58 Case Report Volume 4 No. 1, 2007

INTRODUCTION

West Nile virus (WNV) is a single-stranded RNAvirus of the Flaviridae family. In North America,human infection occurs predominantly between

June and November, with a peak in mid-July and mid-September reflecting the seasonal activity cycle of mosquitovectors.1 The first Canadian cases of human WNV infectionwere documented in 2002 and by 2003 WNV was present inseven provinces with more than 1300 confirmed symptomaticcases.2 In 2004, larvicides were used to control the mosquitopopulation in many locations of high WNV activity. This mayhave lead to the reduction in human cases in 2004 when only26 cases were reported across Quebec, Ontario, Manitoba,Saskatchewan and Alberta.2 Alternatively, widespread inocula-tion may have selected out those individuals immunologicallyvulnerable to developing West Nile Neurological Syndrome(WNNS).

Cases of asymptomatic infection outnumber symptomaticillness by a ratio of approximately 150:1.(2,3,4,5) Of thoseaffected, the most common presentation is West Nile fever(WNF), an uncomplicated and short-lived febrile illness.3,4,5

WNF begins 2 to 14 days post-infection with a sudden-onset ofsymptoms that may include: fever, myalgia, nausea, vomiting,eye-pain, rash or headache, gastrointestinal symptoms, arthral-gia, red maculopapular rash and lymphadenopathy.3,4,5 WNF

usually lasts less than one week although fatigue commonlypersists beyond this time.6,4,5

Despite increased clinical manifestations during recent out-breaks, less than 1% of individuals infected with WNV devel-op WNNS consisting of severe neurological disease (i.e., acuteflaccid paralysis (AFP), encephalitis or meningitis).1,3,4,5,6,7

These patients often present with a prodrome of fever,headache, low back pain or other non-specific flu-like symp-toms.5 Following this period, WNNS may present as isolatedAFP or as the full triad characterized by changes in mental sta-tus, vomiting and coma.5 AFP in WNNS results from the neu-rotropic infection of anterior horn cells and thus mimicspoliomyelitis.1,6 The patient presents with severe asymmetriclower motor neuron weakness of one or more limbs. As inpoliomyelitis, the sensory system is spared and the prognosis ispoor with minimal long-term motor recovery.1,4,7 PositiveIgM titres are required for early diagnosis however our casedemonstrates that chronic WNV IgG titres can be useful to con-firm the diagnosis of WNNS even many years after initial dis-ease onset.

CASE REPORTA 53-year-old right-hand dominant gentleman was referred

for unresolved left leg weakness that had been present for threeyears. In September 2002, while vacationing in Germany, he

CASE REPORT

Positive IgG Flavivirus Serology in a Patient Presentingwith Acute Flaccid Paralysis

Emily Crookshank, BSc, OTSteven K. Baker, MSc, MD

ABSTRACTBackground: Since the emergence of West Nile Virus (WNV) in North America in 1999, increasing progresshas been made in the identification of clinical manifestations and diagnosis of the illness. West NileNeurological Syndrome (WNNS) is described as a significant neurological disease and includes acute flaccidparalysis (AFP), encephalitis and meningitis. Typically, the diagnosis of WNNS is supported by identificationof WNV-specific IgM antibody in serum or cerebrospinal fluid (CSF) 500 days post-infection, prior toseroconversion.Case Summary: Herein, we report a patient who presented with an AFP while vacationing in Germany. Hisneurological condition went undiagnosed for almost three years. Subsequent positive chronic IgG flavivirustitres, in the context of his clinical examination and electrophysiology, secured the diagnosis of WNNS. Conclusion: This case highlights the value of late immunologic testing for infectious etiologies of AFP inpatients in which the diagnosis has remained elusive.

MUMJ Case Report 59

developed an acute, flaccid, segmental, asymmetric paresiswhich was most severe in his left leg. This was preceded by afive-day history of fever, headache and malaise. He experi-enced significant back pain on day four of the prodrome lead-ing to his rapid deterioration and hospitalization.

A chart review from the Rhein-Mosel-Fachklinik Centre forPsychiatry, Psychotherapy and Neurology in Andernach,Germany indicated that he was febrile with a core temperatureof 39.2oC. His mental status was normal. Motor exam demon-strated mild generalized paresis with near-flaccid paralysis ofhis left lower-extremity. There was no evidence of sensory dis-turbance or autonomic dysfunction. Laboratory investigationswere negative for serum and cerebrospinal fluid (CSF) viraltiters of Lyme disease, Herpes Simplex Virus 1 and 2, Polio,Cytomegalovirus, and Human Immunodeficiency Virus (HIV).An empiric trial of gentamycin, ceftriaxone, and acyclovir did

not improve his clinical status. A lumbar puncture demonstrat-ed pleocytosis with no frank cytoalbuminologic dissociation.Compression ultrasonography was negative for deep veinthrombosis. Computerized tomography (CT) of his headand lumbosacral magnetic resonance imaging (MRI) were non-contributory.

