Overview

Amyotrophic Lateral Sclerosis (ALS), also known as Lou Gehrig’s disease, is a progressive neurodegenerative condition that primarily affects motor neurons in the brain and spinal cord. These motor neurons control voluntary muscle movements such as walking, speaking, swallowing, and breathing. As ALS progresses, these neurons deteriorate and die, leading to muscle weakness, atrophy, and eventually complete loss of voluntary movement. ALS does not typically affect mental abilities or senses, but it is a life-limiting condition with no known cure.

Causes

The exact cause of ALS remains unknown in most cases, but several factors have been associated with its development:

• Sporadic ALS: The most common form, accounting for 90-95% of cases, with no clear familial link.
• Familial ALS: About 5-10% of cases are inherited, usually linked to specific genetic mutations such as SOD1, C9orf72, TARDBP, and FUS genes.
• Genetic Mutations: Genetic testing can identify mutations in familial ALS and in some sporadic cases.
• Environmental Factors: Possible risk factors include exposure to toxins, heavy metals, military service, smoking, and head trauma, though definitive evidence is limited.
• Glutamate Toxicity: High levels of glutamate, a neurotransmitter, may contribute to nerve cell damage in ALS patients.
• Immune System Dysfunction: Some research suggests the immune system may attack healthy motor neurons, contributing to disease progression.

Symptoms

ALS symptoms typically develop gradually and worsen over time, affecting different muscle groups as the disease advances:

• Muscle Weakness: Often begins in the hands, arms, legs, or speech muscles, causing difficulties with everyday tasks.
• Muscle Twitching (Fasciculations): Involuntary muscle twitching, especially in arms, shoulders, or tongue.
• Muscle Cramps and Stiffness: Painful cramps and spasticity are common.
• Slurred Speech and Difficulty Swallowing (Dysphagia): As bulbar muscles are affected, speech and swallowing become impaired.
• Breathing Problems: As respiratory muscles weaken, breathing difficulties occur, often requiring ventilatory support in advanced stages.
• Progressive Paralysis: Gradual loss of voluntary motor function leads to complete paralysis over time.
• Normal Cognitive Function: In most cases, intellect, senses, and bladder/bowel functions are preserved, though some may experience frontotemporal dementia (FTD).

Diagnosis

There is no single test for ALS. Diagnosis is primarily clinical, supported by diagnostic testing to rule out other conditions:

• Neurological Examination: Detailed evaluation of muscle strength, reflexes, coordination, and muscle tone.
• Electromyography (EMG): Measures electrical activity in muscles and helps identify nerve damage characteristic of ALS.
• Nerve Conduction Studies (NCS): Evaluate nerve function and help exclude other neuropathies.
• Magnetic Resonance Imaging (MRI): Used to rule out structural causes like tumors or spinal cord compression.
• Blood and Urine Tests: Helps exclude other metabolic or infectious diseases.
• Genetic Testing: Recommended if there is a family history or early onset of symptoms.
• Lumbar Puncture (Rare): Sometimes performed to exclude inflammatory or infectious causes of motor neuron disease.

Treatment

Although there is no cure for ALS, treatment focuses on slowing disease progression, managing symptoms, and improving quality of life:

Medications

• Riluzole: The first FDA-approved drug that modestly prolongs survival by reducing glutamate activity.
• Edaravone: Approved to slow functional decline in some patients with early-stage ALS.
• Symptom-Specific Medications: Drugs to manage spasticity, pain, depression, drooling, and sleep disturbances.

Supportive Therapies

• Physical Therapy: Exercises to maintain mobility, reduce spasticity, and prevent joint contractures.
• Speech Therapy: Techniques and assistive devices to aid in communication as speech declines.
• Nutritional Support: High-calorie diets and feeding tubes (PEG) help prevent malnutrition.
• Respiratory Support: Non-invasive ventilation (BiPAP) or tracheostomy in advanced stages to assist breathing.
• Assistive Devices: Use of wheelchairs, walkers, and communication devices to enhance independence.

Prognosis

ALS is a progressive and fatal disease. Most patients experience steady functional decline, with life expectancy typically ranging from 2 to 5 years after diagnosis. However, some individuals live longer, with 10% surviving more than 10 years. Early diagnosis, supportive care, and advanced therapies can help extend life and improve comfort. Multidisciplinary care teams, including neurologists, therapists, and palliative care specialists, play a key role in enhancing quality of life throughout the course of the disease.