Neurologic Manifestations and Outcome of West Nile Virus Infection

BRIEF REPORT

James J. Sejvar, MD Context The neurologic manifestations, laboratory findings, and outcome of patients Maryam B. Haddad, MSN, MPH, FNP with West Nile virus (WNV) infection have not been prospectively characterized. Bruce C. Tierney, MD Objective To describe prospectively the clinical and laboratory features and long- term outcome of patients with neurologic manifestations of WNV infection. Grant L. Campbell, MD, PhD Design, Setting, and Participants From August 1 to September 2, 2002, a com- Anthony A. Marfin, MD, MPH munity-based, prospective case series was conducted in St Tammany Parish, La. Stan- Jay A. Van Gerpen, MD dardized clinical data were collected on patients with suspected WNV infection. Con- firmed WNV-seropositive patients were reassessed at 8 months. Aaron Fleischauer, PhD Main Outcome Measures Clinical, neurologic, and laboratory features at initial A. Arturo Leis, MD presentation, and long-term neurologic outcome. Dobrivoje S. Stokic, MD Results Sixteen (37%) of 39 suspected cases had antibodies against WNV; 5 had men- Lyle R. Petersen, MD, MPH ingitis, 8 had encephalitis, and 3 had poliomyelitis-like acute flaccid paralysis. Movement disorders, including tremor (15 [94%]), myoclonus (5 [31%]), and parkinsonism (11 [69%]), OST HUMAN INFECTIONS were common among WNV-seropositive patients. One patient died. At 8-month follow- with West Nile virus up, fatigue, headache, and myalgias were persistent symptoms; gait and movement dis- (WNV) are subclinical or orders persisted in 6 patients. Patients with WNV meningitis or encephalitis had favorable outcomes, although patients with acute flaccid paralysis did not recover limb strength. manifest as a mild fe- brileM illness, but a small proportion of Conclusions Movement disorders, including tremor, myoclonus, and parkinson- patients (Ͻ1%) develop acute neuro- ism, may be present during acute illness with WNV infection. Some patients with WNV 1-4 infection and meningitis or encephalitis ultimately may have good long-term out- logic illness. Although recent WNV come, although an irreversible poliomyelitis-like syndrome may result. outbreaks have been associated with se- JAMA. 2003;290:511-515 www.jama.com vere neurologic disease,1-5 retrospec- tive studies have failed to identify clinical features that distinguish WNV from count; or cerebrospinal fluid [CSF] pleo- electrophysiologic findings were re- other viral encephalitides.1,5-9 The US cytosis) along with clinical evidence of corded and updated 1 week following outbreak of WNV in 200210 presented meningitis, encephalitis, or acute focal initial assessment, during repeat neu- an opportunity to assess neurologic weakness (BOX). Infection with WNV rologic evaluation. manifestations, laboratory and neuro- was confirmed if WNV-specific antibod- Approximately 8 months later (March diagnostic findings, and outcome as- ies were detected in acute-phase serum 15-April 4, 2003), patients with con- sociated with WNV infection.1,7,11 or CSF samples by IgM antibody- firmed WNV infection were reexam- capture enzyme-linked immunosor- ined. The Centers for Disease Control METHODS bent assay (MAC-ELISA)12 and were and Prevention institutional review From August 1 to September 2, 2002, confirmed by plaque-reduction neutral- 13 Author Affiliations: Division of Viral and Rickettsial patients from St Tammany Parish, La, ization assay. Diseases (Dr Sejvar) and Division of Vector-Borne In- with suspected WNV infection were Eligible enrollees were assessed on fectious Diseases (Drs Campbell, Marfin, and Petersen), National Center for Infectious Diseases, and Epi- identified through state-based surveil- presentation to medical care. Patients demic Intelligence Service, Epidemiology Program Of- lance at local hospitals and regional medi- were approached under the auspices of fice (Drs Tierney and Fleischauer and Ms Haddad), Cen- a public health event; oral consent was ters for Disease Control and Prevention, Atlanta, Ga; cal centers. Suspected WNV infection was Department of Neurology, Ochsner Clinic, New Or- defined as illness with evidence of an obtained. Standardized case histories leans, La (Dr Van Gerpen); Center for Neuroscience and initial symptoms and signs were and Neurological Recovery, Methodist Rehabilita- acute infectious process (eg, tempera- tion Center, Jackson, Miss (Drs Leis and Stokic). ture Ն39°C; elevated white blood cell collected. One neurologist (J.J.S.) ex- Corresponding Author and Reprints: James J. Sejvar, amined each patient; a second neurolo- MD, Division of Viral and Rickettsial Diseases, Na- gist verified findings for 7 patients. tional Center for Infectious Diseases, Centers for Dis- See also p 524 and Patient Page. ease Control and Prevention, 1600 Clifton Rd, MS Laboratory results, neuroimaging and A-39, Atlanta, GA 30333 (e-mail: [email protected]).

