Mayo Clin Proc, October 2003, Vol 78 1245Flaccid Paralysis Due to West Nile Virus

piratory function was not compromised. During the next 3days, the patient’s facial diplegia became more pro-nounced, he had new weakness of spinal accessory inner-vated muscles, and his arm weakness progressed such thathe was able to move only his left wrist and fingers. Hebecame afebrile, and antibiotics were discontinued. A re-peated CSF examination 3 days after admission showed aprotein level of 86 mg/dL, a glucose level of 74 mg/dL, and220 nucleated cells (79% lymphocytes, 17% monocytes,4% neutrophils). West Nile IgM titer in CSF was positive(1:2.98; normal <1:2.0) and was confirmed with a plaquereduction assay. Bacterial serologic (brucella, ehrlichiosis,Whipple disease), fungal serologic (Coccidioidis,Sporothrix, Cryptococcus, Histoplasma, blastomycosis),Borrelia burgdorferi, Lyme disease, syphilis, leptospira,viral serologic (California virus, St Louis encephalitis,mumps, western equine encephalitis, hepatitis, and humanimmunodeficiency virus), and parasitic serologic (Toxo-plasma gondii) tests were all negative. Head and cervicalspine MRI with gadolinium showed normal findings.

During rehabilitation, approximately 3 weeks after ad-mission, the patient experienced transient worsening of hisleft upper extremity weakness with involvement of C7-T1innervated muscles. Four months after presentation, hisfacial weakness had resolved partially, but he continued tohave asymmetrical flaccid bibrachial paralysis (Figure 1)with profound loss of proximal muscle bulk. Nine monthslater, some improvement was noted, with electro-physiologic evidence of activation of his right deltoid andtriceps muscles and ongoing reinnervation.

For editorial comment, see page 1205.

Results of serial electrophysiologic tests are summa-rized in Table 1. The nerve conduction findings includedlow-amplitude motor responses at each location and anabsent blink reflex. No conduction block or dispersion ofcompound muscle action potentials was found on anynerve, including the spinal nerve, supraclavicular stimula-tion of the ulnar nerve, or supraclavicular stimulation of themusculocutaneous nerve. Amplitudes of the compoundmuscle action potentials decreased markedly during thecourse of the illness, primarily between the first and secondstudy with the ulnar motor unit number estimate as low as12 (normal >100). The amplitude reduction was accompa-nied by some slowing of conduction that occurs with loss

Mayo Clin Proc. 2003;78:1245-1248 1245 © 2003 Mayo Foundation for Medical Education and Research

Brief Communication

Since its emergence on the eastern seaboard, followedby a major endemic in the summer of 2002, West Nile

virus infection has been an important cause of meningoen-cephalitis in the United States.1 Early reports of survivorsnoted the occasional presence of flaccid weakness super-ficially mimicking Guillain-Barré syndrome (GBS).2-4

However, more recent preliminary reports describe electro-physiologic findings reminiscent of infectious poliomyeli-tis.5-7 We present 2 cases of West Nile virus infectioncomplicated by flaccid weakness in unusual patterns, withdetailed electrophysiologic studies consistent with damageto anterior horn cells or their axons.

Report of CasesCase 1.—A 34-year-old man with a medical history

remarkable for peptic ulcer disease, carpal tunnel syn-drome, and splenectomy after a motor vehicle crash pre-sented with fever of 5 days’ duration, upper respiratorytract symptoms, headache, tinnitus, and photophobia. Inthe preceding weeks, he remembered multiple mosquitobites while working in a swampy area.

On admission to the hospital, the patient was febrile(temperature, 38.4°C), had tachycardia, and appeared ill.He was alert but displayed meningismus. Computed tomo-graphic findings of the brain were normal. Cerebrospinalfluid (CSF) examination showed a protein level of 69 mg/dL, glucose level of 61 mg/dL, and 164 nucleated cells(77% neutrophils, 14% lymphocytes, 9% monocytes).Gram stain and latex agglutination test results were nega-tive. West Nile IgM titer in CSF was normal. Broad-spec-trum antibiotics were given.

