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PURPOSE: SLC4A10 encodes a plasma membrane-bound transporter, which mediates Na+-dependent HCO3- import, thus mediating net acid extrusion. Slc4a10 knockout mice show collapsed brain ventricles, an increased seizure threshold, mild behavioral abnormalities, impaired vision, and deafness. METHODS: Utilizing exome/genome sequencing in families with undiagnosed neurodevelopmental disorders and international data sharing, 11 patients from 6 independent families with biallelic variants in SLC4A10 were identified. Clinico-radiological and dysmorphology assessments were conducted. A minigene assay, localization studies, intracellular pH recordings, and protein modeling were performed to study the possible functional consequences of the variant alleles. RESULTS: The families harbor 8 segregating ultra-rare biallelic SLC4A10 variants (7 missense and 1 splicing). Phenotypically, patients present with global developmental delay/intellectual disability and central hypotonia, accompanied by variable speech delay, microcephaly, cerebellar ataxia, facial dysmorphism, and infrequently, epilepsy. Neuroimaging features range from some non-specific to distinct neuroradiological findings, including slit ventricles and a peculiar form of bilateral curvilinear nodular heterotopia. In silico analyses showed 6 of 7 missense variants affect evolutionarily conserved residues. Functional analyses supported the pathogenicity of 4 of 7 missense variants. CONCLUSION: We provide evidence that pathogenic biallelic SLC4A10 variants can lead to neurodevelopmental disorders characterized by variable abnormalities of the central nervous system, including altered brain ventricles, thus resembling several features observed in knockout mice.
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Deficiência Intelectual , Transtornos do Neurodesenvolvimento , Animais , Humanos , Camundongos , Bicarbonatos/metabolismo , Antiportadores de Cloreto-Bicarbonato/metabolismo , Deficiência Intelectual/genética , Proteínas de Membrana Transportadoras , Camundongos Knockout , Transtornos do Neurodesenvolvimento/genética , Sódio/metabolismo , Bicarbonato de Sódio/metabolismo , Simportadores de Sódio-Bicarbonato/genéticaRESUMO
In the field of rare diseases, progress in molecular diagnostics led to the recognition that variants linked to autosomal-dominant neurodegenerative diseases of later onset can, in the context of biallelic inheritance, cause devastating neurodevelopmental disorders and infantile or childhood-onset neurodegeneration. TOR1A-associated arthrogryposis multiplex congenita 5 (AMC5) is a rare neurodevelopmental disorder arising from biallelic variants in TOR1A, a gene that in the heterozygous state is associated with torsion dystonia-1 (DYT1 or DYT-TOR1A), an early-onset dystonia with reduced penetrance. While 15 individuals with AMC5-TOR1A have been reported (less than 10 in detail), a systematic investigation of the full disease-associated spectrum has not been conducted. Here, we assess the clinical, radiological and molecular characteristics of 57 individuals from 40 families with biallelic variants in TOR1A. Median age at last follow-up was 3 years (0-24 years). Most individuals presented with severe congenital flexion contractures (95%) and variable developmental delay (79%). Motor symptoms were reported in 79% and included lower limb spasticity and pyramidal signs, as well as gait disturbances. Facial dysmorphism was an integral part of the phenotype, with key features being a broad/full nasal tip, narrowing of the forehead and full cheeks. Analysis of disease-associated manifestations delineated a phenotypic spectrum ranging from normal cognition and mild gait disturbance to congenital arthrogryposis, global developmental delay, intellectual disability, absent speech and inability to walk. In a subset, the presentation was consistent with foetal akinesia deformation sequence with severe intrauterine abnormalities. Survival was 71%, with higher mortality in males. Death occurred at a median age of 1.2 months (1 week-9 years), due to respiratory failure, cardiac arrest or sepsis. Analysis of brain MRI studies identified non-specific neuroimaging features, including a hypoplastic corpus callosum (72%), foci of signal abnormality in the subcortical and periventricular white matter (55%), diffuse white matter volume loss (45%), mega cisterna magna (36%) and arachnoid cysts (27%). The molecular spectrum included 22 distinct variants, defining a mutational hotspot in the C-terminal domain of the Torsin-1A protein. Genotype-phenotype analysis revealed an association of missense variants in the 3-helix bundle domain to an attenuated phenotype, while missense variants near the Walker A/B motif as well as biallelic truncating variants were linked to early death. In summary, this systematic cross-sectional analysis of a large cohort of individuals with biallelic TOR1A variants across a wide age-range delineates the clinical and genetic spectrum of TOR1A-related autosomal-recessive disease and highlights potential predictors for disease severity and survival.