of the 15 WNV-seropositive patients Box. Diagnostic Criteria with headache described it as frontal/ West Nile Meningitis retro-orbital, and 5 of the 16 WNV- A. Clinical signs of meningeal inflammation, including nuchal rigidity, Kernig or seropositive patients reported a rash. Brudzinski sign, or photophobia or phonophobia Fifteen WNV-seropositive patients re- B. Additional evidence of acute infection, including 1 or more of the following: ported “shakiness” or “twitching,” with fever (Ͼ38°C) or hypothermia (Ͻ35°C); cerebrospinal fluid pleocytosis (Ն5 5 describing it as notable in the evening leukocytes/mm3); peripheral leukocyte count Ͼ10000/mm3; neuroimaging find- prior to sleep. Among patients with ings consistent with acute meningeal inflammation WNE, the most common complaints West Nile Encephalitis were behavioral or personality changes, A. Encephalopathy (depressed or altered level of consciousness, lethargy, or per- manifested as irritability, confusion, or sonality change lasting Ն24 hours) disorientation. Two patients with WNM B. Additional evidence of central nervous system inflammation, including 2 or more and 1 patient with WNE reported dif- of the following: fever (Ն38°C) or hypothermia (Յ35°C); cerebrospinal fluid ficulty with balance and gait. Five pa- pleocytosis (Ն5 leukocytes/mm3); peripheral leukocyte count Ͼ10000/mm3; tients reported weakness, which was fo- neuroimaging findings consistent with acute inflammation (with or without cal in the 3 patients developing AFP and involvement of the meninges) or acute demyelination; presence of focal neu- was generalized in 2 patients. rologic deficit; meningismus (as defined in A); electroencephalography find- The 8 patients with WNE had a mean ings consistent with encephalitis; seizures, either new onset or exacerbation of previously controlled admission Glasgow Coma Scale score of 11 (range, 4T [intubated] to 15). A Acute Flaccid Paralysis median of 3 days passed between symp- A. Acute onset of limb weakness with marked progression over 48 hours tom onset and changes in mental sta- B. At least 2 of the following: asymmetry to weakness; areflexia/hyporeflexia of tus. Cranial nerve and bulbar abnor- affected limb(s); absence of pain, paresthesia, or numbness in affected limb(s); cerebrospinal fluid pleocytosis (Ն5 leukocytes/mm3) and elevated protein lev- malities were observed in several patients els (Ն45 mg/dL); electrodiagnostic studies consistent with an anterior horn cell with WNE. Results of formal strength process; spinal cord magnetic resonance imaging documenting abnormal in- testing displayed mild-to-moderate dif- creased signal in the anterior gray matter fuse weakness in 4 patients and focal weakness in the 3 patients with AFP. New sensory abnormalities were not board approved the follow-up proto- tients, 5 were classified as having West observed. Four patients with WNE and col. Using a standardized question- Nile meningitis (WNM), 8 as having 1 patient with WNM displayed abnor- naire, patients were queried about symp- West Nile encephalitis (WNE), and 3 mal hyperreflexia; the 3 patients with toms, functional status, and ability to as having acute flaccid paralysis (AFP) AFP all had areflexia or hyporeflexia of perform daily activities. The