Amyotrophic Lateral Sclerosis

Amyotrophic lateral sclerosis (ALS), commonly referred to as motor neuron disease or Lou Gehrig's disease, is a rare, difficult to diagnose, ultimately fatal, progressive, neurodegenerative disorder. Lengthy delays in diagnosis are common1 because these patients often present to neurosurgeons, orthopedic surgeons, otolaryngologists, and other specialists, rather than neurologists. Hand surgeons are likely to be at the forefront of this initial evaluation and must be prepared to consider ALS in the differential diagnosis of patients presenting with motor deficits in the hand without associated sensory changes.

Amyotrophic lateral sclerosis typically involves men 50 to 70 years of age. The incidence of ALS is 1 to 2 per 100,000, with equal prevalence across racial and geographic distributions.2 Only 10% have a clear genetic link; the remaining 90% of cases are sporadic. ALS is progressively fatal, with a mean life expectancy of 3 to 5 years once the diagnosis has been made.2 Lengthy delays in diagnosis are often encountered. Belsh and Schiffman found that patients were evaluated by an average of 3.7 physicians before being correctly diagnosed with ALS, and 38% saw at least 4 physicians.3

The underlying pathology of ALS is the degeneration and eventual loss of motor neurons in the brain stem and anterior horn of the spinal cord. Therefore, the disease primarily affects motor function. Clinical hallmarks of ALS include progressive weakness and evidence of involvement of both upper and lower motor neuron pathways. Lower motor neuron findings include weakness, atrophy, fasciculations, and hyporeflexia. Upper motor neuron findings include slowed movement, spasticity, hyperreflexia, and pathological reflexes (including upgoing great toes on Babinski testing and positive Hoffman sign). Weakness usually presents in a single extremity or, on occasion, as bulbar symptoms (dysarthria or dysphagia). These symptoms and signs worsen progressively in the area of initial presentation and then spread to affect other regions of the body. A common presentation, for example, is isolated upper extremity weakness with loss of fine motor function and dexterity, and complaints of frequently dropping objects. These reports overlap with those of common compression neuropathies of the upper extremities and may lead to an initial referral to a hand surgeon. Indeed, early in the disease process, symptoms may involve only a single nerve. We have recently cared for a patient who presented with what appeared to be an isolated posterior interosseous nerve palsy, including a supportive electromyography study. A few weeks later, when similar symptoms presented in the contralateral limb, tongue fasciculations and a repeat electromyography led to the new and, ultimately, accurate diagnosis. This scenario is common because as the disease progresses, a more systemic pathologic process becomes apparent. A second patient who was referred to us for persistent bilateral carpal tunnel syndrome was observed to have profound bilateral thenar atrophy and weakness but normal sensation and unimpressive nerve conduction studies. She, too, eventually was diagnosed with ALS.

Historically, ALS has been considered a clinical diagnosis of exclusion for combined upper and lower motor neuron pathway involvement. However, ancillary testing is commonly used in the initial workup of patients. The specifics are beyond the scope of this review, but electrophysiological evaluation can assist the clinician in the diagnosis of ALS. Common findings include evidence of widespread acute and chronic denervation, no evidence of motor conduction block, and relatively normal motor and sensory nerve conduction studies.4 In addition, other potential diagnoses of lesser consequence are eliminated. There is a limited role for specific imaging studies. Magnetic resonance imaging is typically normal but may suggest upper motor neuron damage. Classification systems have been created in an effort to better standardize this difficult diagnosis. The reference standard classification is the World Federation of Neurology's El Escorial criteria. Originally created for research purposes, the El Escorial criteria incorporate clinical data, electrophysiological studies, neuroimaging, and neuropathology to classify patients as “definite,” “probable,” and “possible” cases of ALS.

There is only 1 medication approved currently for treatment of ALS. Riluzole, an inhibitor of presynaptic glutamate release, has been shown to prolong life by 2 to 3 months. Treatment is mainly supportive, including tracheostomy and gastrostomy tube placement. Although there are no curative treatments for ALS, a timely and accurate diagnosis may prevent unnecessary treatments and surgery. In a review of 260 patients, Srinivasan et al.5 found that 34 patients (13%) underwent surgery for symptoms that later were found to be manifestations of ALS.

Hand surgeons will continue to be involved routinely in the early evaluation of patients with ALS. It is imperative to consider this devastating disease in the differential diagnosis of any patient who presents with isolated weakness in 1 upper extremity and is found to have signs and symptoms that are consistent with ALS. The presence of both upper and motor neuron disease are the most pathognomonic signs, but any nerve deficit that cannot be explained fully by a more common entity should warrant suspicion. This alone can allow hand surgeons to contribute something positive to an otherwise dismal prognosis.

Several points bear repeat mention: (1) ALS should be considered in the differential diagnosis of patients presenting with motor deficits in the hand without associated sensory changes; (2) clinical hallmarks of ALS include progressive weakness and evidence of involvement of both upper and lower motor neuron pathways; (3) common findings on electrophysiological assessment include evidence of widespread acute and chronic denervation, no evidence of motor conduction block, and relatively normal motor and sensory nerve conduction studies; and (4) riluzole, an inhibitor of presynaptic glutamate release, has been shown to prolong life by 2 to 3 months.