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BACKGROUND: Radiologically isolated syndrome (RIS) is a condition characterized by asymptomatic, incidentally detected demyelinating plaques in the CNS in a patient without typical clinical findings of multiple sclerosis (MS). This study aimed to compare the mental status and cognitive functions of child and adolescent RIS cases with healthy controls and to investigate the relationship between psychometric test results and the demyelinating lesion characteristics. METHODS: The mental status and cognitive functions of 12 RIS cases and 12 healthy controls were compared. Semi-structured interviews, behavioral evaluations, depression and anxiety scales, neuropsychological test battery, and an intelligence test were applied for the evaluation of mental state and cognitive functions. These results were compared with the number and localization of demyelinating lesions. RESULTS: Sustained attention, visual-motor coordination, short-term memory skills, and ability to use visual-spatial information were found worse in the RIS group. There was no correlation between mental state and cognitive functions, and the number and localization of demyelinating lesions. CONCLUSION: Our study showed that pediatric RIS cases may have worse cognitive performance than healthy controls, but no correlation was found between the number and location of demyelinating lesions and psychiatric findings. Although it is controversial whether psychiatric disorders and cognitive disabilities have predictive value in terms of MS conversion in pediatric RIS cases, these subjects were not included in the scope of this study.
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Pruebas Neuropsicológicas , Humanos , Adolescente , Masculino , Femenino , Niño , Disfunción Cognitiva/etiología , Disfunción Cognitiva/diagnóstico , Disfunción Cognitiva/fisiopatología , Disfunción Cognitiva/diagnóstico por imagen , Enfermedades Desmielinizantes/diagnóstico por imagen , Enfermedades Desmielinizantes/diagnóstico , Imagen por Resonancia Magnética , Cognición/fisiología , Desempeño Psicomotor/fisiologíaRESUMEN
Horizontal gaze palsy with progressive scoliosis (HGPPS) is a rare, autosomal recessively inherited disorder characterized by a congenital absence of conjugated horizontal eye movements with progressive scoliosis developing in childhood and adolescence. HGPPS is caused by mutations of the ROBO3 gene that disrupts the midline crossing of the descending corticospinal and ascending lemniscal sensory tracts in the medulla. We present two siblings, 5-year-old and 2-year-old boys with HGPPS, from non-consanguineous parents. The older brother was brought for the evaluation of moderate psychomotor retardation. He had bilateral horizontal gaze palsy with preserved vertical gaze and convergence. Scoliosis was absent. Cranial MRI showed brainstem abnormalities, and diffusion tensor imaging showed absent decussation of cortico-spinal tracts in the medulla. Clinical diagnosis of HGPPS was confirmed by sequencing of ROBO3 gene, IVS4-1G > A (c.767-1G > A) and c.328_329delinsCCC (p.Asp110Profs*57) compound heterozygous variations were found, and segregated in parents. The younger boy was first reported at 16 months of age and had the same clinical and neuroradiological findings, unlike mild psychomotor retardation. ROBO3 gene analysis showed the same variants in his brother. Our cases show the importance of evaluating eye movements in children with neurodevelopmental abnormalities and looking for brainstem abnormalities in children with bilateral horizontal gaze palsy.
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Pontocerebellar hypoplasia (PCH) is a heterogeneous group of neurodegenerative disorders characterized by hypoplasia and degeneration of the cerebellum and pons. We aimed to identify the clinical, laboratory, and imaging findings of the patients with diagnosed PCH with confirmed genetic analysis. We collected available clinical data, laboratory, and imaging findings in our retrospective multicenter national study of 64 patients with PCH in Turkey. The genetic analysis included the whole-exome sequencing (WES), targeted next-generation sequencing (NGS), or single gene analysis. Sixty-four patients with PCH were 28 female (43.8%) and 36 (56.3%) male. The patients revealed homozygous mutation in 89.1%, consanguinity in 79.7%, pregnancy at term in 85.2%, microcephaly in 91.3%, psychomotor retardation in 98.4%, abnormal neurological findings in 100%, seizure in 63.8%, normal biochemistry and metabolic investigations in 92.2%, and dysmorphic findings in 51.2%. The missense mutation was found to be the most common variant type in all patients with PCH. It was detected as CLP1 (n = 17) was the most common PCH related gene. The homozygous missense variant c.419G > A (p.Arg140His) was identified in all patients with CLP1. Moreover, all patients showed the same homozygous missense variant c.919G > T (p.A307S) in TSEN54 group (n = 6). In Turkey, CLP1 was identified as the most common causative gene with the identical variant c.419G > A; p.Arg140His. The current study supports that genotype data on PCH leads to phenotypic variability over a wide phenotypic spectrum.
