A brief report of West Nile Virus neuroinvasive disease in the summer of 2012 in Hamilton , Ontario

West Nile neuroinvasive disease is a severe infectious disease that is associated with a high mortality rate, especially in immunocompromised hosts. Physicians who are aware of its clinical presentations may be able to order diagnostic tests more appropriately and avoid inappropriate treatment. In the present series, the cases of seven patients admitted to Hamilton Health Sciences (Hamilton, Ontario) in the summer of 2012 with a diagnosis of West Nile neuroinvasive disease were retrospectively reviewed based on available medical records. According to the clinical and laboratory criteria published by the Centers for Disease Control and Prevention, five cases were diagnosed as encephalitis, one case as meningitis and one case as meningomyelitis. Patients were managed supportively. Forty-three percent (three of seven) presented with rash, 71% (five of seven) did not report headache despite exhibiting neurological symptoms, 43% (three of seven) did not have fever on presentation and 37.5% of cerebrospinal fluid samples exhibited a neutrophil predominance. The mortality rate in the present series was 14.3% (one of seven), and 57.1% (four of seven) of the patients had residual symptoms on discharge and at follow-up.

West Nile neuroinvasive disease is a severe infectious disease that is associated with a high mortality rate, especially in immunocompromised hosts.Physicians who are aware of its clinical presentations may be able to order diagnostic tests more appropriately and avoid inappropriate treatment.In the present series, the cases of seven patients admitted to Hamilton Health Sciences (Hamilton, Ontario) in the summer of 2012 with a diagnosis of West Nile neuroinvasive disease were retrospectively reviewed based on available medical records.According to the clinical and laboratory criteria published by the Centers for Disease Control and Prevention, five cases were diagnosed as encephalitis, one case as meningitis and one case as meningomyelitis.Patients were managed supportively.Forty-three percent (three of seven) presented with rash, 71% (five of seven) did not report headache despite exhibiting neurological symptoms, 43% (three of seven) did not have fever on presentation and 37.5% of cerebrospinal fluid samples exhibited a neutrophil predominance.The mortality rate in the present series was 14.3% (one of seven), and 57.1% (four of seven) of the patients had residual symptoms on discharge and at follow-up.Les patients ont reçu une prise en charge de soutien.Quarante-trois pour cent d'entre eux (trois sur sept) ont eu une éruption, 71 % (cinq sur sept) n'ont pas déclaré de céphalée malgré les symptômes neurologiques, 43 % (trois sur sept) ne faisaient pas de fièvre à la présentation et 28 % (deux sur sept) avaient une prédominance de neutrophiles dans les prélèvements de liquide céphalorachidien.Le taux de mortalité observé s'élevait à 14,3 % (un cas sur sept), et 57,1 % des patients (quatre sur sept) présentaient des symptômes résiduels au congé et au suivi.

A brief report of West Nile Virus neuroinvasive disease in the summer of 2012 in Hamilton, Ontario
Lei Jiao MD PhD 1 , Cheryl Main MD FRCPC W est Nile Virus (WNV) is a major vector-borne virus that poses an increasing threat to health care (1).Early diagnosis of neuroinvasive WNV is difficult because clinical presentations are nonspecific and may mimic other infections such as bacterial meningitis.
The virus has been endemic in Africa, Europe and Asia since it was first isolated from the blood of a febrile woman in the West Nile area of Uganda in 1937.WNV has quickly spread in North America since its introduction to the United States in 1999, and large outbreaks have been documented (1).A wide spectrum of symptoms may develop, depending on phenotypes of WNV and the status of host immunity.The majority of infected individuals are asymptomatic, while 20% may present with West Nile fever, with symptoms ranging from generalized malaise, mild fever, headache, arthralgia and nausea, to maculopapular rash (2).Less than 1% of infected individuals develop West Nile neuroinvasive disease (WNND), which is categorized as aseptic meningitis, encephalitis or acute flaccid paralysis (3).
As demonstrated in the surveillance statistics released by Hamilton Public Health (4), there was a dramatic increase in the rate of WNV infection in Hamilton, Ontario, in the summer of 2012, with 20 confirmed cases, a considerable increase from the average rates of zero to four cases per year over the past nine years.In the present article, seven patients with WNND admitted to Hamilton Health Sciences (Hamilton, Ontario) during this period are described.The clinical symptoms, radiological imaging, serological diagnosis, treatment and prognosis in this group of patients are summarized.

