eMedicine Specialties > Emergency Medicine > Neurology

Amyotrophic Lateral Sclerosis

Author: Kathleen Clem, MD, FACEP, Chair, Department of Emergency Medicine, Loma Linda University Medical Center
Coauthor(s): Joel C Morgenlander, MD, Professor, Division of Neurology, Duke University School of Medicine; Consulting Staff, Electromyography Laboratory, Muscular Dystrophy Association Clinic, Duke University Medical Center
Contributor Information and Disclosures

Updated: Sep 15, 2009

Introduction

Background

Amyotrophic lateral sclerosis (ALS) is a disease of unknown cause characterized by slowly progressive degeneration of upper motor neurons (UMNs) and lower motor neurons (LMNs). The UMN findings include hyperreflexia and spasticity. They result from degeneration of the lateral corticospinal tracts in the spinal cord. The LMN findings include weakness, atrophy, and fasciculations. They are a direct consequence of muscle denervation. ALS is eventually fatal because of respiratory muscle weakness. Aspiration pneumonia and medical complications of immobility contribute to morbidity.

Amyotrophic lateral sclerosis terminology is derived from the combination of the clinical examination findings of amyotrophy with the pathological finding of lateral sclerosis.

Because Charcot made the first clinical description in the 1860s, the disease is named for him in Europe. In the United States, the disease often is called Lou Gehrig disease after the baseball legend who died from ALS in 1941.

Pathophysiology

No single cause for amyotrophic lateral sclerosis (ALS) explains its entire pathology; indeed, there may be multiple causes resulting in phenotypic similarity. While ALS is ultimately a diffuse disease, onset is often focal and asymmetric. At onset, bulbar motor neurons can be involved, resulting in bulbar weakness (progressive bulbar palsy), or spinal cord anterior horn cells can be affected, resulting in limb weakness (spinal muscular atrophy). When upper motor neuron involvement of bulbar muscles occurs, a syndrome of pseudobulbar palsy results, causing spastic dysarthria, dysphagia, and emotional incontinence. Upper motor neuron involvement of spinal cord tracks results in spastic weakness of the limbs (primary lateral sclerosis). Later, spread to other motor areas produces the classic combination of upper and lower motor neuron dysfunction recognized as ALS.

Five to 10% of patients with ALS have a family history following an autosomal dominant pattern of inheritance. About 20% of these patients have a mutation of the superoxide dismutase 1 (SOD1) enzyme. This mutation is believed to make a defective protein that is toxic to motor nerve cells. The SOD1 mutation, however, accounts for only 1 or 2% of ALS cases, or 20% of the familial (inherited) cases. This enzyme functions as an antioxidant. Glutamate toxicity, mitochondrial dysfunction, and autoimmunity all may play a role in causation.

Frequency

United States

Approximately 5,600 people in the United States are diagnosed with ALS each year. The incidence of ALS (2-3 per 100,000 people) is 5 times higher than Huntington disease and about equal to multiple sclerosis. It is estimated that as many as 30,000 Americans may have the disease at any given time.

International

No ethnic or racial predisposition to ALS is apparent worldwide, and the incidence is believed to be the same as that in the United States.

Mortality/Morbidity

ALS is a fatal disease. Median survival is 3-5 years. However, longer survival is not rare. About 30% of patients with ALS live 5 years after diagnosis, and about 10-20% survive for greater than 10 years. Long-term survival is associated with a younger age at onset, being male, and limb rather than bulbar symptom onset. Rare reports of spontaneous remission exist.¹

Race

The incidence of ALS is higher in men than in women prior to the age of 65-70 years, but, thereafter, the gender incidence is equal.

Sex

Incidence is higher in men than in women, with a male-to-female ratio of 1.6:1.

Age

Onset of ALS usually occurs in patients aged 40-60 years. Mean age of onset of sporadic ALS is 56 years; mean age of onset of familial ALS is 46 years.

Clinical

History

The diagnosis of amyotrophic lateral sclerosis (ALS) is primarily clinical. Electrodiagnostic testing contributes to the diagnostic accuracy. ALS can be differentiated from stroke or trauma due to the subacute or chronic progression of symptoms. When focal limb weakness occurs, ALS is differentiated from a root or peripheral nerve lesion by the lack of pain or sensory symptoms. While ALS is a slowly progressive disease, a precipitous event may occur to bring the patient to the ED.