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Spondyloenchondrodysplasia (SPENCD) is a rare spondylometaphyseal skeletal dysplasia with characteristic lesions mimicking enchondromatosis and resulting in short stature. A large spectrum of immunologic abnormalities may be seen in SPENCD, including immune deficiencies and autoimmune disorders. SPENCD is caused by loss of tartrate-resistant acid phosphatase activity, due to homozygous mutations in ACP5 , playing a role in nonnucleic-acid-related stimulation/regulation of the type I interferon pathway. In this article, we presented a 19-year-old boy with SPENCD, presenting with recurrent autoimmune hemolytic anemia episodes since he was 5 years old. He had short stature, platyspondyly, metaphyseal changes, intracranial calcification, spastic paraparesis, and mild intellectual disability. He also had recurrent pneumonia attacks. The clinical diagnosis of SPENCD was confirmed by sequencing of the ACP5 gene, and a homozygous c.155A > C (p.K52T) variation was found, which was reported before as pathogenic. In conclusion, in early onset chronic autoimmune cytopenias an immune dysregulation may often have a role in the etiology. Associating findings and immunologic functions should be carefully evaluated in such patients in the light of the literature. The present case shows the importance of multisystemic evaluation for the detection of SPENCD that has a monogenic etiology.
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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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Esclerosis Amiotrófica Lateral , Paraplejía Espástica Hereditaria , Niño , Humanos , Lactante , Cinesinas/genética , Mutación/genética , Fenotipo , Proteínas/genética , Estudios Retrospectivos , Paraplejía Espástica Hereditaria/genética , Ubiquitina-Proteína Ligasas/genética , Preescolar , AdolescenteRESUMEN
BACKGROUND: To assess vessel density (VD) and flow of retinal plexuses and peripapillary region related with the pediatric radiologically isolated syndrome (RIS) and multiple sclerosis (MS). METHODS: We analyzed 24 eyes of 12 participants with the diagnosis of RIS, 24 eyes of 12 participants with the diagnosis of MS, and 26 eyes of 13 age- and sex-matched healthy controls in this prospective, cross-sectional study. The superficial capillary plexus (SCP) and deep capillary plexus, foveal avascular zone, and the flow of choriocapillaris were investigated using optical coherence tomography angiography. RESULTS: Parafoveal VD and all subregion parameters in SCP were significantly decreased in the MS group compared with the controls, whereas only nasal and inferior VD were significantly decreased in the pediatric RIS group compared with the controls. Ganglion cell layer (GCL) thickness of all subregions of the inner ring was significantly decreased in the pediatric MS group compared with the control group. No significant difference was observed between the pediatric RIS group and the control group regarding thickness. CONCLUSIONS: We showed lower parafoveal VD in all subregions of SCP in pediatric MS, whereas only parafoveal nasal and inferior VD were decreased in pediatric RIS. GCL thickness of inner ring was significantly decreased in the pediatric MS, whereas GCL thickness did not change in pediatric RIS. Therefore, a decrease of parafoveal nasal and inferior VD without a decrease in thickness implies an early impairment of microvasculature in the RIS before impairment of thickness and that microvascular alterations begin from highly vascular superficial parafovea.