neuro- (TABLE). One patient classified with the affected limbs. logic assessment was repeated (J.J.S.). AFP also had encephalitis. Informa- Dyskinesias (ie, movements includ- Exact Wilcoxon rank-sum test was tion regarding the initial presentation ing tremor, myoclonus, and features of used for comparison of medians. Statis- of 3 patients with AFP had been re- parkinsonism) were observed in 15 of the tical analyses were performed using SAS, ported previously.14,15 Patients with 16 WNV-seropositive patients (Table). version 8.1 (SAS Institute, Cary, NC). WNM (median age, 35 years) were Tremor was observed in 15 patients; 9 younger than those with WNE (me- had onset of tremor after day 5 of ill- RESULTS dian, 70 years) (P=.003). One patient ness. Tremor in all 15 patients was static Clinical Features with severe WNE had systemic lupus or kinetic, asymmetric, and involved the Of 39 patients evaluated, WNV infec- erythematosis and was treated with cor- upper extremities. Two patients addi- tion was confirmed in 16 patients. Dis- ticosteroids. No other WNV-seroposi- tionally displayed intentional move- charge diagnoses of the 23 patients tive patient had a clear condition indi- ment dysmetria. Myoclonus was di- without WNV infection included viral cating immunocompromise. rectly observed in 10 patients. meningitis (n=6), headache (n=5), vi- The 16 WNV-seropositive patients Parkinsonism was observed in all 3 pa- ral encephalitis (n=4), unspecified vi- were hospitalized a median of 2.5 days tients with AFP, 6 of 8 patients with ral illness (n=4), and encephalopathy after symptom onset; the median hos- WNE, and 2 of 5 patients with WNM. (n=1). Final diagnoses were unavail- pital stay was 12 days (Table). Five pa- Resting tremor was not observed. Sei- able for 3 patients. tients spent a median of 10 days (range, zures were documented using electro- Eleven (69%) of the 16 WNV- 3-19 days) in intensive care. encephalography in 1 patient with WNE. seropositive patients were white (popu- Self-reported symptoms were simi- All 3 patients with AFP had asym- lation of St Tammany Parish is 74% lar among all patients presenting with metric limb weakness within 48 hours white), and 9 were male. Of the 16 pa- possible WNV infection (Table). Eleven of initial symptom onset. Pain, pares-

512 JAMA, July 23/30, 2003—Vol 290, No. 4 (Reprinted) ©2003 American Medical Association. All rights reserved. NEUROLOGIC MANIFESTATIONS OF WEST NILE VIRUS INFECTION thesias, or acute sensory loss were not pons on T2- and diffusion-weighted se- Electroencephalograms were ob- observed. All 3 patients experienced quences in 2 severely ill patients with tained for 7 patients with WNE. Ab- bowel and bladder dysfunction. WNE (FIGURE). Findings of magnetic normal findings included electro- resonance imaging of the cervical, tho- graphic seizures in 1 patient, focal sharp Neuroimaging and racic, and lumbosacral spine for the 2 pa- waves in 1 patient, and diffuse irregu- Electrophysiologic Studies tients with AFP with lower extremity in- lar slow waves in 6 patients. No corre- None of the WNV-seropositive patients volvement showed enhancement of the lation between electroencephalo- showed acute abnormalities on com- cauda equina and nerve root clumping