Prevalence and spectrum of residual symptoms in Lyme neuroborreliosis after pharmacological treatment: a systematic review
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Controversy exists about residual symptoms after pharmacological treatment of Lyme neuroborreliosis. Reports of disabling long-term sequels lead to concerns in patients and health care providers. We systematically reviewed the available evidence from studies reporting treatment of Lyme neuroborreliosis to assess the prevalence and spectrum of residual symptoms after treatment. A literature search was performed in three databases and three clinical trial registers to find eligible studies reporting on residual symptoms in patients after pharmacological treatment of LNB. Diagnosis must have been performed according to consensus-derived case definitions. No restrictions regarding study design or language were set. Symptom prevalence was pooled using a random-effects model. Forty-four eligible clinical trials and studies were found: 8 RCTs, 17 cohort studies, 2 case–control studies, and 17 case series. The follow-up period in the eligible studies ranged from 7 days to 20 years. The weighted mean proportion of residual symptoms was 28 % (95 % CI 23–34 %, n = 34 studies) for the latest reported time point. Prevalence of residual symptoms was statistically significantly higher in studies using the “possible” case definition (p = 0.0048). Cranial neuropathy, pain, paresis, cognitive disturbances, headache, and fatigue were statistically significantly lower in studies using the “probable/definite” case definition. LNB patients may experience residual symptoms after treatment with a prevalence of approximately 28 %. The prevalence and spectrum of residual symptoms differ according to the applied case definition. Symptoms like fatigue are not reported in studies using the “probable/definite” case definition. As the “possible” case definition is more unspecific, patients with other conditions may be included. Reports of debilitating fatigue and cognitive impairment after LNB, a “post-Lyme syndrome”, could therefore be an artifact of unspecific case definitions in single studies.
KeywordsLyme disease Lyme neuroborreliosis Systematic review Prevalence review Residual symptoms Fatigue
Compliance with ethical standards
The manuscript does not contain a primary clinical study or patient data.
Conflicts of interest
SR reports receiving consulting and lecture fees, grant and research support from Bayer Vital GmbH, Biogen Idec, Merck Serono, Novartis, Sanofi-Aventis, Baxter, RG, and Teva. Furthermore, SR indicates that he is a founding executive board member of ravo Diagnostika GmbH. All other authors (RD, HS and JJM) declare that they have no competing interests.
- 4.Mygland A, Ljostad U, Fingerle V, Rupprecht T, Schmutzhard E, Steiner I, European Federation of Neurological S (2010) EFNS guidelines on the diagnosis and management of European Lyme neuroborreliosis. Eur J Neurol Off J Eur Fed Neurol Soc 17(8–16):e11–e14Google Scholar
- 7.Wormser GP, Dattwyler RJ, Shapiro ED, Halperin JJ, Steere AC, Klempner MS, Krause PJ, Bakken JS, Strle F, Stanek G et al (2006) The clinical assessment, treatment, and prevention of lyme disease, human granulocytic anaplasmosis, and babesiosis: clinical practice guidelines by the Infectious Diseases Society of America. Clin Infect Dis Off Publ Infect Dis Soc Am 43:1089–1134CrossRefGoogle Scholar
- 17.Stanek G, Fingerle V, Hunfeld KP, Jaulhac B, Kaiser R, Krause A, Kristoferitsch W, O’Connell S, Ornstein K, Strle F, Gray J (2011) Lyme borreliosis: clinical case definitions for diagnosis and management in Europe. Clin Microbiol Infect Off Publ Eur Soc Clin Microbiol Infect Dis 17:69–79Google Scholar
- 18.Yates F (1934) Contingency table involving small numbers and the χ 2 test. J R Stat Soc 1:217–235Google Scholar
- 20.The R Project for Statistical Computing. (http://www.r-project.org/)
- 21.GraphPad Prism. (http://www.graphpad.com/)