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OBJECTIVES: In this study, we examined whether epilepsy and drug-resistant epilepsy are associated with neuroimaging findings in children with cerebral palsy (CP). METHODS: Magnetic resonance imaging classification system (MRICS) proposed by Surveillance of Cerebral Palsy in Europe (SCPE) was used for classification of different MRI patterns in patients with cerebral palsy. We reviewed the brain MRI scans and medical records of children with CP who were followed-up in our clinic between 2019 and 2023. Patients were divided into three categories: CP without epilepsy, CP with controlled epilepsy and CP with DRE. MRI patterns were grouped as maldevelopments, predominant white matter injury, predominant gray matter injury, miscellaneous (delayed myelination, cerebral atrophy, cerebellar atrophy, brainstem lesions and calcifications, lesions that were not classified under any other group) and normal according to MRICS of the SCPE. RESULTS: There were 325 CP patients. The most common MRI patterns were predominant white matter injury (47.6%) and gray matter injury (23.8%). There was a 1.5-fold reduction in the risk of epilepsy in patients with predominant white matter injury (OR = 1.54, 95% CI 1.23-1.94). In contrast, children in the miscellaneous group had significantly higher risks of epilepsy (p < 0.001), and we were able to determine that miscellaneous findings increased the risk by 1.8 times (OR = 1.77, 95% CI 1.47-2.12). CONCLUSION: In conclusion, more than half of the children with CP had epilepsy, 40.7% of whom had DRE. On MRI, miscellaneous findings may indicate a poor prognosis for epilepsy, while predominant white matter injury may indicate a good outcome. Children with CP, especially those with miscellaneous findings on MRI, should be closely monitored for epilepsy development.
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Paralisia Cerebral , Epilepsia , Criança , Humanos , Paralisia Cerebral/complicações , Paralisia Cerebral/diagnóstico por imagem , Paralisia Cerebral/epidemiologia , Encéfalo/diagnóstico por imagem , Encéfalo/patologia , Neuroimagem , Epilepsia/epidemiologia , Imageamento por Ressonância Magnética , Atrofia/patologiaRESUMO
BACKGROUND: Hereditary spastic paraplegias (HSPs) are a group of genetically heterogeneous neurodegenerative disorders. Our objective was to determine the clinical and molecular characteristics of patients with genetically confirmed childhood-onset HSPs and to expand the genetic spectrum for some rare subtypes of HSP. METHODS: We reviewed the charts of subjects with genetically confirmed childhood-onset HSP. The age at the disease onset was defined as the point at which the delayed motor milestones were observed. Delayed motor milestones were defined as being unable to hold the head up by four months, sitting unassisted by nine months, and walking independently by 17 months. If there were no delayed motor milestones, age at disease onset was determined by leg stiffness, frequent falls, or unsteady gait. Genetic testing was performed based on delayed motor milestones, progressive leg spasticity, and gait difficulty. The variant classification was determined based on the American College of Medical Genetics standard guidelines for variant interpretation. Variants of uncertain significance (VUS) were considered disease-associated when clinical findings were consistent with the previously described disease phenotypes for pathogenic variants. In addition, in the absence of another pathogenic, likely pathogenic, or VUS variant that could explain the phenotype of our cases, we concluded that the disease is associated with VUS in the HSP-causing gene. Segregation analysis was also performed on the parents of some patients to demonstrate the inheritance model. RESULTS: There were a total of 18 patients from 17 families. The median age of symptom onset was 18 months (2 to 84 months). The mean delay between symptom onset and genetic diagnosis was 5.8 years (5 months to 17 years). All patients had gait difficulty caused by progressive leg spasticity and weakness. Independent walking was not achieved at 17 months for 67% of patients (n = 12). In our cohort, there were two subjects each with SPG11, SPG46, and SPG 50 followed by single subject each with SPG3A, SPG4, SPG7, SPG8, SPG30, SPG35, SPG43, SPG44, SPG57, SPG62, infantile-onset ascending spastic paralysis (IAHSP), and spastic paraplegia and psychomotor retardation with or without seizures (SPPRS). Eight novel variants in nine patients were described. Two affected siblings had a novel variant in the GBA2 gene (SPG46), and one subject each had a novel variant in WASHC5 (SPG8), SPG11 (SPG11), KIF1A (SPG30), GJC2 (SPG44), ERLIN1 (SPG62), ALS2 (IAHSP), and HACE1 (SPPRS). Among the novel variants, the variant in the SPG11 was pathogenic and the variants in the KIF1A, GJC2, and HACE1 were likely pathogenic. The variants in the GBA2, ALS2, ERLIN1, and WASHC5 were classified as VUS. CONCLUSIONS: There was a significant delay between symptom onset and genetic diagnosis of HSP. An early diagnosis may be possible by examining patients with delayed motor milestones, progressive spasticity, gait difficulties, and neuromuscular weakness in the context of HSP. Eight novel variants in nine patients were described, clinically similar to the previously described disease phenotype associated with pathogenic variants. This study contributes to expanding the genetic spectrum of some rare subtypes of HSP.