graphic findings and the presence of puted tomography. Magnetic reso- consistent with meningitis. Findings of myoclonus or tremor was observed. nance imaging of the brain was per- magnetic resonance images of the cer- Electromyographs and nerve conduc- formed on 10 of the 16 patients: the vical and thoracic spine in a patient with tion studies were performed on the 3 findings showed nonacute abnormali- AFP with right arm involvement showed WNV-seropositive patients and 1 WNV- ties in 8 patients and bilateral, focal le- diffuse degenerative changes without spi- seronegative patient with asymmetric sions in the basal ganglia, thalamus, and nal cord abnormalities. weakness from 3 to 42 days after onset

Table. Clinical Features West Nile West Nile Acute Flaccid West Nile Virus West Nile Virus Meningitis Encephalitis Paralysis Seropositive Patients Seronegative Controls (n=5) (n=8) (n=3) (n = 16) (n = 23) Age, y, median (range) 35 (20 to 39) 70 (46 to 81) 56 (46 to 69) 57 (20 to 81) 32 (2 to 65) Days from illness onset to presentation, 5 (3 to 7) 1.5 (−3 to−14)* 2 (2 to 4) 2.5 (−3 to −14) 4 (0 to 21) median (range) Self-reported symptoms, No. (%) Fever 5 (100) 8 (100) 3 (100) 16 (100) 22 (96) Headache 5 (100) 8 (100) 2 (66) 15 (94) 22 (96)† Nausea 4 (80) 5 (62) 2 (66) 11 (69) 17 (74)† Neck pain 4 (80) 4 (50) 1 (33) 9 (56) 17 (74)† Vomiting 4 (80) 6 (75) 2 (66) 12 (75) 12 (52) Myalgias/body aches 4 (80) 5 (63) 2 (66) 11 (69) 16 (73)† Chills/rigors 3 (60) 4 (50) 2 (66) 9 (56) 13 (57) Low back pain 2 (40) 3 (38) 0 5 (31) 9 (41)† Weakness 1 (20) 1 (13) 3 (100) 5 (31) 9 (41) Neurologic findings, No.(%) Altered mental status 0 8 (100) 1 (33) 9 (56) 4 (17) Weakness 0 4 (50) 3 (100) 7 (47) 3 (13) Tremor 4 (80) 8 (100) 3 (100) 15 (94) 2 (8) Myoclonus 1 (20) 3 (38) 1 (33) 5 (31) 1 (4) Parkinsonism 2 (40) 6 (75) 3 (100) 11 (69) 0 Rigidity 2 (40) 6 (75) 3 (100) 11 (69) 0 Bradykinesia 2 (40) 5 (63) 2 (67) 9 (56) 0 Postural instability 2 (40) 4 (50) 0 6 (38) 0 Nuchal rigidity 5 (100) 5 (63)‡ 1 (33) 11 (69) 4 (17)† Rotatory nystagmus 0 2 (25) 0 2 (13) 0 Dysphagia 0 4 (50) 0 4 (25) 0 Absent corneal/gag reflex 0 3 (38) 0 3 (19) 1 (4) Ataxic/apneustic breathing 0 2 (25) 0 2 (13) 2 (8) Babinski sign 0 3 (38) 0 3 (19) 3 (13) Laboratory results Leukocyte count at admission, ×103/mm3 13.9 (9.8 to 17.1) 7.6 (3.5 to 18.2) 11.8 (9.5 to 13.0) 9.9 (3.5 to 18.2) 7.3 (5.6 to 16.2) Initial CSF leukocyte count, cells/mm3 24 (1 to 2317) 62 (0 to 1168)§ 143 (140 to 329) 140 (0 to 2317) 2 (0 to 189)࿣ Initial CSF protein, mg/dL 57 (40 to 157) 78 (51 to 194)§ 116 (75 to 234) 78 (40 to 234) 45 (13 to 295)࿣ Initial CSF glucose, mg/dL 68 (44 to 113) 54 (37 to 102)§ 74 (60 to 119) 60 (37 to 119) 86 (54 to 156)࿣ Initial CSF lymphocytes, % 21 (2 to 57) 25 (0 to 83)§ 68 (42 to 95) 26 (0 to 95) 63 (4 to 100)࿣ Days hospitalized, median (range) 5 (4 to 8) 15.5 (5 to 35) 14 (7 to 19) 12 (4 to 36) 7 (1 to 66) Abbreviation: CSF, cerebrospinal fluid. SI conversion: For glucose, to convert mg/dL to mmol/L, multiply by 0.06555. *Patient hospitalized for unrelated condition before onset of symptoms associated with acute West Nile virus infection. †Patients who were comatose were not assessed (n = 22). ‡Patients who were comatose were not assessed (n = 7). §n=7. ࿣n = 16.