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Distonia , Distúrbios Distônicos , Malformações do Sistema Nervoso , Masculino , Humanos , Estudos Transversais , Mutação/genética , Fenótipo , Distonia/genética , Distúrbios Distônicos/genética , Chaperonas Moleculares/genéticaRESUMO
BACKGROUND: Idiopathic intracranial hypertension (IIH) is a rare medical condition in children. Based on the different radiological findings reported in various studies in pediatric IIH, this study was conducted to determine the diagnostic value of MRI findings in diagnosing IIH in children. METHODS: In this retrospective study, the medical records of all children aged 1 to 18 years who visited Ghaem Hospital in Mashhad, Iran, between 2012 and 2022 and were diagnosed with IIH were gathered. Forty-nine cases of children with IIH and 48 control cases of children with the first unprovoked seizure with no indications of increased intracranial pressure for comparison were selected. Patient demographic information and MRI findings were extracted. The comparison between different MRI findings in the case and control groups was conducted using statistical tests. RESULTS: In the case group, the mean diameter of the subarachnoid space expansion around the optic nerve was 5.96 ± 1.21, compared to 4.79 ± 0.33 in the control group, with statistically significant difference (P < 0.001). All the patients with flattening of the posterior globe or transverse sinus stenosis were in the case group, and the frequency of these findings in the case group was significantly higher than in the control group (P < 0.001). The majority of patients (95.5%) classified under category 3 and 4 of empty sella were part of the case group, and the statistical test results indicated a significant difference between the two groups (P < 0.001). The optic nerve sheath diameter cut-off of 5.35 mm, when used for expansion of the subarachnoid space around the optic nerve, with a sensitivity of 82% and a specificity of 100% in diagnosing IIH. CONCLUSION: The most reliable diagnostic indicators for diagnosing IIH in children are perioptic subarachnoid space expansion with high sensitivity, and posterior globe flattening and transverse sinus stenosis with high specificity.
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Imageamento por Ressonância Magnética , Pseudotumor Cerebral , Humanos , Masculino , Feminino , Criança , Adolescente , Imageamento por Ressonância Magnética/métodos , Estudos de Casos e Controles , Pré-Escolar , Pseudotumor Cerebral/diagnóstico por imagem , Estudos Retrospectivos , LactenteRESUMO
TAF8 is part of the transcription factor II D complex, composed of the TATA-binding protein and 13 TATA-binding protein-associated factors (TAFs). Transcription factor II D is the first general transcription factor recruited at promoters to assemble the RNA polymerase II preinitiation complex. So far disorders related to variants in 5 of the 13 subunits of human transcription factor II D have been described. Recently, a child with a homozygous c.781-1G>A mutation in TAF8 has been reported. Here we describe seven further patients with mutations in TAF8 and thereby confirm the TAF8 related disorder. In two sibling patients, we identified two novel compound heterozygous TAF8 splice site mutations, c.45+4A > G and c.489G>A, which cause aberrant splicing as well as reduced expression and mislocalization of TAF8. In five further patients, the previously described c.781-1G > A mutation was present on both alleles. The clinical phenotype associated with the different TAF8 mutations is characterized by severe psychomotor retardation with almost absent development, feeding problems, microcephaly, growth retardation, spasticity and epilepsy. Cerebral imaging showed hypomyelination, a thin corpus callosum and brain atrophy. Moreover, repeated imaging in the sibling pair demonstrated progressive cerebral and cerebellar atrophy. Consistently, reduced N-acetylaspartate, a marker of neuronal viability, was observed on magnetic resonance spectroscopy. Further review of the literature shows that mutations causing a reduced expression of transcription factor II D subunits have an overlapping phenotype of microcephaly, developmental delay and intellectual disability. Although transcription factor II D plays an important role in RNA polymerase II transcription in all cells and tissues, the symptoms associated with such defects are almost exclusively neurological. This might indicate a specific vulnerability of neuronal tissue to widespread deregulation of gene expression as also seen in Rett syndrome or Cornelia de Lange syndrome.
