Nusinersen Treatment for Spinal Muscular Atrophy: Retrospective Multicenter Study of Pediatric and Adult Patients in Kuwait.

Spinal muscular atrophy is a neuromuscular genetic condition associated with progressive muscle weakness and atrophy. Nusinersen is an antisense oligonucleotide therapy approved for the treatment of 5q spinal muscular atrophy in pediatric and adult patients. The objective of this clinical case series is to describe the efficacy and safety of nusinersen in treating spinal muscular atrophy in 20 pediatric and 18 adult patients across six treatment centers in Kuwait. Functional motor assessments (Children's Hospital of Philadelphia Infant Test of Neuromuscular Disorders, Hammersmith Functional Motor Scale Expanded, and Revised Upper Limb Module) were used to assess changes in motor function following nusinersen treatment. The safety assessment involved clinical monitoring of adverse events. The results demonstrate clinically meaningful or considerable improvement in motor performance for nearly all patients, lasting over 4 years in some cases. A total of 70% of patients in the pediatric cohort and 72% of patients in the adult cohort achieved a clinically meaningful improvement in motor function following nusinersen treatment. Additionally, nusinersen was well-tolerated in both cohorts. These findings add to the growing body of evidence relating to the clinical efficacy and safety of nusinersen.

Subtelomeric screening in Serbian children with dysmorphic features and unexplained developmental delay/intellectual disabilities.

Developmental delay and intellectual disabilities (DD/ID) are significant health problems affecting 3% of the human population. Submicroscopic chromosomal rearrangements involving subtelomeric regions are often considered to be the cause of unexplained DD/ID. Screening of subtelomeric regions was performed in 80 unrelated patients with DD/ID and normal GTG-banded chromosomes using the MLPA method with two kits (SALSA P070-B1 and P036-E1). The MLPA screening revealed subtelomeric chromosome aberrations in four cases (5%). The aberrations detected were: 1p deletion, 1p deletion combined with 12q duplication, 4p deletion, and 9p deletion combined with 15q duplication. The deletions detected were classified as causative for the patients' observed phenotypes. This study confirms the high frequency of subtelomeric rearrangements in unexplained DD/ID and reinforces the argument for routine subtelomeric screening in order to get a correct diagnosis, establish genotype-phenotype correlations and offer accurate genetic counseling.

Epilepsy in a child with Wolf-Hirschhorn syndrome.

INTRODUCTION: Wolf-Hirschhorn syndrome (WHS) is a rare chromosomal disorder characterized by facial dismorphy, multiple congenital anomalies, delayed psychomotor development and pharmaco-resistant epilepsy. CASE OUTLINE: We present a 5-year-old girl with severe delay in growth and development, microcephaly, mild facial dismorphy and epilepsy. The pregnancy was complicated by intrauterine growth retardation. Generalized muscle hypotonia was observed at birth. First seizures started at age of 9 months as unilateral convulsive status epilepticus (SE), sometimes with bilateral generalization. Seizures were often triggered by fever and were resistant to antiepileptic treatment. Introduction of lamotrigine and valproate therapy led to complete seizure control at the age of 33 months. Electroencephalographic (EEG) finding was typical at the beginning. After transitory improvement between age four and five years, epileptiform EEG activity appeared again at the age of five years, without observed clinical seizures. Magnetic resonance imaging showed diffuse brain atrophy and delay in myelination. Using Multiplex ligation-dependent probe amplification (MLPA) method, we disclosed heterozygote microdeletation of the distal part of the short arm of chromosome 4 (4p16). CONCLUSION: We present a clinical course of epilepsy in a patient with Wolf-Hirschhorn syndrome. The diagnosis was verified by modern molecular technique. This is the first molecular characterization of a patient with WHS performed in our country.

[Refractory convulsive status epilepticus in childhood]. / Rezistentni konvulzivni epilepsijski status u decjem uzrastu.

Refractory convulsive status epilepticus (RCSE) is life-threatening condition, with seizures lasting over one hour and not responding to first and second-line anticonvulsant drug therapy. Any mistreatment or delayed proper treatment significantly increase mortality and neurologic sequelae. First line drugs for convulsion ceasing are benzodiazepines, phenobarbital and phenytoin. In case of refractory status, infusion of midazolam and general anesthesia should be administered. The most important measures of the intensive care are control of vital functions, homeostasis, prevention and therapy for possible brain and systemic complications. Discovery of etiology of status epilepticus is highly important because symptomatic therapy should be administered. Overall mortality rate during RCSE is 13.5%, and is much higher in acute symptomatic group--28.6%. Early sequelae rate is 40.6%, 27.3% and 70% in idiopathic and acute symptomatic groups, respectively.