Follow-up neurologic examination of Patients with AFP reported the low- Figure. T2-Weighted Axial Magnetic Resonance Image From a Patient With the 15 WNV-seropositive patients who est overall functioning scores and had the West Nile Virus Encephalitis survived revealed no neurologic defi- lowest scores on both Barthel and modi- cits in the 5 patients with WNM. Among fied Rankin scoring systems (data not patients with WNE and AFP, tremor was shown). Five of 7 patients who survived present in 5 patients and parkinsonism WNE and 4 of 5 patients who survived in 5. A postural and/or kinetic tremor WNM reported normal functional scores was observed in 5 patients following (data not shown). Seven of the 10 patients recovery from WNE, and in 1 patient, it who were employed before WNV infec- was severe enough to interfere with tion returned to work within 4 months grooming and eating. Parkinsonism per- following hospital discharge. Five sisted in 5 of the 11 patients. In all but patients, including all 3 with AFP, 1 patient (the patient with underlying described continuing difficulties with systemic lupus erythematosis), parkin- daily activities, such as grooming, house- sonism was mild and did not interfere keeping, and mobility. All patients with with daily activities. One patient with AFP required use of a wheelchair for WNE with severe initial parkinsonism ambulation, and 2 patients who had been and postural instability was ambula- independently mobile before infection tory with a walker for 4 months follow- required walkers following recovery from ing illness onset, but by 6 months was WNE. The image displays bilateral increased signal in the pos- able to climb ladders at work. Eight- terior thalami (lower 2 arrowheads) and focal areas month follow-up examination demon- COMMENT of striatum (upper 2 arrowheads). strated only minimal postural instabil- Movement disorders, in particular ity and bradykinesia. The 8-month tremor, myoclonus, and parkinson- of weakness. All WNV-seropositive pa- follow-up examination revealed 2 ism, were prominent among WNV- tients demonstrated findings consis- patients who demonstrated myoclonus seropositive patients, but uncommon tent with a severe, asymmetric process of the upper extremities and face. among WNV-seronegative patients. affecting anterior horn cells. The WNV- Five of 7 patients with severe en- While tremor and myoclonus have been seronegative patient displayed overall cephalitis, as characterized by an ini- documented prospectively in patients findings consistent with a combined axo- tial Glascow Coma Scale score of 12 or with St Louis encephalitis virus 16-18 or nal and demyelinating neuropathy (ie, less or an initial mental status score of other viral infections,19,20 they have not Guillain-Barre´ syndrome). 2 SDs below normal for age, had favor- been described in contemporary WNV able outcomes, defined as achieving or studies.1,2,3,5,6,9,21 Documentation of these Outcome and 8-Month Follow-up exceeding their level of functioning be- findings in 15 of 16 WNV-seroposi- One patient with WNE remained co- fore illness. Two patients with particu- tive patients suggests that these find- matose and ventilator-dependent un- larly guarded prognoses during acute ings have diagnostic relevance. til death, which occurred 2.5 months illness were functioning at baseline level Previous immunohistological assess- after onset of illness. All surviving pa- by 6 months, with no residual symp- ments have detected WNV in the basal tients eventually were discharged home. toms. Recovery to normal or near- ganglia, thalamus, and pons in patients However, 3 patients with AFP and 2 pa- normal functioning occurred within 4 with severe encephalitis,22 suggesting the tients with WNE were initially dis- months in all cases of improvement. possibility of