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Microcefalia , Doenças Neurodegenerativas , Fator de Transcrição TFIID , Atrofia/complicações , Criança , Humanos , Microcefalia/genética , Mutação , Doenças Neurodegenerativas/complicações , Fenótipo , RNA Polimerase II , Proteína de Ligação a TATA-Box/genética , Fator de Transcrição TFIID/genéticaRESUMO
Developmental and epileptic encephalopathy 35 (DEE 35) is a severe neurological condition caused by biallelic variants in ITPA, encoding inosine triphosphate pyrophosphatase, an essential enzyme in purine metabolism. We delineate the genotypic and phenotypic spectrum of DEE 35, analyzing possible predictors for adverse clinical outcomes. We investigated a cohort of 28 new patients and reviewed previously described cases, providing a comprehensive characterization of 40 subjects. Exome sequencing was performed to identify underlying ITPA pathogenic variants. Brain MRI (magnetic resonance imaging) scans were systematically analyzed to delineate the neuroradiological spectrum. Survival curves according to the Kaplan-Meier method and log-rank test were used to investigate outcome predictors in different subgroups of patients. We identified 18 distinct ITPA pathogenic variants, including 14 novel variants, and two deletions. All subjects showed profound developmental delay, microcephaly, and refractory epilepsy followed by neurodevelopmental regression. Brain MRI revision revealed a recurrent pattern of delayed myelination and restricted diffusion of early myelinating structures. Congenital microcephaly and cardiac involvement were statistically significant novel clinical predictors of adverse outcomes. We refined the molecular, clinical, and neuroradiological characterization of ITPase deficiency, and identified new clinical predictors which may have a potentially important impact on diagnosis, counseling, and follow-up of affected individuals.
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Epilepsia Generalizada , Microcefalia , Pirofosfatases , Humanos , Inosina , Inosina Trifosfato , Microcefalia/patologia , Mutação , Prognóstico , Pirofosfatases/genética , Inosina TrifosfataseRESUMO
The redox state of the neural progenitors regulates physiological processes such as neuronal differentiation and dendritic and axonal growth. The relevance of endoplasmic reticulum (ER)-associated oxidoreductases in these processes is largely unexplored. We describe a severe neurological disorder caused by bi-allelic loss-of-function variants in thioredoxin (TRX)-related transmembrane-2 (TMX2); these variants were detected by exome sequencing in 14 affected individuals from ten unrelated families presenting with congenital microcephaly, cortical polymicrogyria, and other migration disorders. TMX2 encodes one of the five TMX proteins of the protein disulfide isomerase family, hitherto not linked to human developmental brain disease. Our mechanistic studies on protein function show that TMX2 localizes to the ER mitochondria-associated membranes (MAMs), is involved in posttranslational modification and protein folding, and undergoes physical interaction with the MAM-associated and ER folding chaperone calnexin and ER calcium pump SERCA2. These interactions are functionally relevant because TMX2-deficient fibroblasts show decreased mitochondrial respiratory reserve capacity and compensatory increased glycolytic activity. Intriguingly, under basal conditions TMX2 occurs in both reduced and oxidized monomeric form, while it forms a stable dimer under treatment with hydrogen peroxide, recently recognized as a signaling molecule in neural morphogenesis and axonal pathfinding. Exogenous expression of the pathogenic TMX2 variants or of variants with an in vitro mutagenized TRX domain induces a constitutive TMX2 polymerization, mimicking an increased oxidative state. Altogether these data uncover TMX2 as a sensor in the MAM-regulated redox signaling pathway and identify it as a key adaptive regulator of neuronal proliferation, migration, and organization in the developing brain.
