Motor neuron diseases are characterized by weakness and wasting of affected muscles, without accompanying sensory changes. Werdnig-Hoffman disease and Kugelberg-Welander syndrome occur in infants or children. Motor neuron disease in adults generally commences between 30 and 60 years of age. There is degeneration of the anterior horn cells in the spinal cord, the motor nuclei of the lower cranial nerves, and the corticospinal and corticobulbar pathways. The disorder
is usually sporadic, but familial cases may occur.
Five varieties have been distinguished on clinical grounds.
A. Progressive Bulbar Palsy: Bulbar involvement predominates owing to disease processes affecting primarily the motor nuclei of the cranial nerves.
B. Pseudobulbar Palsy: Bulbar involvement predominates in this variety also, but it is due to bilateral corticobulbar disease and thus reflects upper motor neuron dysfunction.
C. Progressive Spinal Muscular Atrophy: This is characterized primarily by a lower motor neuron deficit in the limbs due to degeneration of the anterior horn cells in the spinal cord.
D. Primary Lateral Sclerosis: There is a purely upper motor neuron deficit in the limbs.
E. Amyotrophic Lateral Sclerosis (Lou Gehrig’s Disease): A mixed upper and lower motor neuron deficit is found in the limbs. This disorder is sometimes associated with dementia or parkinsonism.
A. Symptoms and Signs: Difficulty in swallowing, chewing, coughing, breathing, and talking (dysarthria) occur with bulbar involvement. In progressive bulbar palsy, there is drooping of the palate, a depressed gag reflex, pooling of saliva in the pharynx, a weak cough, and a wasted, fasciculating tongue. In pseudobulbar palsy, the tongue is contracted and spastic and cannot be moved rapidly from side to side. Limb involvement is characterized by motor disturbances
(weakness, stiffness, wasting, fasciculations) reflecting lower or upper motor neuron dysfunction; there are no objective changes on sensory examination, though there may be vague sensory complaints. The sphincters are generally spared.
The disorder is progressive and usually fatal within 3–5 years; death usually results from pulmonary infections. Patients with bulbar involvement generally have the poorest prognosis.
B. Laboratory and Other Studies: Electromyography may show changes of chronic partial denervation, with abnormal spontaneous activity in the resting muscle and a reduction in the number of motor units under voluntary control. In patients with suspected spinal muscular atrophy or amyotrophic lateral sclerosis, the diagnosis should not be made with confidence unless such changes are found in at least three extremities. Motor conduction velocity is usually normal
but may be slightly reduced, and sensory conduction studies are also normal. Biopsy of a wasted muscle shows the histologic changes of denervation. The serum creatine kinase may be slightly elevated but never reaches the extremely high values seen in some of the muscular dystrophies.
The cerebrospinal fluid is normal.
A familial form of amyotrophic lateral sclerosis has been described with autosomal dominant inheritance, related to mutations in the copper-zinc superoxide dismutase gene on the long arm of chromosome 21. X-linked bulbospinal neuronopathy is associated with an expanded trinucleotide repeat sequence on the androgen receptor gene and carries a more benign prognosis than other forms of motor neuron disease. There have been recent reports of juvenile spinal muscular atrophy due to hexosaminidase deficiency, with abnormal findings on rectal biopsy and reduced hexosaminidase A in serum and leukocytes. Pure motor syndromes resembling motor neuron disease may also occur in association with monoclonal gammopathy or multifocal motor neuropathies with conduction block. A motor neuronopathy may also develop in Hodgkin’s disease and has a relatively benign prognosis.
Riluzole, which reduces the presynaptic release of glutamate, may slow progression of amyotrophic lateral sclerosis. There is otherwise no specific treatment except in patients with gammopathy, in whom plasmapheresis and immunosuppression may lead to improvement.
Therapeutic trials of various neurotrophic factors to slow disease progression are, however, in progress. Symptomatic and supportive measures may include prescription of anticholinergic drugs (such as trihexyphenidyl, amitriptyline, or atropine) if drooling is troublesome, braces or a walker to improve mobility, and physical therapy to prevent contractures. Spasticity may be helped by baclofen or diazepam. A semiliquid diet or nasogastric tube feeding may be needed if dysphagia is severe. Gastrostomy or cricopharyngomyotomy is sometimes resorted to in extreme cases of predominant bulbar involvement, and tracheostomy may be necessary if respiratory muscles are severely affected; however, in the terminal stages of these disorders, the aim of treatment should be to keep patients as comfortable as possible.
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