viral involvement of these charged to long-term rehabilitation fa- Patients with AFP showed no im- structures with resultant parkinsonism cilities. At 8 months, 11 patients were provement in limb weakness. Bladder and tremor. Magnetic resonance imag- home and functioning independently; symptoms in the patients with AFP had ing findings in 2 patients correlated clini- 3 were home, but dependent; and 1 was resolved. Electromyographs and nerve cally with the findings of parkinsonism undergoing rehabilitation. conduction studies performed at the and tremor; however, in 8 patients, par- At 8 months, 10 WNV-seropositive 8-month follow-up examination re- kinsonian features were present with- patients reported persistent fatigue, 3 vealed chronic denervervation and mo- out abnormal findings on magnetic reso- persistent myalagias, and 2 persistent tor axon loss in affected limbs. One pa- nance imaging. Parkinsonism has been headache. Four patients with WNE re- tient with AFP experienced continued observed with Japanese encephalitis vi- ported persistent cognitive deficits, in- severe dyspnea. Chest and diaphrag- rus infection,23-26 a related flavivirus. cluding difficulties with memory, short- matic fluoroscopy performed 3 months Some prior studies have suggested long- term recall, and slowness of thought. after illness onset revealed right hemidia- term persistence of signs,23-25 while oth- One patient had mental status scores phragmatic paralysis consistent with cen- ers have reported parkinsonism as a more significantly below baseline levels. tral nervous system etiologic findings. transient feature.27 In our study, the pa-

514 JAMA, July 23/30, 2003—Vol 290, No. 4 (Reprinted) ©2003 American Medical Association. All rights reserved. NEUROLOGIC MANIFESTATIONS OF WEST NILE VIRUS INFECTION tient with severe persistent parkinson- Analysis and interpretation of data: Sejvar, Haddad, United States. Clin Diagnostic Lab Immunol. 2002; Marfin, Van Gerpen, Fleischauer, Stokic, Petersen. 9:544-549. ism at 8-month follow-up had shown Drafting of the manuscript: Sejvar, Haddad, Tierney, 13. Martin D, Muth D, Brown T, et al. Standardiza- persistence of abnormalities in the basal Petersen. tion of immunoglobulin M capture enzyme-linked im- Critical revision of the manuscript for important in- munosorbent assays for routine diagnosis of arbovi- ganglia, thalamus, and substantia nigra tellectual content: Sejvar, Campbell, Marfin, Van ral infections. J Clin Microbiol. 2000;381:823-826. on magnetic resonance imaging. Gerpen, Fleischauer, Leis, Stokic, Petersen. 14. Centers for Disease Control and Prevention. Acute All patients with WNM had favor- Statistical expertise: Sejvar, Haddad, Fleischauer. flaccid paralysis associated with West Nile virus infec- Obtained funding: Marfin. tion—Mississippi and Louisiana, July-August 2002. able outcome; all returned to work and Administrative, technical, or material support: Sejvar, MMWR Morb Mortal Wkly Rep. 2002;51:825-828. reported normal or near-normal func- Haddad, Campbell, Marfin, Van Gerpen, Petersen. 15. Sejvar J, Leis A, Stokic D, et al. Acute flaccid pa- Study supervision: Petersen. ralysis associated with West Nile virus infection. Emerg tioning at 8-month follow-up. In addi- Funding/Support: The study was supported by pro- Infect Dis. 2003;9:788-793. tion, 5 patients with severe WNE had ex- gram funds for West Nile virus through the Depart- 16. Southern P, Smith J, Luby J, et al. Clinical and labo- ment of Health and Human Services, Centers for Dis- ratory features of epidemic St Louis encephalitis. Ann cellent outcomes, achieving premorbid ease Control and Prevention. Intern Med. 1969;71:681-689. levels of functioning without residual dis- Acknowledgment: We wish to acknowledge the con- 17. Monath T, Brinker K. The acute disease. In: