Amyotrophic lateral sclerosis (ALS), often called Lou Gehrig's disease, causes rapidly progressive muscle atrophy and weakness resulting from the degeneration of both upper and lower motor neurons. ALS leads to varying degrees of spasticity, hyperreflexia, and muscle paralysis, eventually resulting in pulmonary complications and the need for mechanical ventilatory support. Because there is no cure, clinicians attempt to slow disease progression and preserve function as much as possible. Medical management is directed at preventing pulmonary infections and forestalling terminal respiratory failure.
Since 2009, 13 genes and loci have been identified that are associated with the disease.1 Inclusions in the TAR DNA-binding protein-43 have been found in both ALS and frontotemporal dementia.2 Environmental exposures are suspected to increase the risk of ALS, but no specific ones have been identified to date.3
Gross CNS pathology includes frontal cortical atrophy, degeneration of both the corticospinal and spinocerebellar tracts, a reduction in large cervical and lumbar motor neurons, and cranial nerve nuclei degeneration. Both motor and sensory peripheral nerves undergo axonal degeneration and segmental demyelination, including motor end plate and axon terminal involvement.
Upper motor neuron demyelination and dysfunction cause limb spasticity, hyperreflexia (including Babinski sign and a brisk jaw-jerk reflex), and emotional lability. Limb weakness, a lower motor neuron dysfunction, is the first symptom in 65% of patients.4 Other associated lower motor neuron dysfunctions include atrophy, cramps, fasciculations, dysarthria, dysphagia, and difficulty in mastication. At the time of initial presentation, asymmetric extremity cramping, fatigue, weakness, muscle fasciculations, and atrophy can be seen, especially in the upper extremities.5 Facial weakness, dysarthria, tongue weakness, atrophy, and fasciculations can be seen with bulbar lower motor neuron dysfunction. Despite these profound motor findings, sensory and cognitive function is usually spared. Regardless of the initial symptoms, widespread motor and respiratory dysfunction progresses within weeks to months. Significant extremity atrophy occurs, as well as fasciculations, hyperreflexia, foot drop, and claw deformity of the hand. Patients also may develop monotonous speech caused by tongue atrophy, despite the relative sparing of facial and eye movements. Some patients eventually diagnosed as having ALS present initially with cervical or back pain consistent with an acute compressive radiculopathy. Despite successful operative intervention, significant muscle wasting consistent with motor neuron dysfunction develops shortly after the procedure.6 Progressive respiratory muscle weakness initially causes exertional dyspnea and eventual dyspnea at rest. Overt dementia and parkinsonism may occur in up to 15% of patients, especially those with ALS. Other cognitive problems, such as apathy, poor attention and motivation, and altered social skills, may be noted.
The clinical diagnosis of ALS is suggested when there are signs of both upper and lower motor neuron dysfunction, including weakness, muscle atrophy, fasciculations, and hyporeflexia without other CNS dysfunction.7 Given the complexity of diagnosing ALS, the median time to diagnosis is 14 months....