Feline neuromuscular diseases may be classified according to their location as (1) those involving peripheral nerves and/or nerve roots (or neuropathies), (2) those involving the neuromuscular junction (or "junctionopathies"), and (3) those that involve muscle (or myopathies). Each of these neuromuscular diseases will produce clinical signs of lower motor neuron (LMN) dysfunction, however significant variation in clinical signs may occur. Neuromuscular diseases result in varying degrees of paresis, muscle atrophy, hyporeflexia, and hypotonia. Hyporeflexia, hypotonia, ataxia and proprioceptive positioning deficits are most characteristic of peripheral nerve disease. Some primary muscle disorders may be characterized by muscle hypertrophy rather than atrophy. Neuromuscular junction disorders may result in a variety of clinical signs, that range from flaccid paralysis to exercise-induced weakness.

Cervical ventroflexion is a dramatic sign of generalized neuromuscular weakness in cats. The chin usually rests near the thoracic inlet, with the eyes positioned dorsally to maintain a straight-ahead gaze. Other common physical examination findings are a slight protrusion of the dorsal aspects of the scapulae when weight is placed on thoracic limbs, and a stiff thoracic limb gait. A crouched, wide based stance is often seen in pelvic limbs. Possible causes to consider for this posture are: subacute or chronic organophosphate toxicity, potassium-depletion myopathy, thiamine-responsive neuromuscular weakness, hyperthyroidism, immune-mediated (idiopathic) polymyositis, myasthenia gravis, polyneuropathy, hypernatremic polymyopathy, ammonium chloride toxicity, hereditary myopathies (Burmese, Devon Rex), hypocalcemia, and portosystemic encephalopathy.

Megaesophagus has rarely been reported in cats, although a predisposition has been noted in Siamese and Siamese-related breeds. In most cats the cause of acquired megaesophagus is unknown; however, the condition has been associated with several systemic neuromuscular disorders, such as myasthenia gravis, botulism, polymyositis, polyradiculoneuritis, tick paralysis, lead toxicosis, feline muscular dystrophy-like conditions, laryngeal paralysis/polyneuropathy complex, and glycogen storage diseases.

Diagnosis of feline neuromuscular diseases requires a complete neurological examination, minimum data base (full blood count, serum biochemistry panel, urinalysis, thoracic radiographs, abdominal ultrasound), electrophysiological evaluation, and muscle/nerve biopsies.

NEURONOPATHIES

Motor Neuron Disease

Motor neuron disease (MND) is characterized by degeneration and loss of motor neurons. Adult-onset MND has been reported in cats.

Feline Dysautonomia

Feline dysautonomia (Key-Gaskell syndrome) is a generalized disorder of autonomic. There is no age or breed predilection for this disease. The disorder is a neuronal disorder; however, clinical signs relate more to autonomic dysfunction, and are largely gastrointestinal in nature.

Tetanus

Although cats are supposedly resistant to the effects of the Clostridium tetani exotoxin, several cases of tetanus have been reported in cats. Localized tetanus has been reported in cats, where the disease is characterized by tonic rigidity of a single limb.

INHERITED POLYNEUROPATHIES

Sphingomyelinase-deficiency Polyneuropathy

Niemann-Pick disease (NPD) is an autosomal-recessive lysosomal-storage disease characterized by a deficiency of sphingomyelinase. A NPD-associated primary polyneuropathy has been described in 3 Siamese cats (2-5 months of age).

Hyperchylomicronemia-associated Neuropathy

Inherited primary hyperchylomicronemia is a suspected autosomal-recessive disease characterized by fasting hyperlipemia, lipemia retinalis, and peripheral neuropathy. Clinical signs are usually not seen prior to 8 months of age.

Hyperoxaluric Peripheral Neuropathy

Primary hyperoxaluria is a suspected autosomal-recessive disease of domestic shorthair cats in Great Britain. Acute renal failure, in cats between 5 and 9 months of age, results from renal tubular deposition of oxalate crystals. Severe generalized LMN weakness accompanies the renal failure

Hypertrophic Polyneuropathy

Hypertrophic polyneuropathy has been described in 2 unrelated 12-month-old cats. Affected cats had intention tremors, decreased postural reactions, hyporeflexia, and mild sensory loss.

