characterized by macrocephaly and a slowly progressive clinical course. It is one of the most commonly reported leukoencephalopathies in Turkey. Mutations in the MLC1 gene are the main cause of the disease. We report two patients with megalencephalic leukoencephalopathy with subcortical cysts with confirmed mutations in the MLC1 gene. The mutation in the second patient was novel. We also review identified mutations in the Turkish population.

Status epilepticus triggers a mixture of apoptotic and necrotic cell death within the hippocampus. This neuronal loss may result in the development of epilepsy and cognitive deficits. Erythropoietin mediates a number of biological actions within the central nervous system and has been shown to be neuroprotective. In the present study, we investigated the effects of recombinant human erythropoietin on hippocampus of rat after lithium-pilocarpine induced status epilepticus. Twenty-one dam reared Wistar male rats, 21-day-old were divided into three groups: control group, lithium-pilocarpine induced status epilepticus and lithium-pilocarpine induced status epilepticus and erythropoietin treated group. Erythropoietin treated group received recombinant human erythropoietin 10 U/g intraperitoneally 40 min after pilocarpine injection for 5 days. Rats were sacrificed and brain tissues were collected at 5th day of experiment. Neuronal cell death and apoptosis were evaluated. Histopathological examination showed that erythropoietin significantly decreased neuronal cell death in CA1, CA2, CA3 and dentate gyrus regions of hippocampus. It also diminished apoptosis in the CA1 and dentate gyrus regions of hippocampus. In conclusion, erythropoietin may preserve the number of neurons and decrease apoptosis in model of status epilepticus induced by lithium-pilocarpine. This experimental study suggests that erythropoietin administration may be neuroprotective in status epilepticus. (C) 2011 The Japanese Society of Child Neurology. Published by Elsevier B.V. All rights reserved.

The differences in growth patterns in breast-fed (BF) and formula-fed (FF) infants remain poorly understood. The aim of this study was to examine the relation of serum ghrelin and leptin concentrations to the different growth patterns between the formula-fed and breast-fed babies. Feeding behaviors and anthropometric data were noted at the 3rd and 6th months of age. Serum ghrelin and leptin levels in both groups and breast-milk ghrelin and leptin levels in the mothers of the BF group were determined at the 3rd month of age. Body weight, length, TSF (triceps skin fold thickness), postnatal weight gain, and serum ghrelin levels were higher in BF babies than in the FF group. In BF babies, serum ghrelin was correlated to TSF, and serum leptin was correlated to weight, TSF and weight gain at three months of age. As the serum leptin increased, energy intake from supplemental foods decreased in the BF group at the 6th month. Higher serum ghrelin in BF babies might have played a role in their faster growth rate during the first three months of age. On the other hand, lower energy intake from supplemental foods in correlation with higher serum leptin in BF babies may explain why these babies show marked decline in growth rate compared to FF babies after three months of age.

Dentatorubral pallidoluysian atrophy is a neurodegenerative disease that generally presents in adulthood. Although rare, it can be observed in childhood due to extreme expansion of the triplet repeat size during spermatogenesis. The diagnosis in childhood is very difficult in the absence of family history. Here we describe a 12-year-old girl with dentatorubral pallidoluysian atrophy who presented with progressive myoclonic epilepsy and ataxia. Family history exhibited similarly affected cases on the paternal side. Molecular testing for dentatorubral pallidoluysian atrophy revealed abnormal "cytosine-adenine-guanosine" expansion in the atrophin-1 gene.

Children with autism often display difficult behaviors including tantrums, extreme irritability, and physical aggression. There is emerging evidence that olanzapine is useful in decreasing these disruptive behaviors. The most common adverse effects are weight gain and short-term sedation. On the other hand, olanzapine rarely causes rhabdomyolysis. We report a case with rhabdomyolysis in an autistic child just after 2 doses of olanzapine treatment. Initial creatine kinase value was 30,690 IU/L (range, 5-130 U/L), and rhabdomyolysis resolved with hydration and alkalinization over 7 days. Monitoring serum creatine kinase levels may be useful in pediatric cases after initiation of olanzapine treatment.

