Bilateral multifocal chorioretinitis as the only presentation of acute West Nile virus infection: a case report.

BACKGROUND: To describe a case of bilateral multifocal chorioretinitis as the only presentation of acute West Nile virus (WNV) infection in the absence of neurological involvement. CASE PRESENTATION: A 78-year-old Italian woman was admitted to our emergency department because she noticed blurry vision in both eyes. She did not report fever, fatigue, or neurological symptoms in the last few days. Multimodal imaging showed the presence of bilateral hyperfluorescent lesions with a linear distribution, that corresponded to hypocyanescent spots on indocyanine green angiography. Antibody serology showed the presence of IgM antibodies, IgG antibodies, and ribonucleic acid (RNA) for WNV. Magnetic resonance imaging (MRI) of the brain ruled out central nervous system involvement. Three months later, the patient reported spontaneous resolution of her symptoms and remission of the chorioretinal infiltrates. CONCLUSIONS: In endemic areas, it is important to think of acute WNV infection as an explanatory etiology in cases of multifocal chorioretinitis, even without neurological involvement.

[West Nile Infection and Kidney Disease: Description of Two Clinical Cases in Peritoneal Dialysis Patients].

The West Nile Virus (WNV), an RNA arbovirus, has been transmitted by wild birds and conveyed by ticks and mosquitoes, with wide diffusion all over the world; it is not transmitted from human to human. It can give clinical symptoms only in a minority of infected subjects such as fever, headache, muscle tiredness, visual disturbances, drowsiness, convulsions and muscle paralysis; in the most serious cases even potentially fatal encephalitis. In the literature there are few reports on WNV infection in patients with kidney diseases: here we report our experience on two patients on peritoneal dialysis infected by WNV with a revision of the literature.

Neuroinvasive West Nile Virus Infection in Immunosuppressed and Immunocompetent Adults.

Importance: West Nile virus (WNV) is the leading cause of human arboviral disease in the US, peaking during summer. The incidence of WNV, including its neuroinvasive form (NWNV), is increasing, largely due to the expanding distribution of its vector, the Culex mosquito, and climatic changes causing heavy monsoon rains. However, the distinct characteristics and outcomes of NWNV in individuals who are immunosuppressed (IS) and individuals who are not IS remain underexplored. Objective: To describe and compare clinical and radiographic features, treatment responses, and outcomes of NWNV infection in individuals who are IS and those who are not IS. Design, Setting, and Participants: This retrospective cohort study used data from the Mayo Clinic Hospital system collected from July 2006 to December 2021. Participants were adult patients (age ≥18 years) with established diagnosis of NWNV infection. Data were analyzed from May 12, 2020, to July 20, 2023. Exposure: Immunosuppresion. Main Outcomes and Measures: Outcomes of interest were clinical and radiographic features and 90-day mortality among patients with and without IS. Results: Of 115 participants with NWNV infection (mean [SD] age, 64 [16] years; 75 [66%] male) enrolled, 72 (63%) were not IS and 43 (37%) were IS. Neurologic manifestations were meningoencephalitis (98 patients [85%]), encephalitis (10 patients [9%]), and myeloradiculitis (7 patients [6%]). Patients without IS, compared with those with IS, more frequently reported headache (45 patients [63%] vs 18 patients [42%]) and myalgias (32 patients [44%] vs 9 patients [21%]). In contrast, patients with IS, compared with those without, had higher rates of altered mental status (33 patients [77%] vs 41 patients [57%]) and myoclonus (8 patients [19%] vs 8 patients [4%]). Magnetic resonance imaging revealed more frequent thalamic T2 fluid-attenuated inversion recovery hyperintensities in individuals with IS than those without (4 patients [11%] vs 0 patients). Individuals with IS had more severe disease requiring higher rates of intensive care unit admission (26 patients [61%] vs 24 patients [33%]) and mechanical ventilation (24 patients [56%] vs 22 patients [31%]). The 90-day all-cause mortality rate was higher in the patients with IS compared with patients without IS (12 patients [28%] vs 5 patients [7%]), and this difference in mortality persisted after adjusting for Glasgow Coma Scale score (adjusted hazard ratio, 2.22; 95% CI, 1.07-4.27; P = .03). Individuals with IS were more likely to receive intravenous immunoglobulin than individuals without IS (12 individuals [17%] vs 24 individuals [56%]), but its use was not associated with survival (hazard ratio, 1.24; 95% CI, 0.50-3.09; P = .64). Conclusions and Relevance: In this cohort study of individuals with NWNV infection, individuals with IS had a higher risk of disease complications and poor outcomes than individuals without IS, highlighting the need for innovative and effective therapies to improve outcomes in this high-risk population.