Birman Cat Distal Polyneuropathy

A degenerative polyneuropathy has been reported in several litters of Birman cats bred from the same parents. A recessive mode of inheritance is suspected

ACQUIRED POLYNEUROPATHIES

Diabetic Polyneuropathy

A distal polyneuropathy has been reported in cats with uncontrolled or poorly controlled diabetes mellitus. Neurological abnormalities include a plantigrade stance, progressive paraparesis, muscle atrophy, and patellar hyporeflexia. The cause of this polyneuropathy is incompletely understood.

Ischemic Neuromyopathy

Ischemic neuromyopathy occurs in cats with cardiomyopathy, subsequent to thrombosis of the caudal aorta or its principal branches. The ischemic injury to both muscle and peripheral nerve is produced by collateral circulation vasoconstriction induced by substances such as serotonin and thromboxane A2 released by platelets trapped in the thrombus.

Trauma

Brachial plexus avulsion produced by severe thoracic limb abduction with secondary stretching or tearing of nerve roots is a commonly occurring peripheral nerve injury of cats. Sacroiliac fracture/dislocation, sacral fracture, or caudal vertebral fracture/luxation may result in damage to the sixth and seventh lumbar and first 2 sacral nerve roots.

Mononeuropathies of radial nerve and sciatic nerve occur in cats following mechanical blows, gunshot wounds, fractures, pressure and stretching.

Neoplasia

Feline malignant lymphoma, often associated with FeLV infection, may involve nerve roots or peripheral nerves. Other primary peripheral nerve neoplasms rarely are seen in cats.

Toxic Neuropathies

Drug-induced neuropathies are not well defined in cats. It is likely that as chemotherapeutic treatment of neoplasia becomes more aggressive, more drug-induced neuropathies will be recognized (e.g., vincristine). A delayed neurotoxicity may occur in cats days or weeks after minimal exposure to organophosphates. Lesions are associated with distal degeneration of motor nerves that begins in the periphery (dying-back axonopathy). Peripheral neuropathy may occur sporadically with spontaneous lead-poisoning. Megaesophagus and partial laryngeal paralysis, believed to be due to lead-associated neuropathy, have been reported in a cat.

Laryngeal Paralysis

Acute laryngeal paralysis was diagnosed in 3 cats with signs of upper airway obstruction, including dysphonia, absence of purring, and progressive inspiratory dyspnoea. Varying degrees of paralysis of vocal folds and arytenoid cartilages were noted. One cat was positive for FeLV. Underlying responsible mechanisms were not defined.

Miscellaneous Peripheral Polyneuropathies

Single case reports exist of a variety of peripheral neuropathies in cats. These include: 2 cats with histologically-confirmed inflammatory polyneuropathy (a chronic relapsing polyradiculoneuritis) and an acute polyneuritis, an idiopathic chronic relapsing polyneuropathy responsive to immunosuppressive glucocorticoid therapy and an acute brachial plexus neuropathy with a suspected relationship to a previous vaccination. It is reasonable to expect that there will be future reports regarding FeLV and FIV infections and their association with neuromuscular diseases of cats, particularly polyneuropathies. Paraneoplastic neuropathies and radiation-induced neuropathies of cats are likely to be reported in the future.

"JUNCTIONOPATHIES"

Myasthenia Gravis

Myasthenia gravis is a condition that results from either a congenital or an acquired reduction of acetylcholine receptors of neuromuscular junctions. Both forms have been reported to occur in cats. Two of the acquired cases were associated with thymoma, and another with a cystic thymus. Acquired myasthenia gravis has been reported frequently in Abyssinians and Somalis (closely related to Abyssinians), which may suggest a possible association with the major histocompatibility complex, as in humans. The most consistent signs in cats include tremors, initial stiffness with progression to generalized weakness on exercise, cervical ventroflexion, dysphagia, dysphonia, ptyalism, facial weakness, and dyspnea. Overt megaesophagus or esophageal hypomotility is common.

Miscellaneous "Junctionopathies"

Abnormalities in neuromuscular junction function may also result from tick paralysis, administration of certain drugs, selected toxins, or from envenomation. Botulism has not been reported as a clinical entity in cats, however, it may be produced experimentally in cats. Paraneoplastic junctionopathies are likely to be reported in cats in the future. The association of acquired myasthenia gravis and thymoma in cats is a good example of a paraneoplastic junctionopathy.

