Abstract
Neuromuscular diseases include: Neuropathies. Characterised by ataxia, paresis or paralysis with proprioceptive dysfunction, altered muscle tone, hypo or areflexia and muscle atrophy Impairment of sensation is variable.
The diagnosis of neuromuscular disease depends on full assessment of the patient and should include:
a complete physical and neurological examination
clinicopathological examination including haematology serum chemistries (especially creatine kinase [CK] and electrolytes)
electrodiagnostic testing: electromyography (EMG), nerve conduction velocity measurements, evoked potential recordings with repetitive nerve stimulation
muscle biopsy examination including histopathology and immunohistochemical analysis
special tests may include: muscle percussion, serology for pathogens eg, toxoplasma, measurement of acetylcholine receptor antibody and molecular techniques
Inherited neuropathies
Hyperoxaluric neuropathy
Cats with low concentrations of the enzyme D-glycerate dehydrogenase develop an unexplained axonopathy with lower motor neuron dysfunction. Affected cats excrete excessive L-glycerate in their urine, have an intermittent oxalaturia and develop oxalate crystals in the kidneys and renal failure. Affected cats are young and die from renal failure before 1 year of age.
Neuropathy associated with hyperchylomicronemia
Monoparesis, Horner's syndrome, facial and masticatory muscle paralysis may occur in cats with primary inherited hyperchylomicronemia due to compression of peripheral nerves by lipid granulomas. Affected cats have low lipoprotein lipase activity and elevated plasma triglyceride and cholesterol. Clinical signs resolve if cats are fed a low fat diet.
Neuropathy associated with sphingomyelinase deficiency
Progressive clinical signs of neuromuscular disease develop in 2–5 month old Siamese kittens. There is an autosomal recessive inherited deficiency of the enzyme sphingomyelinase which results in a demyelinating polyneuropathy. The affected cats have a progressive lower motor neuron paresis, muscle tremor and hepatosplenomegaly.
Distal axonopathy of Birman cats
Birman cats with this condition show a degenerative neuropathy of the sciatic nerves in addition to several areas in the brain and spinal cord. A proximal-distal selectivity of the peripheral nerves as well as the spinal cord lesions define the disorder as a dying back disease. The disease affects 6–10 week old male Birman cats which develop a progressive hind limb ataxia.
Acquired neuropathies
Ischaemic polyneuropathy
Thromboembolism of the terminal aorta occurs in cats with hypertrophic cardiomyopathy, leading to ischaemia of hind limb muscles and nerves. The ischaemia is produced by vasoconstriction of collateral circulation induced by serotonin and thromboxane A2 from platelets. Clinical signs include paresis/paraplegia with cold extremities, absent femoral pulses, firm painful muscles, absent sensation and signs of cardiomyopathy. Some cats recover but with some permanent disability and a high chance of recurrence.
Polyneuropathy associated with salinomycin
In 1995 there was an outbreak of neurological dysfunction in cats in the Netherlands and Switzerland. Signs ranged from mild paresis to severe tetraparesis, with respiratory and autonomic signs. Electrophysiological studies indicated the signs were due to a peripheral neuropathy. Histological studies confirmed the presence of a primary axonopathy with secondary destruction of myelin.
Studies confirmed contamination of the cats' food with salinomycin, an ionophore anticoccidial agent used in rearing broiler chickens.
Diabetic polyneuropathy
Cats with uncontrolled or poorly controlled diabetes mellitus may develop a distal polyneuropathy involving the hind limbs. There is a plantigrade posture, progressive paresis, hyporeflexia and muscle atrophy. If treated early and the diabetes is well controlled, most cats will show significant improvement and may return to normal.
Neoplasia
Peripheral nerves can be affected by primary neoplasms (neurofibroma, Schwannoma), compressed by adjacent neoplasms or infiltrated by neoplastic cells (lymphoma). There may be paresthesia and excessive licking at the site of the sensory dermatome as well as motor signs.
Trauma
Various traumatic injuries cause peripheral nerve dysfunction. The prognosis depends on the degree of axonal disruption. Nerve root avulsion has the worst prognosis. The severity of the injury should be assessed by clinical and neurological examination and electrophysiological testing. In stretch and compression injuries, recovery times vary from one week to several months. Demyelination is rapidly repaired but axonal disruption requires regeneration.