The aim of this study is to evaluate the carotid artery intima media thickness and serum lipids in pediatric patients with epilepsy treated with valproic acid. The study included 44 pediatric epileptic and 40 healthy children. Intima media thickness of left common carotid artery and fasting lipid profile (total cholesterol, triglycerides, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol) were assessed. Although we did not observe any differences regarding serum lipid profiles, intima media thickness of common carotid artery was significantly higher in epileptic patients treated with valproic acid. We suggest that this increase in intima media thickness of common carotid artery may be due to epilepsy and/or valproic acid treatment. (C) 2008 Elsevier B.V. All rights reserved.

Spinocerebellar ataxia type 2 is a neurodegenerative disease caused by a CAG repeat expansion in the ataxin-2 gene. Gain-of-toxic effects caused by expanded polyglutamine tracts are important for the disease pathogenesis and there is an inverse relationship between the number of CAG repeats and the age of onset and clinical severity. Previously, we reported an extended Turkish family with spinocerebellar ataxia type 2 with several affected members in three generations. Two sisters in this generation showed an earlier age of onset (5 and 7 years, respectively) than their father (30 years). In this paper, we present a further interesting finding regarding the disease onset and manifestation in the two sisters. Interestingly, the age of onset was delayed and the clinical severity of the disease was milder in the child who had more CAG repeats (84 vs. 70). This finding suggests that there are other factors contributing to the age of onset and clinical severity in spinocerebellar ataxia type 2 other than the increased CAG repeat.

To evaluate the influence of 'only electroencephalographic (EEG)' and 'EEG plus clinical' seizures during neonatal period on neurodevelopment of the infants.The long-term digital-video- EEG tracings of the first 3 days of life of 30 neonates were assessed. The babies were subdivided into three groups: Group 1 had neither EEG nor clinical seizures. Group 2 had EEG seizures but no clinical seizures. Group 3 experienced both EEG and clinical seizures. The groups were compared in regard to psychomotor retardation and epilepsy at corrected age of 1 year.The mean birthweight was 1952.50 +/- 978.74 (685-4103) g. The mean gestational age was 32.53 +/- 4.26 (24-40) weeks. In regard to sex, gestational age and birth weight, there was no significant difference between the three groups. Ten percent of newborns in Group 1 and 53.8% of newborns in Group 3 had psychomotor retardation. No babies in Group 2 experienced psychomotor retardation. The differences between the Groups 1 and 3 and Groups 2 and 3 were found statistically significant. Only one baby in Group 3 had epilepsy. In Groups 1 and 2, no babies had epilepsy. The differences between the groups were not significant.Neonatal seizures, but not silent EEG seizures are in relationship with poor neurodevelopmental outcome evaluated at corrected age of 1 year in newborns.

Dystonia is a movement disorder that causes involuntary contractions of the muscles. Dystonia can affect just 1 muscle, a group of muscles, or all of the muscles. The most common cause acquired dystonia in childhood is drugs. Cetirizine is widely used for allergic disorders in childhood. It is without central nervous system side effects at recommended dosages. There is only 1 case of cetirizine-induced dystonia in the literature. We report a second case of cetirizine-induced acute acquired dystonia whose symptoms completely resolved after the discontinuation of the drug.

The purpose of this study is to evaluate parenchymal diffusion properties and metabolite ratios in affected brain tissues of inherited neurometabolic brain diseases with an overview of the current literature about the diagnostic data of both techniques in childhood inherited metabolic brain diseases. The study group was consisting, 19 patients (15 males, 4 females; mean age, 54 months (4.5 years); age range, 1-171 months (14.25 years)) diagnosed with inherited neurometabolic brain disease. Single- and multivoxel proton MRS was carried out and NAA/Cr, Cho/Cr, mI/Cr, Glx/Cr ratios were calculated. Presence of lactate peak and abnormal different peaks were noted. ADC values were calculated from brain lesions. Results are compared with age and sex matched normal subjects. Elevated NAA/Cr ratio (Canavan disease), galactitol peak (galactosemia) at 3.7 ppm, branched chain amino acids (Maple syrup urine disease-MSUD) at 0.9 ppm were seen on different diseases. In Leigh disease and MSUD restricted diffusion was detected. Different diffusion properties were seen only in one Glutaric aciduria lesions. NAA/Cr ratios and calculated ADC values were significantly different from normal subjects (p

