Context The neurologic manifestations, laboratory findings, and outcome of patients with West Nile virus (WNV) infection have not been prospectively characterized. Objective To describe prospectively the clinical and laboratory features and longterm outcome of patients with neurologic manifestations of WNV infection. Design, Setting, and Participants From August 1 to September 2, 2002, a community-based, prospective case series was conducted in St Tammany Parish, La. Standardized clinical data were collected on patients with suspected WNV infection. Confirmed WNV-seropositive patients were reassessed at 8 months. Main Outcome Measures Clinical, neurologic, and laboratory features at initial presentation, and long-term neurologic outcome. Results Sixteen (37%) of 39 suspected cases had antibodies against WNV; 5 had meningitis, 8 had encephalitis, and 3 had poliomyelitis-like acute flaccid paralysis. Movement disorders, including tremor (15 [94%]), myoclonus (5 [31%]), and parkinsonism (11 [69%]), were common among WNV-seropositive patients. One patient died. At 8-month followup, fatigue, headache, and myalgias were persistent symptoms; gait and movement disorders persisted in 6 patients. Patients with WNV meningitis or encephalitis had favorable outcomes, although patients with acute flaccid paralysis did not recover limb strength. Conclusions Movement disorders, including tremor, myoclonus, and parkinsonism, may be present during acute illness with WNV infection. Some patients with WNV infection and meningitis or encephalitis ultimately may have good long-term outcome, although an irreversible poliomyelitis-like syndrome may result.

Acute muscular fatigue is associated with the development of oxidative stress in humans. Strenuous contraction increases free radical production by human limb muscle (1) and fatiguing exercise alters biochemical indices of oxidative stress including glutathione status (2, 3) and markers of lipid peroxidation (4, 5). Such biochemical changes can be inhibited by chronic supplementation with antioxidant vitamins (4, 5) but nutritional supplements have not improved exercise performance (6-9). Thus, experiments to date have not determined whether oxidative stress is a cause of muscular fatigue in humans or simply an effect.In order to establish a cause/effect relationship, it is critical to demonstrate that exogenous antioxidants inhibit the loss of mechanical function during fatigue. This study tested this relationship using an experimental design that differs from previous human studies in two aspects. First, rather than using chronic nutritional supplements, we pretreated subjects with the nonspecific antioxidant N-acetylcysteine (NAC)' (10) by intravenous infusion immediately before fatiguing exercise. Second, rather than using volitional exercise to induce peripheral fatigue, we electrically stimulated tibialis anterior to repetitively contract under quasi-isometric conditions. This technique was developed previously (11) to evoke peripheral fatigue in the absence of central neural processes (e.g., inhibitory reflexes, coordination, motivation, learning) that can importantly influence volitional

Acute weakness associated with West Nile virus (WNV) infection has previously been attributed to a peripheral demyelinating process (Guillain-Barré syndrome); however, the exact etiology of this acute flaccid paralysis has not been systematically assessed. To thoroughly describe the clinical, laboratory, and electrodiagnostic features of this paralysis syndrome, we evaluated acute flaccid paralysis that developed in seven patients in the setting of acute WNV infection, consecutively identified in four hospitals in St. Tammany Parish and New Orleans, Louisiana, and Jackson, Mississippi. All patients had acute onset of asymmetric weakness and areflexia but no sensory abnormalities. Clinical and electrodiagnostic data suggested the involvement of spinal anterior horn cells, resulting in a poliomyelitis-like syndrome. In areas in which transmission is occurring, WNV infection should be considered in patients with acute flaccid paralysis. Recognition that such weakness may be of spinal origin may prevent inappropriate treatment and diagnostic testing.

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.