INHERITED MYOPATHIES

Muscular Dystrophy

Muscular dystrophy of cats has been reported. To date all affected cats have been males, which suggests an X-linked inheritance. Clinical signs may first be seen in cats at 5-6 months of age, and include generalized skeletal muscle hypertrophy, excessive salivation, reduced exercise tolerance, stiff gait and "bunny-hopping" when running, difficulty in jumping, adducted hocks, cervical rigidity, vomiting/regurgitation, and partial protrusion of the tongue.

Hereditary Myopathy of Devon Rex Cats

This is a congenital myopathy of Devon Rex cats. Characteristic clinical signs, including ventroflexion of the head and neck, protrusion of the scapulae, and esophageal weakness, all reflect dysfunction of striated muscle, while skeletal muscle pathology is suggestive of a muscular dystrophy.

Myotonia Congenita

Myotonia congenita has been reported in cats. The mode of inheritance and actual molecular defect have not been identified. Clinical signs in affected kittens include a stiff choppy gait that improves with exercise, abducted limbs, enlarged proximal appendicular muscles, difficulty in opening the mouth, enlargement and percussion dimpling of the tongue, delayed relaxation of the facial muscles after activity, dysphonia, stridor, and difficulty eating.

Miscellaneous Inherited Myopathies

Nemaline myopathy and myositis ossificans have been reported in cats. Glycogen storage diseases (or glycogenoses) are rare disorders of cats. Deficient activity of one of the enzymes involved in glycogen degradation or synthesis results in inadequate glycogen utilization, and in glycogen accumulation within various tissues, including muscle. There are several reports of glycogenoses in cats. Glycogen storage disease Type IV has been reported in 3 young related Norwegian forest cats.

ACQUIRED MYOPATHIES

Infectious Polymyositis

Infectious myositis may occur in association with bacterial infection, migrating parasites, or protozoan disease. Whilst cats are the only definitive hosts for Toxoplasma gondii (and a majority of cats may have serum antibodies to this organism) muscle involvement is not an outstanding feature of Toxoplasma infection of cats. Experimental inoculation of cats with the protozoan Neospora caninum may produce fatal, necrotizing encephalomyelitis, polymyositis, pneumonia and hepatitis. Naturally-occurring feline neosporosis has not been reported to date.

Immune-mediated (or Idiopathic) Polymyositis

Polymyositis occurs sporadically in cats, occasionally in association with thymoma. Inflammatory infiltrates are predominantly mononuclear with small lymphocytes and macrophages. Neutrophils are seen infrequently. Eosinophils are rarely seen. Clinical signs are characterized by a persistent cervical ventroflexion, appendicular weakness, painful muscles, and exercise intolerance. Serum levels of creatine kinase and aldolase are elevated. A report of polymyositis in a cat in association with myasthenia gravis and thymoma further supports an immune-mediated etiology.

Potassium-depletion Polymyopathy

This acute feline polymyopathy, resulting from a severe total body potassium depletion, is usually secondary to a reduced potassium intake and increases in the fractional excretion of potassium in urine (due to renal dysfunction). Clinical signs include muscle weakness, cervical ventroflexion, stiff and stilted gait, and muscle pain. A similar syndrome with a suspected hereditary basis has been reported to occur in Burmese cats.

Miscellaneous Myopathies

There are a number of case reports of muscle-related diseases of cats. Descriptions include: nutritional myopathy secondary to vitamin E deficiency myositis secondary to Clostridium chauvoei and Clostridium septicum infections fibrotic myopathy of the semitendinosus muscle and quadriceps contracture secondary to trauma. Episodic weakness and signs of depression have been noted in young domestic short-hair cats (less than 1 year of age) with hypernatremia secondary to hypodipsia. The most common clinical sign of hypernatremic myopathy is ventral flexion of the neck. Causes of hypodipsia include lesions of the hypothalamus, and mechanical inability to swallow--a potentially serious complication of hypertrophic feline muscular dystrophy. The association between myositis and malignant neoplasia (paraneoplastic myopathy) is likely to be reported in the future. Myopathies in cats may occur in association with FeLV or FIV infections (e.g., FeLV-associated immunosuppression may enable encystment of Sarcocystis spp. in muscle).