Neuromuscular disease implies a disorder of the peripheral nerve, neuromuscular junction or muscle.
Weakness is the predominant sign of neuromuscular disease. Mild cases may only have exercise intolerance whereas severe cases may be unable to stand. The gait is often characteristic – initially relatively normal then becoming progressively more stilted and weak. Cats will often “bunny-hop”. Poor “hopping” responses can often demonstrate the weakness. Conscious proprioception and the time taken to correct a knuckled over paw is usually normal. If spinal and/or cranial nerve reflexes are depressed then a neuropathy is more likely. Myasthenic animals often have an absent or fatigable palpebral reflex and poor eye movement.
The list of causes of neuromuscular disease is huge and, as with most of neurology, it is easiest to subcategorise then with the DAMNIT(V) format. There are many neuromuscular diseases that have not been classified.
Blood samples – haematology and biochemistry
Many diseases can be eliminated/suggested by routine tests for example electrolyte disorders (hypokalaemia, hypocalcaemia,) and endocrinopathies (Cushing’s syndrome, hypothyroidism, hyperthyroidism, diabetes mellitus). A significantly elevated creatine kinase (>500u/l) indicates muscle damage and is suggestive of a dystrophy, inflammation or metabolic imbalance such as hypokalaemia. However creatine kinase can also increase after prolonged recumbency or because the animal is breaking down muscle for energy. In protozoal diseases such as toxoplasmosis or Neosporosis, liver parameters may also be elevated.
Other blood tests
If serum biochemistry is suggestive then specific tests for endocrine disorders may be recommended. Blood samples may also be recommended to test for myasthenia gravis (acetylcholine receptor antibody); protozoal problems (Toxoplasma gondii and Neospora caninum) and / or mitochondrial myopathies(blood pH and abnormal levels of organic acids). It pet’s problem suggests a specific inherited problem then a specific genetic test may be recommend e.g. Centronuclear Myopathy (Labrador retriever myopathy) or exercise induced collapse in Labrador Retrievers.
electrophysiology (electromyography (EMG) with nerve function tests) is used for diagnosing neuromuscular disease and specifically localising the problem to the nerve, neuromuscular junction or a neuropathy. It can also provide information as to the aetiology of the problem; for example it is possible to ascertain if the disease is more likely to involve the myelin or the axon.
An EMG recording from a muscle. Abnormal spontaneous activity can indicate a neuropathy or myopathy
Trace of a sciatic motor nerve conduction velocity.
The amplitude of the compound muscle action potential (numbered wave form) is reduced and so is the conduction velocity (53.1m/s). This dog had a neuropathy.
Muscle and nerve biopsy
Although relatively easy to perform it is important that biopsies are handled correctly and submitted to an appropriate laboratory. A dedicated neuromuscular laboratory should be able to provide the full range of histologic and histochemical stains and electron microscopy e.g. Comparative Neuromuscular Laboratory, Davis University, California http://neurolab.vet.ed.ac.uk
Other tests e.g.radiographs or ultrasound may be recommended to look for associated or contributing diseases e.g. myasthenia gravis can be induced by thymoma. Although extravagantly expensive MRI can be useful to identify disease muscle to increase accuracy of biopsy
How is neuromuscular disease treated?
Therapy obviously depends as to the precise nature of the problem. Some neuromuscular diseases have a specific therapy for example endocrine disorders (hyperthyroidism, diabetes mellitus); Myasthenia gravis (Pyridostigmine and immunosuppressive therapy); and antiprotozoal agents for Toxoplasmosis and Neosporosis. For many degenerative neuropathies there is no treatment however some improve when given dietary supplements such as the mitochondrial co-factor L-Carnitine 50mg/kg twice daily and anti-oxidants such as gamma linoleic acid and omgea-3-fatty acids. Many severely tetraparetic animals will require considerable supportive care as well. For example, a pet which is unable to swallow may require feeding through a (PEG) tube into the stomach.
- Feed from a height
- Stairs if unable to stand
- Maintain raised position 10mins after feeding
- Small meals 4-6 per day
- High calorie (e.g. Hills p/d or n/d)
- Experiment food types (e.g. sticky food in small balls)
- Low dose erythromycin
- gastrointestinal pro-kinetic (stimulates motilin receptors)
- 5-1mg/kg PO q8hours (paediatric suspension)
- Treatment myasthenia gravis
- Pyridostigmine bromide
- Immunosuppression (steroids and other agents)
Differentials of myopathies – common conditions highlighted in bold
|D||Degenerative||E.g. Hereditary myopathies such as muscular dystrophy|
|A||Anomalous||Myotonic myopathy, Myositis ossificans (progressive calcification of connective tissue in striated muscle)|
|M||Metabolic||Hypokalemia, Hypernatraemia, Hypocalcaemia, Hyperkalemic periodic paralysis, Hypokalemic periodic paralysis, Hyperthyroidism, Hypothyroidism, Hyperadrenocorticism, Hypoadrenocorticism, Primary hyperparathyroidism, Hypoparathyroidism, mitochondrial myopathy, lipid storage myopathy|
|N||(para) Neoplastic||Thymoma, Bronchogenic carcinoma, Myeloid leukaemia, Tonsillar carcinoma|
|Nutritional||Vitamin E / Selenium deficiency.
