Amyotrophic Lateral Sclerosis (ALS): Lou Gehrig’s Disease

Do you remember the ice bucket challenge? Did you participate? While the act of pouring a bucket of cold, icy water over your head for amyotrophic lateral sclerosis (ALS) awareness was all the rage years ago, much of the population are still unaware of the devastating effects of ALS—also known as Lou Gehrig’s Disease. Continue reading to learn the risk factors, signs, symptoms, treatments, and the way in which amyotrophic lateral sclerosis (ALS), motor neuron condition, influences the brain.

Amyotrophic Lateral Sclerosis
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What is Amyotrophic Lateral Sclerosis?

ALS is a neurodegenerative disease that causes motor neurons (i.e. nerve cells) to die. The role of motor neurons in the body is to transmit messages to those areas to coordinate muscle control. Beginning in the brain, upper motor neurons communicate messages to lower neurons in the spinal cord, as well as the brain’s nuclei. Both upper and lower neurons degenerate in ALS. When neurons die off, they stop communicating with the muscles that control voluntary muscle movements. Gradually over time, the muscles atrophy as they lose function and the brain can no longer coordinate movements.

Approximately 14,000 – 15,000 Americans are diagnosed with ALS as estimated by the Centers for Disease Control and Prevention. This severe motor neuron disease drastically affects one’s life because of the extent to which motor neurons influence muscle movements. People lose their mobility along with their ability to speak, eat, and breathe. Life expectancy ranges from 3 to 10 years after onset, which is typically in later adulthood due to respiratory failure.

Early Signs of Amyotrophic Lateral Sclerosis

While it is true each person with ALS is unique in their combination of symptoms, the signs of ALS are relatively consistent. The onset of ALS is gradual, progressing over a period of time. The first evident symptom for most patients is muscle weakness with fatigue of the limbs. Generalized clumsiness, such as dropping objects, and tripping are common. Muscle cramps, twitches, stiffness, speech or swallowing difficulties, and uncontrollable laughing or crying are also hallmark signs of the condition.

The Motor Symptoms of Amyotrophic Lateral Sclerosis

The motor symptoms of ALS are what the disorder is known for. Death of the nerve cells that send signals to the brain does not function properly. This triggers a cascade of muscular atrophy.

Its symptoms are divided between upper and lower neuron motor symptoms. Upper motor neurons are in the brain. Its symptoms consist of spasticity, which is tightness or stiffness of the muscles. Upper motor neurons are responsible for poor balance, incoordination, and slowed movements often mistaken as clumsiness towards the beginning of disease onset. Lower motor neurons originate in the spinal cord and brainstem. The muscle weakness, atrophy (weakening_ and twitching stem from the degeneration of lower motor neurons. ALS results in a combination of upper and lower motor symptoms.

Because of the motor symptoms provoking widespread weakness, people with ALS lose their ability to walk, speak, breathe, and once the muscle wasting affects the facial muscles, patients cannot swallow to feed themselves.

Cognitive Behavioral Changes in Amyotrophic Lateral Sclerosis

ALS is not only associated with motor symptoms of the muscles. Up to half of the patients encounter cognitive-behavioral changes with the diagnosis. Cognitive impairment does not prevent patients from daily tasks, but they do display differences in thinking. These symptoms are milder than dementia, which does hinder them from activities.

The cognitive-behavioral changes are usually displayed through embarrassing behaviors. The patient may begin talking child-like, inappropriately express opinions, and disregard manners or hygiene. Communication is impaired by loss of word meaning and regression of spelling or grammar rules. Other common signs of cognitive impairment are mood changes such as increased aggression, memory loss, and problems with reasoning and attention: poor concentration, inability to follow instruction, and a decline in judgment.

Dementia In Amyotrophic Lateral Sclerosis

Dementia is an umbrella term for a cluster of symptoms impacting thinking and cognitive skills. Memory, language, problems with attention, and social skills are affected by dementia. Fronto-temporal dementia, a non- Alzheimer’s form of dementia, is noted in ALS. Patients who develop dementia related to motor neuron degeneration manifest with the below symptoms to a greater severity than just cognitive impairment:

  • Memory loss
  • Speech loss
  • Restlessness
  • Apathy
  • Mood swings
  • Decreased reasoning
  • Compulsive behavior (i.e. hoarding, wondering, inappropriate urination/defecation)

Psychological Disorders and Amyotrophic Lateral Sclerosis

As a result of progressive degeneration of motor neurons, psychological disorders can arise from ALS. Throughout history, schizophrenia has been connected to motor neuron changes. Schizophrenia is a mental disorder affecting the ability to think, feel, and behave. It is characterized by a combination of hallucinations and delusions that cause cognition to become out of touch with reality. Someone with ALS is at a higher risk of schizophrenia around one year proceeding ALS progression. According to Zucchi (2019), episodes of psychosis warrants an evaluation for schizophrenia when presenting alongside the sensory disturbances found in approximately one-half of ALS patients.