The developing nervous system is sensitive to supraphysiological oxygen concentrations. Recent studies showed that exposure to hyperoxia in infant rats leads to extensive apoptotic degeneration in the cortex and white matter of the developing brain. A wide variety of experimental studies have shown that erythropoietin exerts a remarkable neuroprotection in both cell cultures and in animal models of nervous system disorders. In the present study, we investigated the effect of erythropoietin against hyperoxia-induced neurodegeneration in the developing brain. Eighteen Wistar rat pups were divided into three groups: control group, hyperoxia+saline-treated group and hyperoxia+erythropoietin-treated group. Hyperoxia groups were exposed to 80% oxygen (n=12) in a plexiglas chamber in which the oxygen concentration was monitored twice daily front birth until postnatal clay 5. Hyperoxia exposure was 24 h/day for 5 days. The hyperoxia+erythropoietin group received all intraperitoneal injection of recombinant human erythropoietin at a dose of 1000U/(kg day). At postnatal day 5, all animals were sacrificed. Neuronal cell death and apoptosis were evaluated. Histopathological examination showed that erythropoietin significantly diminished apoptosis in the CA1 region and dentate gyrus of hippocampus and parietal cortex in hyperoxia+erythropoietin-treated group. Regarding the safety profile of erythropoietin in premature and mature infants, this agent may be potentially beneficial in preventing hyperoxic brain injury. (C) 2008 Elsevier Ireland Ltd. All rights reserved.

Nonketotic hyperglycinemia is an autosomal recessive disorder of glycine metabolism. Patients generally present in the neonatal period with lethargy, feeding difficulty, hypotonia, apnea, poorly controlled convulsions, and coma. Myoclonic seizures and burst suppression pattern on electroencephalography are major findings of disease, but development of hydrocephalus is not an expected finding. The present case is that of an infant with acquired hydrocephalus, psychomotor retardation, and myoclonic seizures in whom the final diagnosis was nonketotic hyperglycinemia. (C) 2009 by Elsevier Inc. All rights reserved.

An 8-month-old girl and a 20-month-old boy who presented with motor and developmental delay and long-standing fever are presented. The patients were diagnosed as Angelman syndrome with fluorescence in situ hybridization (FISH) analysis. Despite extensive clinical and laboratory examinations, no inflammatory or infectious origin for the fever was found. It was considered that the long-standing fever observed in these cases was due to hypothalamic dysfunction for thermoregulation.

Multiple sulfatase deficiency (MSD) is an inherited lysosomal storage disease that affects post-translational activation of all of the sulfatases. Since biochemical and clinical findings are variable, the diagnosis is difficult in most of the cases. Missense, nonsense, microdeletion and splicing mutations in SUMF1 gene were found in all of the MSD patients analyzed. Here, we present clinical findings of two consanguineous patients with multiple sulfatase deficiency. They were found to be homozygous for a novel missense mutation c.739G > C causing a p.G247R amino acid substitution in the SUMF1 protein. (c) 2007 Elsevier B.V. All rights reserved.

The pathological nature of Leigh syndrome is highly variable and depends on the underlying mitochondrial or nuclear genome defect. Mitochondrial m.8993T>G and m.8993T>C mutations are responsible for both NARP (neurogenic weakness, ataxia and retinitis pigmentosa) and Leigh syndrome depending on the amount of mutant mtDNA. The clinical findings of Leigh syndrome caused by the m.8993T>C mutation are less severe than those associated with the m.8993T>G mutation, and ragged red fibers, oligoclonal bands in cerebrospinal fluid, and additional deficiencies of respiratory enzyme complexes are usually not found. This report presents a two year old girl with Leigh syndrome caused by a m.8993T>C mutation. Interestingly she had ragged red fibers in muscle tissue, oligoclonal bands in CSF and focal deficient histochemical staining for complexes I and IV. (C) 2008 European Paediatric Neurology Society. Published by Elsevier Ltd. All rights reserved.