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Enfermedades Autoinmunes del Sistema Nervioso , Enfermedades Desmielinizantes , Esclerosis Múltiple , Humanos , Niño , Vasos Retinianos/diagnóstico por imagen , Angiografía con Fluoresceína/métodos , Esclerosis Múltiple/diagnóstico por imagen , Estudios Transversales , Estudios Prospectivos , Coroides/diagnóstico por imagen , Tomografía de Coherencia Óptica/métodosRESUMEN
INTRODUCTION: Pediatric epilepsy surgery is an effective treatment modality for patients with drug-resistant epilepsy (DRE). Early pediatric surgery yields favorable results for DRE in terms of seizure control and neurophysiological outcome. In this study, pediatric patients were categorized based on their age (above 3 years old and below 3 years old) to demonstrate the effectiveness and safety of surgical procedures. METHODS: In this retrospective, single-center study, 60 pediatric patients who underwent epilepsy surgery at Istanbul Faculty of Medicine between 2002 and 2018 were evaluated. Overall morbidity and mortality rates, as well as seizure outcomes of the patients, were assessed and compared based on two age groups: those aged 3 years old or younger and those older than 3 years old. The effectiveness of invasive monitoring was also evaluated in relation to pathological results. The postoperative seizure outcome rates were evaluated using Engel's classification, with an average follow-up period of 8.7 years. RESULTS: Out of the total number of patients, 47 (78.4%) underwent resective surgery, while 13 (21.6%) had palliative surgery. Ten patients (16.6%) had invasive monitoring. Among all patients, 34 were classified as Engel I and II (56.6%), while 26 were classified as Engel III and IV (43.4%) postoperatively. 47% of patients who were under 3 years old, 60.4% of patients who were over 3 years old, and 50% of patients who underwent invasive monitoring had a favorable seizure outcome (Engel I-II). Postoperative morbidity and mortality rates were 35% (n = 21) and 1.6% (n = 1), respectively. CONCLUSION: Pediatric epilepsy surgery is an important treatment modality for preserving cognitive abilities and providing effective treatment for pediatric DRE. In our study, we claim that both invasive monitoring and epilepsy surgery lead to favorable seizure outcomes for all age groups. Further clinical studies should be conducted to provide more reliable data on the safety and effectiveness of the surgery, particularly in patients under the age of three.
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Epilepsia Refractaria , Epilepsia , Niño , Humanos , Preescolar , Epilepsia Refractaria/cirugía , Estudios Retrospectivos , Electroencefalografía , Epilepsia/cirugía , Convulsiones , Resultado del TratamientoRESUMEN
BACKGROUND: Various etiologies may underlie optic neuritis, including autoantibody-mediated disorders described in the last decade. We re-examined demographic, clinical, laboratory features and prognostic factors in pediatric patients with autoimmune optic neuritis according to current knowledge. METHODS: Cases of pediatric ON from 27 centers in Türkiye diagnosed between 2009 and 2022 were included for retrospective evaluation. RESULTS: The study included 279 patients, 174 females and 105 males, with a female-to-male ratio of 1.65. The average age at onset was 12.8 ± 3.4 years, and mean follow-up, 2.1 years (range: 1-12.1 years). Patients <10 years old were grouped as "prepubertal" and those ≥10 years old as "others". The diagnoses made at the end of follow-up were multiple sclerosis associated optic neuritis (n = 90, 32.3 %), single isolated optic neuritis (n = 86, 31 %), clinically isolated syndrome (n = 41, 14.7 %), myelin oligodendrocyte glycoprotein antibody associated optic neuritis (n = 22, 7.9 %), and relapsing isolated optic neuritis (n = 18, 6.5 %). Predominant diagnoses were myelin oligodendrocyte glycoprotein antibody associated optic neuritis and acute disseminated encephalomyelitis associated optic neuritis in the prepubertal group and multiple sclerosis associated optic neuritis in the older group. Recurrences were observed in 67 (24 %) patients, including 28 with multiple sclerosis associated optic neuritis, 18 with relapsing isolated optic neuritis, 11 with myelin oligodendrocyte glycoprotein antibody associated optic neuritis, 8 with aquaporin-4 antibody related optic neuritis, and 2 with chronic relapsing inflammatory optic neuropathy. Recurrences were more common among female patients. Findings supporting the diagnosis of multiple sclerosis included age of onset ≥ 10 years (OR=1.24, p = 0.027), the presence of cranial MRI lesions (OR=26.92, p<0.001), and oligoclonal bands (OR=9.7, p = 0.001). Treatment in the acute phase consisted of intravenous pulse methylprednisolone (n = 46, 16.5 %), pulse methylprednisolone with an oral taper (n = 212, 76 %), and combinations of pulse methylprednisolone, plasmapheresis, or intravenous immunoglobulin (n = 21, 7.5 %). Outcome at 12 months was satisfactory, with 247 out of 279 patients (88.5 %) demonstrating complete recovery. Thirty-two patients exhibited incomplete recovery and further combination treatments were applied. Specifically, patients with relapsing isolated optic neuritis and aquaporin-4 antibody related optic neuritis displayed a less favorable prognosis. CONCLUSION: Our results suggest optic neuritis is frequently bilateral in prepubertal and unilateral in peri or postpubertal patients. Age of onset 10 or older, presence of oligoclonal bands, and brain MRI findings reliably predict the development of multiple sclerosis. The risk of developing multiple sclerosis increases mostly during the second and third years of follow-up. Relapsing isolated optic neuritis remains a separate group where the pathogenesis and outcome remain unclear. Investigation of predisposing and diagnostic biomarkers and long follow-up could help to define this group.