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Encefalopatias/patologia , Encéfalo/anormalidades , Deficiências do Desenvolvimento/patologia , Proteínas de Membrana/metabolismo , Mitocôndrias/metabolismo , Tiorredoxinas/metabolismo , Adolescente , Adulto , Encefalopatias/genética , Encefalopatias/metabolismo , Criança , Pré-Escolar , Estudos de Coortes , Deficiências do Desenvolvimento/genética , Deficiências do Desenvolvimento/metabolismo , Feminino , Fibroblastos/metabolismo , Fibroblastos/patologia , Seguimentos , Humanos , Lactente , Recém-Nascido , Masculino , Proteínas de Membrana/genética , Mitocôndrias/patologia , Oxirredução , Prognóstico , Pele/metabolismo , Pele/patologia , Tiorredoxinas/genética , TranscriptomaRESUMO
Biallelic pathogenic variants in the genes encoding the dolichol-phosphate mannose synthase subunits (DPM) which produce mannosyl donors for glycosylphosphatidylinositols, N-glycan and protein O- and C-mannosylation, are rare causes of congenital disorders of glycosylation. Pathogenic variants in DPM1 and DPM2 are associated with muscle-eye-brain (MEB) disease, whereas DPM3 variants have mostly been reported in patients with isolated muscle disease-dystroglycanopathy. Thus far, only one affected individual with compound heterozygous DPM3 variants presenting with myopathy, mild intellectual disability, seizures, and nonspecific white matter abnormalities (WMA) around the lateral ventricles has been described. Here we present five affected individuals from four unrelated families with global developmental delay/intellectual disability ranging from mild to severe, microcephaly, seizures, WMA, muscle weakness and variable cardiomyopathy. Exome sequencing of the probands revealed an ultra-rare homozygous pathogenic missense DPM3 variant NM_018973.4:c.221A>G, p.(Tyr74Cys) which segregated with the phenotype in all families. Haplotype analysis indicated that the variant arose independently in three families. Functional analysis did not reveal any alteration in the N-glycosylation pathway caused by the variant; however, this does not exclude its pathogenicity in the function of the DPM complex and related cellular pathways. This report provides supporting evidence that, besides DPM1 and DPM2, defects in DPM3 can also lead to a muscle and brain phenotype.
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Encefalopatias , Deficiência Intelectual , Humanos , Deficiência Intelectual/patologia , Homozigoto , Músculo Esquelético/patologia , Encefalopatias/patologia , Convulsões/patologia , Manosiltransferases/genética , Proteínas de Membrana/genéticaRESUMO
BACKGROUND: Zinc is an essential element for normal embryogenesis and embryonic and neonatal development. Therefore, we compared the birth weights of neonates born to mothers who consumed zinc supplement during pregnancy with that of neonates born to mothers who did not. METHODS: In a cross-sectional study, we divided 200 pregnant mothers into two groups: case group (mothers receiving zinc supplement during pregnancy) and control group (mothers not receiving zinc supplement during pregnancy) Then, the neonate's cord zinc level and mother's serum level were measured and neonate's growth charts (weight, height and head circumference)were completed. RESULTS: In this study, both groups of mothers were observed to have zinc deficiency; 35% of the mothers who consumed zinc supplements and 81% of the mothers who did not consume zinc supplements (P < 0.001). Based on the results, maternal serum of zinc (P < 0.001), neonatal birth weight (P = 0.008), maternal age (P < 0.001) and parity (P < 0.01) in zinc-supplemented group were higher. Neonatal birth weight was associated moderately with mother's zinc serum levels and poorly with neonatal serum zinc levels. CONCLUSION: Zinc consumption during pregnancy increases serum zinc level of mother and neonatal weight. Neonatal weight has a higher correlation to maternal serum zinc level.