The kyphoscoliotic type of Ehlers-Danlos syndrome (EDS VI) (OMIM 225400) is an inherited connective tissue disorder characterized by hypotonia and kyphoscoliosis at birth, joint hypermobility, and skin hyperelasticity and fragility. Biochemically, it is characterized by a deficiency of collagen lysyl hydroxylase (EC 1.14.11.4) due to mutations in PLOD1. This deficiency results in underhydroxylation of collagen lysyl residues and, hence, an abnormal pattern of lysyl pyridinoline (LP) and hydroxylysyl pyridinoline (HP) crosslinks excreted in the urine. Because of hypotonia and delay in gross motor development, a neuromuscular disease is usually suspected, and in most cases the diagnosis is considered only very late, after performing an invasive neuromuscular work-up with normal results. We report a 12-month-old boy with kyphoscoliosis and delayed gross motor development, in whom the differential diagnosis of kyphoscoliotic type of Ehlers-Danlos syndrome (EDS VI) was initially suspected and successively confirmed by the abnormal urinary ratio of total pyridinolines (LP to HP), and by mutation analysis. We advocate the analysis of urinary pyridinolines in all infants with severe hypotonia which is highly specific and sensitive, quick and inexpensive.

A patient with isolated 3-methylcrotonyl-CoA carboxylase (MCC) deficiency with an unusual clinical presentation is described. The patient presented with clusters of seizures with two or three months disease free interval in the first year of life which then evolved into attacks of status epilepticus after the age of 12 months. MCC deficiency was suspected because of elevated C5-OH-carnitine in tandem mass spectrometry and elevated 3-hydroxy-isovaleric acid in urine organic acid analysis. Deficiency of MCC was confirmed in cultured fibroblasts and mutation analysis revealed a novel mutation in MCCB, p.S39F. Attacks of status epilepticus as a predominant symptom have not been described before in isolated MCC deficiency. (c) 2007 Elsevier B.V. All rights reserved.

Chronic inflammatory demyelinating polyneuropathy is an acquired neuropathy which is rarely seen pediatric patients. It is characterised by chronic progressive or relapsing remitting weakness. The prognosis in childhood is good compared to adult patients. We present an eight year old girl with chronic inflammatory demyelinating polyneuropathy whose response to prednisone treatment was excellent. The diagnosis of chronic inflammatory demyelinating polyneuropathy should not be missed because it is one of the acquired neurologic disorders that respond to treatment.

Schwartz-Jampel syndrome is a rare autosomal recessive disorder with joint contractures, generalized myotonia, skeletal anomalies, and facial dysmorphism. The patients with Schwartz-Jampel syndrome have muscle stiffness and electromyography reveals complex, repetitive discharges as myotonic discharges. It is unusual for a Schwartz-Jampel syndrome case to have recurrent gastrointestinal bleeding episodes. The stable endothelial barrier is provided by perlecan which is an important component of vascular structures. Thus, perlecan deficiency may cause recurrent gastroduodenal bleeding. Our report is unique with being the first reported Schwartz-Jampel syndrome case with gastrointestinal bleeding.

The aim of this study is to investigate the homocysteine, folic acid, and vitamin B12 levels in epileptic children receiving antiepileptic drugs. A total of 25 children with idiopathic epilepsy (8 valproate, 11 carbamazepine, and 6 oxcarbazepine) and 10 healthy children were included in the study. The mean homocysteine, folic acid, and vitamin B12 levels in the study group were 7.57 ± 3.78 µmol/L (normal = 5-15 µmol/L), 10.19 ± 4.05 ng/mL (normal = 3.0-17 ng/mL), and 428.20 ± 256.12 pg/mL (normal = 193-983 pg/mL), respectively. The differences between the mean plasma homocysteine, folic acid, and vitamin B12 levels of the study and control groups were not significant ( P = .522; P = .855; P = .798, respectively). However, plasma homocysteine levels were higher than the normal cutoff point accepted for childhood in 4 (16%) of the study patients. Out of these 4 children, 3 were from the carbamazepine group and 1 was from the valproate group. Although the number of the study patients is limited, the authors recommend assessment of plasma homocysteine, serum vitamin B12, and folic acid levels in children receiving enzyme-inducing antiepileptic drugs.

Prothrombin G20210A mutation is an important prothrombotic condition for venous thrombosis. Recently, some studies have also considered it to be a risk factor for arterial ischemic stroke in children. A 10-year-old boy with basilar artery thrombosis who was heterozygous for prothrombin G20210A mutation is described. In concordance with the previous literature, the present case suggests that prothrombin G20210A mutation may be a risk factor for arterial ischemic stroke in childhood.

