Risdiplam in Spinal Muscular Atrophy: Safety Profile and Use Through The Early Access to Medicine Scheme for the Paediatric Cohort in Great Britain.

Background: Spinal muscular atrophy (SMA) is a progressive neuromuscular disease caused by mutations in Survival motor neuron 1 (SMN1) gene, leading to reduction in survival motor neuron protein (SMN), key for motor neuron survival and function in the brainstem and spinal cord. Risdiplam is an orally administered SMN2-splicing modifier which increases production of functional SMN protein. Risdiplam was offered in the UK under early access to medicines scheme (EAMS) to SMA type 1 and 2 patients aged 2 months and older, not suitable for authorised treatments from September 2020 to December 2021.

Quality of life and neurological disability in children and young people with ataxia telangiectasia.

Aim: To explore neurological factors affecting quality of life (QoL) in children and young people with ataxia-telangiectasia (A-T), from both child and parent perspective.

Method: 24 children/young people with A-T (mean age 11.2 ± 3.

LBSL: Case Series and DARS2 Variant Analysis in Early Severe Forms With Unexpected Presentations.

Objective: Leukoencephalopathy with brainstem and spinal cord involvement and lactate elevation (LBSL) is regarded a relatively mild leukodystrophy, diagnosed by characteristic long tract abnormalities on MRI and biallelic variants in , encoding mitochondrial aspartyl-tRNA synthetase (mtAspRS). variants in LBSL are almost invariably compound heterozygous; in 95% of cases, 1 is a leaky splice site variant in intron 2. A few severely affected patients, still fulfilling the MRI criteria, have been described.

Multiparametric cerebellar imaging and clinical phenotype in childhood ataxia telangiectasia.

Background: Ataxia Telangiectasia (A-T) is an inherited multisystem disorder with cerebellar neurodegeneration. The relationships between imaging metrics of cerebellar health and neurological function across childhood in A-T are unknown, but may be important for determining timing and impact of therapeutic interventions.

Purpose: To test the hypothesis that abnormalities of cerebellar structure, physiology and cellular health occur in childhood A-T and correlate with neurological disability, we performed multiparametric cerebellar MRI and establish associations with disease status in childhood A-T.

The clinical spectrum of the congenital myasthenic syndrome resulting from COL13A1 mutations.

Next generation sequencing techniques were recently used to show mutations in COL13A1 cause synaptic basal lamina-associated congenital myasthenic syndrome type 19. Animal studies showed COL13A1, a synaptic extracellular-matrix protein, is involved in the formation and maintenance of the neuromuscular synapse that appears independent of the Agrin-LRP4-MuSK-DOK7 acetylcholine receptor clustering pathway. Here, we report the phenotypic spectrum of 16 patients from 11 kinships harbouring homozygous or heteroallelic mutations in COL13A1.

Early discharge and rehabilitation in paediatric acquired brain and neurological injury: a transferable model.

Children and young people who require rehabilitation following sustaining an acquired brain injury often experience long lengths of stay (LOS) and potentially poorer recovery outcomes due to limited access to therapy and little proactive discharge planning. After stakeholder enquiry we launched a new team and pathway with a primary aim to reduce LOS. The secondary aims were to pilot an outreach model, reduce cost and improve patient and family satisfaction.

Evaluation of an internet-based animated preparatory video for children undergoing non-sedated MRI.

Objectives: We evaluate the value of an internet-based educational animated video designed to prepare children for MRI scans, and whether this video reduces scan-related anxiety in children with a neurological disorder, and healthy controls.

Methods: Participants completed a pre- and post-scan questionnaire evaluating participant online viewing behaviour, understanding of the MRI procedure, anxiety regarding the MRI, impact of animation in preparing the child and whether the child's expectation of the MRI scan matched their experience.

Results: 21 children were recruited (12 healthy controls) ranging in age from 6.

Clinical features, course, and outcomes of a UK cohort of pediatric moyamoya.

Objective: To describe characteristics and course of a large UK cohort of children with moyamoya from multiple centers and examine prognostic predictors.

Methods: Retrospective review of case notes/radiology, with use of logistic regression to explore predictors of outcome.

Results: Eighty-eight children (median presentation age 5.

Longitudinal analysis of the neurological features of ataxia-telangiectasia.

Aim: To assess the relationship between genotype and neurological progression in ataxia-telangiectasia (A-T).

Methods: Clinical and laboratory data were extracted retrospectively from the records of patients attending the UK National Ataxia-Telangiectasia Clinic. Neurological assessments were performed using the A-T Index (Crawford Score) and the A-T Neurological Examination Scale Toolkit (A-T NEST).

Congenital Myasthenic Syndrome Type 19 Is Caused by Mutations in COL13A1, Encoding the Atypical Non-fibrillar Collagen Type XIII α1 Chain.