Once his condition stabilized, he returned to Canada. Forapproximately 18 months he required the use of a wheelchairfor mobility but eventually learned motor adaptive skills towalk safely with the use of Lofstrand forearm orthoses. AnMRI of his head and cervical spine was completed in Januaryof 2003 and was non-contributory (Figure 1).

At the time of presentation to the neuromuscular clinic inAugust of 2005, he had become proficient in the use of a caneand left knee-ankle-foot orthosis to ambulate. On examination,his mental status and cranial nerves were normal. He showed

Figure 1. T2-weighted MRI of the patient’s head and cervical spine were unremarkable and non-contributory.

60 Case Report Volume 4 No. 1, 2007

normal bulk and tone through his upper extremities and rightleg. The left leg had near flaccid hypotonia with significantproximal and distal atrophy. No fasciculations were observed.Manual muscle testing demonstrated normal power in the rightarm and leg. Left shoulder abduction was graded at 4+ withelbow flexion being slightly weaker at grade 4 on the MRCscale (Medical Research Council). Left hip flexion was grade2 whereas knee and ankle strength were graded at 1. Musclestretch reflexes were 2+ throughout with the exception ofabsent left knee and Achilles responses. Plantar responses weredowngoing bilaterally. Sensory examination showed normalpan-modal perception. An upper extremity low amplitude pos-tural tremor was observed.

Electrodiagnostic evaluation demonstrated sensory nerveaction potentials (SNAP). By contrast, compound motor unitaction potentials (CMAP) were absent from the left extensordigitorum brevis and severely reduced from the left abductorhallicus. The conduction velocities were within normal limits.Right peroneal and tibial studies were normal. Monopolar nee-dle electromyography revealed 2+ spontaneous activity in theforms of positive sharp waves and fibrillation potentials in theleft vastus medialis and tibalis anterior. The correspondingmotor units were neurogenic with large long-duration poten-tials. The right vastus medialis and tibalis anterior exhibitednormal wave-form morphology and recruitment patterns withno spontaneous activity.

Laboratory investigations demonstrated normal serum com-plete blood count, calcium, magnesium, erythrocyte sedimenta-tion rate, C-reactive protein, antinuclear antibody, extractablenuclear antigens, complement levels, total protein, albumin,and liver function tests. Hepatitis serology did not reveal anti-bodies to the hepatitis B surface antigen or to anti-hepatitis Cvirus. Creatine kinase (CK) was elevated at 421 U/L. Covalentenzyme-linked immunosorbent assays were negative for IgG,IgA, and IgM asialoganglioside-GM1, monosialoganglioside-

GM1, and disialoganglioside-GD1b autoantibodies.Additionally, anti-myelin associated glycoprotein and sulfoglu-curonyl paragloboside autoantibody titers were negative. HisIgG but not IgM flavivirus serology was reactive.

Given the history of prodromal malaise and acute onset lowback pain followed by asymmetric paralysis with documentedIgG flavivirus seropostivitity a diagnosis of WNNS was made.

DISCUSSIONAcute flaccid paralysis (AFP) has been described as a com-

plex clinical syndrome and has a vast array of possible etiolo-gies. Appropriate treatment and prognosis are dependent onaccurate diagnosis of AFP.8 Consideration of the etiologic dis-tribution by age, gender, time, ethnicity and geographicalregion are important, as is the anatomic and pathophysiologicmechanisms associated with causes of AFP. A thorough clini-cal description of symptomatology should be obtained such asonset of fever, myalgia, presence or absence of sensory involve-ment and timing and progression of paralysis. Assessment ofthe patient’s medical history is also necessary to help narrowdown a differential diagnosis. Recent illness, travel, exposureto chemicals, insects or snakes, food and water consumption,vaccinations and history of trauma should be kept in mind. Acomprehensive neurologic examination should be performed.CSF protein elevation and pleocytosis is common but cannotrule out conditions such as Lyme disease, neoplasia, HIV andsarcoid meningitis.9 Electrophysiological studies and neu-roimaging studies are helpful for assisting with the diagnosisand prognosis and typically show markedly decreased or absentCMAPs in paretic limbs, preserved SNAPs and asymmetricmuscle denervation.10,11,12

Our patient’s clinical history, physical examination and elec-trodiagnostic findings were most consistent with an acute,infectious, anterior horn cell disorder. The development of hissymptoms in the context of the 2002 WNV outbreak in south-