• Bulbar symptoms: The patient's family first notices slurring of words or choking during a meal. An aspiration event or acute respiratory symptoms of air hunger occur.
• Extremity weakness: The patient notices wrist drop interfering with his or her work performance. Or, the patient may find reduced finger dexterity, cramping, stiffness, and weakness or wasting of intrinsic hand muscles. Less frequently, the patient may develop foot drop resulting in a fall or sprain.
• Fasciculations may present early on the disease, particularly in the tongue.

Physical

Lower motor neuron signs include weakness, atrophy, fasciculations, and depressed reflexes. Fasciculations are observed with the muscle at rest.

Upper motor neuron signs include an upper motor neuron pattern of weakness (greatest in the extensors of the arm and flexors of the leg), spastic bulbar and limb muscles, hyperreflexia, and extensor plantar responses. A hyperreflexic jaw jerk helps to confirm upper motor neuron involvement causing dysarthria and dysphagia.

Tendon reflexes are paradoxically brisk.

In patients with pseudobulbar palsy, emotional incontinence may cause the patient to over-react to sad or funny things. The patient is aware of the lack of control. Cognitive impairment, if present, most often is observed in patients with bulbar involvement.

Muscle cramps are common for patients with lower motor neuron involvement, while patients with upper motor neuron dysfunction can have clonus or painful extensor spasms.

Ocular, sensory, or autonomic dysfunction occurs only very late in the disease course, usually in patients living with ventilatory support.

The key finding in an involved limb is the combination of lower and upper motor neuron dysfunction with a weak, atrophic, fasciculating muscle occurring in combination with increased tone and hyperreflexia. 

When ALS first clinically manifests in the lower extremities, foot drop is common. Patients may report a "slapping" gait. Proximal pelvic girdle onset is less common, but, when it occurs, patients complain that they have difficulty climbing stairs and/or moving from a chair to standing. Patients may present to the emergency department due to tripping and falling.

Bulbar symptoms manifest as dysarthria or dysphagia and are the next most common presentation (20%). The symptoms may become worse after extended use of the voice. Patients may have more trouble with swallowing of thin liquids then thick, and they may need to swallow multiple times to complete transport of liquids through the esophagus to the stomach.

Rarely, patients with ALS may present with respiratory muscle weakness, generalized weakness, and difficulty with head control. They may develop disturbed nocturnal sleep and exhibit excessive daytime sleepiness.

When patients have axial truncal weakness they have difficulty maintaining an erect posture when standing and may support their trunk by placing their hands in their thighs and "walking" them up their leg to assist in standing erect. Some patients feel more secure when pushing a heavy object on wheels such as a grocery cart.

A link exists between ALS and frontotemporal executive dysfunction that may precede or follow the onset of ALS, but most patients with ALS do not have overt dementia, and cognitive impairment is usually subtle. The proportion of patients with ALS who meet criteria for frontotemporal dementia is 15%. When ALS is associated with frontotemporal dementia, there is an associated shorter survival than with ALS alone.²

• Lower motor neuron signs include atrophy and fasciculations.
• Upper motor neuron (ie, corticospinal tract) signs include spasticity and hyperactive tendon reflexes and may include the Babinski sign.
• No loss of anal sphincter tone occurs. Cardiac and smooth muscle are not involved.
• The course is progressive, and initial symptoms primarily are those of weakness.
• Weakness often is asymmetric and begins in the legs, arms, or oropharyngeal muscles with approximately equal frequency. Masticatory weakness occurs late. Ultimately, weakness becomes symmetrical.
• Ocular musculature is not involved.
• Muscle atrophy and weight loss almost always are recognized by the time the patient seeks medical treatment.
• Fasciculations may be quite widespread and active. Surprisingly, the patient often ignores this symptom.
• Patients may have inappropriately active tendon reflexes and weak, wasted, twitching muscles.
• Muscle cramps are common.
• Dysarthria, exaggeration of motor expressions, and emotional lability (pseudobulbar affect) may occur when the disease process involves the corticobulbar projections to the brainstem.
• Decubitus ulcers are rare.
• Hypoxia or cardiac arrhythmias are the most common cause of death in patients with ALS. The primary cause of death among patients electing to use ventilatory support is pulmonary infection.

Causes

The specific cause of amyotrophic lateral sclerosis (ALS) is unknown. Recent evidence suggests the existence of clusters of cases.³ Further evaluation of clusters may provide epidemiologic data associated with causes.

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