ALS: Symptoms, Causes & Treatment Guide

What Is ALS (Amyotrophic Lateral Sclerosis)?

ALS (amyotrophic lateral sclerosis) is a progressive neurodegenerative disease that destroys motor neurons—the nerve cells in the brain and spinal cord that control voluntary muscle movement. As motor neurons die, muscles weaken and waste away, eventually affecting walking, speaking, eating, and breathing.

Amyotrophic lateral sclerosis, commonly known as ALS or Lou Gehrig's disease (named after the famous baseball player who was diagnosed in 1939), belongs to a broader group of disorders called motor neuron diseases. The name itself describes the pathology: "amyotrophic" means muscle wasting, "lateral" refers to the areas of the spinal cord affected, and "sclerosis" describes the scarring or hardening that occurs as motor neurons degenerate.

The disease affects both upper motor neurons (in the brain) and lower motor neurons (in the brainstem and spinal cord). Upper motor neuron damage causes stiffness, spasticity, and exaggerated reflexes, while lower motor neuron damage leads to muscle weakness, twitching (fasciculations), and atrophy. This combination of upper and lower motor neuron signs is a hallmark of ALS and helps distinguish it from other neurological conditions.

Understanding what ALS does and does not affect is crucial. While the disease progressively weakens voluntary muscles—those controlling movement, speech, and breathing—it typically spares several important functions. Most people with ALS maintain their cognitive abilities, personality, and memory throughout the disease. The senses of sight, hearing, taste, smell, and touch remain intact. Bladder and bowel control are usually preserved until very late stages, and eye muscles are generally spared, allowing many patients to communicate through eye-tracking devices even when other muscles have failed.

However, it's important to note that approximately 15-20% of ALS patients develop some degree of frontotemporal dementia (FTD), which can affect behavior, personality, and language. Another 30-50% may experience milder cognitive or behavioral changes. This overlap between ALS and FTD has led researchers to understand these conditions as existing on a spectrum of related disorders.

How Common Is ALS?

ALS is considered a rare disease, but it is the most common form of motor neuron disease. Globally, approximately 2-3 people per 100,000 are diagnosed with ALS each year. The lifetime risk of developing ALS is about 1 in 400, meaning that while relatively rare, it affects more people than commonly assumed. In the United States alone, approximately 5,000 new cases are diagnosed annually, and at any given time, about 30,000 Americans are living with the disease.

The incidence of ALS appears to be relatively consistent worldwide, though some geographic clusters have been identified. For example, higher rates have been observed in parts of Guam, the Kii Peninsula of Japan, and Western New Guinea. These clusters have provided valuable clues for researchers investigating potential environmental and genetic factors in ALS development.

What Are the Symptoms of ALS?

Early ALS symptoms include muscle weakness in a hand, arm, or leg; muscle twitching (fasciculations); difficulty speaking or swallowing; cramping; and stiffness. Symptoms typically begin in one area and gradually spread to other parts of the body over months to years.

The symptoms of ALS vary significantly from person to person, both in terms of where they first appear and how quickly they progress. This variability can make early diagnosis challenging, as initial symptoms may be subtle and easily attributed to other causes. Understanding the range of potential symptoms helps individuals recognize when to seek medical evaluation.

ALS symptoms generally fall into two categories based on where they first appear: limb-onset ALS (about 75% of cases) and bulbar-onset ALS (about 25% of cases). In limb-onset ALS, symptoms typically begin in the arms or legs, while bulbar-onset ALS first affects speech and swallowing. Regardless of where symptoms begin, they eventually spread to other body regions as the disease progresses.

