Amyotrophic lateral sclerosis
ALS
ALS is a progressive and fatal degenerative disease of motor neurons. ALS is caused by the degeneration of motor neurons in the central nervous system that control skeletal muscle. Due to the degeneration and death of upper and lower motor neurons, muscles gradually weaken and atrophy. Finally, the brain completely loses its ability to control voluntary movements. This eventually leads to impaired pronunciation, swallowing, and breathing functions.
In Europe and the United States, approximately 2.2 per 100,000 people are diagnosed with ALS each year. About 90% to 95% of people with ALS have an unknown cause, whereas the remaining 5% to 10% is thought to be related to genetic factors. Although there are more than 50 genetic mutations implicated, the outcome is that they all lead to the death of neurons that control muscles. The diagnosis of ALS is a clinical one, based on examination of the patient’s signs and symptoms and the exclusion of similarly presenting disorders.
At present, there is no cure for ALS. Most patients eventually die of respiratory failure. A drug called riluzole can extend survival by about 2 to 3 months. Non-invasive ventilation can improve the quality of life and prolong life. The average survival from onset to death is 3 to 4 years. About 10% of patients survive for more than ten years.
Epidemiology
Incidence of ALS has not been reported in many parts of the world. In Europe, about 2.2 per 100,000 people diagnosed each year. In the United States more than 5,600 people are diagnosed each year. There are about 200,000 patients in China, and this number is increasing year by year. ALS is categorized as a rare disease. However, it is the most common motor neuron disease.
Signs and symptoms
Early symptoms are difficult to detect. The earliest typical symptoms to present are usually marked muscle weakness and/or atrophy. Other overt symptoms include difficulty with swallowing, muscle spasms, or stiffness. Muscle weakness commonly affects the extremities, and patients may exhibit slurred speech. The early presentation of ALS depends on which motor neurons are affected first. About 75% of patients first experience symptoms in the arms and legs. People with leg weakness may fall or trip while walking or running, or drag their legs when walking. Another 25% of patients suffer from “medulla oblongata onset ALS,” which is characterized by dysarthria or dysphagia as primary manifestations. Speech may be slurred or have a “nasal” quality with phonation, or unintelligible. Other symptoms include loss of tongue flexibility. A very small proportion of patients have “respiratory onset ALS,” which is characterized by labored or difficulty breathing due to weakened intercostal muscles.
As the disease progresses, patients experience difficulty with exercise, dysphagia, and dysarthria. Symptoms of upper motor neuron involvement include muscle stiffness, spasms, exaggerated reflexes (hyperreflexia), and gag vomit reflection. A hallmark of upper motor neuron involvement is the presence of the “Babinski’s sign” which is typically absent in adults. Symptoms of lower motor neuron degeneration include muscle weakness and atrophy, and transient muscle twitching (fibrillation) that may be seen. About 15-45% of patients experience pseudobulbar symptoms — a neurological disorder characterized by emotional lability that includes uncontrollable laughter, crying, or smiling. The presence of upper and lower motor neuron signs should warrant suspicion of ALS with careful consideration and exclusion of other causes. For advanced ALS patients, though ventilators may relieve breathing problems and prolong survival, it may not slow the course of ALS. Most people with ALS die within 3 to 5 years of onset due to respiratory failure. The median survival from time of diagnosis is 39 months; about 4% of patients survive more than 10 years.
In the later stages of the disease, dysphagia may result in aspiration pneumonia. The patient may experience weight loss as the patient will have difficulty consuming food, therefore likely necessitating a feeding tube. As the diaphragm and intercostal muscles weaken, breathing also begins to weaken. Lung function indicators, such as vital capacity and inspiratory pressure, decrease. In patients with respiratory onset, these symptoms may precede the onset of the extremities.
Treatment
Current treatments are very limited. RiluzoleIt is a drug that can slightly improve the survival rate of patients with ALS. It prolongs survival by several months and may be more effective in prolonging survival in patients with bulbar onset disease.
Nusinersen is a recently developed drug and is the first drug to treat spinal muscular dystrophy and ALS. Nusinersen is an antisense oligonucleotide drug. It is reported that it reduces mortality and mitigates the risk of respiratory function loss, and improves motor function. However, it is not currently a routine treatment for spinal muscular dystrophy.
Other drugs are mostly used for symptomatic treatment such as to relieve muscle spasms or to reduce salivation and mucus production. Medications can also help patients relieve symptoms such as pain, depression, sleep disturbances, difficulty swallowing, constipation, etc. When patients with ALS have difficulty swallowing saliva, trihexyphenidyl or amitriptyline may be used.