Neuromuscular Disorders Overview

From WikiMSK

This article is still missing information.

There has been a lot of progress over the years in diagnostic testing, defining new diseases, and emerging therapies in the realm of neuromuscular disease. Neuromuscular disorders do not only affect the neurological system. Many neuromuscular disorders can affect other organ systems including gastrointestinal, pulmonary, cardiac, and the musculoskeletal system.


Myopathies - A myopathy is a diseases of muscle in which the muscle fibres do not function properly, resulting in muscular weakness.

Neuromuscular junction diseases - Neuromuscular junction disorders result form the destruction, malfunction, or absence of one or more key proteins involved in the transmission of signals between muscles and nerves

Peripheral nerve disorders - In peripheral nerve diseases, the motor and sensory nerves that connect the brain and spinal cord to the rest of the body are affected, causing impaired sensations, movement, or other functions

Motor neuron diseases - In motor neuron disease, nerve cells called motor neurons progressively lose function, causing the muscles they control to become weak and then nonfunctional.

Genetic Testing

Genetic testing is much more affordable than it used to be and is cost-effective including out-of-pocket. It helps with guiding discussions, preventing unnecessary treatments (e.g. avoiding immunotherapy for "seronegative" cases when a genetic cause is found), family planning, and participation in clinical trials. (See also Diagnosis)

Overseas there are many sponsored genetic testing programs. Unfortunately this does not appear to exist in New Zealand as of December 202.


This includes:

  • Inflammatory: Polymyositis, Dermatomyositis, Inclusion Body Myositis, Juvenile Dermatomyositis, Vasculitis, Overlap Syndromes (SLE, SS, Sjogrens, RA)
  • Endocrinopathies: Hypothyroidism, Cushing's syndrome
  • Electrolyte disorders: Hypokalaemia, hypophosphataemia, hypocalcaemia, Hyper/hyponatraemia
  • Genetic: Glycogen Storage Diseases, disorders of lipid and purine metabolism, Muscular Dystrophies
  • Drugs and Toxins: cocaine, heroin, alcohol, glucocorticoids, colchicine, antimalarials, statins, penicillamine, zidovudine
  • Infections; Viruses (influenza, parainfluenza, cytomegalovirus, HIV, echovirus, adenovirus, EBV), bacteria (pyomyositis, lyme), fungal, parasites (trichinosis, toxoplasmosis)
  • Rhabdomyolysis

It can sometimes be challenging to differentiate between inflammatory versus hereditary myopathy. The neurological examination is vital. However, characteristic examination findings are not always seen. EMG and biopsy can be inconclusive and non-specific. Antibody testing can be very helpful. They can inform treatment, prognosis, and alert to associated conditions. Gene testing can also be considered.

Inflammatory Myopathies

Muscle biopsy is the gold standard test. However antibody testing should be done for all inflammatory myopathy patients. Chest x-ray should be done to look for interstitial lung disease and cancer (especially for dermatomyositis).

Myositis antibodies can be requested through a myositis panel. Myositis specific antibodies include:

  • Mi2 ab - Dermatomyositis. Low risk of cancer, responds well to immunotherapy, overall favourable prognosis
  • TIF1y, NXP2 - Dermatomyositis. High risk of cancer
  • MDA5 - Dermatomyositis. Rapidly progressive interstitial lung disease
  • SRP Ab - aggressive and difficult to control muscle disease
  • Anti-Jo1 - strong association with interstitial lung disease
  • NT5C1A - inclusion body myositis

Treatment is with steroids. Depending on the type steroid sparing agents may be considered.

Genetic Causes

Pattern of weakness in different types of muscular dystrophies

Muscular dystrophies are progressive genetic diseases of muscle. They include Duchenne, Becker, Facioscapulohumeral, Myotonic, Limb Girdle, and Emery-Dreifuss, and Myotonic Dystrophy. The most common muscular dystrophy in adults is Myotonic Dystrophy.

The dystrophinopathies includes Duchenne muscular dystrophy and Becker muscular dystrophy seen in children. Facioscapulohumeral Dystrophy is seen in teens and adults.

Ion channel diseases are associated with defects in proteins called ion channels typically are marked by muscular weakness, absent muscle tone, or episodic muscle paralysis

Classification of myotonic diseases:

  • Myotonic dystrophy
    • DM type 1 (DMPK)
    • DM type 2 (CNBP)
  • Non-dystrophic myotonias
    • Chloride channelopathies (CLCN1)
    • Sodium channelopathies (SCN4A)
      • Sodium channel myotonia
      • Paramyotonia congenita
      • Hyperkalaemic periodic paralysis
    • Chondrodystrophic myotonia
  • Drug induced (statins, fibrates, cyclosporine, chloroquine)

The most common glycogen storage disease in adults is either Pompe Disease or McArdle Disease depending on the study.

Neuromuscular Junction Diseases

Myasthenia Gravis

There are three antibodies associated with MG - AChR antibody, MuSK antibody, and LRP4 antibody. Current therapies for Myasthenia Gravis includes pyridostigmine, immunotherapy, thymectomy (generalised AChR antibody positive), and exercise.

Congenital Myasthenic Syndrome

There are over 30 subtypes of CMS with pre-synaptic, synaptic, and post-synaptic forms. Current therapies for Congenital Myasthenic Syndrome depends on the subtype but includes beta agonists, pyridostigmine, and amifampridine.

Diagnostic Strategies

Advanced diagnostic testing includes antibody testing, imaging (ultrasound, muscle MRI), muscle biopsy, neurophysiology, and gene testing.

Genetic testing is key for both diagnosis and management. It is important to clarify the pattern of inheritance - i.e. autosomal dominant or recessive or X-linked. Many hereditary myopathies have prominent cardiac involvement and so clarifying the diagnosis alerts towards that possibility in terms of screening.

There is a risk of identifying a "Variant of Uncertain Significance" (VUS). However as knowledge expands many VUS's will later become classified as pathogenic. New diseases are being constantly defined. Pathogenic variants have been found in over 500 genes.


Multidisciplinary care is often key for optimal care. The types of health care providers can include neurology, musculoskeletal medicine, neurogenetics, orthopaedics, cardiology, respiratory medicine, rheumatology, speech therapy, physiotherapy, occupational therapy, dietetics, gastroenterology, social work, podiatry, and psychology.

Palliative care is important for assisting with symptom management and family support.

There has been an exponential growth in treatment advances. For example there are now groundbreaking therapies for Spinal Muscular Atrophy, Myaesthenia Gravis, Duchenne Muscular Dystrophy, and necrotizing myopathy.

The next frontier is probably gene therapy.


Mcdonald2012 neuromuscular disorders.pdf
good overview of the various acquired and heritable neuromuscular disorders

Video lectures EURO-NMD here and MDA here

Neuromuscular disease center - many helpful articles


Literature Review