Amyotrophic lateral sclerosis (ALS) is a progressive motor neuron disease involving muscle weakness and wasting. The prevalence of ALS has been estimated at 5.2 cases per 100,000 population and affects approximately 16,500 individuals in the United States.1 ALS is usually diagnosed in patients between the ages of 40 and 70 years, although diagnosis can also occur as early as age 20 and in those aged >80 years.2 ALS is more common in men until the seventh decade, after which women and men are equally affected by the disease.2
ALS is categorized into 2 types: sporadic and familial. Sporadic ALS comprises 90% to 95% of cases without a known genetics or environmental cause.3 Potential causes of sporadic ALS include excess glutamate production, viral infections, and inflammatory processes.4 Alternatively, familial ALS has an autosomal-dominant inheritance pattern and presents similarly to sporadic ALS.2 Two genetic mutations are known to cause familial ALS: C9orf72 gene mutation, which is located on the ninth chromosome, and superoxide dismutase type 1 (SOD1) gene mutation on the 22nd chromosome.5-7
History and Physical Findings
ALS is purely a motor neuron disease; sensory neurons are not affected.4 A diagnosis of ALS can be overlooked by clinicians unfamiliar with the various signs of the disease. Although a number of diseases affect either the upper motor neurons (ie, primary lateral sclerosis) or the lower motor neurons (ie, progressive bulbar palsy), ALS characteristically affects both upper and lower motor neurons simultaneously, which is a unique trait of this disease.2,4
The majority of patients with ALS present with asymmetric muscle weakness and wasting in an upper limb that progresses to a lower limb. Upper motor neuron lesions can be identified during physical examination by observing the Babinski sign, slowed rapid alternating movements, and increased deep tendon reflexes. Upper motor neuron lesion complaints include difficulty picking up delicate objects or fastening buttons, tripping, stumbling, and difficulty coordinating leg movements.11 Lower motor neuron complaints usually involve upper and lower extremity muscle atrophy, weakness, twitching, and cramping.2 Lower motor neuron lesions contribute to difficulty squatting, foot drop, waddling gate, muscle atrophy, and fasciculations.2 Signs and symptoms of ALS are reviewed in Table 1.2
Approximately 30% of patients with ALS present with bulbar signs and symptoms (Table 2).8-10 Dysphagia, excessive salivation, and exaggerated emotional responses are types of upper and lower motor neuron bulbar symptoms experienced by patients with ALS.4 Excess salivation and drooling are directly related to a patient’s difficulty swallowing saliva and liquids; they often experience less difficulty swallowing solids.2 Difficult articulation, hoarseness, and diminished volume are speech defects that cause communication challenges for patients with ALS and may eventually progress to the inability to speak.2,4 Patients with ALS also tend to experience pseudobulbar affect, or brief episodes of exaggerated emotional responses consisting of laughter or crying that emerge rapidly, without warning.2,12 During physical examination, bulbar symptoms present with facial weakness and atrophy, slow tongue movements, and poor soft palate and uvula rise upon phonation.
As ALS progresses, respiratory muscle involvement increases resulting in respiratory failure, which is the most common cause of death related to ALS.13,14 Signs of respiratory distress include tachypnea, use of accessory respiratory muscles, and abdominal paradox, while symptoms of respiratory distress include dyspnea, weak cough, and sleep-disordered breathing.2 Though unlikely, patients may initially present with the previously stated respiratory symptoms or axial symptoms (ie, difficulty holding head upright or maintaining an upright seated position, imbalance, and abdominal protuberance) due to weak abdominal muscles.2
Extraocular muscle movements, bladder and bowel movements, or sensory function are not affected by ALS.4 Additionally, patients with ALS do not experience skin integrity issues; however, they may develop pressure ulcers from immobility.4