Amyotrophic Lateral Sclerosis (ALS) – Diagnosis, Symptoms, and Treatment

What is Amyotrophic Lateral Sclerosis?

Amyotrophic lateral sclerosis (ALS) or Lou Gehrig disease is a neurologic condition characterized by upper and lower motor neuron degeneration.  Patients typically develop muscle weakness and spasticity resulting in progressive immobility and, ultimately, death.  Patients typically have signs of upper motor neuron disease such as muscle stiffness and hyperactive reflexes.  They also have lower motor neuron signs such as muscle atrophy (shrinkage) and fasciculations.  The reproductive system is not affected. Therefore, patients with ALS typically do not have trouble with erectile dysfunction or infertility.  A small subset of individuals have cognitive dysfunction.

Over time, the disease progresses to involve the respiratory muscles (e.g., diaphragm), leading to problems breathing, pneumonia, respiratory failure, and death.

What Causes Amyotrophic Lateral Sclerosis?

The exact cause of amyotrophic lateral sclerosis is not clear.  What is clear is that upper motor neurons and lower motor neurons degenerate over time.  Upper motor neurons include neurons in the brain and the motor portion of the spinal cord.  Lower motor neurons are nerve cells that start in the spinal cord and exit to innervate muscles in the periphery.

When upper motor neurons die, this typically causes signs such as muscle rigidity, weakness, and hyperactive reflexes.  When lower motor neurons die, this typically results in atrophy or wasting of the muscles.  The muscle becomes weak and may demonstrate a phenomenon called fasciculations – this is the medical term for muscle twitching.

Risk factors for ALS typically include:

• Advanced age
• Family history
• Cigarette smoking

How Common is Amyotrophic Lateral Sclerosis?

Amyotrophic lateral sclerosis is an uncommon neurologic disorder.  The condition typically requires referral to a neurology specialist.

In Europe and North America, ALS’s incidence is approximately 1.5-2.7 cases per 100,000 people per year.  The prevalence of ALS in these countries is about 2.7-7.4 cases per 100,000 people.  The disease is slightly more common in men, although it is equally prevalent in men and women after age 70.  The incidence of ALS increases every 10 years, particularly after age 40.

Signs and Symptoms

Symptoms and signs of amyotrophic lateral sclerosis typically include upper and lower motor neuron disease findings:

Upper motor neuron features:

• Muscle weakness
• Spasticity – increase muscle tone
• Hyperactive reflexes
• Pathologic reflexes – Babinski sign

Lower motor neuron features:

• Muscle atrophy – shrinking and wasting of muscle
• Fasciculations – muscle twitching

These symptoms progressively worsen over time and often affect muscles involved in limb movement, swallowing, speaking, and breathing.  The sensation is typically preserved.

In advanced cases, patients lose complete mobility and are confined to a wheelchair.  This results in impaired physical function and an inability to care for oneself.  Patients ultimately lose their ability to breathe and may require a breathing tube and assistance with a breathing machine.  Complications include pneumonia, respiratory failure, and death.  Most patients die within 3-5 years of being diagnosed.

Diagnosis

The diagnosis of amyotrophic lateral sclerosis is suggested based on symptoms and physical examination. Individuals typically have upper motor neuron and lower motor neuron disease that is not explained by another medical condition.

Your doctor will typically confirm the diagnosis with electrodiagnostic testing such as nerve conduction studies and electromyography.  These tests evaluate your nerves and muscles to determine if there are any signaling abnormalities.  They may also obtain an MRI of your brain and spine to evaluate other disorders such as tumors or stroke.  MRI in ALS is usually normal.

They may obtain a lumbar puncture (spinal tap) – during this procedure, a needle is inserted into the fluid-filled pocket surrounding your spinal cord.  This fluid is then extracted and sent to the laboratory to be analyzed for its color and appearance.  Further testing is usually performed to evaluate cell counts, protein, glucose levels, and bacteria.

Patients with advanced disease often develop respiratory failure or pneumonia.  If you have a fever, cough, chest pain, or difficulty breathing, your doctor will usually order a chest x-ray.  Patients with ALS typically have pulmonary function tests performed every 3 months to assess parameters such as vital capacity and maximal inspiratory pressures.

Commonly ordered blood tests include a CMP (comprehensive metabolic panel), CBC (complete blood cell count), thyroid function tests (TSH, free T4), muscle enzymes (creatine phosphokinase), and diabetes screening.  Your doctor may also evaluate inflammatory disorders such as myositis with an erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP).

Amyotrophic Lateral Sclerosis Medication and Treatment

Palliative care should be implemented at the start of diagnosis to help patients deal with undesirable symptoms and decreased quality of life.

Individuals that are recently diagnosed and have no trouble breathing may benefit from disease-modifying therapy - this typically includes the medication Rilutek (riluzole).

Patients with trouble swallowing and weight loss may be candidates for percutaneous gastrostomy tube (PEG) placement.  During this procedure, a tube is surgically inserted into the gastrointestinal tract to provide nutrition and tube feeding in patients that cannot chew, swallow, or eat.

Individuals with breathing difficulties and diaphragm weakness may ultimately lose their ability to breathe independently. These patients typically require placement of a breathing tube (tracheostomy) and assistance with a breathing machine (mechanical ventilation).

Patients with a life expectancy less than 6 months should generally establish care with hospice for comfort measures.

References:

1. Krivickas LS. Amyotrophic lateral sclerosis and other motor neuron diseases. Phys Med Rehabil Clin N Am 2003; 14:327. - https://www.ncbi.nlm.nih.gov/pubmed/12795519
2. Gordon PH, Cheng B, Katz IB, et al. The natural history of primary lateral sclerosis. Neurology 2006; 66:647. - https://n.neurology.org/content/66/5/647
3. de Carvalho M, Dengler R, Eisen A, et al. Electrodiagnostic criteria for the diagnosis of ALS. Clin Neurophysiol 2008; 119:497. - https://www.ncbi.nlm.nih.gov/pubmed/18164242