MetHODs
According to the clinical and laboratory criteria published by the Centers for Disease Control and Prevention (Georgia, USA) (3), WNND was defined by the presence of acute neurological illness and laboratory evidence of WNV infection including WNV-specific immunoglobulin M (IgM) antibody detected by ELISA, and a confirmatory plaque reduction neutralization test in acute-phase cerebrospinal fluid (CSF) or serum samples.These criteria were followed, and positive laboratory results from the laboratory information system were identified.All tests were performed at the Toronto Public Health Laboratory (Toronto, Ontario).Seven patients with a diagnosis of WNND were recruited into the present case series, based on available medical records.The present study was reviewed and approved by the Research Ethics Board at Hamilton Health Sciences.In the present series, five patients were diagnosed with encephalitis, one patient with meningitis and one patient with meningomyelitis.

ResuLts
The patients were between 36 and 82 years of age.The ratio of men to women was 3:4.Comorbidities are outlined in Table 1; however, 42.9% (three of seven) had no preceding medical conditions.Nonspecific clinical features included fever (100%), nausea and vomiting (57.1%), diarrhea (42.9%), rash (42.9%) and headache (28.6%).In three of seven patients, rashes appeared on day 0 to day 10 post-onset of disease (POD), and lasted three to eight days.
The rashes were maculopapular, nonitchy and involved the chest, back and limbs in a nonspecific pattern.Four of seven patients (57%) experienced gastrointestinal symptoms preceding their neurological abnormality by one to 10 days.Less common and transient presentations, such as dizziness, psychiatric symptoms and eye complaints, were also reported in the present series.As presented in Table 1, neurological manifestations included: muscle weakness (57.1%); changes in mental status (57.1%); focal neurological deficiency (28.6%); and extrapyramidal symptoms (14.3%) such as noncogwheel rigidity, increased muscle tone and tremor.Mental status changes occurred as early as day 1 POD and improved over three to five days with supportive care, except in patient 3, who died after prolonged loss of consciousness/coma in the intensive care unit.Most patients denied neck stiffness (42.9%) and 33% of patients denied headaches.Neuromuscular weakness is a well-recognized feature of WNND.Five of seven patients (71.4%) complained of limb weakness.Patient 1 presented with right-sided weakness in the arm and leg from day 4 until day 53 POD.
CSF analysis revealed that 37.5% of the samples had elevated neutrophil counts.All samples had normal or elevated glucose levels, and 87.5% had elevated protein levels.Anti-WNV IgM was detected in all CSF samples from day 4 to day 28 POD.Notably, 71.1% of the patients were found to have normal peripheral white blood cell (WBC) counts on admission.All patients underwent computed tomography scans and four underwent magnetic resonance imaging (MRI).Neuroimaging abnormalities were only revealed in two patients on MRI.An MRI of patient 3 showed hyperintensity initially involving a small posterior periventricular area on day 10 POD, which subsequently spread to the bilateral thalami, midbrain and cerebellar peduncle on day 28 POD.MRI of patient 6 showed slight hyperintensity in bilateral sulci on day 7 POD, possibly due to intracranial hypertension.To evaluate disease etiology and prognosis, electromyography was performed in three of five patients with neuromuscular weakness, and only patient 1 was diagnosed with poliomyelitis with confirmed motor neuron damage in the anterior horn of the spinal cord, which suggested unfavourable strength recovery.Of note, patient 3 had symptoms similar to those observed in Guillain-Barré syndrome, with complete absence of motor and sensory nerve conduction on electromyography.
Patients were managed supportively, as shown in Table 1.Two patients (3 and 6) were admitted to the intensive care unit due to respiratory failure and/or decreased level of consciousness.The mortality rate in the present series was approximately 14.3%, and 57.1% of the patients had residual symptoms on discharge and on follow-up.