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Desenvolvimento Infantil/efeitos dos fármacos , Desenvolvimento Embrionário/efeitos dos fármacos , Zinco/administração & dosagem , Adulto , Peso ao Nascer/efeitos dos fármacos , Estudos Transversais , Suplementos Nutricionais , Feminino , Gráficos de Crescimento , Humanos , Recém-Nascido , Idade Materna , Paridade , Gravidez , Oligoelementos/administração & dosagem , Oligoelementos/sangue , Resultado do Tratamento , Zinco/sangueRESUMO
Objectives: Cerebral palsy (CP) is one of the most common causes of serious physical disability in childhood and is a persistent movement disorder before the age of three. This disorder can negatively affect both the child and their family. In recent years, the use of melatonin as a safe, effective, and cheap drug has been expanding in improving the sleep disorders of these children. Therefore, this study aimed to investigate melatonin's effect on sleep disorders in children with CP. Materials & Methods: This double-blind clinical trial was conducted on children aged 2 to 12 years with CP who were referred to the pediatric neurology clinic for sleep problems. The participants were included in the study by convenience sampling. After obtaining informed consent from parents, patients were divided randomly into two intervention (melatonin) and control (placebo) groups. In the intervention group, patients received oral melatonin tablets, and in the control group, patients received a placebo (3 mg oral lactose) 30 minutes before going to sleep. Results: The results of this study showed no significant relationship between age and gender with sleep disorders in children with CP (P>0.05). A significant effect of melatonin on sleep disorders was found in children with CP. The greatest effect of melatonin is the time required to start falling asleep. Melatonin was associated with decreased time needed to fall asleep and increased sleep duration. Conclusion: The results of the study demonstrated that sleep disorders are prevalent among children with CP. Therefore, proper and timely treatment of these children is crucial. According to the present study's findings, melatonin effectively improves the time of falling asleep and these children's sleep duration.
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INTRODUCTION: Riboflavin Transporter Deficiency (RTD) is a rare neurological disorder characterized by pontobulbar palsy, hearing loss, and motor cranial nerve involvement. SLC52A3 and SLC52A2 mutations are causes of RTD. SLC52A2 mutations are usually found in childhood onset cases. Fifteen Iranian RTD diagnosed patients without SLC52A2 mutations have been previously described. We aimed to identify causative mutations in two childhood cases. METHODS: We recruited patients with diagnosis of BVVL. Comprehensive clinical evaluations were performed on the patients. SLC52A3 and SLC52A2 genes were PCR-amplified and Sanger sequenced. Candidate disease causing variations were screened for segregation with disease status in the respective families and control individuals. RESULTS: A novel homozygous SLC52A3 mutation (p.Met1Val) and a heterozygous SLC52A2 mutation (p.Ala288Val) were both observed in one proband with typical RTD presentations. The aggregate of presentations in the early stages of disease in the second patient that included weakness in the lower extremities, absence of bulbar or hearing defects, prominent sensory polyneuropathy as evidenced in electrodiagnostic studies, and absence of sensory symptoms including sensory ataxia did not prompt immediate RTD diagnosis. Dysarthria and decreased hearing manifested later in the disease course. A novel homozygous SLC52A2 (p.Val314Met) mutation was identified. CONCLUSION: A literature search found recent reports of other atypical RTD presentations. These include MRI findings, speech understanding difficulties accompanied by normal hearing, anemia, and left ventricular non-compaction. Knowledge of unusual presentations lessens the chance of misdiagnosis or delayed RTD diagnosis which, in light of favorable effects of riboflavin supplementation, is of immense importance.
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Proteínas de Membrana Transportadoras , Mutação , Humanos , Masculino , Mutação/genética , Proteínas de Membrana Transportadoras/genética , Paralisia Bulbar Progressiva/genética , Paralisia Bulbar Progressiva/diagnóstico , Feminino , Receptores Acoplados a Proteínas G/genética , Criança , Linhagem , Doenças dos Gânglios da Base , Perda Auditiva NeurossensorialRESUMO
BACKGROUND: Drug-resistant epilepsy is a challenging problem in pediatrics. Transcranial direct current stimulation (TDCS) is a non-invasive neurostimulation technique suggested as a promising method for treating epilepsy. This study aims to evaluate the efficacy of TDCS in focal epilepsy in children with drug-resistant epilepsy. METHOD: We conducted a randomized sham-controlled study with 18 subjects between 6 and 16 years of age, divided equally into two groups. TDCS was performed in 20-minute daily stimulation protocol for five days for both groups. The current intensity was one mA for the first three days, increasing to 1.5 mA on day four and 2 mA on the last day of stimulation. EEG was done before and after the intervention. RESULTS: There was a significant reduction in seizure duration in the case group compared with the sham group. CONCLUSION: five consecutive days of performing TDCS significantly reduced seizure duration in children with focal Drug-resistant epilepsy. However,further studies in this field are necessary to test the effectiveness and set up a coherent and comprehensive protocol.