Depression is a mood disorder of persistent unexplainable sadness, while anxiety is marked by overwhelming worry about daily life situations. Both psychological disorders are implicated in ALS. Patients are bound to feel the emotions of either of these psychological diagnoses due to the progressive nature of their condition. Symptoms are persistent in up to 75% of ALS cases. A study by Thakore and Pioro (2016) observed 17% of ALS patients diagnosed with major depressive disorder with half of them on antidepressant medications diagnosed up to one year before the onset of ALS motor symptoms. This further supports the connection. It is important for diagnosticians to differentiate symptoms of anxiety or depression, like apathy, loss of interest, and emotional blunting with the cognitive-behavioral symptoms of the neurodegenerative disorder.

Risk Factors For Amyotrophic Lateral Sclerosis

  • Family history—Having a family member with ALS makes one more likely to develop the disorder.
  • Sex—Women develop ALS than men before the age of 60. After age 60, the prevalence of the disorder is equal amongst men and women.
  • Age—ALS is typically a late-onset disorder. The risk increases between the ages of 40 and 60.
  • Toxin exposure—Exposure to lead and agricultural environmental toxins is a risk factor still being researched for its possible link to ALS.
  • Smoking—Experts theorize that tobacco products contribute to the death of the motor neurons leading to ALS symptoms.

Causes of Amyotrophic Lateral Sclerosis

Nearly 90-95% of cases account for sporadic ALS. Sporadic ALS occurs when there is not an obvious cause or risk factor. Patients with sporadic ALS have no family history of the condition, nor risk factors such as poor diet, excessive drug or alcohol consumption, or toxic exposure to harmful substances.  

The remaining 5-10% of cases are familial and a genetic mutation is responsible for causing the disorder. Dr. Robert Brown identified that gene mutations for the superoxide dismutase 1 or copper-zinc superoxide dismutase lead to ALS.

While there are many unknowns regarding the cause of ALS, researchers have been diligent in discovering various potential reasons for the death of motor neurons. The HSS cites viral infections, mitochondrial dysfunction, autoimmune conditions, or free radical injury.

Diagnosing Amyotrophic Lateral Sclerosis

ALS is commonly diagnosed by a neurologist—a doctor who specializes in the nervous system. No one test can diagnose ALS. The diagnosis relies on obtaining a full medical history, signs observed during the physical evaluation, and tests to exclude alternative reasons for the patient’s symptoms.

Amyotrophic Lateral Sclerosis (ALS): Lou Gehrig's Disease
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Neurological Evaluation

After a family and medical history has been established, the physician performs a neurological evaluation as part of the ALS diagnostic process. During the neurological evaluation, the doctor is observing for not only weakness, difficulties with speech and swallowing, and unsteadiness of gait, but also for specific upper and lower motor neuron manifestations. Upper motor neuron symptoms indicative of ALS include muscle spasms, abnormal reflexes, stiffness or spasticity, and decreased dexterity. Lower motor neuron findings are breathing difficulties, a foot drop, atrophy of muscles, cramping of muscles, muscle twitching or fasciculations, and depressed reflexes.

Blood and Urine Tests

With the clinical evaluation underway, the next step in diagnosing ALS is taking simple blood and urine samples. While these tests do not prove ALS directly, they do rule out conditions that may be responsible for the patient’s neurological symptoms. Thyroid hormone levels, a 24-hour urine collection for heavy metals, and vitamin levels are recommended.

Muscle and Nerve Tests

To access for ALS, an electromyogram (EMG) is helpful. An electromyogram measures how the muscles respond to nerve stimulation through an electrode placed under the skin. Abnormal EMG results are associated with neuromuscular disorders like ALS. Additionally, nerve conduction studies may also reveal relevant information. Nerve conduction studies measure how the nerves send signals to the muscles.

Imaging Tests

Imaging tests, commonly referred to as magnetic resonance imaging (MRI), give detailed images of the brain and spinal cord. These images cannot directly diagnose ALS, but show tumors and herniated discs that can be responsible for the patient’s symptoms.

Conditions Commonly Mistaken For Amyotrophic Lateral Sclerosis

Other conditions share the signs and symptoms of ALS. Physicians must be thorough during the diagnostic process to ensure the patient is not misdiagnosed with a similar neuromuscular disorder that affects different motor neurons.

  • Primary Lateral Sclerosis— A rare neuromuscular disease in which damaged nerves prevent signals from reaching upper motor neurons in the spinal cord. It is characterized by progressive muscle weakness in the voluntary muscles accompanied by upper motor signs like rigidity and spasticity.
  • Progressive Bulbar Palsy—Primarily involving lower motor neurons, degeneration of the brainstem destroys the cranial nerve controlling speech, swallowing, chewing, and other facial movements. The condition progresses into limb weakness.
  • Pseudobulbar Palsy—Associated with various neuromuscular diseases, pseudobulbar palsy is the inability to control facial movements like speaking, swallowing, and chewing.
  • Progressive Muscular Atrophy—Lower motor neurons are affected to cause progressive muscle weakness without rigidity.