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Esclerose Lateral Amiotrófica , Paraplegia Espástica Hereditária , Criança , Humanos , Lactente , Cinesinas/genética , Mutação/genética , Fenótipo , Proteínas/genética , Estudos Retrospectivos , Paraplegia Espástica Hereditária/genética , Ubiquitina-Proteína Ligases/genética , Pré-Escolar , AdolescenteRESUMO
BACKGROUND: Chronic inflammatory demyelinating neuropathy has been reported after the use of tumor necrosis factor inhibitors. The mechanisms of nerve injury caused by tumor necrosis factor inhibitors are not yet well understood. CASE: In this paper, we report a 12 year and nine month old girl who developed chronic inflammatory demyelinating neuropathy in the course of juvenile idiopathic arthritis after etanercept withdrawal. She became non-ambulant with four-limb involvement. She received intravenous immunoglobulins, steroids, and plasma exchange, but had a limited response. Finally, rituximab was given and a slow, but progressive clinical improvement was seen. She was ambulant four months after rituximab treatment. We considered chronic inflammatory demyelinating neuropathy as a probable adverse effect of etanercept. CONCLUSIONS: Tumor necrosis factor inhibitors could elicit the demyelinating process, and chronic inflammatory demyelinating neuropathy might persist despite treatment discontinuation. First-line immunotherapy may be inefficient as in our case, and aggressive treatment may be necessary.
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Artrite Juvenil , Etanercepte , Polirradiculoneuropatia Desmielinizante Inflamatória Crônica , Feminino , Humanos , Artrite Juvenil/tratamento farmacológico , Etanercepte/efeitos adversos , Imunoglobulinas Intravenosas/uso terapêutico , Rituximab/uso terapêutico , Inibidores do Fator de Necrose Tumoral/efeitos adversos , Polirradiculoneuropatia Desmielinizante Inflamatória Crônica/induzido quimicamente , Polirradiculoneuropatia Desmielinizante Inflamatória Crônica/tratamento farmacológico , CriançaRESUMO
Introduction: Previous reports described a pattern of hypoglycemia-induced damage predominantly affecting the parieto-occipital regions. The long-term neurological sequelae of severe neonatal hypoglycemic encephalopathy include developmental delay, poor head growth, learning or behavioral difficulties, visual impairment, and epilepsy. This study reports neurodevelopmental outcome of children with neonatal hypoglycemia-associated parieto-occipital brain injury who were evaluated in our pediatric neurology outpatient clinic for different neurological complaints. Methods: We retrospectively reviewed patients who were followed at Kocaeli University Hospital, Pediatric Neurology Department between 2007 and 2015. Patients (n=42) with predominately parieto-occipital lesions on magnetic resonance imaging (MRI) with the typical pattern of neonatal hypoglycemia were evaluated. Patients with documented hypoglycemia (n=21) were included in this study. Patients (n=9) with recurrent episodes of hypoglycemia longer than 12 hours were evaluated as prolonged hypoglycemia. Results: Eleven patients (52.4%) experienced seizures in the neonatal period. Eighteen patients (85.7%) developed epilepsy during the follow-up. Refractory seizures were observed in 8 patients (38.1%). Nine patients (42.9%) manifested microcephaly, seven patients (33.3%) manifested cerebral palsy. Parieto-occipital involvement and the spasticity rate were statistically high in patients with prolonged hypoglycemia (p<0.01). Two patients had autistic features and four patients (19%) had attention deficit hyperactivity disorder. VEP studies could be performed in 18 of 21 patients. All patients had abnormal VEP results. Conclusion: We are of the opinion that most patients of neonatal hypoglycemia are not always documented. Patients under risk and patients with symptoms of hypoglycemia should be vigorously screened and treated to prevent neurologic impairments including cerebral palsy, epilepsy and visual disturbance.