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Epilepsia Resistente a Medicamentos , Epilepsias Parciais , Estimulação Transcraniana por Corrente Contínua , Humanos , Criança , Estimulação Transcraniana por Corrente Contínua/métodos , Método Duplo-Cego , Epilepsias Parciais/terapia , Epilepsia Resistente a Medicamentos/terapia , Convulsões/terapiaRESUMO
The current study evaluates a rare case of parietal bone osteoid osteoma in pediatrics and review the differential diagnosis of button sequestrum sign in the literature. A 12-year-old girl expressed localized pain in the right parietal bone. MRI represented enhancing nodule with button sequestrum sign appearance.
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BACKGROUND: Recurrent painful ophthalmoplegic neuropathy (RPON) is a rare disorder with a unilateral headache accompanied by ipsilateral episodes of painful ocular cranial nerve neuropathy, which typically occurs in childhood. CASE REPORT: We report an 8-year-old female with four episodes of RPON involving unilateral third and fourth cranial nerves. Right eye exotropia and complete ptosis were detected on examination. Brain MRI images revealed right third nerve enhancement where it exits from the brainstem. She completely recovered after 5 weeks with the administration of prednisolone and indomethacin. DISCUSSION AND CONCLUSION: Due to the rarity of this condition in children, recurrent painful ophthalmoplegic neuropathy should be considered as a differential diagnosis of unilateral or bilateral painful ophthalmoplegia, particularly with a history of migrainous headache. Since it is a treatable entity, and repeated attacks may lead to permanent sequela, early intervention is crucial.
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Oftalmoplegia , Enxaqueca Oftalmoplégica , Doenças do Nervo Troclear , Feminino , Criança , Humanos , Enxaqueca Oftalmoplégica/complicações , Enxaqueca Oftalmoplégica/diagnóstico , Doenças do Nervo Troclear/complicações , Doenças do Nervo Troclear/diagnóstico , Oftalmoplegia/diagnóstico , Oftalmoplegia/complicações , Prednisolona/uso terapêutico , IndometacinaRESUMO
Posterior reversible encephalopathy syndrome (PRES) has a broad spectrum of clinical presentations and radiological features. Diagnosis of PRES is established based on reversible clinical manifestations and sequential neuroimaging findings. Atypical MRI features include hemorrhage, restricted diffusion or contrast enhancement of lesions, and involvement of the temporal and frontal lobes, brainstem, basal ganglia, corpus callosum, cerebellum, and spine. Atypical PRES, with or without spinal cord involvement, is a rare presentation, especially in children. Until 2020, only five cases of PRES with spinal cord involvement (PRES-SCI) were reported in the pediatric population. Case Report: Here, we present the youngest diagnosed case of PRES-SCI so far. According to the literature, all six cases of PRES-SCI showed high signal intensities on T2-weighted images of the brainstem and cervical cord, which had completely resolved in the follow-up MRI of the brain and spinal cord. All six patients had hypertension due to renal disease, except one girl with chemotherapy-induced hypertension. Headache, altered mental status, seizure, and visual impairment were the most common symptoms, respectively. Facial palsy was a remarkable warning sign in some patients before hospitalization.Although PRES-SCI is rare in children, since it is a reversible condition, prompt diagnosis and management can positively affect its prognosis.