Early Warning Signs

The earliest symptoms of ALS are often subtle and may be overlooked or misattributed to other conditions. Many people report noticing small changes in muscle function months or even years before diagnosis. Common early signs include:

• Muscle weakness: Difficulty with fine motor tasks like buttoning shirts, turning keys, or writing; tripping or stumbling while walking; dropping objects
• Muscle twitching (fasciculations): Involuntary muscle contractions visible under the skin, often in the arms, shoulders, legs, or tongue
• Muscle cramps: Painful cramping, particularly in the legs and feet, often occurring at night
• Stiffness or spasticity: A feeling of tightness or rigidity in muscles, particularly noticeable when moving
• Speech changes: Slurred speech (dysarthria), softer voice, or difficulty projecting
• Swallowing difficulties: Choking on food or liquids, excessive drooling, or prolonged meal times

It's important to note that muscle twitching alone, without accompanying weakness, is very common in the general population and is usually benign. However, when fasciculations occur alongside progressive weakness or other neurological symptoms, medical evaluation is warranted.

Symptoms by Type of Onset

Progression of Symptoms

As ALS progresses, symptoms gradually spread from the initial site of onset to other parts of the body. The rate of progression varies considerably—some people experience rapid decline over months, while others progress slowly over many years. On average, symptoms spread to new body regions every 6-12 months.

Progressive muscle weakness eventually affects most voluntary muscles. Walking becomes increasingly difficult, and many people eventually require wheelchairs for mobility. Arm and hand weakness can make daily tasks like eating, dressing, and personal care challenging. Speech may become increasingly difficult to understand, and swallowing problems can lead to weight loss and nutritional challenges.

The most serious progression involves the respiratory muscles. Weakness of the diaphragm and other breathing muscles leads to respiratory insufficiency, which is the most common cause of death in ALS. Early signs of respiratory involvement include shortness of breath during exertion, difficulty breathing when lying flat (orthopnea), morning headaches from CO2 retention, and fatigue. Respiratory support with non-invasive ventilation (NIV) can significantly extend survival and improve quality of life.

What Causes ALS?

The exact cause of ALS is not fully understood. About 5-10% of cases are inherited (familial ALS), while 90-95% occur without family history (sporadic ALS). Research has identified multiple contributing factors including genetic mutations, protein abnormalities, oxidative stress, and mitochondrial dysfunction.

Despite decades of research, the precise mechanisms causing motor neuron death in ALS remain incompletely understood. What is clear is that ALS likely results from a complex interplay of genetic susceptibility and environmental factors, leading to a cascade of cellular damage that ultimately kills motor neurons. Understanding these mechanisms is crucial for developing effective treatments.

Genetic Factors

Genetics play an important role in ALS, even in cases without a clear family history. Approximately 5-10% of ALS cases are classified as familial ALS (fALS), meaning there is a known genetic mutation passed through families. The remaining 90-95% are classified as sporadic ALS (sALS), occurring without obvious genetic inheritance—though research increasingly suggests that genetic factors contribute to sporadic cases as well.

Over 30 genes have been linked to ALS. The most commonly mutated genes include:

• C9orf72: The most common genetic cause, responsible for about 40% of familial ALS and 5-10% of sporadic cases. This gene contains an abnormally repeated DNA sequence.
• SOD1: The first ALS gene discovered (1993), accounting for about 20% of familial ALS. SOD1 mutations lead to toxic protein accumulation.
• TARDBP (TDP-43): Causes about 5% of familial ALS. The protein produced by this gene aggregates abnormally in most ALS cases.
• FUS: Similar to TARDBP, causes protein aggregation and accounts for about 5% of familial ALS.

Genetic testing is available and may be recommended for individuals with a family history of ALS, those diagnosed at a young age, or patients considering participation in clinical trials targeting specific genetic forms of the disease.

Cellular Mechanisms

Research has revealed several cellular processes that go wrong in ALS, though it remains unclear whether these are causes or consequences of the disease:

Protein aggregation: In nearly all ALS cases, abnormal clumps of proteins accumulate inside motor neurons. TDP-43 protein aggregates are found in about 97% of ALS cases. These aggregates may interfere with normal cell function and contribute to neuron death.

