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Subacute sclerosing panencephalitis (SSPE) is a serious, often fatal disease that responds poorly to current treatment modalities. Recently, the ability of mesenchymal stem cells (MSCs) to produce neurotrophic factors and inflammatory molecules has placed them among potential treatment agents for neurological conditions. We report the results of four patients treated with MSC for SSPE. The patients were followed up clinically, and by periodical laboratory evaluations, magnetic resonance imaging (MRI), and electroencephalography. One patient deteriorated to stage III of the disease, two patients remained in the same stage, and one died from disease progression and respiratory problems. Neurological findings and electroencephalography scores were consistent with the clinical course of the patient whereas MRI showed new inflammatory lesions in two patients. This is the first report of the application of MSC in SSPE. No benefit is demonstrated., (© 2015 Mac Keith Press.)

Objective: The aim of this study was to evaluate the clinical and imaging characteristics, treatment results, and prognosis of patients with electrical status epilepticus during sleep (ESES)., Method: A total of 22 patients with ESES pattern on EEG were retrospectively studied., Results: The first neurological symptoms were seen at a mean age of 4.4years. The first symptoms in 77% of the patients were seizures. Other symptoms were hyperactivity, restlessness, insomnia, disinhibition, autistic behavior, speech retardation and deterioration in school performance. Diagnosis of ESES was made at a mean age of 7.45years, approximately 3years after the first symptom. Magnetic resonance imaging (MRI) was abnormal in 36% of the patients. Single photon emission computed tomography (SPECT) showed focal hypoperfusion after resolution of ESES involving left temporoparietal and right posterior temporal areas in four patients including three with normal MRI, and one with periventricular leukomalacia without focal cortical lesion. First line treatment with valproic acid monotherapy was not effective. Electrical status epilepticus during sleep disappeared in 82% of the patients on clobazam and 70% of the patients on clonazepam in combination with valproic acid within a few months. Topiramate was not found to be effective. A significant decrease in intelligence quotient (IQ) scores was found in 66% of the patients compared to the baseline., Conclusions: ESES should be considered in children with new onset behavioral, cognitive, and speech problems with or without seizures. The high frequency of focal seizures and focal findings on SPECT suggest a focal origin. Clonazepam and clobazam were most effective in our cohort., (Copyright © 2014 The Japanese Society of Child Neurology. Published by Elsevier B.V. All rights reserved.)

Intellectual disability formerly called mental retardation (MR) is defined as having an IQ score below 70; the term "developmental delay" (DD) is preferred for young children. A detailed clinical history including a three-generation pedigreee and physical examination are the fundamental steps in achieving an etiological diagnosis in MR. Physical examination should be performed with special emphasis on dysmorphological and neurological exam. Genetic studies have priority in the laboratory investigation of a child with MR. Routine karyotyping is recommended regardless of the degree of MR. Fragile X studies are strongly recommended in both females and males with unexplained MR, especially in patients with a positive family history and typical physical and behavioral features. FISH analysis of subtelomeric regions should be reserved for selected patients. Inborn errors of metabolism are seldom seen as the causes of isolated MR but should be considered in the differential diagnosis of patients with MR/DD in populations where the rate of consanguineous marriages is high. Neuroimaging studies should be performed on an indication basis such as abnormal brain size or neurological findings. It is essential to diagnose the underlying etiology of MR for recognition of treatable disorders, determining prognosis, family counseling, and providing prenatal diagnosis when possible., (Copyright © 2013 Elsevier B.V. All rights reserved.)

Absence seizures are idiopathic epilepsies characterized by impairment of consciousness and generalized 2.5-4 Hz spike and slow wave discharges. This prospective study was performed to classify and define properties of subgroups of absence epilepsies. We included 31 patients, of whom seven were in the differential diagnosis group. On admission, absence epilepsy provisional diagnosis was considered in 16 patients clinically and in the other 15 patients based on routine EEG findings. Ictal EEGs were recorded by video-EEG monitoring in 23 of the patients (totally 202 ictal recordings). Patients were diagnosed as childhood absence epilepsy (n=8), juvenile absence epilepsy (n=10), juvenile myoclonic epilepsy (n=3), eyelid myoclonia with absences (n=2), and perioral myoclonia with absences (n=1). Neuroimaging, video-EEG monitoring and especially ictal recordings are important for classification of epilepsies in addition to history, physical examination and routine EEG findings. Video-EEG monitoring is required to classify, to make differential diagnosis and to determine the treatment plan and prognosis.

