The patient history may reveal other family members with ALS if the problem was inherited. In the early disease stages, the patient may report asymmetrical weakness first noticed in one limb. He also usually reports fatigue and easy cramping in the affected muscles. Inspection may reveal fasciculations in the affected muscles if these muscles aren't concealed by adipose tissue and muscle atrophy. Fasciculations and atrophy are most obvious in the feet and hands.
As the disease progresses, the patient may report progressive weakness in muscles of the arms, legs, and trunk. Inspection reveals atrophy and fasciculations. Neurologic examination often reveals brisk and overactive stretch reflexes. Muscle strength tests confirm the reported muscle weakness.
When the disease progresses to involve the brain stem and the cranial nerves, the patient has difficulty talking, chewing, swallowing and, ultimately, breathing. In these patients, auscultation may reveal decreased breath sounds.
In some patients (about 25%), muscle weakness begins in the musculature supplied by the cranial nerves. When this occurs, initial patient history reveals difficulty talking, swallowing, and breathing. Occasionally, the patient may report choking. Inspection may reveal some shortness of breath and, occasionally, drooling.
EPIDEMIOLOGY & DEMOGRAPHICS
INCIDENCE: 0.5 to 2 cases/100,000 persons. Onset is usually between the ages of 50 and 70 years. The male:female ratio is 2:1.
PREVALENCE: 5 in 100,000 persons
GENETICS: 5% of cases are familial in an autosomal dominant pattern; some but not all families map to the gene for superoxide dismutase on chromosome 21.
PHYSICAL FINDINGS & CLINICAL PRESENTATION
• Lower motor neuron signs (asymmetric muscle weakness, wasting, fasciculations)
• Upper motor neuron signs (Babinski’s sign, clonus)
• Unexplained weight loss, slurring of speech
• Difficulty walking and swallowing
• The cause of ALS is unknown. Mutations in a single gene can initiate a process that leads to the selective degeneration of motor neurons.
• A familial form is transmitted in an autosomal dominant pattern.
• Ingestion of the cycad nut may be associated with ALS-Parkinson-dementia complex of Guam.
• Cervical spondylotic myelopathy
• Spinal stenosis with compression of lumbosacral nerve roots
• Lead axonal neuropathy
• Multifocal motor neuropathy with conduction block
• Syphilitic myelitis with amyotrophy
• Delayed effects of electrical injury to spinal cord
• Late-onset hexosaminidase deficiency
• Polyglucosan body disease
• Spinal AV malformations
• EMG and nerve conduction studies
• Lumbar puncture and CSF analysis
• Bone marrow examination to exclude myeloma, Waldenstrom disease, or other lymphoproliferative disease if CSF protein content exceeds 75 mg/dl
• Serum protein immunofixation electrophoresis on warm blood (allowed to clot at 37° C to avoid loss of the monoclonal proteins as a cryoglobulin)
• Quantitative immunoglobulin analysis
• Antibodies to GM1 and myelin-associated glycoprotein
• Heavy metal testing: generally not indicated
• Chest x-ray examination
• MRI in selected cases to exclude disorders listed in differential diagnosis
• Modified barium swallow to evaluate risk of choking
Treatment, which is supportive and based on the patient's symptoms, may include diazepam, dantrolene, or baclofen for spasticity and quinidine for relief of painful muscle cramps that occur in some patients. I.V. or intrathecal administration of thyrotropin-releasing hormone temporarily improves motor function in some patients but has no long-term benefits. Klonopin or inderal may be given for cerebellar dysfunction. Rehabilitative measures can help patients function effectively for a longer period, and mechanical ventilation can help them survive longer.
• Family planning for chronic illness (discussion of living will, financial matters, and DNR orders)
• Emotional support for patient and family members
• Prosthetic devices (e.g., wheelchair)
• Discussion regarding preparation for tracheostomy
• Noninvasive positive-pressure ventilation for patients with ALS and respiratory insufficiency
• Physical therapy, speech therapy
ACUTE GENERAL Rx
Riluzole (Rilutek) is the only medication approved to extend survival in patients with ALS. Dosage is 50 mg q12h, at least 1 hr before or 2 hr after meals. Benefits are marginal (prolonged survival by 3-6 months) and the medication is very expensive.
• Supportive care to prevent complications (aspiration, decubitus ulcerations, malnutrition)
• Relief of spasticity with baclofen, dantrolene, or diazepam
• Treatment of depression
• Mean duration of symptoms is 2 to 4 yr.
• About 20% of patients survive >5 yr.
• There have been reports of spontaneous arrest of the disease.
• Referral to a neurologist is recommended to confirm diagnosis.
• Surgical referral for tracheostomy may be needed to prevent aspiration as the disease progresses.
• Psychiatric referral for counseling on associated anxiety and depression may be necessary in selected cases.
• Nursing home placement and/or hospice may be necessary in advanced stages of the disease.
• GI referral for PEG placement may be needed.
Amyotrophic lateral sclerosis
Lateral sclerosis means disease of the lateral corticospinal tracts (i.e. one cause of spastic paraparesis). Amyotrophy means muscle atrophy, i.e. wasting, unusual in most other forms of spastic tetraparesis or paraparesis. The course is progressive spastic tetraparesis or paraparesis with added lower motor neurone signs and fasciculation. ALS is the term used for MND in the USA.
Amyotrophic lateral sclerosis (ALS) is a progressive neuromuscular condition affecting upper and lower motor neurons, characterized pathologically by degeneration of motor neurons in the brainstem and spinal cord and by degeneration of neurons in the motor cortex and corticospinal tracts.
Lou Gehrig’s disease
Signs and symptoms of ALS depend on the location of the affected motor neurons and the severity of the disease. Keep in mind that muscle weakness, atrophy, and fasciculations are the principal symptoms of the disorder, the disease may begin in any muscle group and, eventually, all muscle groups become involved. Unlike other degenerative disorders such as Alzheimer's disease, ALS doesn't affect mental function.