A Specific Pattern of Routine Cerebrospinal Fluid Parameters Might Help to Identify Cases of West Nile Virus Neuroinvasive Disease

Abstract

Background: Viral meningitis/encephalitis (ME) is a rare but potentially harmful disease. The prompt identification of the respective virus is important to guide not only treatment but also potential public health countermeasures. However, in about 40% of cases, no virus is identified despite an extensive diagnostic workup. The aim of the present study was to analyze demographic, seasonal, and routine cerebrospinal fluid (CSF) parameters in cases of viral ME and assess their utility for the prediction of the causative virus.

Methods: Demographic data, season, and routine CSF parameters (total leucocytes, CSF cell differentiation, age-adjusted CSF/serum albumin ratio, and total immunoglobulin ratios) were retrospectively assessed in cases of viral ME.

Results: In total, 156 cases of acute viral ME (74 female, median age 40.0 years) were treated at a tertiary-care hospital in Germany. Specific viral infections were detected in 93 (59.6%) cases. Of these, 14 (9.0%) cases were caused by herpes simplex virus (HSV), 36 (23.1%) by varicella-zoster virus (VZV), 27 (17.3%) by enteroviruses, 9 (5.8%) by West Nile virus (WNV), and 7 (4.5%) by other specific viruses. Additionally, 64 (41.0%) cases of ME of unknown viral etiology were diagnosed. Cases of WNV ME were older, predominantly male, showed a severe disruption of the blood-CSF-barrier, a high proportion of neutrophils in CSF, and an intrathecal total immunoglobulin M synthesis in the first CSF sample. In a multinominal logistic regression analysis, the accuracy of these CSF parameters together with age and seasonality was best for the prediction of WNV (87.5%), followed by unknown viral etiology (66.7%), VZV (61.8%), and enteroviruses (51.9%).

Conclusions: Cases with WNV ME showed a specific pattern of routine CSF parameters and demographic data that allowed for their identification with good accuracy. These findings might help to guide the diagnostic workup in cases with viral ME, in particular allowing the timely identification of cases with ME due to WNV.

Keywords: West Nile virus; cerebrospinal fluid; climate change; encephalitis; immunoglobulin M; meningitis.

Figure 1

Intrathecal synthesis of immunoglobulins G, M, and A (Reiber diagram) in viral meningitis/encephalitis (ME) via herpes simplex virus (HSV), varicella-zoster virus (VZV), enterovirus, and West Nile virus (WNV) and in ME of unknown viral etiology. Genomes of the specific viruses were detected in the cerebrospinal fluid (CSF) via real-time polymerase chain reaction. The diagnosis of a ME of unknown viral etiology was made after an extensive diagnostic workup without evidence for a specific pathogen or autoimmune cause. The x-axis represents the quotient (Q) of albumin (Alb) in the CSF and the serum (Q_Alb = Alb_CSF/Alb_serum), while the y-axis shows the quotient of the immunoglobulin (G, A, M) concentration in the CSF and the serum (Q_Ig = Ig_CSF/Ig_serum). The ratios of Q_Alb and Q_Ig were plotted into the diagram. The bold printed curve stands for the upper reference range and represents the discrimination line between brain-derived and blood-derived immunoglobulin fractions in the CSF.