The evening of admission (6 days after onset of illness),the patient experienced rapidly progressive weakness of hisarms and facial muscles. Neurologic examination revealedsevere flaccid proximal and distal weakness of the rightarm (Medical Research Council score of 2 [in which 0 isparalysis and 5 is normal strength]), moderate flaccidweakness of the left arm (Medical Research Council scoreof 3, primarily in C5 and C6 innervated muscles), mildbifacial weakness, and normal strength in the legs, wherefasciculations were visible. Reflexes were diminished inproportion to weakness. Sensation remained normal. Res-

Clinical and Electrophysiologic Patterns of Flaccid ParalysisDue to West Nile Virus

Address reprint requests and correspondence to Eelco F. M.Wijdicks, MD, Department of Neurology, Mayo Clinic, 200 First StSW, Rochester, MN 55905 (e-mail: wijde@mayo.edu)

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Mayo Clin Proc, October 2003, Vol 781246 Flaccid Paralysis Due to West Nile Virus

of fast-conducting large axons. F-wave latencies were ab-sent (markedly reduced in number on the third study).Median, and to a much lesser extent ulnar, motor distallatencies were prolonged on all studies. Other distal laten-cies and conduction velocities were normal. Sensory con-duction studies showed low-amplitude median responseswith prolonged distal latencies, consistent with thepatient’s history of carpal tunnel syndrome. Ulnar sensoryresponses were borderline low, possibly due to his largethick hands and fingers. Needle electromyography showedmarkedly reduced recruitment throughout, consistent withthe pronounced clinical weakness. Fibrillation potentialsbecame progressively more prominent, appearing firstproximally and later distally. No motor unit potentials wereseen in the flaccid muscles.

Case 2.—A 48-year-old previously healthy man experi-enced abrupt onset of right hand weakness and calf pain,followed later in the day by fever. He soon experiencednausea, vomiting, and delirium. Three days after onset ofillness, CSF examination showed a protein level of 104 mg/dL, a nucleated cell count of 120, and a positive West NileIgM level of 1:9.59. After recovery from his acute illness,the patient had generalized weakness but could walk with acane. However, after several days, his leg strength againworsened, and he experienced mild paresthesias of the legsand left ulnar digits. He was treated with intravenous im-

munoglobulin (IVIG), 0.4 mg/kg for 5 days, for presumedGBS, with equivocal improvement. An examination 2months after presentation showed moderate, generalizedflaccid weakness with more pronounced weakness in theleft leg. The quadriceps muscles were relatively spared.Reflexes were diminished in proportion to weakness.Findings on sensory examination were normal. Results ofelectrophysiologic testing performed 3 months after pre-sentation are shown in Table 1. The nerve conductionfindings included low-amplitude ulnar and peroneal motorresponses with no conduction block, no dispersion of thecompound muscle action potential, normal F-wave laten-cies, and normal sensory nerve responses. Needle elec-trode examination revealed fibrillation potentials, fascicu-lation potentials of leg muscles and the thoracic paraspinalmuscles, reduced recruitment, and motor unit action poten-tials of increased duration and amplitude. Substantial im-provement was noted within 3 weeks of hospitalization butthen plateaued.

DiscussionOur 2 patients with meningoencephalitis caused by

West Nile virus had complications of early, severe asym-metrical flaccid weakness. Both patients experienced asubacute period of worsening, and 1 patient’s weaknesstransiently progressed after it had plateaued. These un-

Figure 1. Follow-up after 1 month showing facial weakness with notable asymmetry (left).The right arm is flaccid; the left arm can bend against gravity at the elbow (right).

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Mayo Clin Proc, October 2003, Vol 78 1247Flaccid Paralysis Due to West Nile Virus

Case 1 Case 2 Nor- Studies 10 d 19 d 32 d 90 d mal

Motor conductionMedian—thenar

Amplitude, elbow (mV) 7.4 0.5 0.6 … >4.0Distal latency (ms) 6.0 5.8 6.5 … <4.5Conduction velocity (m/s) 52 42 43 … >50F-wave latency (ms) NR NR NR … <32