Glutamate excitotoxicity: Glutamate is a neurotransmitter essential for nerve signaling. In ALS, glutamate accumulates to toxic levels around motor neurons, overstimulating and damaging them. Riluzole, the first FDA-approved ALS medication, works by reducing glutamate levels.

Oxidative stress: Motor neurons in ALS show signs of damage from reactive oxygen species—harmful molecules that can damage DNA, proteins, and cell membranes. This oxidative stress may accelerate neuron death.

Mitochondrial dysfunction: Mitochondria, the cellular powerhouses that produce energy, function abnormally in ALS. This energy deficit may make motor neurons more vulnerable to stress and damage.

Neuroinflammation: The immune cells of the nervous system become activated in ALS, producing inflammation that may contribute to motor neuron death. Research is exploring whether modulating this immune response could slow disease progression.

Risk Factors

While the cause of sporadic ALS remains unknown, several factors have been associated with increased risk:

• Age: ALS most commonly develops between ages 55-75, though it can occur at any age
• Sex: Men are slightly more likely to develop ALS than women (ratio of about 1.3:1), though this gap narrows at older ages
• Genetics: Having a first-degree relative with ALS increases risk 4-10 fold
• Military service: Veterans have approximately twice the risk of developing ALS, possibly related to environmental exposures
• Smoking: Some studies suggest smoking increases ALS risk, particularly in women
• Environmental exposures: Possible associations have been noted with lead, pesticides, and certain occupations, though evidence remains inconclusive

How Is ALS Diagnosed?

ALS diagnosis is based on clinical examination and tests to rule out other conditions. There is no single definitive test. Diagnosis typically involves neurological examination, electromyography (EMG), nerve conduction studies, MRI scans, blood tests, and sometimes lumbar puncture. Diagnosis can take 9-12 months as other conditions must be excluded.

Diagnosing ALS can be challenging and often takes considerable time—on average, 9-12 months from symptom onset to confirmed diagnosis. This delay occurs because ALS symptoms can mimic many other conditions, and there is no single test that definitively confirms the disease. Instead, diagnosis relies on a combination of clinical examination, electrodiagnostic tests, and exclusion of other possible conditions.

The Diagnostic Process

The diagnostic journey typically begins when a person notices symptoms and seeks medical attention. Primary care physicians often refer patients to a neurologist, ideally one specializing in neuromuscular disorders or motor neuron disease. The diagnostic process includes several components:

Clinical examination: A detailed neurological examination looks for the hallmark combination of upper and lower motor neuron signs. Upper motor neuron signs include increased reflexes (hyperreflexia), muscle stiffness (spasticity), and specific reflex patterns. Lower motor neuron signs include muscle weakness, atrophy (wasting), and fasciculations (twitching). Finding these signs in multiple body regions strengthens the diagnosis.

Medical history: The neurologist will thoroughly review symptom onset, progression, family history, occupational exposures, and other medical conditions. Pattern and rate of symptom spread provide important diagnostic clues.

Diagnostic Tests

Electromyography (EMG): This is the most important test for ALS diagnosis. A small needle electrode is inserted into muscles to record their electrical activity at rest and during contraction. In ALS, EMG shows characteristic patterns indicating both active denervation (ongoing nerve damage) and reinnervation (attempts at nerve repair). The test examines multiple muscles in different body regions.

Nerve conduction studies: These measure how quickly electrical signals travel along nerves. In ALS, motor nerve conduction may slow somewhat, but sensory nerve conduction remains normal—an important distinction from other conditions.

MRI scans: Brain and spinal cord MRI help rule out other conditions that can mimic ALS, such as tumors, cervical spondylosis (neck arthritis pressing on the spinal cord), or multiple sclerosis.

Blood tests: Comprehensive blood work rules out conditions like thyroid disease, vitamin deficiencies, infections, and autoimmune disorders that can cause similar symptoms.