Neurological and neuromuscular manifestations in patients with West Nile neuroinvasive disease, Belgrade area, Serbia, season 2022.

INTRODUCTION: We aimed to describe neurological manifestations and functional outcome at discharge in patients with West Nile neuroinvasive disease. METHODS: This retrospective study enrolled inpatients treated in the University Clinic for Infectious and Tropical Diseases in Belgrade, Serbia, from 1 June until 31 October 2022. Functional outcome at discharge was assessed using modified Rankin scale. RESULTS: Among the 135 analyzed patients, encephalitis, meningitis and acute flaccid paralysis (AFP) were present in 114 (84.6%), 20 (14.8%), and 21 (15.6%), respectively. Quadriparesis/quadriplegia and monoparesis were the most frequent forms of AFP, present in 9 (6.7%) and 6 (4.4%) patients, respectively. Fourty-five (33.3%) patients had cerebellitis, 80 (59.3%) had rhombencephalitis, and 5 (3.7%) exhibited Parkinsonism. Ataxia and wide-based gait were present in 79 (58.5%) patients each. Fifty-one (37.8%) patients had tremor (41 (30.3%) had postural and/or kinetic tremor, 10 (7.4%) had resting tremor). Glasgow coma score (GCS) ≤ 8 and respiratory failure requiring mechanical ventilation developed in 39 (28.9%), and 33 (24.4%) patients, respectively. Quadriparesis was a risk factor for prolonged ventilator support (29.5 ± 16.8 vs. 12.4 ± 8.7 days, p = 0.001). At discharge, one patient with monoparesis recovered full muscle strength, whereas 8 patients with AFP were functionally dependent. Twenty-nine (21.5%) patients died. All of the succumbed had encephalitis, and 7 had quadriparesis. Ataxia, tremor and cognitive deficit persisted in 18 (16.9%), 15 (14.2%), and 22 (16.3%) patients at discharge, respectively. Age, malignancy, coronary disease, quadriparesis, mechanical ventilation, GCS ≤ 8 and healthcare-associated infections were risk factors for death (p = 0.001; p = 0.019; p = 0.004; p = 0.001; p < 0.001; p < 0.001, and p < 0.001, respectively).

Severe Neuroinvasive West Nile Virus in Association With Anti-CD20 Monotherapy for Multiple Sclerosis.

OBJECTIVES: The objective of this study was to report on the development of neuroinvasive West Nile virus (WNV) infection in the context of anti-CD20 monotherapy for multiple sclerosis (MS). METHODS: This is a case series study. RESULTS: In 2021-2022, we observed 4 cases of neuroinvasive WNV infection in our patient population of 2009 patients with MS on ocrelizumab, compared with a total of 46 cases of neuroinvasive WNV infection reported in Pennsylvania and 40 in New Jersey. Odds were 258 times that of the general population (95% confidence interval 97-691), χ2 p < 0.0001). All were women aged 41-61 years with variable disease duration, level of disability, and duration of anti-CD20 therapy. All presented in summer/early fall with fever, headache, and encephalopathy consistent with meningoencephalitis. Three patients had acute cerebellitis. Two had anterior nerve root involvement progressing to quadriparesis, and 1 developed refractory nonconvulsive status epilepticus. All required intubation and experienced significant morbidity. All had CSF pleocytosis. Two patients were WNV IgM positive in both the serum and CSF, 1 patient had positive serum IgM and CSF metagenomic next-generation sequencing (mNGS), while 1 had positive CSF mNGS with negative serum and CSF antibodies. DISCUSSION: Neuroinvasive WNV infection can develop with anti-CD20 monotherapy in the absence of additional immunosuppression. WNV serologies may be negative in the setting of anti-CD20 treatment; in the appropriate clinical context, one should consider direct detection methods such as PCR or mNGS-based testing.

A West Nile Virus infection expressed as unilateral limb paralysis and complicated by Parsonage-Turner syndrome: a case report.