Inherited myopathies
Feline X-linked muscular dystrophy
This rare inherited disease, characterised by an absence of dystrophin, dramatic elevations in serum CK, and severe, generalised EMG changes, has been reported in young (<2 yrs) male cats. Signs include a ‘bunny-hopping’ gait, difficulty in walking and jumping, cervical rigidity, symmetrical muscle hypertrophy, tongue enlargement and tachypnea/dyspnea. Muscle biopsy shows gross muscle pallor and myofibre necrosis, phagocytosis, mineralisation and splitting on histopathology There is no effective treatment.
Laminin α2 (merosin) dystrophy
This disease has been described in two cats, both of which showed hind limb weakness (from 6 months of age), muscle atrophy, and hind limb contracture. Serum CK was elevated and dystrophic changes were present. Immunohistochemical stains confirmed a decreased α2 laminin.
Nemaline myopathy
This suspected inherited myopathy is characterised by large numbers of nemaline rods within myofibres and has been reported in related 6–18 month old cats. All cats showed a reluctance to walk and had a forced, rapid hypermetric gait. There was also muscle atrophy, tremors and hyporeflexia. Electrophysiology was normal and CK marginally elevated.
Generalised ossifying myositis
This is a non-neoplastic form of extraskeletal ossification, affecting skeletal muscle and connective tissue. Young cats present with weakness, stiffness, decreased limb movement and muscle pain. Radiography reveals extensive soft tissue mineralisation. On biopsy, muscles contain differentiated cartilage and bone without inflammation. There is no effective treatment and the prognosis is poor.
Myotonia
Myotonia is the continued active contraction of a muscle after the cessation of voluntary effort and is characterised by muscle spasm and stiffness. Hereditary myotonia has been reported in domestic shorthaired cats. Affected kittens have muscle hypertrophy and walk with an awkward stiff gait and abducted limbs. The mouth cannot be opened fully. There is sometimes mild dysphagia. Startling will often cause spasm of the facial muscles, and sometimes cats will fall into lateral recumbency with their legs stiff and extended.
During anesthesia a characteristic dimpling of the tongue and skeletal muscle is obtained after percussion, and electromyography confirms the presence of spontaneous waxing and waning high frequency discharge (the ‘dive-bomber’ sound) after insertion of the electrode. Clinical chemistry and hematology are normal. Histological examination shows variation in fibre size diameter, few central nuclei and/or proliferation of sarcolemmal nuclei. In other species, myotonic muscles have been shown to be hyperexcitable due to decreased chloride condition causing elevation of cell resting membrane resistance. Treatment is not required for mildly affected cats which are acceptable as ‘interesting’ pets.
Hereditary myopathy of the Devon Rex
Devon Rex myopathy is characterised by muscle weakness and tremor, and has an autosomal recessive mode of inheritance. Clinical signs first appear between 1 and 4 months of age, and include muscle weakness and tremor, especially of the head. Affected kittens walk with a high-stepping gait and develop ventroflexion of the head and neck with the chin tucked into the sternum. Kittens rest often during exercise and frequently adopt an unusual dog-begging posture when resting. Most have difficulty eating and drinking from a bowl, but will eat from a plate, sometimes resting the head on the floor while eating. The neck often remains flexed, and this position can cause difficulty in chewing and swallowing food. Death can occur from choking and asphyxiation.
The cause of the disease is not known. Serum CK is not elevated. Histopathological changes suggest a myopathy with more severe changes in the cervical and proximal limb muscles. Affected cats can have a reasonable quality of life.
Acquired myopathies
Hypokalaemic polymyopathy
There is a congenital form in Burmese cats, and an acquired form in other breeds associated with chronic renal disease. In Burmese kittens the defect causes a shift of potassium between the intracellular and extracellular compartments. In cats with renal insufficiency there is excessive potassium loss and inadequate dietary potassium intake. Affected cats develop generalised weakness with characteristic, persistent cervical ventroflexion, reluctance to move, poor exercise tolerance and muscle pain. Subclinical hypokalaemia may be present for some time but without obvious clinical signs. Severe hypokalaemia may also be associated with impaired renal function, weight loss and lethargy.