Lumbar puncture: Sometimes performed to analyze cerebrospinal fluid and exclude inflammatory or infectious conditions.

Genetic testing: May be recommended for those with family history of ALS, younger patients, or those considering clinical trials.

Diagnostic Criteria

The El Escorial criteria, revised in 2015, are used to classify ALS diagnostic certainty. These criteria consider the number of body regions showing upper and lower motor neuron signs:

• Definite ALS: Upper and lower motor neuron signs in three or more body regions
• Probable ALS: Upper and lower motor neuron signs in two regions
• Possible ALS: Upper and lower motor neuron signs in one region, or upper motor neuron signs in two or more regions

These categories are primarily used for research purposes. A neurologist may diagnose ALS and begin treatment even before criteria for "definite" ALS are met, based on clinical judgment and the overall picture.

How Is ALS Treated?

While there is no cure for ALS, treatments can slow progression and manage symptoms. FDA-approved medications include riluzole and edaravone. Comprehensive care involves a multidisciplinary team providing physical therapy, speech therapy, respiratory support, nutritional care, and assistive devices to maintain quality of life.

ALS treatment focuses on three main goals: slowing disease progression, managing symptoms, and maintaining quality of life for as long as possible. While a cure remains elusive, significant advances in supportive care have improved outcomes. Studies show that multidisciplinary care at specialized ALS clinics can extend survival by 7-12 months compared to standard care.

Disease-Modifying Medications

Riluzole (Rilutek): The first FDA-approved treatment for ALS (1995), riluzole remains a cornerstone of therapy. It works by reducing glutamate levels, which may protect motor neurons from excitotoxicity. Clinical trials demonstrated that riluzole extends survival by an average of 2-3 months, with greater benefits when started early. The medication is taken orally twice daily. Side effects may include fatigue, nausea, and liver function changes requiring monitoring.

Edaravone (Radicava): Approved by the FDA in 2017, edaravone is an antioxidant that may slow functional decline in some patients. It was initially given as an intravenous infusion but is now also available as an oral formulation (Radicava ORS). Research suggests it may be most effective in patients with early-stage ALS and relatively preserved function. Side effects may include bruising, headache, and allergic reactions.

Relyvrio (AMX0035): Approved in 2022, this combination medication (sodium phenylbutyrate and taurursodiol) targets cellular stress pathways. Clinical trials showed it may slow functional decline. However, recent Phase 3 trial results have raised questions about its efficacy, and the manufacturer has announced plans to discontinue it.

Tofersen: Approved in 2023 specifically for ALS caused by SOD1 gene mutations (about 2% of all ALS cases), tofersen is an antisense oligonucleotide that reduces production of the toxic SOD1 protein. It is administered by spinal injection.

Symptom Management

Effective symptom management significantly improves quality of life. Common symptoms and their treatments include:

Muscle cramps and spasticity: Baclofen, tizanidine, or botulinum toxin injections can reduce painful cramping and muscle stiffness. Stretching exercises and physical therapy also help.

Excessive saliva (sialorrhea): Options include glycopyrrolate, atropine drops, botulinum toxin injections into salivary glands, or low-dose radiation therapy.

Pseudobulbar affect: Uncontrollable laughing or crying, unrelated to mood, affects about 50% of patients. Dextromethorphan/quinidine (Nuedexta) is FDA-approved for this symptom.

Pain: While ALS doesn't directly cause pain, muscle cramps, spasticity, and immobility can be painful. NSAIDs, muscle relaxants, and other medications help manage discomfort.

Sleep disturbances: Often related to respiratory issues, pain, or difficulty turning. Non-invasive ventilation, positioning aids, and sleep medications may help.

Depression and anxiety: Common and understandable reactions that respond to counseling and, when needed, antidepressant medications.

