Amyotrophic Lateral Sclerosis (ALS) is a progressive neurodegenerative disease primarily affecting the motor neurons in the brain and spinal cord. This disease causes the gradual atrophy and loss of function of motor neurons, ultimately leading to muscle weakness, paralysis, and in severe cases, life-threatening complications. The progression of ALS varies widely; some patients may deteriorate rapidly within a few years, while others experience a slower progression. Currently, there is no cure, but early diagnosis and multidisciplinary treatment can effectively delay symptom progression and improve patients' quality of life.
ALS mainly affects neurons controlling voluntary muscle movements, including upper motor neurons (located in the brain and spinal cord) and lower motor neurons (located in the spinal cord and brainstem). When these neurons are damaged, muscles cannot receive nerve signals, leading to atrophy and loss of control. The disease usually manifests in middle-aged or elderly individuals, but a small number of cases occur in younger populations. Statistically, approximately 2 to 3 per 100,000 people are diagnosed each year worldwide, with a male-to-female ratio of about 2:1. Although the exact cause of ALS remains unclear, interactions between genetic, environmental, and biological factors are considered key contributors.
About 5-10% of ALS patients have a family history of the disease, with approximately 20% associated with specific gene mutations, such as SOD1, C9ORF72, and TARDBP. These genetic abnormalities may lead to protein accumulation or cellular metabolic dysregulation, triggering neuronal death. Hereditary ALS often manifests at a younger age, with multiple generations affected within families.
The causes of sporadic ALS are more complex, potentially involving multiple mechanisms including oxidative stress, protein misfolding, and neuroinflammation. Recent research suggests that dysfunction of the intracellular glutathione system may reduce antioxidant capacity, accelerating neuronal damage.
Early symptoms of ALS are often subtle and easily overlooked. Patients may initially experience unilateral limb weakness, such as difficulty controlling hand muscles, leading to problems with writing or buttoning clothes. About 40% of patients first notice symptoms in the hand, while 30% begin with leg weakness, such as stumbling or gait instability. Additionally, some patients may exhibit muscle fasciculations or atrophy, but these signs can be mistaken for fatigue or sports injuries in the early stages.
Speech and swallowing functions may also be affected. Approximately 25% of patients experience slurred speech (dysarthria), hoarseness, or slow speech early on, impacting communication. Dysphagia may cause prolonged eating times or a sensation of food sticking in the throat.
As the disease progresses, symptoms spread throughout the body. Patients may lose the ability to walk and rely on wheelchairs. Weakness of respiratory muscles can lead to inadequate ventilation, requiring ventilatory support. Severe impairment of speech and swallowing may necessitate gastrostomy or speech aids for communication and nutrition.
Diagnosing ALS involves ruling out other neurological diseases, requiring multiple steps. First, neurologists conduct detailed medical histories and physical examinations, assessing muscle strength, reflexes, and signs of muscle atrophy. Electrophysiological tests such as electromyography (EMG) and nerve conduction studies help confirm the extent of motor neuron damage.
Imaging tests like MRI and muscle/neural biopsies are used to exclude multiple sclerosis, spinal cord injuries, or other neurodegenerative diseases. Blood tests screen for genetic mutations or metabolic abnormalities. The diagnosis relies on the "El Escorial criteria," which require evidence of simultaneous upper and lower motor neuron involvement across at least two different spinal segments.
The only FDA-approved drugs currently are riluzole and edaravone, which can slow neuronal damage but do not halt disease progression. Riluzole works by inhibiting excessive glutamate release, reducing oxidative stress in neurons, while edaravone has antioxidant properties. Clinical trials show these drugs can extend survival by approximately 2-3 months on average.
Symptom management remains central to treatment. Muscle spasticity can be alleviated with baclofen or diazepam; sialorrhea (excess saliva) can be managed with anticholinergic medications. As respiratory function declines, bronchodilators or ventilatory support may be necessary. Nutritional support involves dietitians designing high-calorie diets based on swallowing ability; in severe cases, gastrostomy feeding is recommended.
Stem cell therapy and gene therapy are current research hotspots. Stem cell transplantation aims to replace damaged motor neurons, while gene therapy targets correcting mutations in hereditary ALS. Additionally, neuroprotective agents like ciltacabtagene autotemcel are in clinical trials, attempting to slow neuronal death by modulating immune responses.
There is currently no evidence that specific measures can prevent ALS, but avoiding known risk factors may reduce potential risks. It is recommended to minimize exposure to pesticides, heavy metals, and industrial chemicals, especially for those engaged in agriculture or chemical industries. Maintaining regular exercise and a balanced diet helps preserve neuronal antioxidant capacity.
Individuals with a family history should undergo genetic counseling and testing, particularly if carrying known mutations. Regular neurological check-ups are advised; early evaluation is recommended if unexplained muscle weakness or cramps occur. Although prevention is not fully possible, early detection and treatment can significantly improve quality of life.
If you experience the following symptoms, seek medical attention promptly: persistent unexplained muscle weakness lasting several weeks, unexplained weight loss, significant decline in hand coordination, or persistent hoarseness when speaking. While these symptoms may be caused by other conditions, early assessment can help exclude or confirm ALS and initiate treatment.
If there is a family history of ALS, even mild symptoms should prompt genetic risk assessment. Doctors may recommend nerve conduction studies or genetic testing to differentiate ALS from other motor neuron diseases such as spinal muscular atrophy (SMA) or multiple sclerosis (MS).
Early symptoms of ALS, such as muscle weakness or tremors, can be confused with multiple sclerosis or spinal cord injuries. The key is to evaluate the selective involvement of motor neurons, such as fine motor impairment in the hands accompanied by fasciculations, which typically require electrophysiological and neuroimaging examinations for confirmation. Early persistent unexplained muscle atrophy warrants prompt medical consultation.
What emerging treatments are available to slow disease progression?Recent studies show that, besides traditional drugs like riluzole, antioxidants such as edaravone have been proven to delay functional decline in some patients. Gene therapy and neuroprotective treatments are in clinical trials, and patients should discuss the latest options and risks with their healthcare providers.
What measures in daily care can effectively improve patients’ quality of life?Physical therapists recommend regular passive exercises to prevent joint contractures, while speech therapists assist with swallowing and communication training. Using assistive devices such as speech synthesizers and electric wheelchairs can enhance independence. Family members should learn proper transfer techniques to avoid secondary injuries.
Does dietary adjustment help delay disease progression?Although there is no direct evidence that specific diets can cure ALS, balanced nutrition helps maintain muscle energy supply and slow muscle atrophy caused by malnutrition. Patients with swallowing difficulties may need soft or semi-liquid foods, and consulting a dietitian for personalized plans is advisable.
What psychological support resources are available for patients and families?Patients often experience anxiety due to the incurable nature of the disease. Participating in support groups or consulting psychologists is recommended. In Taiwan, several ALS patient associations offer free counseling and resource links. Hospital social workers can assist with applying for long-term care subsidies, and psychological support should be integrated with medical care.
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