Ulnar—hypothenarAmplitude, elbow (mV) 7.4 3.0 2.1 5.2 >6.0Distal latency (ms) 3.9 3.5 4.0 3.3 <3.6Conduction velocity (m/s) 60 55 54 53 >53F-wave latency (ms) NR NR 34.7 34.2 <32

Musculocutaneous—bicepsAmplitude, axilla (mV) … 0 0.7 … >4.0Distal latency (ms) … NR 8.4 … <7.0

Accessory—trapeziusAmplitude (mV) … 0.3 0.3 … >4.0Latency (ms) … 3.4 2.9 … <3.5

Facial—nasalisAmplitude (mV) 1.6 0.2 0.2 … >1.0Latency (ms) 3.2 4.5 4.1 … <3.5

Peroneal—EDBAmplitude, knee (mV) … … … 1.0 >2.0Distal latency (ms) … … … 6.6 <5.8Conduction velocity (m/s) … … … 41 >41F-wave latency (ms) … … … 54.4 <56

Tibial—abductor hallucisAmplitude, knee (mV) 4.5 5.9 … 5.7 >4.0Distal latency (ms) 4.4 5.0 … 4.9 <6.5Conduction velocity (m/s) 41 47 … 43 >41F-wave latency (ms) 57 57 … 57.7 <62

Sensory conductionMedian—digit 2

Amplitude (uV) 9 7 … 36 >15Distal latency (ms) 5.5 5.0 … 3.3 <3.6Conduction velocity (m/s) NR NR … 63 >54

Ulnar—digit 5Amplitude (uV) 8 10 6 … >10Distal latency (ms) 2.4 2.9 3.1 … <3.2Conduction velocity (m/s) 59 63 … … >54

Sensory conduction (continued)Radial—digit 1

Amplitude (uV) … … 22 … >20Distal latency (ms) … … 2.1 … <3.0

Medial plantarAmplitude (uV) 7 … … … >5Latency 3.4 … … … <4.0

Superficial peronealAmplitude (uV) … … … 7 >6Distal latency (ms) … … … 3.9 <4.4

Blink reflex (ms)R1 … NR NR … <13.0R2 … NR 35 … <42

Needle electromyography†Right distal arm-Fib 0 0 + ++ 0

Reduced recruitment ++ +++ +++ 0 0Abnormal MUP 0 0 0 + 0

Right proximal arm-Fib 0 + +++ … 0Reduced recruitment +++ +++ +++ … 0Abnormal MUP 0 0 0 … 0

Right distal leg-Fib 0 0 0 ++ 0Reduced recruitment 0 0 0 + 0Abnormal MUP 0 0 0 ++ 0

Right proximal leg-Fib … … … ++ …Reduced recruitment … … … ++ …Abnormal MUP … … … ++ …

Right paraspinal-Fib 0 + ++ + 0Reduced recruitment ++ ++ ++ + 0Abnormal MUP 0 0 0 + 0

Right cranial-Fib … ± + … 0Reduced recruitment … +++ +++ … 0Abnormal MUP … 0 0 … 0

Left side-Fib 0 0 + … 0Reduced recruitment ++ ++ ++ … 0Abnormal MUP 0 0 0 … 0

Table 1. Results of Electrophysiologic Testing*

Case 1 Case 2 Nor- Studies 10 d 19 d 32 d 90 d mal

*Ellipses = not done; EDB = extensor digitorum brevis; Fib = fibrillation; MUP = motor unit potential; NR = no response; 0 = no abnormality; + = mildabnormality; ++ = moderate abnormality; +++ = severe abnormality.

usual manifestations together with constitutional symp-toms are of interest and should increase the suspicion ofWest Nile virus infection in the appropriate season. Al-though early reports suggested a process analogous toGBS, the damage more likely involves anterior horn cells.Notably, in an autopsy study of infected horses, lesions werefound in the ventral and lateral horns of the spinal cord butnot in the peripheral ganglia or peripheral nerve samples.8 Ina recent autopsy study of a patient who developed flaccidweakness after West Nile virus infection, examination of thespinal cord showed focal loss of anterior-horn neurons, ac-companied by gliosis, occasional macrophages (CD68+),neuronophagia, and perivascular lymphocytes.9

Electrophysiologic studies were recently published in 6other patients with West Nile virus infection and included

documented prolonged distal motor and F-wave latenciesin some of the patients. Although these findings couldsuggest demyelination, muscle biopsy in one of these pa-tients showed inflammation in intramuscular nerve twigs.The authors suggested that this pathologic finding couldexplain the prolonged latencies.