We aimed to investigate in children with a history of acute pyelonephritis the influence of unilateral post-pyelonephritic renal scarring detected by DMSA scan on serum (S(CysC)) and urine cystatin C (U(CysC)) as well as upon other traditional markers of renal damage.Children with DMSA proven pyelonephritis (n = 28) were grouped as either scar [+] (n = 19, unilateral renal scarring) or scar [-] (no scarring, n = 9). The scar [+] group was further divided into scar-1 (differential DMSA uptake, Delta(DMSA)/= 10%; n = 8) and scar-2 (Delta(DMSA)10%, n = 11) subgroups. S(CysC), serum creatinine, urine NAG, microalbumin, protein, fractional sodium excretion (FE(Na)), tubular phosphate reabsorption (TPR), and U(CysC/Cr) were evaluated in all patients.Neither S(CysC) nor U(CysC) were affected by age, height, and weight. scar [+] versus scar [-] groups and scar-1 versus scar-2 subgroups were not different with regard to all studied parameters. S(CysC) did not increase in children with post-pyelonephritic unilateral renal scarring. However, 11 children with slightly increased (0.95 mg/l) S(CysC) levels in scar [+] group tended to have higher Delta(DMSA), albeit not significantly. Furthermore, U(CysC/Cr) correlated well with urine microalbumin, NAG, and FE(Na) in all children and the scar [+] group (P0.05).S(CysC) and U(CysC) did not differ among pediatric patients with and without unilateral post-pyelonephritic renal scarring. However, Delta(DMSA) uptake between the two kidneys tended to be raised in children with S(CysC) levels higher than the reference ranges. Additionally, U(CysC/Cr) exhibits parallelism with tubular functions.

Walker-Warburg syndrome (WWS), the most severe alpha-dystroglycanopathy, is characterized by brain and eye anomalies, and congenital muscular dystrophy (CMD). So far at least four genes (POMT1, POMT2, Fukutin, and FKRP gene) have been implicated in WWS, accounting for about 30% of all cases. We report a male patient with WWS resulting from a homozygous nonsense mutation (R514X) in the POMT1 gene. The patient had congenital hydrocephalus which was detected at 29 weeks of gestation. A brain MRI obtained after birth revealed type II lissencephaly, hydrocephalus, and pontocerebellar hypoplasia. The case also exhibited severe ocular malformations and muscular hypotonia due to CMD. (c) 2006 Published by Elsevier Ltd. on behalf of European Paediatric Neurology Society.

Objective Subacute sclerosing panencephalitis is caused by persistent brain infection of mutated virus, showing inflammation, neurodegeneration, and demyelination. Although many factors are emphasized in the pathogenesis of subacute sclerosing panencephalitis, the exact mechanism of neurodegeneration remains unknown. Micro-RNAs are small, noncoding RNAs that regulate gene expression at the posttranscriptional levels. Micro-RNAs are essential for normal immune system development; besides they are also implicated in the pathogenesis of many chronic inflammatory disorders. The aim of this study is to investigate the expression patterns of micro-RNAs 146a, 181a, and 155 in peripheral blood mononuclear cells of patients with subacute sclerosing panencephalitis. Methods We enrolled 39 patients with subacute sclerosing panencephalitis and 41 healthy controls. Quantitative analysis of micro-RNAs 146a, 181a, and 155 were performed using specific stem-loop primers followed by real-time polymerase chain reaction. Results All of 3 micro-RNAs were upregulated in subacute sclerosing panencephalitis patients. In addition, the level of micro-RNA 155 expression was higher in stage 3 patients. But, micro-RNA 146a and 181a expression levels showed no association or correlation with clinically relevant data. Conclusion Alteration of peripheral blood mononuclear cell micro-RNAs in subacute sclerosing panencephalitis may shed new light on the pathogenesis of disease and may contribute to the aberrant systemic rise in mRNA levels in subacute sclerosing panencephalitis.