Muscles hot, swollen and painful. Poor hair coat.
|Infectious||Neosporosis, Toxoplasmosis, Trichinella,|
|T||Traumatic||Myositis ossificans traumatica|
Differentials of neuromuscular transmission disorders – common conditions highlighted in bold
|A||Anomalous||Congenital myasthenia gravis|
|N||(para) Neoplastic||Thymoma (myasthenia gravis – especially Abyssinian)
Lambert-Eaton syndrome – antibodies against Ca 2+channels (not reported veterinary medicine)
|I||Inflammatory||Acquired myasthenia gravis|
|T||Toxico-infectious||Botulism – unlikely in cats
Tick paralysis (dogs in appropriate areas only)
Aminoglycosides, Tetracyclines, lincomycin, clindamycin
Differentials of peripheral neuropathies – common conditions highlighted in bold
|D||Degenerative||Idiopathic (in many cases a degenerative neuropathy may be diagnosed without determining a cause; some may be associated with an age-related degeneration)
Breed related disorders (see additional table)
Storage diseases, primary hyperoxaluria, peripheral and central axonopathy
|M||Metabolic||Diabetes mellitus, Hyperthyroidism, Cushing’s syndrome, Hypothyroidism, Insulinoma|
|N||(Para)neoplastic||Bronchogenic carcinoma, Thymoma, Mammary adenocarcinoma, Malignant melanoma, Osteosarcoma, Thyroid adenocarcinoma, Mast cell tumour, Lymphosarcoma, leiomyosarcoma, haemangiosarcoma, synovial cell sarcomas, adrenal adenocarcinoma|
|I||Inflammatory||Acute polyradiculoneuritis , Post vaccinal acute polyradiculoneuritis|
|Infectious||Rabies, Toxoplasmosis, Neosporosis,|
|Idiopathic||Idiopathic Polyradiculoneuritis, facial neuropathy, laryngeal neuropathy, distal denervating disease|
|T||Traumatic||Brachial plexus avulsion, Sacrocaudal fractures|
|Toxic||Lead, Mercury, Thallium, Acrylamide, Hexacarbon, Ionophores, Salinomycin, Organophosphate (delayed), Coyotillo (Buckthorn), Dysautonomia|
Table 2 Inherited peripheral nervous system or muscular disease for which there is a DNA test and / or breed screening program
|Disease||Breed||Test||Other info / Laboratory|
|Centronuclear Myopathy (Hereditary Myopathy)||Labrador retrievers||DNA (mouth swabs)||Animal Health Trust
Laboklin, Alfont University
|Hypokalemic myopathy||Burmese cat||DNA||Langford veterinary Services
|Leonberger||DNA (blood, mouth swabs)||University of Minnesota,
University of Bern
|Malignant Hyperthermia||All breeds||DNA (blood, mouth swabs)||Laboklin|
|Muscular Dystrophy||Golden Retriever||DNA (blood, mouth swabs)||Laboklin|
|Myostatin Deficiency (“Bully” Whippet)/ Double Muscling||Whippet||DNA (blood, mouth swabs)||Laboklin|
|Myotonia congenita||Schnauzer||DNA (blood, mouth swabs)||Laboklin|
|Pyruvate Dehydrogenase Phosphate 1 Deficiency (PDP1)||Sussex Spaniels
|DNA (mouth swabs)||Animal Health Trust,
|Polyneuropathy, neuropathy||Greyhound||DNA (blood, mouth swabs)||Optigen,
|Spinal Muscular Atrophy||Maine Coon||DNA (blood, mouth swabs)||Antagene|
# testing recommended but not required for the Kennel Club Assured Breeder Scheme
Animal Health Trust http://www.aht.org.uk/cms-display/genetics_tests.html
Langford Veterinary Services http://www.langfordvets.co.uk/lab_pcr_tests.htm#gen
University of Missouri / Orthopaedic Foundation for Animals http://www.offa.org/dnatesting/dm.html
University of Minnesota http://www.vdl.umn.edu/ourservices/canineneuromuscular/canineneuro/home.html
Universiteitskliniek voor Gezelschapsdieren, DNA diagnostiek, Q. Stassen, PO box 80.154, NL-3508 Utrecht email@example.com