The neuromuscular junction (NMJ) consists of a tripartite synapse with a presynaptic nerve terminal, Schwann cells that ensheathe the terminal bouton, and a highly specialized postsynaptic membrane. Synaptic structural integrity is crucial for efficient signal transmission. Congenital myasthenic syndromes (CMSs) are a heterogeneous group of inherited disorders that result from impaired neuromuscular transmission, caused by mutations in genes encoding proteins that are involved in synaptic transmission and in forming and maintaining the structural integrity of NMJs.

Trismus in the paediatric population.

Trismus is a rare presentation affecting neonates, children, and adults. In newborns there are serious implications, with potential to affect feeding, cause airway problems, and make intubation difficult. Causes of trismus seen in the paediatric patient are discussed in this review article; they are divided into intra- and extra-articular types.

Fifteen-minute consultation: the child with idiopathic intracranial hypertension.

Idiopathic intracranial hypertension (IIH) is a rare condition where intracranial hypertension is found in the context of normal brain parenchyma and no mass lesion, ventriculomegaly, underlying infection, or malignancy. Our understanding of this condition has greatly improved in the recent years with neuroimaging features and normal values for lumbar puncture opening pressure now well defined. This article provides a review of IIH in children and revised diagnostic criteria based on recent evidence and published opinion.

Neurological manifestations of influenza infection in children and adults: results of a National British Surveillance Study.

Background: The emergence of influenza A(H1N1) 2009 was met with increased reports of associated neurological manifestations. We aimed to describe neurological manifestations of influenza in adults and children in the United Kingdom that presented at this time.

Methods: A 2-year surveillance study was undertaken through the British adult and pediatric neurological surveillance units from February 2011.

Dual diagnosis of dihydropyrimidine dehydrogenase deficiency and GM₁ gangliosidosis.

An 8-month-old girl, born to consanguineous parents, presented with developmental delay, decreased muscle tone, disinterest in her surroundings, and sleepiness. Tests revealed a marked excretion of thymine with significantly increased uracil excretion in the urine, indicating a pyrimidine catabolic disorder, i.e.

Neurologic presentation of triple A syndrome.

"Triple A" syndrome is a rare, autosomal recessive condition whose main clinical features are alacrima, achalasia, and adrenal failure. Most patients also develop some neurologic abnormalities. We describe an 11-year-old boy with triple A syndrome who presented with progressive axonal motor neuropathy.

Insight into on-wafer crystallization of pure-silica-zeolite films through nutrient replenishment.

Tetraethylorthosilicate (TEOS) is added to a pure-silica-zeolite MEL nanoparticle suspension and the mixture is subsequently used for preparing spin-on low-dielectric constant (low-k) films. The films are then characterized by ellipsometric porosimetry, transmission electron microscopy (TEM), and nanoindentation. Investigation into the film microstructure indicates that the addition of TEOS significantly increases the fraction of the crystalline domains, decreases the inter-crystal mesopore size, and narrows the pore size distribution.

Familial idiopathic intracranial hypertension with variable phenotype.

Familial occurrence of Idiopathic intracranial hypertension has been rarely reported in the literature. Idiopathic intracranial hypertension, both with and without papilloedema is only described in two families before, though one had a probable diagnosis. We report a family of mother and her two daughters.

Genotype-phenotype correlation in a large population of muscular dystrophy patients with LAMA2 mutations.

Merosin deficient congenital muscular dystrophy 1A (MDC1A) results from mutations in the LAMA2 gene. We report 51 patients with MDC1A and examine the relationship between degree of merosin expression, genotype and clinical features. Thirty-three patients had absence of merosin and 13 showed some residual merosin.

A case of infantile neuroaxonal dystrophy: connatal Seitelberger disease.

We present a male stillbirth with infantile neuroaxonal dystrophy (connatal Seitelberger disease). Following the development of polyhydramnios with an ultrasound scan showing severe distal arthrogryposis, the mother was induced at 38 weeks. A moderately macerated severely intrauterine growth restricted male stillbirth was delivered.

Case of X-linked myopathy with excessive autophagy.

We report a 12-year-old boy with a vacuolar myopathy with clinical and histologic features of X-linked myopathy with excessive autophagy. This is a rare and slowly progressive disease of skeletal muscle without cardiac, nervous system, or other organ involvement. The differential diagnosis of vacuolar myopathy includes acid maltase deficiency, Danon disease, and X-linked myopathy with excessive autophagy.

Predictors of mortality and neurological morbidity in children undergoing extracorporeal life support for cardiac disease.

Objectives: The objective of this study was to determine the incidence and risk factors for death and adverse neurological outcomes in children receiving extracorporeal life support (ECLS) for cardiac indications.

Methods: A retrospective single centre consecutive cohort study was conducted in children who received ECLS for cardiac indications between January 1990 and June 2000. Health records and neuroimaging films were assessed, and long-term outcomes were obtained by standardized telephone follow-up or by assessments performed in outpatient clinic.