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Acuaporinas , Esclerosis Múltiple , Neuromielitis Óptica , Neuritis Óptica , Humanos , Masculino , Adolescente , Femenino , Niño , Estudios Retrospectivos , Glicoproteína Mielina-Oligodendrócito , Bandas Oligoclonales , Turquía/epidemiología , Neuritis Óptica/diagnóstico , Esclerosis Múltiple/complicaciones , Autoanticuerpos , Metilprednisolona , Acuaporina 4 , Neuromielitis Óptica/complicacionesRESUMEN
OBJECTIVES: To evaluate clinical characteristics, imaging features and etiological profile of Radiologically Isolated Syndrome (RIS) along with clinical and radiological follow-up. METHODS: Demographic, clinical and radiological data of patients younger than 18 years fulfilling the criteria for RIS were retrospectively analyzed. RIS was defined by the detection of lesions meeting the revised 2010 McDonald Criteria for dissemination in space on magnetic resonance imaging (MRI) in the absence of any symptoms of demyelinating disease or an alternative cause for the MRI findings. RESULTS: There were total 69 patients (38 girls, 31 boys). The median age at index MRI was 15.7 years, and median follow-up time was 28 months. The most common reason for neuroimaging was headache (60.9%). A first clinical event occurred with median 11 months in 14/69 (20%) of cases. Those with oligoclonal bands (OCB) in cerebrospinal fluid (CSF) and follow-up longer than 3 years were more likely to experience a clinical event (p<0.05): 25% of those with OCB manifested clinical symptoms within the first year and 33.3% within the first two years compared to 6.3% and 9.4%, respectively in those without OCB. Radiological evolution was not associated with any variables: age, sex, reason for neuroimaging, serum 25-hydroxyvitamin D level, elevated IgG index, OCB positivity, total number and localization of lesions, presence of gadolinium enhancement, achievement of 2005 criteria for DIS and duration of follow-up. CONCLUSION: Children and adolescents with RIS and CSF OCB should be followed-up for at least 3 years in order to detect any clinical symptoms suggestive of a demyelinating event. Because disease-modifying treatments are not approved in RIS and no consensus report justifies their use especially in pediatric RIS, close follow-up of OCB-positive patients is needed for early recognition of any clinical event and timely initiation of specific treatment.