The development of the human cerebral cortex is an orchestrated process involving the generation of neural progenitors in the periventricular germinal zones, cell proliferation characterized by symmetric and asymmetric mitoses, followed by migration of post-mitotic neurons to their final destinations in six highly ordered, functionally specialized layers. An understanding of the molecular mechanisms guiding these intricate processes is in its infancy, substantially driven by the discovery of rare mutations that cause malformations of cortical development. Mapping of disease loci in putative Mendelian forms of malformations of cortical development has been hindered by marked locus heterogeneity, small kindred sizes and diagnostic classifications that may not reflect molecular pathogenesis. Here we demonstrate the use of whole-exome sequencing to overcome these obstacles by identifying recessive mutations in WD repeat domain 62 (WDR62) as the cause of a wide spectrum of severe cerebral cortical malformations including microcephaly, pachygyria with cortical thickening as well as hypoplasia of the corpus callosum. Some patients with mutations in WDR62 had evidence of additional abnormalities including lissencephaly, schizencephaly, polymicrogyria and, in one instance, cerebellar hypoplasia, all traits traditionally regarded as distinct entities. In mice and humans, WDR62 transcripts and protein are enriched in neural progenitors within the ventricular and subventricular zones. Expression of WDR62 in the neocortex is transient, spanning the period of embryonic neurogenesis. Unlike other known microcephaly genes, WDR62 does not apparently associate with centrosomes and is predominantly nuclear in localization. These findings unify previously disparate aspects of cerebral cortical development and highlight the use of whole-exome sequencing to identify disease loci in settings in which traditional methods have proved challenging.

Neuropsychiatric involvement is an important cause of morbidity and mortality in systemic lupus erythematosus (SLE) and it has been reported to occur in 22-95% of the childhood SLE patients. The aim of this study was to evaluate the neuropsychiatric involvement in our juvenile SLE patients. This was a cross-sectional assessment of patients to investigate the relationship between the involvement of the nervous system and the clinical factors, including autoantibodies, renal involvement and disease activity. We used Symptom Checklist-90-R (SCL-90-R), designed to measure the psychopathological symptoms. As controls, we used 20 healthy adolescents and 20 patients with chronic diseases without any neuropsychiatric manifestations. Overall, 55% (n= 11) of the patients displayed neurological symptoms and/or signs. However, central nervous system (CNS) imaging showed pathological findings only in four of these patients. Patients with headache only had normal CNS imaging. Nine patients had moderate to severe depression. When SLE patients were compared to healthy controls and to adolescents with chronic diseases, they were found to be significantly more depressed. In conclusion, pediatric rheumatologists should be aware of the frequency of neuropsychiatric disturbances in SLE. The neuropsychiatric disorders do not always correlate with disease activity and these children need professional psychological evaluation.

Patients with malformations of cortical development (MCD) present with a wide spectrum of clinical manifestations ranging from asymptomatic cases to those with epilepsy and neurodevelopmental problems. Thorough clinical delineation of patients with MCD may provide clues for future phenotype-genotype correlation studies. We studied clinical features of patients with MCD, including developmental risk factors and family history. We evaluated 10 patients with MCD at Hacettepe University Children's Hospital, Department of Pediatric Neurology. All patients underwent neurological evaluation with detailed medical and family history, and neuropsychological evaluation. Routine EEG and MRI were obtained. The patients were between 1 month and 19 years of age (mean: 6.1 +/- 4.4 years). Fifty-four patients were diagnosed with polymicrogyria (PMG), 23 patients with lissencephaly, 12 patients with schizencephaly, and 12 patients with heterotopia. Parents were relatives in 31.7% of the cases; consanguinity was most common in patients with lissencephaly and other MCDs with diffuse/bilateral involvement. Initial clinical presentation was seizures in 61.4% of the cases, developmental delays in 12.9%, and microcephaly in 9.9%. Neurological evaluation revealed most severe abnormalities in patients with lissencephaly, and relatively better outcome in patients with heterotopias. Cognitive functions were better in patients with heterotopias compared to other groups. Overall, 71.3% of patients ha epilepsy. In conclusion, initial presentation and clinical course of patients with MCD are variable and seem to be correlated with the extent of cortical involvement. Epilepsy and mental retardation are the most common problems. The most severe clinical outcome was seen in patients with lissencephaly.