Table 1. Canadian surveillance data on reported WNV infections for 2003 to 2005

Province/Territory Total Reported West Nile Virus Cases by Year2005 2004 2003

Newfoundland and Labrador 0 0 0Prince Edward Island 1 0 0Nova Scotia 1 0 2New Brunswick 1 0 1Quebec 6 3 17Ontario 101 14 89Manitoba 58 3 142Saskatchewan 58 5 947Alberta 10 1 275British Columbia 0 0 20Yukon 0 0 1Northwest Territories 0 0 0Nunavut 0 0 0Total 236 26 1494

Public Health Agency of Canada

MUMJ Case Report 61

Table 2a. Sensory Nerve Conduction Studies of the Patient

Sensory Nerve Conduction Velocities

Nerve Stimulus Recording LatOn (ms) P-Pamp (mV) Dist (mm) CV (m/s)L R L R L R L R

Peroneal Ankle EDB NR 4.58 NR 9.75 NR NR NR NRFibular Head NR 11.67 NR 8.28 NR 320 NR 45.2Popliteal Fossa NR 14.33 NR 7.85 NR 100 NR 37.5

Tibial Ankle AH 5.25 4.75 1.40 16.48 NR NR NR NRPopliteal Fossa 14.92 14.92 0.90 10.07 360 410 37.2 40.3

Median Wrist Wrist 5.42 4.17 9.88 10.34 NR NR NR NRElbow 10.83 10.25 9.15 10.41 270 275 49.8 45.2

Ulnar Wrist ADM 3.00 NR 15.85 NR NR NR n/a NRB. Elbow 6.23 NR 14.93 NR 210 NR 64.9 NRA. Elbow 8.07 NR 14.82 NR 120 NR 65.5 NRAxilla 9.80 NR 14.57 NR 100 NR 57.7 NR

Table 2b. Motor Nerve Conduction Studies of the Patient

Nerve Stimulus Recording Latency (ms) NegPamp (mV) CV (m/s)L R L R L R

Peroneal Ankle EDB NR 4.58 NR 9.75 - -Fibular Head NR 11.67 NR 8.28 NR 45.2Popliteal Fossa NR 14.33 NR 7.85 NR 37.5

Tibial Ankle AH 5.25 4.75 1.40 16.48 - -Popliteal Fossa 14.92 14.92 0.90 10.07 37.2 40.3

Median Wrist APB 5.42 4.17 9.88 10.34 - -Elbow 10.83 10.25 9.15 10.41 49.8 45.2

Ulnar Wrist ADM 3.00 NP 15.85 NP - -Below Elbow 6.23 NP 14.93 NP 64.9 NPAbove Elbow 8.07 NP 14.82 NP 65.5 NPAxilla 9.80 NP 14.57 NP 57.7 NP

AH, abductor hallicus; ADM, abductor digiti minimi; CV, conduction velocity; EDB, extensor digitorum brevis; ms, milliseconds; mV, millivolts; NegPamp, negative peakamplitude; NR, no response; NP, not performed. Note: These studies were conducted 3 years after symptom onset.

Table 2c. Electromyography of the Patient

Side Muscle Root Ins Act Fibs PSW Polyph MU Amp MU Dur

Left Vastus Medialis Femoral Normal 2+ 2+ Normal Large LongL2-L4

Tibialis Anterior Deep Peroneal Normal 2+ 2+ Normal Large LongL4-L5

Right Vastus Medialis Femoral Normal None Normal Normal Large LongL2-L4

Tibialis Anterior Deep Peroneal Normal None Normal Normal Normal NormalL4-L5

Ins. Act, insertional activity; Fibs, fibrillation (0 - 4+); PSW, positive sharp waves (0 - 4+); Polyph, polyphasia; MU Amp, Motor unit amplitude; MU Dur, motor unit dura-tion. Note: These studies were conducted 3 years after symptom onset.

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western Ontario empirically made WNNS the most probablediagnosis, which is known to present with AFP. The finding ofa positive IgG flavivirus titer supports the diagnosis. Althoughthe flavivirus serology is not specific for WNV, there were noother documented cases of alternate flaviviridae infections suchas a dengue virus or St. Louis encephalitis virus at that time inOntario.12 Sevar and colleagues outlined clinical, laboratoryand diagnostic findings commonly found in those with AFPsecondary to WNV which were compatible with our patientspresentation (Table 2).13

Acute motor axonal neuropathy (AMAN) is a variant ofGuillain-Barre syndrome (GBS) and was considered in our dif-ferential diagnosis. It also presents with reduced CMAP ampli-tude and preserved SNAP’s and although electrodiagnosticstudies can not distinguish loss of anterior horn cells from lossof motor axons, the patient’s clinical presentation and ethnicbackground was not consistent with those seen in AMAN.9,13