BACKGROUND: West Nile Virus is a single-stranded Ribonucleic Acid arbovirus of the Flaviviridae family that is transmitted to humans by Culex species mosquitoes. West Nile Virus infection is asymptomatic in the majority of affected people. Of those who develop symptoms, the usual manifestation is a febrile syndrome, while only 1% develop neurological symptoms due to a neuroinvasive form of infection, including encephalitis, meningitis, asymmetrical flaccid paralysis, or a combination of all these features. Parsonage-Turner syndrome is a rare disorder characterized by sudden painful symptoms and subsequent paralysis, involving a shoulder or one of the upper limbs due to post-infective brachial plexopathy. The etiology is unknown, although it can be considered a multifactorial process: a predisposing factor, such as viral infection or strenuous upper-extremity exercise, can trigger an immune-mediated process localized in the brachial plexus. CLINICAL PRESENTATION: In late summer, a 79-year-old male Italian patient was admitted to the emergency department for acute right upper limb weakness and high fever, without any mental status impairment, pain, sensory alterations, or signs of meningeal irritation. Laboratory tests confirmed acute West Nile Virus infection, expressed as a unilateral upper limb flaccid paralysis. After a few days, the patient reported an acute pain in the right upper limb scarcely responsive to nonsteroidal anti-inflammatory drug therapy and a subsequent wider distribution of flaccid paralysis. After multiple examinations, Parsonage-Turner syndrome could be suspected. Patient was treated with steroids and reported an improvement of clinical condition after 2 months, with complete pain remission but partial strength recovery in the affected limb. CONCLUSIONS: West Nile Virus disease has a broad spectrum of neurological manifestations, among which the most common are signs of meningeal irritation or cognitive impairment. We report an unusual presentation of neuroinvasive West Nile Virus infection with arm weakness as expression of unilateral viral neuritis, followed by a post-infective brachial plexopathy consistent with Parsonage-Turner syndrome diagnosis. We diagnosed Parsonage-Turner syndrome after excluding the most common causes of atraumatic acute upper limb pain, through a challenging differential diagnosis in a patient with several comorbidities.

Severe Arboviral Neuroinvasive Disease in Patients on Rituximab Therapy: A Review.

With increasing use of rituximab and other B-cell depleting monoclonal antibodies for multiple indications, infectious complications are being recognized. We summarize clinical findings of patients on rituximab with arboviral diseases identified through literature review or consultation with the Centers for Disease Control and Prevention. We identified 21 patients on recent rituximab therapy who were diagnosed with an arboviral disease caused by West Nile, tick-borne encephalitis, eastern equine encephalitis, Cache Valley, Jamestown Canyon, and Powassan viruses. All reported patients had neuroinvasive disease. The diagnosis of arboviral infection required molecular testing in 20 (95%) patients. Median illness duration was 36 days (range, 12 days to 1 year), and 15/19 (79%) patients died from their illness. Patients on rituximab with arboviral disease can have a severe or prolonged course with an absence of serologic response. Patients should be counseled about mosquito and tick bite prevention when receiving rituximab and other B-cell depleting therapies.

Neuroinvasive West Nile virus infection in solid organ transplant recipients.

BACKGROUND: Literature on the natural course of neuroinvasive West Nile virus (WNV) infection in solid organ transplant (SOT) recipients is sparse. In the setting of a 2021 WNV outbreak in Arizona, we reviewed our institution's experience with neuroinvasive WNV infection in patients with SOT. METHODS: We retrospectively identified SOT recipients treated for neuroinvasive WNV at Mayo Clinic in Arizona from 2007 through 2021. Clinical manifestations, disease course, and outcomes were analyzed. RESULTS: Among 24 SOT recipients with WNV infection identified during the study period, 13 infections occurred in 2021. Most patients had gastrointestinal tract symptoms and fever at disease presentation. Five patients had cognitive impairment, and 14 initially or eventually had acute flaccid paralysis. Clinically significant deterioration occurred at a median of 4 (range, 1-11) days after hospital admission. Seventeen patients (71%) were transferred to the intensive care unit, with 15 requiring mechanical ventilation. Initial cerebrospinal fluid analysis mainly demonstrated a neutrophil-predominant pleocytosis. Almost all patients (n = 23) were treated with intravenous immunoglobulin alone or in combination with interferon alfa-2b. Sixteen patients had clinical improvement, 4 of whom recovered completely. Six patients died during hospitalization due to complications of neuroinvasive WNV infection. Two patients were discharged to hospice without clinical recovery. The overall 30-day mortality rate was 36%. CONCLUSION: Despite advances in supportive care, neuroinvasive WNV infection is associated with substantial morbidity and mortality in SOT recipients. Flaccid paralysis is an indicator of poor prognosis.