DIsCussION
Clues to WNND on history Multiple risk factors have been associated with the development of neuroinvasive diseases after WNV infection, such as advanced age, male sex, hypertension, diabetes mellitus, history of cardiovascular disease and immunosuppression (5).Major risk factors identified in the present study included hypertension, diabetes mellitus and advanced age.Consistent with previous case series (6) and outbreak reports (7), we found that the elderly were more susceptible to encephalitis,  (9).In the present case series, 87.5% of patients exhibited increased CSF protein levels.Patient 5 (with meningitis) had a normal protein level, while all patients with encephalitis had elevated levels (>0.85 g/L).
The finding that patients with encephalitis had higher CSF protein levels than those with meningitis has also been noted in other studies (6,9).However, only modest predictive value was identified for protein level and disease outcome according to multivariate analysis (9).Interestingly, 71.1% of our patients presented with normal peripheral WBC counts on admission, which may further prompt physicians to consider WNV infection in response to neutrophil-dominant CSF.Similar findings of 60% with normal WBC counts have been reported in a recent outbreak in Israel (10).One-half of MRIs performed were found to be normal, comparable with previously reported abnormality rates of 20% to 70% (3).Finally, anti-WNV IgM in CSF was detected in all of our patients, which is widely accepted as one of the diagnostic criteria for WNND due to the impermeability of the blood-brain barrier.However, it is critical for physicians to realize the limitations to this test such as cross-reaction with other members of the Flavivirus genus (11), antibody persistence in CSF for up to seven months postinfection (12) and the necessity of repeating serology during both acute and convalescent phases (two to three weeks later), if indicated (13).
treatment Supportive care is the mainstay of treatment for WNND infection, with no specific anti-WNV treatment currently approved by the Food and Drug Administration.Multiple promising interventions are currently under investigation (3,14,15).

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Jiao, C Main.A brief report of West Nile Virus neuroinvasive disease in the summer of 2012 in Hamilton, Ontario.Can J Infect Dis Med Microbiol 2014;25(1):24-26.

Table 1 Features of West Nile neuroinvasive disease cases Cases Case 1 Meningomyelitis Case 2 encephalitis Case 3 encephalitis Case 4 encephalitis Case 5 Meningitis Case 6 encephalitis Case 7 encephalitis
IgM Immunoglobulin M; LOC Decreased level of consciousness; N/A Not available; WBC White blood cellswhile young patients were more likely to develop meningitis.The five patients with encephalitis in the present series were all older than 69 years of age, while the two patients with meningitis were 36 and 38 years of age.Only two of seven patients recalled receiving mosquito bites.No significant immune deficiency was identified in this group.Patient histories from our group indicative of WNND included outdoor activity during WNV season, living close to stagnant water, recollection of mosquito bite within the incubation period of WNV Typical CSF findings indicative of WNND include universal pleocytosis, elevated protein level and normal to elevated glucose level.CSF analysis provides physicians with evidence to differentiate between bacterial and viral etiology.The neutrophil predominance in CSF typically indicates bacterial meningitis; however, almost one-half of the patients in the present series exhibited a neutrophil predominance in their CSF.Similar findings have been reported in a study involving 250 patients with serologically confirmed WNND, of whom 41.1% had at least 50% neutrophils in their initial CSF specimen *All symptoms and accessory examinations are documented as the day (D) of appearance from the onset of disease if available from the medical records; † Traumatic tap, with red blood cell count of 1056 x10 6 /L; ‡ D 10 Magnetic resonance imaging (MRI) showed hyperintensity in small posterior periventricular area; § D 28 MRI showed hyperintensity at the bilateral thalami, midbrain and cerebellar peduncle; ¶ D 7 MRI showed slight hyperintensity in bilateral sulci, possibly consistent with intracranial hypertension (HTN); **Supportive + Intravenous immunoglobulin (IVIG) D 15 × 5 days.CSF Cerebrospinal fluid; DM Diabetes mellitus;