The landscape of childhood neuromuscular disorders management has transformed in the last 30 years, with dramatic improvements in quality of life and survival. This is due to several reasons, some disorder-specific. But one fundamental common factor across all neuromuscular disorders is the now well-established concept of multidisciplinary management which is the core theme of this book. The authors have skilfully organized the book into eight sections, each section covering various topics in individual chapters. The book starts from a parental perspective and provides an in-depth insight into various aspects of the journey of the child (and family) with a neuromuscular disorder. The summary of key points from a parental perspective on diagnosis, quality of life, and advance care planning are food for thought for all clinicians. The highlight of the book is the individual detailed sections on topics like cardiology, respiratory, orthopaedic, etc. which will be of interest not only to neurologists but to all specialists who are involved in the care of children with neuromuscular disorders. The chapter on assessments is a helpful guide as many of these are rarely performed out of clinical trials; but with newer treatments, some of these might become routine clinical assessments mandated by funding bodies. The cognitive, psychosocial aspects, sexual health, and transition to adult services are well addressed. The clinical vignettes at the end of the chapters are an excellent addition. The individual chapters are smaller compared to other books, making them easier to use in daily clinical practice. They cover the essential aspects required for a clinician including diagnosis, genetics, management, and recent newer treatment options. There are also good references for those who want to explore these topics further. Genetic testing is now bypassing previously routinely done investigations on the diagnostic pathway. Unfortunately, genetic result can frequently throw the clinician into a conundrum rather than providing answers. In such situations, in the search for more diagnostic evidence, we need traditional procedures (muscle biopsy) as well as newer technologies (muscle magnetic resonance imaging). The lack of dedicated chapters on these two tools is the only shortcoming of this book. Overall the authors have succeeded in providing a holistic and comprehensive overview of neuromuscular disorders in children and its management. There is something for everyone in this book from trainee neurologists, to neurologists who only occasionally see children with neuromuscular disorders, to the neuromuscular experts. I would recommend this book as an addition to bookshelves in every paediatric neurology department. As we move to the much anticipated revolutionary era of novel treatments, it is imperative to get the basics right. This book will be sure to serve as a guide to many.
Optic neuritis (ON) is an acquired disorder of the optic nerve due to inflammation, demyelination or degeneration. We report a child who presented with acute onset bilateral visual loss who, following a diagnosis of ON, was treated and had excellent visual recovery. Paediatric ON is considered to be different clinical entity to adult ON. Although in children ON is usually parainfectious or postinfectious, it can be the first presenting feature of multiple sclerosis or neuromyelitis optica spectrum disease. In this paper, we discuss the literature on treatment of ON and prediction of risk of recurrence.
Introduction Spinal muscular atrophy (SMA) is a rare autosomal recessive neuromuscular disease which is characterised by muscle atrophy and early death in most patients. Risdiplam is the third overall and first oral drug approved for SMA with disease-modifying potential. Risdiplam acts as a survival motor neuron 2 (SMN2) pre-mRNA splicing modifier with satisfactory safety and efficacy profile. This review aims to critically appraise the place of risdiplam in the map of SMA therapeutics.Areas covered This review gives an overview of the current market for SMA and presents the mechanism of action and the pharmacological properties of risdiplam. It also outlines the development of risdiplam from early preclinical stages through to the most recently published results from phase 2/3 clinical trials. Risdiplam has proved its efficacy in pivotal trials for SMA Types 1, 2, and 3 with a satisfactory safety profile.Expert opinion In the absence of comparative data with the other two approved drugs, the role of risdiplam in the treatment algorithm of affected individuals is examined in three different patient populations based on the age and diagnosis method (newborn screening or clinical, symptom-driven diagnosis). Long-term data and real-world data will play a fundamental role in its future.
Abstract 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. Clinical presentation was mostly at birth with hypotonia and breathing and feeding difficulties often requiring ventilation and artificial feeding. Respiratory crisis related to recurrent apnoeas, sometimes triggered by chest infections, were common early in life but resolved over time. The predominant pattern of muscle weakness included bilateral ptosis (non-fatigable in adulthood), myopathic facies and marked axial weakness, especially of neck flexion, while limb muscles were less involved. Other features included facial dysmorphism, skeletal abnormalities and mild learning difficulties. All patients tested had results consistent with abnormal neuromuscular transmission. Muscle biopsies were within normal limits or showed non-specific changes. Muscle MRI and serum creatine kinase levels were normal. In keeping with COL13A1 mutations affecting both synaptic structure and presynaptic function, treatment with 3,4-diaminopyridine and salbutamol resulted in motor and respiratory function improvement. In non-treated cases, disease severity and muscle strength improved gradually over time and several adults recovered normal muscle strength in the limbs. In summary, patients with COL13A1 mutations present mostly with severe early-onset myasthenic syndrome with feeding and breathing difficulties. Axial weakness is greater than limb weakness. Disease course improves gradually over time, which could be consistent with the less prominent role of COL13A1 once the neuromuscular junction is mature. This report emphasizes the role of collagens at the human muscle endplate and should facilitate the recognition of this disorder, which can benefit from pharmacological treatment.
The objective of this study is to analyse retrospective, observational, longitudinal growth (weight, height and BMI) data in ambulatory boys aged 5-12 years with Duchenne muscular dystrophy (DMD).We considered glucocorticoids (GC) use, dystrophin isoforms and amenability to exon 8, 44, 45, 51 and 53 skipping drug subgroups, and the impact of growth on loss of ambulation. We analysed 598 boys, with 2604 observations. This analysis considered patients from the UK NorthStar database (2003-2020) on one of five regimes: "GC naïve", "deflazacort daily" (DD), "deflazacort intermittent" (DI), "prednisolone daily" (PD) and "prednisolone intermittent" (PI). A random slope model was used to model the weight, height and BMI SD scores (using the UK90).The daily regime subgroups had significant yearly height stunting compared to the GC naïve subgroup. Notably, the average height change for the DD subgroup was 0.25 SD (95% CI - 0.30, - 0.21) less than reference values. Those with affected expression of Dp427, Dp140 and Dp71 isoforms were 0.77 (95% CI 0.3, 1.24) and 0.82 (95% CI 1.28, 0.36) SD shorter than those with Dp427 and/or Dp140 expression affected respectively. Increased weight was not associated with earlier loss of ambulation, but taller boys still ambulant between the age of 10 and 11 years were more at risk of losing ambulation.These findings may provide further guidance to clinicians when counselling and discussing GCs commencement with patients and their carers and may represent a benchmark set of data to evaluate the effects of new generations of GC.
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