Mon- tributions of the following individuals and institutions, ath T, ed. St. Louis Encephalitis. Washington, DC: ability within 4 months of illness. Se- whose assistance made this project possible: Case- American Public Health Association; 1980:503-544. vere encephalitis caused by other viral series participants and their families; R. Ratard, MD, state 18. Wasay M, Diaz-Arrastia R, Suss R, et al. St Louis agents28-30 may often be associated with epidemiologist, A. Vacari, DVM, E. Brewer, MD, J. Hand, encephalitis: a review of 11 cases in a 1995 Dallas, MPH; R. Essien, MSHCN, Louisiana Office of Public Texas, epidemic. Arch Neurol. 2000;57:114-118. severe persistent cognitive and neuro- Health; M. Bunning, DVM, P. Collins, MS, S. Mont- 19. Huang C, Liu C, Chang Y, et al. Neurologic com- logic deficits; by comparison, this group gomery, DVM, MPH, A. Kipp, MPH, C. Chow, MD, plications in children with enterovirus 71 infection. D. Martin, PhD, Division of Vector-Borne Infectious Dis- N Engl J Med. 1999;341:936-942. of patients with WNE displayed a low in- eases, National Center for Infectious Diseases, Cen- 20. Goh K, Tan C, Chew N, et al. Clinical features of cidence of persistent sequelae. Severity ters for Disease Control and Prevention; D. Cashen, RN, Nipah virus encephalitis among pig farmers in Malay- Lakeview Regional Medical Center, Covington, La; K. sia. N Engl J Med. 2000;342:1229-1235. of initial encephalopathy does not nec- Moise, RN, St. Tammany Parish Hospital, Covington, 21. Weiss D, Carr D, Kellachan J, et al. Clinical find- essarily portend poor long-term out- La; P. Vaccaro, RN, North Oaks Regional Medical Cen- ings of West Nile virus infection in hospitalized patients, New York and New Jersey, 2000. Emerg In- come in all patients. ter, Hammond, La; B. Meiche, RN, North Shore Re- gional Medical Center, Slidell, La; T. Croney, RN, Slidell fect Dis. 2001;7:654-658. Two of the 3 patients with AFP devel- Memorial Hospital, Slidell, La; J. Maffei, MD, D. Friloux, 22. Shieh W, Guarner J, Layton M, et al. The role of RN, Charity Hospital, New Orleans, La; D. Baumgar- pathology in an investigation of an outbreak of West oped AFP without associated encepha- Emerg Infect Dis ten, MD; C. Bitar, MD; M. Culasso, MD; R. Duffour, Nile encephalitis in New York, 1999. . 2000;6:370-372. lopathy or meningismus. Clinical find- MD; J. Fitzpatrick, MD; S. Ganji, MD; T. Hall, MD; R. 23. Pradhan S, Pandey N, Shashank S, Gupta R, Houser, MD; S. Kemmerly, MD; J. LeFran, MD; R. Mil- ings and electrodiagnostic data suggested Mathur A. Parkinsonism due to predominant involve- let, MD; C. Nine-Montanez, MD; R. Peltier, MD, S. ment of substantia nigra in Japanese encephalitis. Neu- involvement of anterior horn cells of the Raina, MD, G. Reddi, MD, R. Saguiguit, MD. rology. 1999;53:1781-1786. spinal cord, resulting in a poliomyelitis- 24. Shoji H, Watanabe M, Itoh S, Kuwahara H, Hat- 14,15,31-32 like syndrome. At 8 months, none REFERENCES tatori F. Japanese encephalitis and parkinsonism. J Neu- of the patients had improvement in weak- 1. Campbell G, Marfin A, Lanciotti R, Gubler D. West rol. 1993;240:59-60. Nile virus. Lancet Infect Dis. 2002;2:519-529. 25. Murgod U, Muthane U, Ravi V, Radhesh S, De- ness, and electromyographic data sug- 2. Tsai T, Popovici F, Cernescu C, Campbell G, Ne- sai A. Persistent movement disorders following Japa- gested permanent motor neuron loss, delcu N. West Nile encephalitis epidemic in south- nese encephalitis. Neurology. 2001;57:2313-2315. eastern Romania. Lancet. 1998;352:767-771. 26. Misra U, Kalita J. Movement disorders in Japa- indicating that significant recovery in 3. Chowers M, Lang R, Nassar F, et al. Clinical char- nese encephalitis. J Neurol. 1997;244:299-303. weakness is unlikely. Persistent dys- acteristics of the West Nile fever outbreak, Israel, 2000. 