CK is elevated, and serum potassium is <3 mmol/l. Muscle biopsy may show evidence of myonecrosis. There is a rapid response to dietary supplementation with potassium gluconate (2–4 mmol potassium per kg daily in divided doses). A response is expected in 24–48 h. Severely affected cats may require intravenously administered potassium (0.5 mmol/kg/h).
Polymyositis and polymyopathy
Toxoplasma gondii can produce a polymyositis in affected cats, often in combination with respiratory and nervous signs.
A polymyopathy of unknown cause has been diagnosed in cats. The clinical signs include persistent ventroflexion of the neck, appendicular weakness, painful muscles and exercise intolerance. Serum CK is elevated and EMG evidence of muscle disease is present. Histological findings include myonecrosis, with lymphocytic infiltrates. An immune-mediated pathogenesis is suspected. Some cats recover spontaneously and others respond to glucocorticoid therapy.
Neuromuscular junction diseases
Myasthenia gravis
Myasthenia gravis (MG) is a rare disease in the cat. The number of functional acetylcholine receptors on the post-synaptic membrane of the neuromuscular junction is reduced. Autoantibodies against acetylcholine receptors have been measured in the acquired form. The mechanism that triggers such antibody production is unknown but sometimes there is a concurrent thymoma.
Generalised muscle weakness is brought on by exercise. Affected cats tire easily, show muscle tremors, and are reluctant to exercise. These cats often move with a crouching gait and then flop onto their sides with the head resting on the paws. Collapse may occur after only a few steps. Dyspnoea and an altered meow have been described and some cats show dysphagia and regurgitation of food.
A diagnosis of MG must be confirmed by intravenous administration of 0.2 to 0.5 mg of the cholinesterase inhibitor edrophonium chloride (Tensilon–Roche). An improvement in muscle strength will be seen for a short period (2 to 10 min).
Treatment is with long acting cholinesterase inhibitors. Pyridostigmine is administered orally at 0.5 to 3.0 mg/kg daily in divided doses; the dose is selected according to the response of the individual cat. Thymectomy or chemotherapy must be considered if thymoma is diagnosed. Prednisone (2 to 4 mg/kg) should be administered daily with a gradual reduction in dose over 6–8 weeks.
Organophosphate toxicity
A delayed form of neurotoxicity can occur in cats after prolonged exposure to organophosphate compounds, or even days to weeks after minimal exposure. The delayed form of toxicity is characterised by neuromuscular weakness.
Low serum cholinesterase values can confirm a diagnosis. In contrast to myasthenia gravis, signs worsen after edrophonium administration. Most cats improve without treatment, however diphenhydramine (4 mg/kg q 8 h) can improve the weakness and without re-exposure cats will return to normal.
Snake bite and tick paralysis
The neurotoxic components of some snake (Elapidae) venoms cause weakness and paralysis through their effect on the neuromuscular junction. There is also significant elevation of CK. Clinical signs of tick paralysis include weakness and paresis through the effect of neurotoxins on the neuromuscular junction.
Autonomic nervous system
Dysautonomia
In this disease of mostly young adult cats there is acute autonomic denervation syndrome with signs of depression, anorexia, constipation, a dry rhinarium, decreased tear production, megaesophagus, fixed dilated pupils and, less commonly, xerostomia, third eyelid prolapse, vomiting, bradycardia, urinary/fecal incontinence and anal areflexia. Signs reflect a decrease in the number of neurons within both the para-sympathetic and sympathetic ganglia, with milder involvement of the sensory ganglia and the ventral horn cells. Diagnosis is based on thoracic and abdominal radiographs, pharmacological testing of ocular function and decreased plasma catecholamine concentrations. Treatment is palliative and consists of fluid therapy, parenteral feeding, artificial tears, laxatives, physostigmine eye drops and bethanechol. The survival rate is poor (20–30% recovering). This disease was more common and severe in the early 1980s, but the signs have decreased in severity and now it is rare.