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Background: Biallelic QRSL1 mutations cause mitochondrial 'combined oxidative phosphorylation deficiency-40' (COXPD40). COXPD40 has been reported to be invariably lethal in infancy. Adrenal insufficiency was weakly reported and investigated among seven previously reported patients with COXPD40. Objective: We report the clinical, biochemical, molecular, and functional characteristics of a patient with adrenal insufficiency due to COXPD40. Methods: The medical history and adrenal function tests were examined. Genetic analysis was performed using whole-exome sequencing. Mitochondrial function was tested using mitochondrial membrane potential (MMP) and superoxide dismutase (SOD) enzyme assays. Results: An 8-year-old boy was investigated for adrenal insufficiency. He also had mild developmental delay, sensorineural hearing loss, hypertrophic cardiomyopathy, nephrocalcinosis, elevated parathyroid hormone and creatine kinase, and lactic acidosis. Biallelic novel QRSL1 variants (c.300T>A;Y100* and c.610G>A;G204R) were identified. Oxidative damage in mitochondria was shown by reduced MMP and SOD assays in the patient compared to controls (P < 0.0001). Adrenal function tests revealed a 'primary adrenal insufficiency other than congenital adrenal hyperplasia' (non-CAH PAI) with an isolated glucocorticoid deficiency. In the 8-year follow-up, having the longest survival of reported COXPD40 patients, he had preserved mineralocorticoid functions and gonadal steroidogenesis. Conclusion: Biallelic QRSL1 mutations can cause non-CAH PAI. Adrenal functions should be monitored in mitochondrial disorders to improve clinical outcomes.
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Doença de Addison , Hiperplasia Suprarrenal Congênita , Insuficiência Adrenal , Hiperplasia Suprarrenal Congênita/genética , Insuficiência Adrenal/genética , Criança , Humanos , Masculino , Mutação/genética , Superóxido Dismutase/genéticaRESUMO
AIM: We aim to describe the demographic characteristics, etiology, neurophysiology, imaging findings, treatment, prognosis, and prognostic factors of acute flaccid myelitis. METHODS: The clinical data, laboratory test and, magnetic resonance imaging (MRI) results of pediatric patients diagnosed with acute flaccid myelitis according to the Centers for Disease Control criteria between August 1, 2016, and December 31, 2018, from 13 centers in Turkey were reviewed. RESULTS: Of the 34 cases identified, 31 were confirmed (91.2%). Eighteen patients (55.9%) were boys. The median patient age was 4 years (interquartile range 2.5-6.9 years). Most of the patients were admitted in 2018 (n = 27). A preceding history of a febrile illness was reported in all patients, with a median of 4 days (interquartile range 3-7 days) before symptom onset. Thirty-one patients had T2 hyperintensity on spinal MRI, and 18 patients had cerebrospinal fluid pleocytosis. The most common infectious agents were entero/rhinoviruses (n = 5) in respiratory specimens. All patients except one received immunotherapy either alone or in combination. Among 27 patients with follow-up data 24 had persistent weakness. Involvement of four limbs together with an abnormal brain MRI at onset were associated with a poor prognosis. CONCLUSION: The number of patients with acute flaccid myelitis increased since 2012, spiking with every 2-year interval, largely in the pediatric population. The median age decreases with every outbreak. Clinicians should be aware of the clinical picture for early collection of specimens and early start of rehabilitation programs. Further studies are needed to better characterize the etiology, pathogenesis, risk factors, and treatment of this rare condition.