Our electrophysiologic studies are consistent with local-ization in the anterior horn cell. Neither of our patients hadevidence of demyelination or clear sensory fiber impair-ment due to the acute disease. Patient 1 had electro-physiologic evidence of severe, acute proximal and distalaxonal loss in the distribution of his weakness withoutsigns of demyelination, even with direct spinal nervestimulation and recording of ulnar motor fibers. He had noconduction block or dispersion of compound muscle action

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Mayo Clin Proc, October 2003, Vol 781248 Flaccid Paralysis Due to West Nile Virus

potentials; he had carpal tunnel syndrome. The borderlineulnar sensory response could have been due to proximalloss of sensory axons, but his thick hands were an equallylikely cause. In patient 1, the sensory nerve changes werelikely incidental; mild, direct involvement of sensory axonscannot be excluded, particularly since other reports havedescribed similar changes. Needle examination showedevolving changes consistent with severe proximal axonalloss. In patient 2, sensory conduction studies were normaldespite the patient’s sensory symptoms. He had no conduc-tion block or dispersion of compound muscle action poten-tials, and F-wave latencies were normal. Thus, our patientsshowed no evidence of a polyradiculopathy of the type seenwith the typical demyelinating GBS, but the electro-physiologic findings in individual nerves are similar tothose in the axonal form of GBS. However, that type ofGBS does not show the focal distribution seen in our 2patients and in patients with poliomyelitis. Thus, our pa-tients had anterior horn cell damage from the virus, ratherthan more peripheral axonal damage.

The value of MRI in West Nile paralytic illness remainsundetermined. In both our patients, findings on MRI werenormal. However, MRI signal abnormality in the anteriorhorns and cauda equina contrast enhancement were notedrecently.10-13 Although use of MRI in West Nile virus infec-tion needs further study, pathological changes are expectedbecause abnormal T2-weighted MRI scans of the spinalcord have been reported in flaccid weakness caused byenterovirus and poliovirus.10-13 Also, MRI abnormalitiesmay be seen if meningoencephalitis is particularly severeand catastrophic.

The pattern of weakness described with West Nile virusinfection is often asymmetrical and has varied frommonoplegia to tetraplegia with respiratory failure. Facialweakness is common, but extraocular muscle palsy has notyet been reported. With such a spectrum of impairment,there are likely to be index cases of West Nile meningoen-cephalitis in which mild weakness is overlooked or attrib-uted to systemic illness. Given the axonal damage inflicted,recovery is slow, probably unsatisfactory, and dependenton collateral sprouting in which sufficient viable axonsremain. One of our patients received IVIG with no measur-able effect. Two of 6 patients recently reported in detailwere also treated with IVIG with no noticeable improve-ment.10 The role of IVIG remains unclear, and initial expe-rience with this costly therapy is not encouraging.

To our knowledge, our cases are among the first detaileddescriptions of the neuromuscular complications of WestNile virus infection, including electrophysiologic testing ofproximal and distal motor axons. The entire clinical spec-

trum of this entity is unknown.13,14 However, asymmetrical,new-onset weakness with CSF pleocytosis in a patient pre-senting in the summer should alert physicians to this virus.

Matthew L. Flaherty, MDEelco F. M. Wijdicks, MDJ. Clarke Stevens, MDJasper R. Daube, MDDepartment of Neurology

Eric C. Chenworth, DOEmelie F. Helou, MDDepartment of Internal Medicine

Muhammad R. Sohail, MDDivision of Infectious Diseases and Internal MedicineMayo ClinicRochester, Minn

Dr Flaherty is now with the University of Cincinnati, Cincinnati, Ohio.

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12. Malzberg MS, Rogg JM, Tate CA, Zayas V, Easton JD. Poliomy-elitis: hyperintensity of the anterior horn cells on MR images of thespinal cord. AJR Am J Roentgenol. 1993;161:863-865.

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