An HIV patient with West Nile encephalitis and Amphiphysin antibodies - More on "West Nile infection triggering autoimmune encephalitis: Pathophysiological and therapeutic implications" by Moutsopoulos et al.

We have encountered a patient with HIV who developed rapid worsening altered mental status positive for both acute West Nile encephalitis and amphiphysin antibodies. Upon literature review, we read Dr. Moutsopoulos's paper from your journal with great interest (Karagianni et al., 2019 [1]). While an autoimmune encephalitis following West Nile encephalitis is not novel, there are several interesting features in a patient we have encountered. Firstly, amphiphysin antibodies coexisting with West Nile encephalitis has not been described before. Second, the fact that the clinical course is monophasic, not biphasic, may lead to the suggestion that autoimmune encephalitis triggered by, or coexisting with, West Nile encephalitis may be grossly underrecognized. Third, our patient was HIV positive, but not grossly immunocompromised, which may have played a factor in the autoimmune status.

Analytical Approaches to Uncover Genetic Associations for Rare Outcomes: Lessons from West Nile Neuroinvasive Disease.

West Nile viral infection causes severe neuroinvasive disease in less than 1% of infected humans. There are no targeted therapeutics for this serious and potentially fatal disease, and to date no vaccine has been approved for humans. With climate change expected to result in rising incidence of West Nile and other related vector-borne viral infections, there is an increasing need to identify those at risk for serious disease and potential leads for therapeutic and vaccine development. Genetic variation, particularly in genes whose products are either directly or indirectly connected to immune response to infections, is a critical avenue of investigation to identify those at higher risk of clinically apparent West Nile infection. Given the small percent of infections that progress to severe disease and the relatively low numbers of reported infections, it is challenging to conduct well-powered studies to identify genetic factors associated with more severe outcomes. In this chapter, we outline several approaches with the objective to take full advantage of all available data in order to identify genetic factors which lead to increased risk of severe West Nile neuroinvasive disease. These methods are generalizable to other conditions with limited cohort size and rare outcomes.

Neuroinvasive disease due to West Nile virus: Clinical and imaging findings associated with a re-emerging pathogen.

The West Nile virus (WNV) is an arbovirus than can infect human beings and cause severe neuroinvasive disease. Taking the outbreak that occurred in Spain in 2020 as a reference, this article reviews the clinical and imaging findings for neuroinvasive disease due to WNV. We collected demographic, clinical, laboratory, and imaging (CT and MRI) variables for 30 patients with WNV infection diagnosed at our center. The main clinical findings were fever, headache, and altered levels of consciousness. Neuroimaging studies, especially MRI, are very useful in the diagnosis and follow-up of these patients. The most common imaging findings were foci of increased signal intensity in the thalamus and brainstem in T2-weighted sequences; we illustrate these findings in cases from our hospital.

Acute Fever of Unknown Origin: A Presentation of West Nile Encephalitis.

INTRODUCTION: West Nile virus is an asymptomatic infection in most cases, but it can present with a rare complication of deadly neuroinvasive disease. CASE PRESENTATION: A 81-year-old White man presented with altered mental status and fever of unknown origin. After extensive workup, he was diagnosed with West Nile encephalitis based on positive serology, lumbar puncture, and clinical presentation. DISCUSSION: West Nile virus is a mosquito-borne RNA arbovirus that, in rare cases, can lead to encephalitis, which is a challenging diagnosis. There is no current treatment; however, a 5-day course of intravenous immunoglobulin seemed to show acute clinical improvement in both mentation and magnetic resonance imaging of the head and no long-term effects. CONCLUSION: We report this case to increase awareness among clinicians to include West Nile virus in the differential diagnosis of encephalitis with fever of unknown origin, particularly in endemic areas.

New-onset Bell's palsy after neuroinvasive West Nile virus.

