Neuromuscular disorders in the cat: clinical approach to weakness

Abstract

Practical relevance: Weakness is a relatively common clinical presentation in feline medicine and can be caused by primary neuromuscular disease or by diseases of other body systems affecting the neuromuscular system secondarily. Successful work-up relies on a thorough clinical and neurological examination, and logical problem solving, based on an understanding of the underlying neuroanatomical and pathophysiological mechanisms.

Clinical challenges: Feline neuromuscular diseases can be a diagnostic challenge. On initial inspection, the presenting signs can mimic disorders of other body systems, particularly cardiovascular, pulmonary and orthopaedic disease, or may be confused with systemic illnesses. Additionally, because many different pathologies of the feline neuromuscular system converge to a similar clinical phenotype, further diagnostic steps such as electrodiagnostics, cerebrospinal fluid analysis, and muscle and nerve biopsies must be considered even after neuromuscular dysfunction has been identified.

Audience: This review provides a framework for the clinical approach to the weak cat and gives a practical summary of neuromuscular diseases for the general practitioner and specialist alike.

Evidence base: Many diseases affecting the feline neuromuscular system have been well described in the veterinary literature, mostly based on retrospective case reports and series. The evidence base for the treatment of feline neuromuscular diseases remains very limited.

FIG 1

Generalised polyneuropathy in a kitten. The patient is tetraparetic. Note the raised scapulae and inability to lift the head

FIG 2

Immunemediated conditions responsive to immunosuppressive or immunomodulatory treatment. (a) Teased nerve fibres affected by inflammatory demyelinating polyneuropathy in a domestic shorthair cat. (b, c) Polymyositis. (b) Invasion of myofibres (*) and endomysial interstitium by mononuclear cells (haematoxylin and eosin [HE]). (c) Confirmation of an immune-mediated pathology is based on absence of infectious organisms, negative titres and PCR, and evidence of invasion of predegenerate fibres (arrow; modified Gomori stain)

FIG 3

Muscle processing. Qualitative studies enrol standard HE staining (a), but also special stains such as modified Gomori stain to highlight mitochondrial features (b; arrow indicates subsarcolemmal mitochondrial aggregates). This latter stain, as well as the stains for polysaccharide and lipid storage, do not work in formalin-fixed paraffin-embedded tissue. Hence, special care should be taken to ensure the correct handling and shipping of fresh samples. Quantitative investigations are accomplished by myofibre typing (c). In the feline limb muscles type II fibres predominate (inset image; green fibres). Muscle diseases may also lead to changes in myofibre diameter, confirmed by myofibre histograms (d)

FIG 4

Morphological analysis of peripheral nerves. Routinely, examination for nerve fibre alterations, and vascular and infiltrative diseases is carried out on semi-thin sections (a) (paraphenylenediamine). (b) Small fibre diseases and lysosomal storage disorders require investigation at electron microscopic level (this shows an ultrathin section). (c) Nerve fibre teasing preparations are superior for the detection of demyelinating diseases; this image shows teasing with micropincette after osmium impregnation. All these procedures rely on proper handling of samples, for which guidance should be sought from the specialised laboratory

FIG 5

Examples of inherited and breed-related neuropathies. (a) Axonal polyneuropathy in Birman cats. Teased fibre preparations show axonal atrophy with secondary myelin sheath pathology such as widening of the node of Ranvier (upper picture) and formation of bands of Büngner (lower picture). Due to progressive fibre loss the muscle becomes denervated and shows angular atrophied fibres (inset; type II fibres in brown). (b) Bengal cat polyneuropathy. Cats present within the first year of life with axonal changes and loss of fibres (semi-thin section; azure blue/safranin stain). (c) Hypertrophic neuropathy. This unusual type of demyelinating neuropathy is characterised by ‘onion bulb’-like Schwann cell proliferates (semi-thin section; azure blue)

FIG 6

Common metabolic causes of neuromuscular disease. (a) Diabetes mellitus is frequently associated with peripheral nerve disease; this specimen is from a 9-year-old British Shorthair cat with chronic diabetic neuropathy. (b) Electrolyte imbalance may culminate in rhabdomyolysis but in the vast majority of cases leads to minor muscle changes, such as occasional fibre atrophy (left picture; HE; white arrow), with or without mitochondrial prominence (right picture; modified Gomori stain; black arrow); these preparations were taken from a domestic shorthair cat with hypokalaemia. Definitive diagnosis requires multimodal testing