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Enfermedades Autoinmunes del Sistema Nervioso , Enfermedades Desmielinizantes , Esclerosis Múltiple , Masculino , Femenino , Humanos , Niño , Adolescente , Esclerosis Múltiple/diagnóstico , Estudios Retrospectivos , Medios de Contraste , Gadolinio , Enfermedades Desmielinizantes/diagnóstico por imagen , Enfermedades Desmielinizantes/líquido cefalorraquídeo , Bandas Oligoclonales/líquido cefalorraquídeo , Imagen por Resonancia MagnéticaRESUMEN
OBJECTIVE: Congenital cytomegalovirus infection is the most common congenital infection. Although screening of congenital cytomegalovirus infection with polymerase chain reaction studies in blood, urine, and saliva samples has been developed in recent years, it is not yet in routine use in any country. MATERIALS AND METHODS: In our study, cytomegalovirus deoxyribonucleic acid analysis was per- formed by real-time polymerase chain reaction method in saliva samples taken before the first feeding during the first day following birth in neonates born in a university hospital between January 2021 and January 2022. To support the diagnosis, additionally, cytomegalovirus deoxy- ribonucleic acid positivity in urine and blood samples was investigated in newborns with cyto- megalovirus deoxyribonucleic acid positivity in saliva. RESULTS: Cytomegalovirus deoxyribonucleic acid was investigated in saliva samples of 545 neonates by real-time polymerase chain reaction method in 1-year period and positiv- ity was found in 6 neonates. Since cytomegalovirus deoxyribonucleic acid was found nega- tive by the real-time polymerase chain reaction method in the urine and blood samples of 5 of these neonates, the positivity in the saliva sample was interpreted as false positivity. In 1 case, cytomegalovirus deoxyribonucleic acid positivity was detected in urine and blood samples 5 weeks later. As a result, definite congenital cytomegalovirus infection could not be diagnosed in 545 cases, while possible congenital cytomegalovirus infection was diag- nosed in 1 case. CONCLUSION: It has been concluded that the frequency of congenital cytomegalovirus infection is low in our study group and studying saliva samples showed high false-positive rates. It is seen that saliva is not a suitable sample for detecting cytomegalovirus deoxyribonucleic acid by real-time polymerase chain reaction method.
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BACKGROUND: Megalencephalic leukoencephalopathy with subcortical cysts (MLC) is a rare leukodystrophy characterized by early-onset macrocephaly and progressive white matter vacuolation. The MLC1 protein plays a role in astrocyte activation during neuroinflammation and regulates volume decrease following astrocyte osmotic swelling. Loss of MLC1 function activates interleukin (IL)-1ß-induced inflammatory signals. Theoretically, IL-1 antagonists (such as anakinra and canakinumab) can slow the progression of MLC. Herein, we present two boys from different families who had MLC due to biallelic MLC1 gene mutations and were treated with the anti-IL-1 drug anakinra. METHODS: Two boys from different families presented with megalencephaly and psychomotor retardation. Brain magnetic resonance imaging findings in both patients were compatible with the diagnosis of MLC. The diagnosis of MLC was confirmed via Sanger analysis of the MLC1 gene. Anakinra was administered to both patients. Volumetric brain studies and psychometric evaluations were performed before and after anakinra treatment. RESULTS: After anakinra therapy, brain volume in both patients decreased significantly and cognitive functions and social interactions improved. No adverse effects were observed during anakinra therapy. CONCLUSIONS: Anakinra or other IL-1 antagonists can be used to suppress disease activity in patients with MLC; however, the present findings need to be confirmed via additional research.
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Proteína Antagonista del Receptor de Interleucina 1 , Megalencefalia , Proteínas de la Membrana , Receptores de Interleucina-1 , Humanos , Masculino , Encéfalo/diagnóstico por imagen , Encéfalo/metabolismo , Cognición , Proteína Antagonista del Receptor de Interleucina 1/farmacología , Megalencefalia/diagnóstico por imagen , Megalencefalia/tratamiento farmacológico , Megalencefalia/genética , Proteínas de la Membrana/genética , Mutación , Receptores de Interleucina-1/antagonistas & inhibidoresRESUMEN
BACKGROUND: Although the underlying genetic causes of intellectual disability (ID) continue to be rapidly identified, the biological pathways and processes that could be targets for a potential molecular therapy are not yet known. This study aimed to identify ID-related shared pathways and processes utilizing enrichment analyses. METHODS: In this multicenter study, causative genes of patients with ID were used as input for Disease Ontology (DO), Gene Ontology (GO), and Kyoto Encyclopedia of Genes and Genomes enrichment analysis. RESULTS: Genetic test results of 720 patients from 27 centers were obtained. Patients with chromosomal deletion/duplication, non-ID genes, novel genes, and results with changes in more than one gene were excluded. A total of 558 patients with 341 different causative genes were included in the study. Pathway-based enrichment analysis of the ID-related genes via ClusterProfiler revealed 18 shared pathways, with lysine degradation and nicotine addiction being the most common. The most common of the 25 overrepresented DO terms was ID. The most frequently overrepresented GO biological process, cellular component, and molecular function terms were regulation of membrane potential, ion channel complex, and voltage-gated ion channel activity/voltage-gated channel activity, respectively. CONCLUSION: Lysine degradation, nicotine addiction, and thyroid hormone signaling pathways are well-suited to be research areas for the discovery of new targeted therapies in ID patients.
