Amyotrophic lateral sclerosis (ALS), often recognized as Lou Gehrig’s disease, is a progressive neurological condition that targets motor neurons. These are crucial nerve cells in the brain and spinal cord responsible for controlling voluntary muscle movements, including vital functions like breathing. In ALS, motor neurons gradually deteriorate and die, disrupting the transmission of signals to muscles. This breakdown leads to muscle weakening, involuntary twitching (fasciculations), and muscle wasting (atrophy). Ultimately, ALS impairs the brain’s capacity to initiate and manage voluntary movements essential for daily living, such as walking, speaking, chewing, and even breathing. ALS is characterized by its progressive nature, meaning symptoms intensify over time.
While several medications have received approval from the U.S. Food and Drug Administration to potentially extend survival, slow disease progression, or alleviate symptoms of ALS, currently, there is no treatment capable of halting or reversing its course.
Early indicators of ALS may include:
- Muscle twitches in areas like the arm, leg, shoulder, or tongue
- Muscle cramps
- Muscle stiffness and tightness (spasticity)
- Muscle weakness affecting limbs or the neck
- Speech difficulties, such as slurring or nasal tone
- Challenges with chewing or swallowing
As ALS advances, muscle weakness and atrophy spread throughout the body. Individuals with ALS may encounter increasing difficulties with:
- Chewing and swallowing food (dysphagia)
- Excessive drooling (sialorrhea)
- Speaking or forming words clearly (dysarthria)
- Breathing (dyspnea)
- Involuntary emotional expressions, such as crying or laughing (pseudobulbar symptoms)
- Constipation
- Maintaining body weight and adequate nutrition
Eventually, ALS can lead to the inability to stand, walk, move in and out of bed independently, use hands and arms, or breathe unaided. Cognitive functions such as reasoning, memory, and understanding typically remain intact, making individuals acutely aware of their functional decline, which can trigger anxiety and depression for both patients and their families. Though less common, some individuals with ALS might also experience cognitive impairments affecting language or decision-making, and some may develop frontotemporal dementia (FTD-ALS).
Respiratory failure, the inability to breathe independently, is the most common cause of death in people with ALS, typically occurring within three to five years from the onset of symptoms. However, approximately 10% of individuals with ALS live for 10 years or longer.
Who is at Risk for Lou Gehrig’s Disease? Understanding ALS Risk Factors
A risk factor is defined as a condition or behavior that is more prevalent among individuals who develop a disease or are at a higher risk of developing it compared to those without the risk factor. While having a risk factor increases susceptibility, it does not guarantee disease development, and conversely, the absence of risk factors does not eliminate the possibility of developing the condition. Risk factors associated with ALS include:
- Age: Although ALS can manifest at any age, symptoms most frequently appear between 55 and 75 years of age.
- Biological Sex: Men are slightly more prone to developing ALS than women. However, this difference diminishes at older ages, where incidence rates become similar for both sexes.
- Race and Ethnicity: Caucasians and non-Hispanic individuals are statistically more likely to be diagnosed with ALS, but the disease affects people from all racial and ethnic backgrounds.
Studies suggest that military veterans have a higher likelihood of developing ALS, approximately one and a half to two times greater than non-veterans. The reasons for this increased risk are not fully understood but potential contributing factors under investigation include exposure to environmental toxins such as lead and pesticides, as well as head injuries. Research into the link between head injuries and ALS risk is ongoing to establish a clearer understanding.
Sporadic Versus Familial ALS: Genetic Considerations in Lou Gehrig’s Disease
The vast majority of ALS cases are classified as sporadic, indicating that the disease arises seemingly at random without clear risk factors or a family history of ALS. While family members of individuals with sporadic ALS have a slightly increased risk compared to the general population, the overall risk remains low for them to develop ALS.
Approximately 10% of ALS cases are familial, meaning they are inherited or genetic. To date, mutations in over a dozen genes have been identified as causes of familial ALS.