Respiratory Care

Respiratory management is perhaps the most critical aspect of ALS care. Weakness of breathing muscles leads to respiratory insufficiency, which is the primary cause of death in ALS. Proactive respiratory care can significantly extend survival:

Non-invasive ventilation (NIV): Using a BiPAP machine, typically started when breathing tests show early decline or when symptoms like morning headaches or breathlessness appear. NIV has been shown to extend survival by 7-13 months and improve quality of life. It is typically used at night initially, then for longer periods as needed.

Cough assist devices: Mechanical insufflation-exsufflation devices help clear secretions when cough strength weakens, reducing pneumonia risk.

Invasive ventilation: Some patients choose tracheostomy and mechanical ventilation for long-term respiratory support. This is a significant decision with implications for quality of life and care needs.

Nutritional Support

Maintaining adequate nutrition is essential but becomes increasingly challenging as swallowing weakens. Malnutrition accelerates muscle loss and worsens outcomes:

Diet modifications: Speech therapists and dietitians can recommend food textures and consistencies that are easier to swallow safely. Thickened liquids reduce choking risk.

Feeding tubes: A percutaneous endoscopic gastrostomy (PEG) tube provides nutrition directly to the stomach. Studies show that placing a PEG tube before respiratory function declines significantly is safer. Many patients use PEG tubes as a supplement to oral eating.

Physical and Occupational Therapy

Therapy helps maintain function and independence for as long as possible:

Physical therapy: Gentle stretching and range-of-motion exercises help prevent contractures and maintain flexibility. Low-impact exercise may help manage fatigue without accelerating weakness.

Occupational therapy: Focuses on adapting daily activities and recommending assistive devices to maintain independence in self-care, eating, and other activities.

Assistive devices: As weakness progresses, devices such as ankle-foot orthoses (AFOs), walkers, wheelchairs, and lifts help maintain mobility and safety.

Communication Support

Maintaining communication is vital for quality of life and end-of-life planning:

Speech therapy: Techniques to maximize speech clarity and strength for as long as possible.

Augmentative and alternative communication (AAC): Devices ranging from simple letter boards to sophisticated eye-tracking systems allow communication when speech fails. Planning early ensures smooth transition.

What Is the Prognosis for ALS?

The average survival after ALS diagnosis is 2-5 years, but prognosis varies widely. About 10% of people live more than 10 years. Factors affecting survival include age at onset, type of onset (limb vs. bulbar), respiratory function, nutritional status, and access to multidisciplinary care.

Understanding ALS prognosis requires recognizing the significant variability in disease course. While statistics provide general guidance, individual outcomes can differ substantially. Many factors influence survival and quality of life, and proactive management can improve outcomes.

Survival Statistics

Survival times for ALS vary considerably:

• Average survival from symptom onset: 3-5 years
• Average survival from diagnosis: 2-3 years
• About 10% survive more than 10 years
• A small percentage (about 5%) survive 20 years or longer
• The most famous long-term survivor, physicist Stephen Hawking, lived more than 50 years after his diagnosis

Factors Affecting Prognosis

Several factors are associated with longer or shorter survival:

Factors associated with longer survival:

• Younger age at onset (especially under 40)
• Limb-onset rather than bulbar-onset
• Longer time from symptoms to diagnosis (suggests slower progression)
• Better respiratory function at diagnosis
• Good nutritional status
• Use of riluzole and other treatments
• Care at a multidisciplinary ALS clinic
• Non-invasive ventilation use

Factors associated with shorter survival:

• Older age at onset (especially over 65)
• Bulbar-onset disease
• Rapid early progression
• Respiratory impairment at diagnosis
• Weight loss and malnutrition
• Concurrent frontotemporal dementia

Quality of Life

Despite the challenges of ALS, many patients report maintaining meaningful quality of life, especially with proper support. Factors contributing to quality of life include:

• Strong social support from family, friends, and caregivers
• Maintaining communication ability (through speech or AAC devices)
• Effective symptom management
• Access to comprehensive multidisciplinary care
• Maintaining a sense of purpose and engagement
• Planning ahead for care needs and end-of-life preferences

What Is It Like Living with ALS?