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Objective: Transforming growth factor-beta (TGF-ß), a group of multifunctional growth factors, plays an important role in the neuron survival and neurodevelopmental functions. Some studies have evaluated the correlation between TGF-ß1 and TGF-ß2 abnormalities and autism spectrum disorders. In this study, we compared the TGF-ß1 and TGF-ß2 levels between autistic and intellectually normal individuals. Materials & Methods: The study population consisted of 39 autistic and 30 age-matched intellectually normal individuals (control group). Blood samples were taken from all individuals, and all patients were divided into 2 groups (mild-to-moderate and severe) according to the childhood autism rating scale. The cytokines levels were measured by Enzyme Linked Immunosorbent Assay (ELISA). Results: The mean concentration of TGF-ß1 was significantly lower (P < 0.0001) in children with autism compared to the control group (25.3 ± 6.5 versus 35.1 ± 9.4 ng/mL, respectively). Also, the mean concentration of TGF-ß2 in children with autism (32.35± 7.75 ng/ mL) was higher compared to those in the control group (30.47± 4.36 ng/mL); however, this difference did not reach statistical significance (P = 0.21). A positive correlation was observed between TGF-ß1 concentration and autism severity (r = 0.41; P = 0.02), whereas a negative correlation was found between TGF-ß2 concentration and autism severity (r = -0.41; P = 0.02). severity (r = 0.41; P = 0.02), whereas a negative correlation was found between TGF-ß2 concentration and autism severity (r = -0.41; P = 0.02). Conclusion: The results of the present investigation suggest that there is a decrease in the levels of TGF-ß1 in the serum of patients with autism and this cytokine may be effective in the treatment of the pathophysiological aspects of autism.
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OBJECTIVE: The current study aimed to investigate the prevalence and risk factors of seizure in acute bacterial meningitis. MATERIALS & METHODS: In the present study, a total of 180 children (age range, 2 months to 14 years) with acute bacterial meningitis, were separated into two groups based on the diagnosis of seizure. The study was conducted in Mashhad (Iran) from 2002 to 2016. RESULTS: Seizure occurred in 37.4% of children with bacterial meningitis. Streptococcus pneumonia (S. pneumonia) was the most common organism. Most of the children with seizures (53.7%) had more than one episode. Also, 35% of patients had neurologic complications. Complications were more related to the seizure occurrence, the number of episodes, prolonged seizure, and being younger than 12 months. Age categories of less than 1 year and 1-5 year were associated with increased risk of seizure (odds ratio: 4.33 and 6.54, respectively). The more episode of seizure was associated with more complications (odds ratio: 6.33). CONCLUSION: The prevalence of seizures in acute bacterial meningitis was 37.4%. Besides, the seizure was associated with more complications. Hence, timely diagnosis and treatment of bacterial meningitis are necessary for preventing future consequences.
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OBJECTIVE: This study aimed at comparing the effect of a newly approved drug leveitiracetam (LEV) versus carbamazepine (CBZ) in the treatment of childhood focal epilepsy. METHODS & MATERIALS: The study population included newly diagnosed children with focal epilepsy (1-16 years old) referring to the Pediatric Neurology Ward of Quaem Hospital, Mashhad, Iran from May 2013 to March 2014. The subjects were randomly treated with LEV or CBZ. Patients were followed for seizure control and drug side effects throughout six months. We assessed liver function and complete blood count for all patients through one month and they were asked about significant side effects, such as drowsinessØ restlessness, and skin reaction. Eventually, they were assigned in two groups (n=25) receiving LEV and CBZ. RESULTS: In our study, two cases in the LEV group were excluded because of severe agitation. Relapsing seizures were observed in 3 (13%) and 10 (40%) patients in LEV and CBZ groups, respectively. The seizure was not repeated in 15 cases (60%) in the CBZ group and 20 cases (87%) in the LEV group. The results of the Chi-squared test showed significant differences in the responses to treatment between the groups (P=0.03). Agitation was the most prevalent complication in the LEV group, whereas drowsiness was more common in the CBZ group. Fortunately, liver enzyme dysfunction and blood cell disturbances were not observed in the subjects. CONCLUSION: According to the findings, there were significant differences in controlling seizures between two groups that indicated the effectiveness of LEV (87%) in the suppression of focal seizure.
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Wilson's disease (WD) is a rare autosomal recessive disease due to copper metabolism disturbance. The clinical presentation spectrum of Wilson's disease is wide and initial findings of the disease depend on the organ involved. Neurologic disorders can develop insidiously or precipitously with intention tremor, dysarthria, rigid dystonia, Parkinsonism, deterioration in school performance or behavioral changes. This article is presenting an 11-yr old boy with chief complaint of falling and upper limb spasm. He referred to the Neurology Department, Ghaem Hospital, Mashhad, northeastern Iran in 2016. His symptoms began from 6 months earlier as mood instability (prolonged spontaneous crying). He was also suffering from occasionally tremor and micrographia. Initial investigations were normal and with diagnosis of depression and psychiatric problems, he had undergone treatment with fluoxetine and risperidone. Wilson's disease should be considered in the diagnosis of all children with psychiatric and musculoskeletal symptoms.