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Viroses do Sistema Nervoso Central/diagnóstico , Viroses do Sistema Nervoso Central/epidemiologia , Viroses do Sistema Nervoso Central/patologia , Surtos de Doenças , Mielite/diagnóstico , Mielite/epidemiologia , Mielite/patologia , Doenças Neuromusculares/diagnóstico , Doenças Neuromusculares/epidemiologia , Doenças Neuromusculares/patologia , Adolescente , Criança , Pré-Escolar , Feminino , Humanos , Lactente , Masculino , Prognóstico , Estudos Retrospectivos , Turquia/epidemiologiaRESUMO
BACKGROUND: Childhood stroke causes significant morbidity and mortality. In this study, we aimed to define the presenting findings, causes, risk factors and motor outcomes of our patients. METHODS: We retrospectively analysed patients aged from 1â¯month to 18â¯years who were diagnosed as having the first onset of stroke between January 2006 and December 2015. Presenting features, causes, risk factors, recurrence rate and motor outcomes were recorded. Motor outcome was evaluated by the gross motor function classification system. RESULTS: Forty-seven children were included in the study. Thirty-eight (78.7%) children had an arterial stroke, 9 (19.1%) had a venous stroke. The median age at the time of presentation was 60â¯months (3-214). Thirty-two patients (68%) presented with a focal neurological sign and 9 presented with seizure (19.1%). Patients who had a venous stroke presented with more diffuse neurological symptoms than those who had an arterial stroke. At least one risk factor for stroke was identified in 74.5% of the patients; the most common causative factor was prothrombotic state seen in 16 patients (33.5%). Stroke recurred in 5 patients (10.6%); coexistence of multiple factors was a risk factor for recurrence. Presenting with seizure was not a facilitator for epilepsy. Thirty-two (68%) patients had a favourable motor outcome. Younger age (24â¯months versus 114â¯months) and presenting with focal neurological signs were related to non-favourable motor outcome. CONCLUSION: Our cohort demonstrates that most of the children had a risk factor for stroke and have had favourable motor outcome. However, younger age and presenting with focal seizures are related to non-favourable motor outcome.
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Atividade Motora , Recuperação de Função Fisiológica , Acidente Vascular Cerebral/epidemiologia , Acidente Vascular Cerebral/fisiopatologia , Adolescente , Criança , Pré-Escolar , Feminino , Humanos , Lactente , Masculino , Recidiva , Estudos Retrospectivos , Fatores de Risco , Acidente Vascular Cerebral/etiologiaRESUMO
Sakarya Günes A, Maras Genç H, Uyur Yalçin E, Yilmaz V, Saruhan Direskeneli G, Kara B. Acute ophthalmoparesis and persistent mydriasis: expanding the clinical spectrum of anti-GQ1b positive cranial neuropathy in a 5.5-year-old girl. Turk J Pediatr 2019; 61: 794-797. Acute ophthalmoparesis without ataxia (AO) is an atypical form of Miller- Fisher syndrome (MFS) and is rare in children. Anti-GQ1b antibodies can be detected in patients with AO, as in MFS. A 5.5-year-old girl had total ophthalmoparesis, blurred vision, ptosis, diplopia and mydriasis non-reactive to light or near stimuli with preserved consciousness and deep tendon reflexes. She had no ataxia. Cerebrospinal fluid (CSF) examination and cranial MRI were normal. Serum antiGQ1b antibodies were positive. She was diagnosed with AO and intravenous Immunoglobulin (IVIG) was ordered, 400 mg/ kg/day, for 5 days. Ophthalmoparesis and blurred vision improved in a few weeks. At the end of the first year, mydriasis still persisted, but improved and became responsive to near stimuli. Pupillary involvement may be seen in approximately 50% of MFS patients, and improvement in a few weeks or months has been reported in adults. Our case shows the expanding clinical spectrum of anti-GQ1b positive cranial neuropathy as early-onset AO and prolonged mydriasis more than one year.
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Síndrome de Miller Fisher/complicações , Síndrome de Miller Fisher/diagnóstico , Midríase/etiologia , Oftalmoplegia/etiologia , Pré-Escolar , Feminino , Humanos , Imageamento por Ressonância MagnéticaRESUMO
The mitochondrial pyruvate dehydrogenase enzyme complex (PDHC) plays an important role in aerobic energy metabolism and acid-base equilibrium. PDHC contains of 5 enzymes, 3 catalytic (E1, E2, E3) and 2 regulatory, as well as 3 cofactors and an additional protein (E3-binding protein) encoded by nuclear genes. The clinical presentation of PDHC deficiency ranges from fatal neonatal lactic acidosis to chronic neurologic dysfunction without lactic acidosis. Paroxysmal neurologic problems such as intermittent ataxia, episodic weakness, exercise-induced dystonia and recurrent demyelination may also be seen although they are rare. Here, we present an 8-year-old boy complaining of acute proximal muscle weakness of upper and lower extremities with normal mental status. He had a history of Guillain-Barré-like syndrome at the age of 2 years. Electrophysiologic studies showed sensorial polyneuropathy findings in the first attack and sensorimotor axonal polyneuropathy findings in the last attack. The genetic analysis revealed a previously reported hemizygote novel mutation of the PDHA1 gene (p.A353T/c.1057G > A), which encodes the E1α subunit of PDHC. Thiamine was ordered (15 mg/kg/day), dietary carbohydrates were restricted and clinical findings improved in a few weeks. This rare phenotype of PDHC deficiency is discussed.