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Discapacidad Intelectual , Tabaquismo , Humanos , Discapacidad Intelectual/genética , Lisina/genética , Tabaquismo/genética , Pruebas Genéticas , Canales Iónicos/genéticaRESUMEN
Opsoclonus-myoclonus-ataxia syndrome (OMAS) in children is most often of paraneoplastic origin, but it can also result from infectious processes, toxic and metabolic disorders, and organic events that cause damage to the brainstem or cerebellum. Post-vaccination OMAS has also been reported. We report the case of a 15-year-old girl who developed OMAS 24 hours after her first dose of mRNA COVID-19 (BioNTech) vaccine.
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Vacunas contra la COVID-19 , COVID-19 , Síndrome de Opsoclonía-Mioclonía , Adolescente , Femenino , Humanos , Ataxia , Cerebelo , COVID-19/complicaciones , Vacunas contra la COVID-19/efectos adversos , Síndrome de Opsoclonía-Mioclonía/etiologíaRESUMEN
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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Variation in the mitochondrial tRNA Lys gene at position 8296 was previously found to be associated with maternally inherited diabetes mellitus and deafness, hypertrophic cardiomyopathy, myoclonic epilepsy with ragged-red fibers and mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes. The pathogenicity of the m.8296A>G variation is unclear. In this study, we aimed to analyze the mitochondrial proteome in a patient with m.8296A>G variation to elucidate the effects of this mutation at the protein level. Whole-exome sequencing and mitochondrial genome analysis were performed in a patient with sensorineural hearing impairment, cognitive impairment, leukodystrophy, migraine-like headaches, and gastrointestinal dysmotility. Mitochondrial genome analysis identified a homoplasmic m.8296A>G variation in the mitochondrial tRNA Lys gene in the proband and unaffected mother. Global mitochondrial proteome analysis was carried out in the muscle mitochondria of the index patient and a control subject. Comparative muscle mitochondrial proteome analysis revealed a total of 13 nuclear-encoded mitochondrial proteins differently expressed with respect to the control. Ten of the 13 proteins were downregulated. Most of the proteins were involved in ATP synthesis and Krebs cycle and have strong interactions with each other. We considered the m.8296A>G variation to be pathogenic with variable penetrance for our patient's phenotype, and this variation led to different expressions of nuclear-encoded proteins involved in energy metabolism.
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BACKGROUND: Juvenile dermatomyositis (JDM) is the most common subtype of idiopathic inflammatory myopathies in childhood. Gottron's papules, shawl sign, periorbital heliotrope rash, and periungual telengiectasis are characteristic skin findings of the disease. Besides characteristic skin involvement, some other skin findings, such as angioedema, may be seen prior or in the course of the disease. The presence of angioedema in JDM is emphasized in this report. CASE PRESENTATIONS: We present 2 unrelated girls, aged 2 (case 1) and 12 years (case 2), who had developed symmetrical weakness in the proximal muscles, muscle pain, elevated muscle enzymes and angioedema. Both cases had abnormal muscle magnetic resonance imaging findings, suggestive of inflammatory myositis. Muscle biopsy was performed only in case 1, and major histocompatibility complex-1 expression on myofibers was shown consistent with JDM. Cases were diagnosed as probable and definite JDM, respectively. Angioedema was prominent, particularly in the lips and extremities of both cases, without laboratory evidence of C1 inhibitor deficiency or capillary leak syndrome, and absence of family history. Mast cell-mediated, acquired angioedema was the most likely diagnosis. In both cases, skin and muscle findings improved significantly with steroid treatment. CONCLUSION: We suggest that angioedema may be among the characteristic skin findings in JDM, and may be included in subsequent definitions.