Living with ALS requires adapting to progressive changes while maintaining quality of life. A multidisciplinary care team, assistive devices, home modifications, caregiver support, and advance care planning are essential. Many people with ALS continue meaningful activities and relationships throughout their illness.

Receiving an ALS diagnosis is life-changing, and adjusting to the disease requires significant physical, emotional, and practical adaptations. However, with proper support and planning, many people with ALS maintain fulfilling lives and meaningful relationships.

Building Your Care Team

Comprehensive ALS care involves multiple specialists working together:

• Neurologist: Coordinates overall care and manages medications
• Pulmonologist: Monitors breathing function and manages respiratory support
• Physical therapist: Helps maintain mobility and prevent complications
• Occupational therapist: Adapts daily activities and recommends assistive devices
• Speech-language pathologist: Addresses speech and swallowing difficulties
• Dietitian: Ensures adequate nutrition
• Social worker: Assists with resources, insurance, and emotional support
• Palliative care team: Focuses on comfort and quality of life
• Mental health professional: Supports emotional wellbeing

Home and Lifestyle Adaptations

As ALS progresses, home modifications and adaptive equipment help maintain independence and safety:

• Ramps and stair lifts for mobility
• Bathroom modifications (grab bars, shower chairs, raised toilets)
• Hospital bed for comfort and positioning
• Communication devices
• Environmental controls (voice or eye-gaze activated)
• Vehicle modifications for accessibility

Emotional and Psychological Support

The emotional impact of ALS affects patients and families alike. Depression, anxiety, grief, and fear are normal reactions. Support options include:

• Individual counseling with therapists experienced in chronic illness
• ALS support groups (in-person or online)
• Family therapy to address relationship challenges
• Spiritual or religious support if desired
• Antidepressant or anti-anxiety medications when appropriate

Advance Care Planning

Planning ahead while still able to communicate clearly is essential. Advance care planning involves:

• Advance directives: Legal documents stating preferences for medical care
• Healthcare proxy: Designating someone to make medical decisions if you cannot
• Discussions about interventions: Deciding preferences for feeding tubes, ventilation, and resuscitation
• End-of-life care preferences: Where and how you wish to spend final days
• Financial and legal planning: Wills, power of attorney, and estate planning

What Research Is Being Done on ALS?

ALS research is advancing rapidly, with numerous clinical trials testing new treatments. Promising areas include gene therapy for genetic ALS forms, antisense oligonucleotides, stem cell approaches, and drugs targeting neuroinflammation and protein aggregation. Several new treatments have been approved in recent years.

The pace of ALS research has accelerated dramatically in recent years, driven by better understanding of disease mechanisms, advances in genetic technology, and increased funding. While a cure remains elusive, multiple promising approaches are in development.

Gene Therapy and Genetic Approaches

For genetic forms of ALS, targeting the underlying genetic defect offers the most direct path to treatment:

• Antisense oligonucleotides (ASOs): Tofersen's approval for SOD1-ALS proves this approach can work. Similar treatments are being developed for C9orf72 and other genetic forms.
• Gene therapy: Viral vectors delivering corrective genes are in early trials.
• Gene editing: CRISPR and related technologies are being explored to correct ALS-causing mutations.

Stem Cell Research

Stem cell approaches are being investigated both to replace lost motor neurons and to provide protective factors:

• Neural stem cells that can develop into neurons or support cells
• Cells engineered to produce growth factors or anti-inflammatory molecules
• Several clinical trials are ongoing with varying results

Biomarker Development

Better biomarkers would enable earlier diagnosis and more efficient clinical trials:

• Neurofilament light chain (NfL): A blood test measuring nerve damage that may help track disease progression
• Imaging biomarkers using advanced MRI techniques
• Electrical measurements of muscle function