- About 25-40% of familial ALS cases, and a smaller percentage of sporadic cases, are linked to defects in the C9orf72 gene. This gene is involved in producing a protein found in motor neurons and brain nerve cells.
- Another 12-20% of familial cases are due to mutations in the SOD1 gene, which plays a role in the production of copper-zinc superoxide dismutase 1, an enzyme.
In 2021, a collaborative research effort led by the NIH discovered a unique genetic form of ALS affecting children as young as age 4. This childhood-onset ALS is associated with the SPTLC1 gene, part of the body’s fat metabolism system, suggesting lipid metabolism abnormalities may be involved.
Lou Gehrig’s Disease Diagnosis: How is ALS Identified?
Obtaining an accurate and timely ALS diagnosis is crucial as early interventions may enhance the effectiveness of treatments. A neurologist experienced in ALS diagnosis is essential for prompt diagnosis following the onset of symptoms.
Currently, there is no single definitive test for ALS diagnosis. The diagnostic process typically involves a comprehensive approach: a thorough physical examination, a detailed review of the individual’s medical history, and a neurologic examination assessing reflexes, muscle strength, and other neurological responses. These evaluations are conducted regularly to monitor symptom progression.
To exclude other conditions and support an ALS diagnosis, healthcare providers may employ various muscle and imaging tests. These may include:
- Electromyography (EMG): This test evaluates the function of nerves and muscles and encompasses:
- Nerve Conduction Study (NCS): Measures the electrical activity of nerves and muscles by assessing nerve signal transmission.
- Needle Exam: Detects electrical activity in muscle fibers using a needle electrode.
- Magnetic Resonance Imaging (MRI): Utilizes magnetic fields and radio waves to generate detailed images of the brain and spinal cord.
Blood and urine tests may be ordered based on individual symptoms, neurological exam findings, and initial test results to rule out other conditions. In certain instances, a spinal tap (lumbar puncture) may be performed to analyze cerebrospinal fluid (CSF), the fluid surrounding the brain and spinal cord. A muscle biopsy might be conducted to differentiate ALS from other muscle diseases.
Lou Gehrig’s Disease Treatment and Management Strategies
Currently, there is no cure for ALS, and damage to motor neurons cannot be reversed. However, treatments are available to potentially slow disease progression, enhance quality of life, and prolong survival. Significant advancements in ALS treatments have emerged in recent years, and ongoing research continues to explore new therapeutic avenues.
Optimal care for individuals with ALS is delivered through integrated, multidisciplinary teams comprising physicians, pharmacists, physical, occupational, speech, and respiratory therapists, nutritionists, social workers, clinical psychologists, and home care and hospice nurses. These teams create personalized treatment plans and provide specialized equipment to maximize mobility, comfort, and independence.
FDA-approved medications used in ALS treatment plans include:
- Riluzole (Rilutek): An oral medication thought to reduce motor neuron damage by decreasing glutamate levels. Clinical studies suggest it may extend survival by a few months. Available in thickened liquid (Tiglutik) and rapidly dissolving tablet (Exservan) forms for swallowing difficulties.
- Edaravone (Radicava): An antioxidant administered intravenously or orally, shown to slow functional decline in some ALS patients. RADICAVA ORS is an oral formulation.
- Sodium phenylbutyrate/taurursodiol (Relyvrio): An oral medication initially proposed to prevent nerve cell death. Although initially approved based on smaller trials, a larger trial failed to confirm efficacy, and it was withdrawn from the market in 2024.
- Tofersen (Qalsody): Administered via spinal injection for ALS patients with SOD1 gene mutations. It aims to reduce neuron damage markers, but its benefits are still under investigation.
Additional medications and treatments may be prescribed to manage specific ALS symptoms like muscle cramps, stiffness, excessive saliva, emotional lability, pain, depression, sleep disturbances, and constipation.