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BACKGROUND: Neonatal hypernatremic dehydration (NHD) is a dangerous condition that can lead to severe weight loss, renal impairment, and central nervous system complications. We aimed to evaluate the consequences of NHD in infants in their second year of life. MATERIALS AND METHODS: This was a prospective case-control study in Ghaem hospital, Mashhad, Iran. Sixty-five healthy breastfed neonates (serum sodium concentration <150 mmol/L) and 65 hypernatremic (serum sodium concentration ≥150 mmol/L) neonates were followed up from 2008 to 2011. Maternal and neonatal factors were compared between the two groups together with their growth parameters, and developmental milestones (using Denver II developmental assessment scores) were assessed and compared in ages 6, 12, 18, and 24 months, respectively. RESULTS: The weight of infants at 6 months of age was significantly different between the two groups (7,264 ± 1,089 g vs. 7,596 ± 957 g, p = 0.009). Twenty-five percent of infants in the group who had developed NHD had a delay in development at 6 months of age, with corresponding values of 21% at 12 months, 19% at 18 months, and 12% at 24 months of age. Developmental delay was â¼0.3% for the control group at similar ages. The severity of hypernatremia was strongly correlated with poor developmental outcome at 6 months (p = 0.001). Serum sodium concentration of neonates was 153-195 mg/dL in the NHD group. Median peak serum sodium was 158 ± 16 in case group and 141 ± 9 in control group. Serious complications were cerebral edema (five cases), hemorrhage (five cases), and kidney stones (six cases). Hypernatremic dehydration has an adverse effect on child development especially in the first year of life, their prevalence decreases with advanced age. Growth problems are also present during their first year of life. The major signs and symptoms of infants with poor prognosis on admission were poor feeding (8 infants, 61.5%), seizure (3 infants, 23.1%), hyperthermia (1 infant, 7.7%), and lethargy (1 infant, 7.7%). CONCLUSIONS: NHD affects growth parameters and developmental milestones of children. Occasionally the child's weight gain was normalized by the end of first year of life; although developmental delay continued, its severity was reduced, with age.
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Aleitamento Materno , Desidratação/fisiopatologia , Deficiências do Desenvolvimento/fisiopatologia , Aleitamento Materno/estatística & dados numéricos , Estudos de Casos e Controles , Desenvolvimento Infantil , Pré-Escolar , Cuidados Críticos , Desidratação/sangue , Desidratação/complicações , Deficiências do Desenvolvimento/etiologia , Feminino , Seguimentos , Humanos , Hipernatremia/sangue , Hipernatremia/complicações , Hipernatremia/fisiopatologia , Lactente , Unidades de Terapia Intensiva Neonatal , Irã (Geográfico)/epidemiologia , Masculino , Prognóstico , Estudos Prospectivos , Sódio/sangueRESUMO
BACKGROUND: This study was performed in children aged <15 years, at the Pediatric Neurology Clinic of Imam Reza Hospital affiliated to Mashhad University of Medical Sciences. The objective of this study was to recognize the main predisposing factors that result in uncontrolled seizures in patients so that we can start the treatment accurately. METHODS: There were two groups of patients; group I, consisted of 51 patients, with minimum refractory seizures of one episode per month while taking at least two antieplieptic drugs, and group II, comprised of 80 well-controlled patients chosen at random, who had no fit within 6 months after starting the treatment. RESULTS: Factors affecting the occurrence of refractory seizures included age <1 year, multiple seizures before starting the treatment, male gender, myoclonic seizures, neurologic defects, neonatal and daily seizures, and first abnormal electroencephalogram and brain computerized tomography scan. CONCLUSION: There are several factors that can predict development of uncontrolled seizures. Knowledge of these factors helps us to discriminate our patients and pay more attention to those at risk of developing uncontrolled seizures.