Objective Status epilepticus triggers a mixture of apoptotic and necrotic cell death within the developing brain which results in the development of epilepsy and cognitive deficits. Simvastatin has been shown to have neuroprotective effects in various models of neurological damage. Recent studies suggest that simvastatin presents the best characteristics for neuroprotection in neurodegenerative conditions due to its high blood-brain barrier penetration capacity and cholesterol-lowering effect on neurons. However, its therapeutic effect on pediatric status epilepticus is still unknown. The aim of this study is to investigate the effect of simvastatin on hippocampus and prefrontal cortex of rat after pentylenetetrazole induced status epilepticus. Methods Twenty-one dam reared Wistar male rats, 21-day-old were divided into three groups: control group, pentylenetetrazole induced status epilepticus, simvastatin treated group. Simvastatin treated group received simvastatin 10 mg/kg intraperitoneally 40 minutes after pentylenetetrazole injection for 5 days. Rats were sacrificed and brain tissues were collected at 5th day of experiment. Neuronal cell death and apoptosis were evaluated. Results Histopathological examination showed that simvastatin significantly decreased neuronal cell death in CA1 and dentate gyrus regions of hippocampus. It also diminished apoptosis in the hippocampus and prefrontal cortex. Simvastatin significantly decreased the number of caspase 3 positive cells and the number of terminal deoxynucleotidyl transferase-mediated dUTP nick end-labeling positive neurons in the hippocampus and prefrontal cortex when compared to pentylenetetrazole induced status epilepticus group (p=0.002 and p=0.002). Conclusion This experimental study suggests that simvastatin administration may be neuroprotective in status epilepticus in the developing brain.

Pseudomonas aeruginosa septicemia is rare in healthy infants and children. Also not common, dermatologic manifestations such as ecthyma gangrenosum and indurated erythematous nodular lesions may be the first signs of pseudomonas infection, or may appear later in the course of the disease. Peripheral facial paralysis and mastoiditis are also rare and serious complications of acute otitis media caused by P. aeruginosa. We report a previously healthy 6-month-old boy who had an uncommon presentation and rare complications during the course of P. aeruginosa sepsis.

Nonconvulsive status epilepticus is characterized by continuous or near continuous epileptiform discharges on electroencephalography without overt motor or sensory phenomena. It is a symptomatic condition related to a disease such as epileptic encephalopathy or a metabolic disorder. Children with isolated nonconvulsive status epilepticus rarely present with global neurodevelopmental delay. This report describes an 18-month-old male who presented with global neurodevelopmental delay and decreased alertness in whom electrical status epilepticus during sleep, which is a form of nonconvulsive status epilepticus, was determined. Metabolic investigations and cranial magnetic resonance imaging were normal. He began to achieve developmental milestones after treatment with valproic acid. Although rare, pediatric neurologists and pediatricians must be aware of this condition in making the differential diagnosis of global neurodevelopmental delay and decreased alertness. (c) 2006 by Elsevier Inc. All rights reserved.

Butamirate citrate is a central-acting antitussive drug and is widely used in clinical practice in childhood. It is thought that to be centrally active antitussive drugs act through receptors in the brainstem to inhibit cough, and these findings were based on the evidence of animal models. Central nervous system adverse effects of cough suppressants are rare and include irritability, lethargy, hallucinations, and dystonic reactions. In this report, we present the first patient who developed cervical dystonia shortly after the first dose of butamirate citrate, and the patient's symptoms improved immediately after a single intramuscular dosage of biperiden.

In cerebral palsy (CP) atrophy of the paretic body half results in disturbed growth. Disturbed growth is also a feature of a rare disorder; Klippel Treunanay syndrome (KTS). Here we report a child with an initial diagnosis of CP because of limping and thinning of the extremities on the right side who had a final diagnosis of KTS. Five year old male was admitted to our department of Pediatric Neurology. He had been followed up with the diagnosis of CP since he started walking because of limping and thinning of the extremities on the right side of his body. His perinatal and natal period was uneventful. Developmental milestones were normal. On physical examination hypertrophy of the left upper and lower extremities with widespread port wine stain on his face, lower lip, arms, legs and trunk were noted. Brain magnetic resonance imaging revealed vascular malformations located periventricularly and adjacent to the corpus callosum. On brain magnetic resonance angiography ectatic, varicose deep veins (venous malformations) were detected. Lower extremity MRI showed hypertrophy of bones and soft tissues on the left side. As the child has capillary malformations (port wine stain), soft tissue and bone hypertrophy and vascular malformations a diagnosis of KTS was made. KTS consists of two major features; congenital vascular malformations and disturbed growth. For diagnosis presence of either capillary or venous malformations with disturbed growth of the bone or soft tissues is required. Children with the diagnosis of CP should be carefully examined for any finding suggesting a genetic disease.