Malformations of cortical development (MCD) form a spectrum of lesions produced by insult to the developing neocortex. Clinical presentation and electrophysiologic findings of MCD are variable and depend on the affected cortical area. We evaluated epilepsy, EEG, and response to antiepileptic treatment in patients with MCD with respect to the neuroimaging findings. We studied 101 patients, ranging between 1 month and 19 years of age. Fifty-four patients were diagnosed with polymicrogyria (PMG), 23 patients with lissencephaly, 12 patients with schizencephaly, and 12 patients with heterotopia. With regards to epilepsy and seizure type, 72/101 (71.3%) patients had epilepsy, and 62/101 (61.4%) patients presented with seizures. Overall, 32.7% of patients had generalized seizures, and 25.7% had complex partial seizures. Mean age at the onset of seizures was 2.7 +/- 3.4 years. The onset of epilepsy tended to be younger in patients with lissencephaly and older in patients with heterotopias. Of the cases, 79.2% had abnormal EEG (56.3% with epileptiform abnormality, 22.9% with non-epileptiform abnormality). EEG was abnormal in 44.9% (13/29) of the cases without epilepsy. EEG showed bilateral synchronous and diffuse epileptiform discharges in 90% of patients with lissencephaly. Patients with schizencephaly had mostly focal epileptiform discharges. Heterotopia cases had a high rate of EEG abnormalities (72.7%). Patients with PMG had epileptiform abnormality in 59.5% of the cases. Patients with heterotopias and PMG achieved better seizure control in comparison with the other groups. In conclusion, epilepsy is the most common problem in MCD. Epilepsy and EEG findings of patients with MCD are variable and seem to be correlated with the extent of cortical involvement.

Introduction: Epilepsy surgery is a standard of care in the treatment of medically intractable epilepsy. Twenty five percent of patients with intractable epilepsy in childhood can be candidates for epilepsy surgery. Corpus callosotomy is a surgical treatment option for patients with potentially injurious drop attacks and disabling generalized seizures. Postoperative improvement of cognition and speech are important gains after epilepsy surgery particularly during childhood. The aim of this study is to evaluate the outcome of corpus callosotomy for the treatment of childhood onset medically intractable epilepsy in a developing pediatric epilepsy surgery center., Method: We report 16 patients who underwent two thirds anterior corpus callosotomy for treatment of refractory seizures in childhood., Results: All patients had drop attacks or multiple types of seizures, yet some showed focal onset with secondary generalization on electroencephalogram (EEG). One patient was seizure free (class 1 outcome), five had class 2A outcome, five had class 2B outcome, and five had class 3 outcome. Overall 11/16 (69%) of our patients improved significantly after anterior callosotomy., Conclusion: Corpus callosotomy remains to be a fairly good choice of surgical treatment for childhood onset medically intractable epilepsy in selected patients.

New generation antiepileptic medications have improved seizure outcome in patients with intractable epilepsy. We studied the efficacy and side effect profile of vigabatrin (VGB) in pediatric patients with intractable seizure disorder. We reviewed the database of our short-term video-EEG monitoring laboratory to screen patients with intractable epilepsy who were on VGB either alone or in combination for three months or more. We subsequently reviewed the medical records of these patients to abstract clinical information regarding age, sex, seizure type, epilepsy syndrome, efficacy and side effects of VGB. Of 111 patients, 75 (68%) were male and 36 (32%) female. Seizure onset was during the newborn period in 12 patients (11%), during the first year of life beyond the newborn period in 47 patients (42%), between 1-5 years in 23 patients (21%), and above five years in the remaining 29 patients (26%). Fifty-four patients (48.6%) had partial onset seizures with or without secondary generalization; 49 patients (44.1%) had primary generalized seizures; 8 patients (7.2%) had two or more types of seizure. Fifty-three percent of patients had mental retardation, and 35% had abnormal findings on physical/ neurological examination. Of 98 patients, 70 (71.4%) had abnormal magnetic resonance imaging (MRI) findings. Ninety-seven percent of patients had been on polytherapy before VGB was added to treatment. VGB reduced seizure frequency by at least 50% in 33.3% of patients with partial seizures, and in 30.6% of patients with primary generalized seizures. Six of the responders with partial seizures had complete resolution of their seizures. Most common side effects included visual field defects, increased appetite and obesity. Vigabatrin seems to be more effective in partial seizures in childhood intractable epilepsy. Patients should be closely monitored regarding side effects of VGB.