Rehabilitation and Supportive Therapies for ALS
A comprehensive ALS treatment plan typically includes rehabilitation tailored to individual needs, encompassing physical, occupational, and speech therapy.
Physical and Daily Living Support
Physical therapy helps maintain physical function, reduce fall risk and joint pain, and maximize independence at different disease stages. Low-impact exercises and range-of-motion exercises are beneficial. Occupational therapists assist with daily living activities and recommend assistive devices for feeding, bathing, and grooming to promote independence.
Speech and Communication Strategies
Speech therapists teach strategies to enhance speech clarity and volume and maintain communication abilities. Computer-based speech synthesizers with eye-tracking technology and voice banking are valuable tools. Brain-computer interfaces (BCIs) are also being developed to enable communication and device control using brain activity.
Nutritional, Respiratory, and Feeding Support
Nutritionists and dieticians help manage chewing and swallowing difficulties, plan nutritious meals, and advise on food modifications. Feeding tubes can be necessary to prevent choking and pneumonia. Respiratory support, including noninvasive ventilation (NIV) and mechanical ventilation, becomes crucial as breathing muscles weaken. Techniques and devices to assist coughing are also important.
Caregiving for Individuals with ALS
As ALS progresses, caregiving demands increase. Support for caregivers is essential, and resources are available for home health care and support services.
Recent Advances in Lou Gehrig’s Disease Research
The NINDS is a leading federal funder of ALS research, with strategic priorities focused on accelerating the development of effective interventions for diagnosis, treatment, management, and prevention of ALS. These priorities are shaped by input from scientists, clinicians, advocates, and individuals affected by ALS. NINDS also supports research on expanded access to investigational drugs for ALS patients ineligible for clinical trials.
Recent scientific discoveries have identified multiple therapeutic targets, leading to FDA approval of several ALS therapies. However, their impact remains modest, highlighting the need to address numerous challenges to develop truly effective treatments. NINDS research goals include understanding cellular mechanisms of ALS, investigating genetic and risk factors, identifying biomarkers, and developing new treatments.
Current research areas include:
Cellular Defects in ALS
Studies aim to understand the mechanisms causing selective motor neuron degeneration in ALS, focusing on cellular defects in protein recycling, gene regulation, and motor neuron structure. The role of glial support cells and inflammation is also under investigation.
Stem Cell Research for ALS
Scientists are utilizing stem cells to model ALS, growing human spinal cord sections on tissue chips to study neuron function in ALS.
Genetic and Epigenetic Factors in ALS
Clinical studies are investigating symptom progression in individuals with C9orf72 mutations and identifying new genes associated with ALS. Large-scale genetic data analysis and epigenetic research are underway to enhance understanding of ALS development.
Biomarkers for ALS Diagnosis and Progression
Biomarker research focuses on identifying biological measures to track ALS progression and treatment effectiveness, using molecules from bodily fluids, brain and spinal cord imaging, and nerve and muscle electrical signal measures.
For further research articles on ALS, PubMed is a valuable resource.
How You Can Contribute to Improving ALS Care
The National ALS Registry collects data on people with ALS in the U.S. to understand the disease’s prevalence, risk factors, and inform research opportunities. Individuals with ALS can contribute their information to the registry.
Participating in clinical trials is crucial for advancing ALS research and treatment options. Information on clinical trials can be found at Clinicaltrials.gov.
Tissue donation to the NIH NeuroBioBank is also vital for ALS research, enabling the study of the neurological basis of the disease.
Resources for More Information on Lou Gehrig’s Disease (ALS)
The following organizations provide support and information for individuals, families, and caregivers affected by ALS:
ALS Therapy Development Institute
Genetic and Rare Diseases (GARD) Information Center
Eldercare Locator
I AM ALS
Les Turner ALS Foundation
MedlinePlus
Muscular Dystrophy Association
National ALS Registry
Project ALS
The ALS Association
