Advances in Neuromuscular Disorders

In the last few years, the dramatic acceleration in the discovery of novel therapeutics for neuromuscular disorders has revolutionized the field. Children with spinal muscular atrophy (SMA) who would never have survived their first years of life, are now gaining milestones and living longer than ever thought possible. This advance of new neuromuscular treatments has also contributed to early and accurate diagnosis of these rare disorders. Screening for hereditary transthyretin amyloidosis (hATTR) is now done routinely for many individuals with unexplained peripheral neuropathy because early diagnosis can substantially impact the effectiveness of recently developed therapies. Sadly, despite the rapid advance of our understanding of many neuromuscular disorders, not all have substantially benefited from therapeutic advances. However, even in the absence of disease-modifying therapies, there are substantial benefits to the relationships between patients with neuromuscular diseases and the medical teams that care for them.

In this issue of Practical Neurology, Drs. Baer and Quinn discuss the difficult topic of Advance Care Planning in Amyotrophic Lateral Sclerosis and provide a helpful heuristic (Feelings, Facts and Family) to help patients make decisions consistent with their goals and circumstances. In Neuromuscular and Autonomic Complications of COVID-19, Dr. Lehmann methodically assesses causality, weighing in on what seems to be a strong association vs what seems unlikely or requires further research. Drs. Zhou and Shin discuss their approach to Small Fiber Neuropathy, addressing potential associations with COVID-19 infection and vaccines and questioning the role of antiTS-HDS and antiFGFR3 antibodies. Drs. Sabouri, Kafaei and Christopher-Stine offer a comprehensive and practical approach to Immune-Mediated Inflammatory Myopathies and their classification, stressing the usefulness of autoantibodies. Drs. Lamb and Dyck review the challenges of diagnosing Chronic Inflammatory Demyelinating Polyradiculoneuropathy (CIDP) and its variants, warn about overreliance on cerebrospinal fluid (CSF) protein results, suggest blink reflexes for evaluation in advanced disease, and discuss recently described antibodies. Drs. Vu and Suresh address autoantibodies in Myasthenia Gravis (MG) and give a detailed overview on novel therapeutics, including complement inhibitors and neonatal Fc receptor modulators. Drs. Pinto and Pinto share a detailed overview of Neuromuscular Amyloidosis and how to differentiate between the different types of amyloidosis in these underdiagnosed, yet treatable, disorders. Finally, Drs. Brandsema and Cappa discuss some of the exciting and revolutionary Genetically Targeted Therapies for Inherited Neuromuscular Disorders, including gene transfer therapy, CRISPR/Cas9 gene editing, and antisense oligonucleotides. Some of these therapies have already dramatically changed the lives of patients and their loved ones while others offer tremendous hope and challenges for patients and their physicians.

This issue is loaded with up-to-date information on many different neuromuscular disorders, yet other, equally important, neuromuscular conditions such as myotonic dystrophy, Charcot Marie Tooth, facioscapulohumeral muscular dystrophy, Guillain Barré Syndrome, and Lambert Eaton myasthenic syndrome are not addressed because of lack of space. Many of those disorders will benefit from therapies discussed in this issue. Autoimmune neuromuscular disorders will certainly benefit from the advances seen in MG. Inherited disorders will benefit from genetically targeted therapies similar to what we are seeing in SMA and hATTR amyloidosis. Hopefully in the next neuromuscular issue of Practical Neurology, we will see updates on these advances.

I would like to thank all the authors who contributed to this issue as well as the editorial team at Practical Neurology. I hope you enjoy reading this issue as much as I did and take part in this new era of diagnosis and treatment of neuromuscular disorders. Truly, what seemed fiction a few years ago, is now reality.