Neurophysiologic abnormalities are frequently seen in organic acidemias, but knowledge of the specific changes in the different types of organic acidemias is lacking. We studied electroencephalogram (EEG), visual evoked potential (VEP) and brain-stem auditory evoked response (BAER) in seven children with glutaric aciduria type I (GA1) to assess the neurophysiologic features in this rare inborn error of metabolism. Age at the time of the diagnosis ranged between 3 months and 36 months. Age at the time of neurophysiologic evaluation ranged between 11 months and 36 months. At the time of neurophysiologic evaluation, severe global developmental delay was seen in four patients, dystonia in four patients, motor delay in two patients, and axial hypotonia in two patients; macrocephaly, spasticity, moderate mental retardation and borderline intelligence were each seen in one patient. One patient had autistic features characterized by lack of language and social skills, poor eye contact and stereotypical behavior. Three of seven patients showed abnormal EEG findings. Two patients showed asymmetry with intermittent occipital delta slowing in one hemisphere. This finding probably indicates underlying cerebral dysfunction, and is not a specific feature. However, it suggests that these patients may develop abnormal EEG features during the course of the disease, and thus a baseline EEG may be useful for comparison over time. One patient showed high amplitude bursts of beta in the occipital regions with left predominance while on clonazepam and baclofen. We believe this finding was due to medication effect, and that what we observed was an exaggarated response to benzodiazepine. The clinical significance of this finding is unclear. VEP and BAER were available in four patients, and we found abnormalities in three of them. Neurophysiologic evaluation may be helpful in patients with GA1 as in other types of organic acidemias to help detect subtle changes that are not reflected by neurological examination or neuroimaging studies, and it may guide future treatment plans. Detailed neurophysiologic analysis in a large series of GA1 may yield further information regarding the extent of cerebral dysfunction.

L-2-hydroxyglutaric aciduria (L2HGA) is a chronic slowly progressive neurodegenerative disease characterized mainly by psychomotor developmental delay and cerebellar dysfunction. We report the clinical, biochemical, and neuroimaging features of 29 patients from 22 families. The mean age at the time of diagnosis was 13.4 years (2.5-32 years). The mean follow-up period of patients was four years (1.5-16 years). The main clinical findings were mental retardation and cerebellar involvement with ataxic gait and intentional tremor. Additional findings were mental retardation, macrocephaly and seizures. Diagnosis was confirmed by increased urinary excretion of L-2-hydroxyglutaric acid in all patients and highly specific magnetic resonance imaging (MRI) pattern showing subcortical leukoencephalopathy with bilateral high signal intensity in dentate nuclei and putamens. During the follow-up period, all patients had a static encephalopathy course. The underlying metabolic defect and the possible role of L-2-hydroxyglutaric acid are studied in a subgroup of these families and under evaluation for publication.

Canavan disease (CD) is a rare autosomal recessive genetic disorder characterized by early onset progressive spongy degeneration of the brain involving the axon's myelin sheath. Patients with CD have leukoencephalopathy and megalencephaly; clinically they show a variable course ranging from slow neurodegenerative course to no neurological development or rapid regression. Current treatment is symptomatic including management of seizures and spasticity. Topiramate (TPM) is a novel antiepileptic drug for treatment of a broad spectrum of seizure types in adults and children. We used TPM in two of our patients diagnosed with CD at six months of age. At seven months and 15 months' follow-up, respectively, each patient showed a decrease in head growth velocity. We suggest that TPM can be used in patients with CD and possibly in other childhood neurodegenerative diseases with leukoencephalopathy and megalencephaly. Further studies are required to reveal the underlying mechanisms that lead to decreased head growth velocity, and to conclude whether this ameliorates the clinical course of CD.