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Angioedema , Dermatomiositis , Miositis , Biopsia , Dermatomiositis/complicaciones , Dermatomiositis/diagnóstico , Dermatomiositis/tratamiento farmacológico , Femenino , Humanos , Miositis/diagnóstico , Miositis/tratamiento farmacológico , PielRESUMEN
Three siblings born to Turkish parents from the same village had normal brain development until acute neurological deterioration between 12 months and 8 years of age. Consequent loss of all acquired motor, social, and language functions following infections was associated with a pontine cyst, calcification, and cerebellar atrophy. Exome sequencing revealed a homozygous c.1297G>A (p.Gly433Ser) alteration in BEND4, which was predicted to be deleterious in in silico analysis tools and segregated in multiple affected individuals in the family. BEND4 has not been associated with any existing disease. Immunofluorescence microscopy analysis of wild-type and mutant BEND4 expressing Vero cells showed nuclear and cytoplasmic localization. Wild-type BEND4 displayed a network-like distribution, whereas mutant BEND4 showed a juxtanuclear distribution pattern. Differential proteome analysis of Vero cells expressing BEND4 revealed that mutant BEND4 expression caused selective increase in reticulocalbin-1 and endoplasmic reticulum resident protein-29. Both proteins are associated with the endoplasmic reticulum and are primarily involved in protein processing and folding pathways. Any defect or stress in protein folding creates stress on cells and may cause chronic damage. This is the first study showing that pathogenic BEND4 variants may lead to an infection-induced acute necrotizing encephalopathy as demonstrated in characteristic neuroimaging findings.
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Congenital CD59 deficiency is an autosomal recessive disease characterized by mild-to-moderate chronic intravascular hemolysis, relapsing demyelinating peripheral neuropathies, and recurrent ischemic central nervous system strokes. We report a 2-year-old Turkish girl with a history of two episodes of Guillain-Barré syndrome-like acute weakness, reversible monocular abducens paralysis, and recurrent blistering skin lesions during periods of upper respiratory tract infections. Reversible monocular abducens palsy and recurrent blistering skin lesions have not been reported previously in cases of congenital CD59 deficiency.
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Enfermedades del Nervio Abducens , Síndrome de Guillain-Barré , Enfermedades del Sistema Nervioso Periférico , Enfermedades del Nervio Abducens/etiología , Anemia Hemolítica , Antígenos CD59 , Preescolar , Femenino , Hemoglobinuria , Hemólisis , Humanos , ParálisisRESUMEN
AIM: To discuss seizure outcomes of patients with invasive electroencephalography (EEG) monitorization (IEM) following their epilepsy surgery at our centre. MATERIAL AND METHODS: Forty-seven patients suffering from refractory epilepsy and who were evaluated by invasive EEG were included in this retrospective study at Istanbul Faculty of Medicine from 2003 to 2017. We examined the Video EEG and invasive EEG monitorization, cranial MRI, SPECT, PET and neuropsychological tests of all patients. Postoperative seizure outcome results were evaluated according to Engel classification. The factors affecting seizure outcomes were discussed. RESULTS: Twenty-six of the patients were female (55.3%), 21 were male (44.7). The average age was 32.0 (± 12.4). Forty-three patients had surgery and the average age of these patients was 26,6 (±11.15). 38.3% of the patients had hippocampal sclerosis (HS), 23.4% had focal cortical dysplasia (FCD), 8.5% had a tumor, 14.9% had sequela lesion and 14.9% had unknown etiology. Postoperative seizure status according to the Engel classification showed that 81.6% of the patients were class I, 10.5% were class II, 2.6% were class III and 5.3% were class IV. CONCLUSION: A significant relation was statistically determined between structural MRI lesion and favorable seizure outcome (p < 0.05). The most frequent etiology was HS in our patients. Of the patients with Engel I, the averages of their ages, ages at onset of epilepsy and ages at surgery were lower than other groups, but the difference was not statistically significant (p > 0.05). We argue that IEM is an essential examination for favorable outcomes for determining the epileptogenic zone and/or the proximity of the functional structures.