Literature
Clinical Pearls & Morning Reports
Published April 17, 2019
What are some of the features of ALS?
Signs of lower motor neuron dysfunction include muscle cramps, atrophy, and fasciculations. Spasticity and hyperreflexia are the most readily identifiable signs of upper motor neuron disease. Read the latest Case Records of the Massachusetts General Hospital here.
Clinical Pearls
Q: What is multifocal motor neuropathy?
A: Multifocal motor neuropathy is an immune-mediated, demyelinating polyneuropathy that causes insidious, progressive, asymmetric weakness of the arms and legs. Nerve-conduction studies typically reveal characteristic features of demyelination. Multifocal motor neuropathy is a treatable disorder; symptoms often improve after treatment with intravenous immune globulin. Among patients with suspected amyotrophic lateral sclerosis (ALS), multifocal motor neuropathy is the most commonly identified mimic that causes lower motor dysfunction.
Q: Do patients with myasthenia gravis uniformly have associated autoantibodies?
A: Fatigable weakness is the hallmark of myasthenia gravis, an autoimmune disorder that affects the postsynaptic neuromuscular junction. Some patients with myasthenia gravis, including 50% of those with isolated ocular myasthenia gravis, are seronegative for the autoantibodies associated with myasthenia gravis; however, only 10 to 20% of patients with myasthenia gravis that causes weakness outside the ocular region are seronegative.
Morning Report Questions
Q: What are some of the features of ALS?
A: To receive a clinical diagnosis of ALS, the patient must have signs of both lower and upper motor neuron degeneration, progressive spread both within and between regions of the body, and no laboratory, electrodiagnostic, or imaging findings suggestive of alternative diagnoses. The distribution of weakness in ALS varies. Insidious, asymmetric weakness of the arms and legs is most common; 25 to 40% of patients present with isolated bulbar weakness. Less than 10% of patients present with symmetric proximal weakness. Elevated creatine kinase levels are not specific for myopathy and can be seen in neuropathic disorders, as well. For example, approximately 40% of patients with ALS have elevated creatine kinase levels, and the levels are typically 1 to 2 times the upper limit of the normal range. Accumulation of intraneuronal TD-P43, a protein that is encoded by the TARDBP gene, is associated with sporadic ALS and with combined ALS and frontotemporal lobar degeneration.
Q: Does the presence of dysfunction of the neuromuscular junction rule out the possibility of ALS?
A: Fluctuating weakness is not exclusive to neuromuscular junction disorders and has been recognized in patients with ALS. In fact, ALS and other disorders may cause secondary dysfunction of the neuromuscular junction. As motor neurons are lost in ALS, surviving neighboring axons attempt to reinnervate muscle fibers that have been denervated, leading to the formation of immature neuromuscular junctions. An abnormal decremental response to repetitive nerve stimulation is typically associated with neuromuscular junction disorders but has been noted in more than one quarter of patients with ALS.