Neurocritical Care

, Volume 27, Issue 3, pp 447–457 | Cite as

The Range of Neurological Complications in Chikungunya Fever

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



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.


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


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.


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).


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.


Chikungunya fever Chikungunya virus Neurological complications Neuro-Chikungunya 



Aedes (a genus of mosquitoes)


Acute disseminated encephalomyelopathy


Bickerstaff’s brainstem encephalitis


Chikungunya fever


Chikungunya virus




Day of illness


Diffusion-weighted imaging


East, Central, and South African




Guillain–Barré syndrome




Miller Fisher syndrome


Modified Rankin scale


Preferred reporting items for systematic reviews and meta-analyses


Reverse transcription Polymerase chain reaction





The following authors of case reports included in this study supplied supplementary data: Dr. Mahesh Gopalakrishnan (India), Dr. Prashanth Prabhu (India), Dr. Sher Bahadur Pun (Nepal), Dr. Suman Das (India), Dr. Anna Bank (USA), Prof. Uday Shankar Ghosh (India), Prof. Dulari Gupta (India), Dr. Penny Lewthwaite (UK), Dr. Bernard-Alex Gaüzère (France), Dr. Anne-Cécile Wielanek-Bachelet (France), Dr. Abhijit Mohite (UK), Dr. Jesse Waggoner and Dr. Benjamin Pinsky (USA), Prof. Alfonso J. Rodriguez-Morales (Colombia), Dr. Adrian C. L. Kee and Dr. Paul A. Tambyah (Singapore), Dr. Steven A. Sparr (USA), Prof. Lalitha Krishnan (India), Dr. Shimin Jasmine Chung (Singapore), Prof. Meenaxi Sharda (India), Dr. S. M. Katrak (India). We are very grateful to these authors for readily offering their time and data to the research community. Special thanks to Dr. Susanne Friedl, Ms. Margaritha Winter, Mr. Kirill Karlin and Ms. Anna Wang (Switzerland), for their support and critical lecture.

Author Contributions

TC was involved in methods, systematic review, data extraction, statistical analysis, results, and discussion. MS was involved in methods, data extraction, statistical analysis, results, and discussion. US was involved in methods, critical review for consistency, errors, and intellectual content. JL was involved in provision of extensive data, critical review for consistency, errors, and intellectual content. PG was involved in provision of extensive data, critical review for consistency, errors, and intellectual content; EK was involved in methods, critical review for consistency, errors and intellectual content.

Compliance with Ethical Standards

Conflict of interest

The authors declare that they have no conflict of interest.

Ethical Standards

As a retrospective study, this article does not contain any studies with human participants or animals performed by any of the authors. The use of the patient’s data for the case report was approved by the ethical commission of the Canton of Zurich, Switzerland.

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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