Correspondence
Nitric Oxide and Motor Neuron Disease
N Engl J Med 1995; 333:522-523August 24, 1995
- Article
To the Editor:
Tsai and Gastfriend (April 13 issue)1 report the case of a 58-year-old woman with primary pulmonary hypertension and a history of alcohol abuse in whom profound weakness developed after a bilateral lung transplantation. They state, “After receiving nitric oxide as a pulmonary dilator postoperatively for 15 days, she was found to be paralyzed and areflexic.” The authors believe that nitric oxide treatment and the up-regulation of N-methyl-d-aspartate (NMDA) receptors by chronic alcoholism “may have caused extensive lower motor neuron disorder.” There are several problems with this hypothesis. First, the localization is uncertain; second, more likely diagnoses have not been excluded; and third, no evidence is provided for the up-regulation of NMDA receptors or motor neuron injury.
Details of the neurologic examination during the course of the illness are not provided. We are told that electromyography demonstrated “extensive denervation,” but there is no information about motor- or sensory-nerve conduction velocities or amplitudes. It is suggested that the disorder is located in the lower motor neurons (neuronopathy), but disease of the peripheral nerves or muscles can also present with profound weakness and areflexia.
This patient was critically ill and ultimately required respiratory support. In this setting, likely diagnoses include the Guillain–Barré syndrome, critical-illness neuropathy, motor axonopathy from prolonged neuromuscular blockade, and acute quadriplegic myopathy.2-4 Electrodiagnosis often provides the key to localization. A diagnosis of the Guillain–Barré syndrome would be supported by elevated levels of protein in cerebrospinal fluid and electrodiagnostic evidence of acquired demyelination. Critical-illness neuropathy is a severe motor and sensory axonopathy causing diffuse denervation and decreased motor-unit recruitment.2,3 Sensory fibers are spared in both acute motor axonopathy and quadriplegic myopathy, but full motor recruitment in weak muscles indicates a myopathy. According to one report, serum creatine kinase levels were normal in 43 percent of patients with quadriplegic myopathy.4
Recovery from a neuronopathy results from axonal sprouting of surviving fibers and is typically prolonged and incomplete. Recovery from axonal or myopathic lesions is usually faster and fuller. The results of testing during convalescence are not reported, but gradual improvement over three months would seem unlikely if paralysis were due to the loss of lower motor neurons.
Finally, there is no evidence of the up-regulation of NMDA receptors. A brain or spinal cord biopsy to obtain samples for definitive binding studies was probably considered too invasive, and there is no specific ligand for noninvasive positron-emission tomographic studies. Association does not imply causation, and this hypothesis is based only on inference from in vitro experiments. The idea merits further investigation and justifies caution in the clinical use of nitric oxide but does not support the claim that nitric oxide caused this patient's weakness.
4 ReferencesL. John Greenfield, Jr., M.D., Ph.D.
James W. Albers, M.D., Ph.D.
University of Michigan Medical Center, Ann Arbor, MI 48104-16871
Tsai GE ,Gastfriend DR . Nitric oxide-induced motor neuron disease in a patient with alcoholism. N Engl J Med 1995;332:1036-1036
Full Text | Web of Science | Medline2
Chad DA ,Lacomis D . Critically ill patients with newly acquired weakness: the clinicopathological spectrum. Ann Neurol 1994;35:257-259
CrossRef | Web of Science | Medline3
Bolton CF ,Gilbert JJ ,Hahn AF ,Sibbald WJ . Polyneuropathy in critically ill patients. J Neurol Neurosurg Psychiatry 1984;47:1223-1231
CrossRef | Web of Science | Medline4
Hirano M ,Ott BR ,Raps EC , et al. Acute quadriplegic myopathy: a complication of treatment with steroids, nondepolarizing blocking agents, or both. Neurology 1992;42:2082-2087
Web of Science | Medline
