Diagnosis and progression of ALS

Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease characterized by loss of upper and lower motor neurons, leading to progressive loss of motor function. The disease is almost always fatal, and approximately 50% of patients die within 3 to 4 years after onset of symptoms. ^[1,2] ALS is more common in men than in women (until age 70, when the rate becomes equal) and, although the average age of onset is in the mid-fifties, the disease can occur at anytime after the teen years. ^[2-4] The disease is a distinct syndrome characterized by a combination of upper motor neuron (UMN) and lower motor neuron (LMN) dysfunction and by generalized distribution and relentless progression. No specific blood test is available to provide an unequivocal diagnosis of ALS, and the clinical diagnosis is usually based on results of physical and neurologic examinations that identify the signs and symptoms of the disease. Because UMN and LMN symptoms associated with a variety of other disorders mimic those seen in ALS patients, an integral part of diagnosing ALS involves excluding other possible causes of the signs and symptoms exhibited by the patients. Diagnostic tests, such as electromyography (EMG), neuroimaging, blood and urine tests and, if indicated, muscle and nerve biopsy, are therefore used in this process.

Types of ALS, hypotheses of pathogenesis, and need for early diagnosis.

Although ALS was first described more than 120 years ago by Charcot, ^[5] it has remained an enigmatic disease. Recently, however, as the result of intense research during the past decade, significant advances have been made in understanding the pathogenesis and etiology of ALS and in identifying potential management strategies for the disease.

More than 90% of ALS cases are classified as "classical," a type of sporadic ALS, and are characterized by a combination of UMN and LMN involvement. ^[2] Among classical ALS patients, more than two-thirds present with …