Treating cognitive impairments in primary central nervous system infections: A systematic review of pharmacological interventions

Abstract

Background: This research synthesized scientific evidence on the use of pharmacotherapy as intervention to reduce cognitive impairments in adult patients with primary central nervous system (CNS) infections. Methods: We searched for experimental studies published in English prior to October 2021 in MEDLINE, Embase and Cochrane databases. We included non-randomized studies (NRS) and randomized control trials (RCT) of pharmacotherapy versus placebo, drug, or a combination of drugs in adults with primary CNS infection. The certainty of the evidence was rated according to GRADE guidelines. Results: We included 8 RCTs and 1 NRS, involving a total of 805 patients (50.77% male patients; mean age 42.67 ± 10.58) with Lyme disease (LD), herpes simplex virus type 1 (HSV-1), or Creutzfeldt–Jakob disease (CJD) studying the efficacy of antibiotics, antiviral, and non-opioid analgesic drugs, respectively. In patients with LD, antibiotics alone or in combination with other drugs enhanced certain cognitive domains relative to placebo. In patients with HSV-1, the results were inconsistent. In patients with CJD, flupirtine maleate enhanced baseline cognitive scores. The quality of RCT studies was low, and the quality of NRS of intervention was very low, suggesting low and very low certainty in the reported results. Conclusion: There is limited evidence and low certainty regarding the efficacy of antimicrobials and analgesics in reducing cognitive impairments in patients with LD, HSV-1, and CJD. Future efforts must be aimed at enhancing attention to clinical trial methodology and reporting, as well as reaching a consensus on outcome measures and the endpoint of clinical trials relevant to patients.