Neuromuscular manifestations of west nile virus infection

Abstract

The most common neuromuscular manifestation of West Nile virus (WNV) infection is a poliomyelitis syndrome with asymmetric paralysis variably involving one (monoparesis) to four limbs (quadriparesis), with or without brainstem involvement and respiratory failure. This syndrome of acute flaccid paralysis may occur without overt fever or meningoencephalitis. Although involvement of anterior horn cells in the spinal cord and motor neurons in the brainstem are the major sites of pathology responsible for neuromuscular signs, inflammation also may involve skeletal or cardiac muscle (myositis, myocarditis), motor axons (polyradiculitis), and peripheral nerves [Guillain-Barré syndrome (GBS), brachial plexopathy]. In addition, involvement of spinal sympathetic neurons and ganglia provides an explanation for autonomic instability seen in some patients. Many patients also experience prolonged subjective generalized weakness and disabling fatigue. Despite recent evidence that WNV may persist long-term in the central nervous system or periphery in animals, the evidence in humans is controversial. WNV persistence would be of great concern in immunosuppressed patients or in those with prolonged or recurrent symptoms. Support for the contention that WNV can lead to autoimmune disease arises from reports of patients presenting with various neuromuscular diseases that presumably involve autoimmune mechanisms (GBS, other demyelinating neuropathies, myasthenia gravis, brachial plexopathies, stiff-person syndrome, and delayed or recurrent symptoms). Although there is no specific treatment or vaccine currently approved in humans, and the standard remains supportive care, drugs that can alter the cascade of immunobiochemical events leading to neuronal death may be potentially useful (high-dose corticosteroids, interferon preparations, and intravenous immune globulin containing WNV-specific antibodies). Human experience with these agents seems promising based on anecdotal reports.

Keywords: West Nile virus; fever; infection; poliomyelitis.

Figure 1

Spectrum of pathological findings in West Nile virus poliomyelitis: (A) Chromatolytic neuron with eccentric nucleus and distended cell body. Chromatolysis is usually triggered by damage to the cell body or axon. Neuronal recovery through regeneration can occur after chromatolysis, but most often it is a precursor of cell death (apoptosis). The event of chromatolysis is also characterized by a prominent migration of the nucleus toward the periphery of the cell and increase in the size of the cell body (hematoxylin–eosin, original magnification ×400); (B) Activated microglial cells surround and ingest a dead neuron (neuronophagia), which is typical of viral infections (hematoxylin–eosin, original magnification ×400); (C) Blood vessel at the interface between ventral horn gray matter and adjacent white matter surrounded by a dense cuff of chronic inflammatory cells (perivascular inflammation); wm, white matter; gm, gray matter (hematoxylin–eosin, original magnification ×100); (D) Cervical sympathetic ganglia. Microglial nodules are clustered around eosinophilic husks of dying ganglion cells. Microglial cells are consuming the pyknotic sympathetic neurons (neuronophagia; hematoxylin–eosin, original magnification ×400).

Figure 2

Electromyographic (EMG) examination in a 50-year-old man with WNV poliomyelitis limited to the right upper limb. Needle examination of the biceps muscle at 1 year follow-up showed persistent profound denervation with only a single voluntarily recruited rapidly firing motor unit potential. Similar denervation was noted in other shoulder girdle muscles. Clinical follow-up 5 years later revealed persistent severe weakness in proximal upper limb muscles.