Fulminant, widespread paralysis with bilateral facial weakness,tongue involvement and normal sensation are characteristic fea-tures of AMAN.8,13 The weakness ascends symmetrically andaffects arms and respiratory muscles, differentiating it fromWNNS which is presents with asymmetric denervation on nee-dle EMG.11 AMAN is most commonly seen during the sum-mer months, among children and young adults in northernChina and is also referred to as “Chinese paralytic syndrome.”8

The possibility of multi-focal motor neuropathy and amy-otrophic lateral sclerosis were entertained however the rapidonset, lower extremity predominance, stable post-infectiousclinical course, the absence of conduction block and anti-GM1antibodies made these diagnoses less likely.14

AFP may complicate HIV infection and is caused by thevirus itself or opportunistic infections. This usually occurs inlater stages of the disease and presents with symmetric paraly-sis, pain and paraesthesia.8 HIV was ruled-out in our patient ashe was not seropositive for HIV and his motor involvement wasasymmetric and his sensation intact.15

During the initial hospitalization of the patient an idiopathicinflammatory myopathy such as polymyosistis may have beenconsidered however the CK at that time was only 132 U/L thusexcluding muscle diseases.16 His CK was later found to be ele-vated at 421 U/L which is commonly found in disorders ofmotor nerves due to neurogenic hyperCKemia.

Toxic neuropathies such as neuropathy associated withLyme borreliosis and Tick-bite paralysis by variousDermacentor and Ixodes species can cause AFP. Althoughthese illnesses are found in North America, their clinicalsequalae are not consistent with our patient’s presentation.Lyme radiculoneuropathy usually presents with a prodrome oferythema migrans. It is painful and asymmetric and may affectboth the lower and upper extremities. It develops within 4weeks after onset, much more slowly than AFP in WNNS andis accompanied by dermatomal sensory loss. Tick bite paraly-sis manifests as pain and paraesthesia in the extremities, ataxiaand symmetrical ascending AFP within 12 to 36 hours.8,17

These were not congruent with our patient’s presentation andlaboratory investigations were negative for serum and cere-

brospinal fluid viral titers of Lyme disease. Neurosarcoidosis was also considered in the differential

diagnosis as it can present as a polyneuropathy, mononeuritismultiplex, focal mononeuropathy, or polyradiculopathy frominvolvement of spinal root sheaths.18,19 This was not thoughtto be the cause of our patient’s AFP as he did not exhibit anyother signs or symptoms typical of neurosarcoid.18,19 TheMRI findings also helped to rule out other potential causes ofAFP such as leptomeningeal metaplasia or stroke.

Table 3. Clinical Criteria for Diagnosis of Suspected WNVAcute Flaccid Paralysis

1. Acute onset of limb weakness with clear progression over 24 hours2. At least 2 of the following:

• Asymmetry of weakness• Areflexia/Hyporeflexia of affected limbs• Absence of pain, paraesthesia or numbness in affected limb(s)• Cerebrospinal-fluid pleocytosis (>5 x 106 leukocytes/L) and

raised protein concentrations (>0.45 g/L) • Electrodiagnostic studies consistent with anterior-horn-cell

process• Spinal cord MRI documenting abnormal increased signal in

the anterior gray matter

Adapted from Sejvar et al. (2003).18

The diagnosis of WNV infection is typically supported byWNV-specific IgM antibody identification in serum or CSFwhich is accomplished using enzyme-linked immunoabsorbentassay (ELISA) testing.2,4,6 It is important to note however thatELISA testing is not conclusive and therefore other diagnosesshould be considered. For example, test cross-reactivity maycause false-positive results due to infection from other flavivi-ral infections or vaccinations such as Dengue viruses orJapanese encephalitis complex of viruses.12 In Addition, IgMhas been documented to persist up to 500 days post infectionand therefore a positive ELISA test can not distinguish betweenan acute and chronic infection. One can however repeat theELISA testing 7 to 14 days later which will show a four-foldrise in an acute infection. In chronic WNNS (500 days postinfection), IgM will be absent and therefore one should test forIgG flavivirus serology which is a permanent marker of sero-conversion.1,3 Such evidence of chronic seroconversion is use-ful for the diagnosis of WNNS in cases where clinical uncer-tainty remains despite years removed from the acute illness asillustrated in the current case.

ACKNOWLEDGEMENTThanks to Dr. Nina Singh, MD, FRCP(C), neuroradiology,

McMaster University for reviewing our neuroimaging studies.

MUMJ Case Report 63

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Author BiographiesEmily Crookshank is a final year medical student at McMaster University.Steven K. Baker is an Assistant Professor at McMaster University in the Department of Medicine, Divisions of PhysicalMedicine and Neurology.