Treating Amyotrophic Lateral Sclerosis

Treatment for ALS is focused on preventing the progression of symptoms. There is no cure, but a successful treatment regimen includes a series of medications, therapies, and surgical interventions to increase the patient’s quality of life and to safely reduce pain.

Medications

Two drugs are FDA approved to treat ALS:

  • Riluzole (Rilutek)—Studies indicate that Riluzole increases life expectancy up to 6 months in cases of ALS. It is taken orally and known to cause dizziness and gastrointestinal side effects.
  • Edaravone (Radicava)—Edaravone is an intravenous option administered through the veins. Aside from ALS, it is also used in stroke patients.

Someone with ALS may take medications other than the drugs above that show evidence of slowing the progression of the disease. These include medications to treat pain like anti-inflammatories and pain relievers. Muscle relaxants treat muscle cramps, spasticity, and spasms. Dextromethorphan (Nuedexta) targets the symptoms of uncontrollable laughing and crying. For patients struggling with oral intake due to weakness or choking, vitamin supplements may be indicated.

Therapy

The typical ALS patient participates in various therapies as part of treatment. The type and timing of therapy evolve with the progression of muscle wasting from the illness. These therapies cannot cure ALS, but they can slow the progression if done regularly.  

Physical Therapy

An effective therapy to address muscle wasting is physical therapy. In physical therapy, a trained professional creates an exercise regimen based on the patient’s needs. Physical activity preserves mobility through stretching and range of motion movements. Stretching is particularly helpful for muscle cramping and range of motion exercises targets pain and stiffness. Strengthening exercises, like exercise requiring weights, does not strengthen weak muscles already wasted in the degeneration process. Instead, aerobic exercises that elevate the heart and respiratory rate are recommended for patients with ALS to enhance overall fitness.

Occupational Therapy

Occupational therapy teaches patients to adapt and adjust to their diagnosis. Occupational therapists exchange information with the patient, accessing which areas of their life can be modified to improve or maintain independence for longer. They prescribe adaptive equipment like canes, wheelchairs, and walkers for mobility. They also may suggest bracing of joints (i.e. ankles, feet, knees, neck) to aid in walking or holding the patient’s head upright when the muscles are too weak to do so. Grab bars can be added to the patient’s home to prevent falls. Tools such as custom eating utensils are additional tools sometimes used in occupational therapy if the patient struggles to feed themselves due to twitching or hand/arm weakness. In those who frequently aspirate or choke while eating, nutritional support via a surgically implanted feeding tube is advised.

Speech Therapy

Speech changes are prevalent as ALS kills neurons in the bulbar region that controls speaking. The muscles of the lips, tongue, jaw, and vocal cords weaken and patients experience a loss of speech, unclear, slurred speech, and a hoarse voice. The goal of speech therapy is to overcome these barriers to communication. Speech pathologists provide tips and lend assistive devices that benefit speech. Based on the patient’s progression, suction devices may be recommended to reduce excessive saliva interfering with speech. Speech generating devices are also used.

Respiratory Therapy

Towards the later stages of ALS, the breathing muscles become affected. These patients eventually require assistive devices to breathe, which is managed by respiratory or breathing therapy. These may include non-invasive ventilation devices worn on the face attached to a machine to force air pressure into the patient’s lungs. For long term around the clock manual ventilation, respiratory therapy manages a patient’s tracheostomy—a surgically made hole in the neck to assist breathing.  

References

Orsini, M., Andorinho de Freitas Ferreira, A. C., Nascimento, O. J., de Souza, J. A., Magalhães, T. N., de Assis, A. C., Westin, L. K., Pessoa, B., Oliveira, A. B., Fiorelli, R., de Freitas, M. R., Bittencourt, J., Fiorelli, S., Moreira, M. F., & Ribeiro, P. (2016). Frontotemporal Dementia in Amyotrophic Lateral Sclerosis: From Rarity to Reality?. Neurology international, 8(2), 6534. https://doi.org/10.4081/ni.2016.6534

Thakore N. J., Pioro E. P. (2016). Depression in ALS in a large self-reporting cohort. Neurology 86 1031–1038. 10.1212/WNL.0000000000002465

Zucchi, E., Ticozzi, N., & Mandrioli, J. (2019). Psychiatric Symptoms in Amyotrophic Lateral Sclerosis: Beyond a Motor Neuron Disorder. Frontiers in neuroscience13, 175. https://doi.org/10.3389/fnins.2019.00175