In this case report, a patient was diagnosed with new-onset Bell's palsy 3 weeks after the onset of neuroinvasive West Nile virus. This was the second case report of West Nile virus-associated Bell's palsy, highlighting the need to monitor these patients for peripheral neuropathies. This case report is also intended to raise awareness about the prevalence of West Nile virus in the USA.

Comorbid conditions as risk factors for West Nile neuroinvasive disease in Ontario, Canada: a population-based cohort study.

West Nile neuroinvasive disease (WNND) is a severe neurological illness that can result from West Nile virus (WNV) infection, with long-term disability and death being common outcomes. Although WNV arrived in North America over two decades ago, risk factors for WNND are still being explored. The objective of this study was to identify WNND comorbid risk factors in the Ontario population using a retrospective, population-based cohort design. Incident WNV infections from laboratory records between 1 January 2002 - 31 December 2012 were individually-linked to health administrative databases to ascertain WNND outcomes and comorbid risk factors. WNND incidence was compared among individuals with and without comorbidities using risk ratios (RR) calculated with log binomial regression.Three hundred and forty-five individuals developed WNND (18.3%) out of 1884 WNV infections. West Nile encephalitis was driving most associations with comorbidities. Immunocompromised (aRR 2.61 [95% CI 1.23-4.53]) and male sex (aRR 1.32 [95% CI 1.00-1.76]) were risk factors for encephalitis, in addition to age, for which each 1-year increase was associated with a 2% (aRR 1.02 [95% CI 1.02-1.03]) relative increase in risk. Our results suggest that individuals living with comorbidities are at higher risk for WNND, in particular encephalitis, following WNV infection.

[Rare neurological manifestations of West Nile virus infection in an immunocompetent patient]. / Association des manifestations neurologiques rares à West Nile virus chez un patient immunocompétent.

BACKGROUND: Neuro-invasive disease is the most dreaded complication of West Nile virus infection. We report the case of an immunocompetent patient who developed a meningeal syndrome associated with cerebellar ataxia, facial diplegia and hemiparesis caused by West Nile virus infection with a favourable outcome. OBSERVATION: A 42-year-old man was admitted for a febrile meningeal syndrome and confusion associated with cerebellar ataxia. The patient had developed facial diplegia, left hemiparesis with worsening cerebellar syndrome. He was diagnosed with neuro-invasive West Nile virus infection given the positive West Nile virus serologies in serum and cerebrospinal fluid as well as West Nile virus polymerase chain reaction in serum and urine. The outcome was favourable. CONCLUSION: Because of the increasing prevalence of West Nile virus, this infection should be suspected in the event of atypical neurological manifestations even in immunocompetent patients.

Progressive MRI findings of West Nile virus encephalitis in a patient with diabetes mellitus.

A man in his 70s was admitted to our hospital with complaints of fatigue, loss of appetite and fever. His neurological examination was normal. He had a medical history of diabetes mellitus for 25 years. Urine analysis showed many leucocytes. Empirical antibiotic treatment was started for urinary system infection. Three days later, his mental status worsened with confusion and disorientation. MRI of the brain was normal. Two days later, the patient was intubated because of respiratory insufficiency. MRI showed restricted diffusion in bilateral thalamic nuclei. Encephalitis and ischaemia were considered in the differential diagnosis. Cerebrospinal fluid IgM antibody for West Nile virus was positive. Sixteen days later, cranial nerve reflexes were lost. MRI showed restricted diffusion and increased T2 signal intensity in the dorsal medulla and increased T2 signal intensity without diffusion restriction in bilateral substantia nigra and dentate nuclei. He died of cardiac arrest 40 days after hospitalisation.

Initial Seronegative West Nile Virus Encephalitis in an Immunocompromised Child.

We present a case of initial seronegative West Nile virus encephalitis in an immunocompromised child due to B-cell acute lymphoblastic leukemia. Although diagnostic guidelines for West Nile virus infection exist, we highlight that these may not be met in immunocompromised patients who may have a delayed immune response.

Rare complication of West Nile viral encephalitis.

In our case report, we are presenting a 72 years old male patient. The patient's symptoms were fever, dizziness, general weakness at the time of admission. The laboratory and CSF tests revealed central nervous system inflammation. West Nile virus was identified from the cerebrospinal fluid. After the symptoms of infection and during supporting treatment, severe, progressing hyponatremia evolved with unknown pathology. According to previous investigations and our diagnostic and therapeutic algorithm cerebral salt wasting syndrome identified as occasion.