Search

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., (© 2023. The Author(s) under exclusive licence to Belgian Neurological Society.)

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., Competing Interests: Declaration of competing interest None. This research received no specific grant from funding agencies in the public, commercial, or not-for-profit sectors., (Copyright © 2024 Elsevier Inc. All rights reserved.)

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.