27. Misra U, Kalita J. Prognosis of Japanese encepha- Emerg Infect Dis. 2001;7:675-678. litis patients with dystonia compared to those with par- pnea in 1 patient with AFP is most likely 4. Centers for Disease Control and Prevention. Se- kinsonian features only. Postgrad Med. 2001;78:238- due to poliomyelitis-like diaphragmatic rosurveys for West Nile virus infection—New York and 241. and intercostal muscle weakness with res- Connecticut counties, 2000. MMWR Morb Mortal 28. Hokkanen L, Launes J. Cognitive outcome in acute Wkly Rep. 2001;50:37-39. sporadic encephalitis. Neuropsychol Rev. 2000;10: 33-35 piratory failure. 5. Platonov A, Shipulin G, Shipulina O, et al. Out- 151-167. We conclude that movement disor- break of West Nile virus infection, Volgograd Region, 29. Gordon B, Selnes O, Hart J, et al. Long-term cog- Russia, 1999. Emerg Infect Dis. 2001;7:128-132. nitive sequelae of acyclovir-treated herpes simplex en- ders, particularly tremor, myoclonus, 6. Mostashari F, Bunning M, Kitsutani P, et al. Epi- cephalitis. Arch Neurol. 1990;47:646-647. and parkinsonism, may be underrecog- demic West Nile encephalitis, New York, 1999. Lan- 30. Solomon T, Vaughn D. Pathogenesis and clini- cet. 2001;358:254-255. cal features of Japanese encephalitis and West Nile nized manifestations of acute WNV ill- 7. Asnis D, Conetta R, Teixeira A, Waldman G, Samp- virus infections. In: Mackenzie J, Barrett A, Deubel ness and have a generally favorable prog- son B. The West Nile virus outbreak of 1999 in New V, eds. Current Topics in Microbiology and Immu- York City. Clin Infect Dis. 2000;30:413-418. nology: Japanese Encephalitis and West Nile Virus nosis. However, complaints of persistent 8. Han L, Popovici F, Alexander J, et al. Risk factors Infections. Vol. 267. Berlin, Germany: Springer- fatigue, headache, and myalgia are com- for West Nile virus infection and meningoencephali- Verlag; 2002:171-194. tis, Romania, 1996. J Infect Dis. 1999;179:230-233. 31. Leis A, Stokic D, Polk J, Dostrow V, Winkelmann mon. Long-term outcome of patients 9. Petrov V, Krasnova Y, Lvov D, et al. Clinical pic- M. A poliomyelitis-like syndrome from West Nile vi- with WNE is variable, and severe ini- ture and epidemiology of West Nile fever in Volgo- rus infection. N Engl J Med. 2002;347:1279-1280. grad Oblast (1999 and 2000) [in Russian]. Moscow 32. Glass J, Samuels O, Rich M. Poliomyelitis due to tial encephalopathy did not necessarily Voprosy Virusologii. 2001;45:22-26. West Nile virus. N Engl J Med. 2002;347:1280-1281. portend poor prognosis. A poliomyelitis- 10. Centers for Disease Control and Prevention. West 33. Modlin J, Coffey D. Poliomyelitis, polio vaccines, Nile virus activity—United States, August 8-14, 2002, and the post-polio syndrome. In: Scheld W, Whitley like syndrome can occur without asso- and Mississippi, July 1-August 14, 2002. MMWR Morb R, Durack D, eds. Infections of the Central Nervous ciated meningitis or encephalitis and has Mortal Wkly Rep. 2002;51:708-709. System. Philadelphia, Pa: Lippincott-Raven Publish- 11. Nash D, Mostashari F, Fine A, et al. The out- ers; 1997:57-72. poor long-term outcome. break of West Nile virus infection in the New York City 34. Alcock A, Hildes J, Kaufert, et al. Respiratory po- Author Contributions: Study concept and design: area in 1999. N Engl J Med. 2001;344:1807-1814. liomyelitis. CMAJ. 1985;130:1305-1310. Sejvar, Haddad, Tierney, Campbell, Marfin, Petersen. 12. Martin D, Biggerstaff B, Allen B, et al. Use of im- 35. Tzeng S. Respiratory paralysis as a presenting Acquisition of data: Sejvar, Haddad, Tierney, Camp- munoglobulin M cross-reactions in differential diag- symptom in Japanese encephalitis—a case report. Chi- bell, Van Gerpen, Leis, Stokic. nosis of human flaviviral encephalitis infections in the nese Med J. 1989;43:208-212.