Neuronal ceroid lipofuscinosis (NCL) is one of the most common progressive neurodegenerative diseases seen in childhood. NCL is inherited as autosomal recessive trait, and is characterized by the accumulation of 'ceroid lipofuscin' in neuronal and extraneuronal cells. Clinical features include seizures, ataxia, myoclonus, loss of vision, and mental and motor deterioration. Although the disease is widely seen across the world, there seems to be an information gap in Asian countries. To date, no comprehensive and detailed studies on NCL have been carried out in Turkey. However, one could predict that the disease is rather frequent in Turkey due to high rates of consanguineous marriages. Thirty-six Turkish patients were evaluated in this study. Sixteen (44.5%) patients were girls, and 20 (55.5%) were boys. Parents were consanguineous in 25 families (80%). In five families (14%), the disease was seen in two sibs. The diagnosis was based on clinical evaluation, and neurophysiological, neuroradiologic, enzymatic, and histopathological studies. Electron microscopic study was the main diagnostic laboratory test. Three patients were classified as infantile NCL, 11 were late infantile NCL, 5 were juvenile type NCL and 17 patients were Turkish variant NCL. In juvenile type, major initial symptom was visual impairment, whereas in all other types seizures were predominantly the first symptom at the onset of the disease. The initial symptoms of Turkish variant NCL were similar to those of late infantile type. Similar age at clinical symptoms and the presence of visual symptoms were common features of Turkish variant and juvenile NCL. Compared to late infantile NCL, Turkish variant, showed a more severe course regarding seizures. Electroencephalogram (EEG) showed abnormal features predominantly in Turkish variant, and were remarkable for occipital spikes. In patients with Turkish variant magnetic resonance imaging of the brain showed brainstem involvement, especially pons, in all patients except one; cerebral and cerebellar atrophy were seen with a slower course compared to late infantile NCL. Clinical picture of NCL in advanced stages of the disease was similar regardless of the subtype.

Noncompaction of myocardium is a rare and recently defined entity that may cause cardioembolism during childhood. We report an 18-month-old girl with noncompaction of the left ventricular myocardium presenting with fatal cardioembolic stroke. The patient had a high factor VIII level, which is known to cause an increased tendency to thromboembolic events. To our knowledge, this is the youngest case with stroke associated with noncompaction of the myocardium. Patients with noncompaction should be considered for prophylactic antithrombotic treatment to prevent mortality and morbidity owing to systemic thromboembolic events, especially if they carry additional risk factors that make them prone to hypercoagulation.

Intractable epilepsies and partial epilepsies, which make up a great majority of epileptic disorders, are not better recognized and their etiologies unveiled with the help of the new imaging techniques. The development of magnetic resonance imaging (MRI) permits the accurate diagnosis while the patients are alive of the neuronal migration disorders (NMD), which constitute an important group of intractable epilepsies. Previously, NMD cases were described by neuropathologists from autopsy materials, and many of these developmental disorders were not considered compatible with prolonged survival. Cerebral malformations due to neuronal migration anomalies are described in association with motor and mental retardation, learning disabilities, microcephaly, dysmorphic features and epilepsy. Neuronal migration takes place in all parts of the central nervous system (CNS) during the shaping process of the CNS; it actually includes both the central and peripheral nervous systems. However, in common usage the meaning of "neuronal migration disorders" is restricted to the neocortex.

Involvement of the gastrointestinal system and vascular lesions are well-known features of von Recklinghausen's disease, but they are rarely detected in childhood. We report a case of von Recklinghausen's disease with intestinal involvement. The excised right hemicolectomy material of a 16-year-old girl was examined, and diffuse neurofibromatous proliferation with ganglioneuromatous features were observed. Vasculopathy was also seen in some arteries throughout the intestinal segment.

An entity including gelastic epilepsy, precocious puberty, polydactyly and a hypothalamic hamartoma type IIa is described in a 16-year-old female patient. Polydactyly was detected at birth, she developed precocious puberty at four years of age, and gelastic epilepsy was diagnosed at age seven. The precocious puberty was successfully treated medically and her treatment was discontinued at the age of 10 years, but the gelastic seizures were difficult to control. When the patient was 11 years old, MRI revealed a hypothalamic hamartoma. The combination of these four features is very rare in the literature.

A case of fatal agranulocytosis in an adolescent who was on carbamazepine therapy is presented. The clinical and laboratory findings suggest that the primary cause of the disorder was neutropenia rather than infection, and the preceding factor for neutropenia was carbamazepine. The timing of occurrence of the hematologic picture, its dependency on dose increments, and the lack of symptoms until infection supervened are consistent with an idiosyncratic-toxic drug reaction (type 2 drug reaction). This is the first reported agranulocytosis case due to crabamazepine in adolescence.