The Range of Neurological Complications in Chikungunya Fever

  • T. Cerny
  • M. Schwarz
  • U. Schwarz
  • J. Lemant
  • P. Gérardin
  • E. Keller
Review Article

Abstract

Background

Chikungunya fever is a globally spreading mosquito-borne disease that shows an unexpected neurovirulence. Even though the neurological complications have been a major cause of intensive care unit admission and death, to date, there is no systematic analysis of their spectrum available.

Objective

To review evidence of neurological manifestations in Chikungunya fever and map their epidemiology, clinical spectrum, pathomechanisms, diagnostics, therapies and outcomes.

Methods

Case report and systematic review of the literature followed established guidelines. All cases found were assessed using a 5-step clinical diagnostic algorithm assigning categories A–C, category A representing the highest level of quality. Only A and B cases were considered for further analysis. After general analysis, cases were clustered according to geospatial criteria for subgroup analysis.

Results

Thirty-six of 1196 studies were included, yielding 130 cases. Nine were ranked as category A (diagnosis of Neuro-Chikungunya probable), 55 as B (plausible), and 51 as C (disputable). In 15 cases, alternative diagnoses were more likely. Patient age distribution was bimodal with a mean of 49 years and a second peak in infants. Fifty percent of the cases occurred in patients <45 years with no reported comorbidity. Frequent diagnoses were encephalitis, optic neuropathy, neuroretinitis, and Guillain–Barré syndrome. Neurologic conditions showing characteristics of a direct viral pathomechanism showed a peak in infants and a second one in elder patients, and complications and neurologic sequelae were more frequent in these groups. Autoimmune-mediated conditions appeared mainly in patients over 20 years and tended to show longer latencies and better outcomes. Geospatial subgrouping of case reports from either India or Réunion revealed diverging phenotypic trends (Réunion: 88% direct viral vs. India: 81% autoimmune).

Conclusions

Direct viral forms of Neuro-Chikungunya seem to occur particularly in infants and elderly patients, while autoimmune forms have to be also considered in middle-aged, previously healthy patients, especially after an asymptomatic interval. This knowledge will help to identify future Neuro-Chikungunya cases and to improve outcome especially in autoimmune-mediated conditions. The genetics of Chikungunya virus might play a key role in determining the course of neuropathogenesis. With further research, this could prove diagnostically significant.

Keywords

Chikungunya fever Chikungunya virus Neurological complications Neuro-Chikungunya 

Abbreviations

Ae

Aedes (a genus of mosquitoes)

ADEM

Acute disseminated encephalomyelopathy

BBE

Bickerstaff’s brainstem encephalitis

CHIKF

Chikungunya fever

CHIKV

Chikungunya virus

d

Days

DOI

Day of illness

DWI

Diffusion-weighted imaging

ECSA

East, Central, and South African

ENMG

Electroneuromyography

GBS

Guillain–Barré syndrome

IFN

Interferon

MFS

Miller Fisher syndrome

mRS

Modified Rankin scale

PRISMA

Preferred reporting items for systematic reviews and meta-analyses

rtPCR

Reverse transcription Polymerase chain reaction

y

Years

Supplementary material

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Copyright information

© Springer Science+Business Media New York 2017

Authors and Affiliations

  1. 1.Neurointensive Care UnitUniversity Hospital ZurichZurichSwitzerland
  2. 2.Department of MicrobiologyIcahn School of Medicine at Mount SinaiNew YorkUSA
  3. 3.Department of NeurologyUniversity Hospital ZurichZurichSwitzerland
  4. 4.Intensive Care UnitCHU de la RéunionSaint PierreFrance
  5. 5.INSERM CIC 1410CHU de la RéunionSaint PierreFrance
  6. 6.CNRS 9192, INSERM U1187, IRD 249, CHU Réunion, Unité Mixte 134 Processus Infectieux en Milieu Insulaire Tropical (PIMIT), CYROIUniversité de La RéunionSainte-ClotildeFrance

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