Kohlhepp 1989.

Methods	Prospective, randomized, parallel‐group, open‐label study with active comparator, no placebo
Participants	75 participants with acute and chronic LNB. 12% of participants had a disease duration of ≥ 1 year with no statistically significant difference between treatment groups Participants had Borrelia burgdorferi‐specific antibodies in serum and at least 3 of the following diagnostic criteria: radicular pain; meningitic symptoms; cranial neuritis; sensory or motor radiculitis, or both; arthritis or carditis or encephalitis or myelitis or peripheral neuritis; tick bite or erythema migrans, or both. All participants were required to also have an elevated B. burgdorferi‐specific antibody titer in the serum. The following CSF laboratory parameters were analyzed: B. burgdorferi‐specific antibody titer; lymphocytic pleocytosis (abnormal if > 4 cells/mm3); elevated CSF protein (> 50 mg/dL); elevated CSF IgM, IgA, and/or IgG index; CSF oligoclonal banding. See Table 2 and Table 3 for diagnostic criteria and additional baseline characteristics.
Interventions	10‐day treatment with either: intravenous doxycycline 200 mg per day for 2 days followed by 100 mg also intravenously per day for another 8 days (N = 39); or intravenous penicillin G 20 mega units per day (N = 36) continuously infused over 16 hours. Participants with any or all of the following were considered a “treatment failure” and were eligible (procedure not clearly defined) for a second course of treatment with penicillin G (30 mega units per day for 10 days): relapse or progression of symptoms at the end of therapy; no improvement in CSF parameters; > 2‐fold increase of B. burgdorferi‐specific antibody concentrations in CSF. Participants with severe residual symptoms 3 months after therapy were offered the same therapeutic regimen. Participants with chronic encephalomyelitis were also treated with intravenous or intrathecal steroids, or both (N = 6) and cytarabine (N = 3).
Outcomes	Clinical follow‐up examination (first outcome) was performed prior to the intervention, and 0, 5, 6, and 12 months after the intervention. Investigators graded the clinical status as “no remission,” “partial remission,” or “full remission.” Secondary outcomes included CSF findings (cell count, total protein, IgM index, and intrathecal B. burgdorferi‐specific Ab production) and B. burgdorferi‐specific IgG concentrations in serum.
Funding	Not disclosed
Conflicts of interest	Not disclosed
Notes
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Unclear risk	Participants were randomly allocated to treatment groups, but the report does not describe the method of randomization.
Allocation concealment (selection bias)	Unclear risk	Not mentioned, not clear if it was done
Blinding of participants and personnel (performance bias) All outcomes	High risk	Not documented. We assume that neither participants nor investigators were blinded to treatment allocation.
Blinding of outcome assessment (detection bias) All outcomes	High risk	Not documented. We assume that outcome assessors were not blinded to treatment allocation.
Incomplete outcome data (attrition bias) All outcomes	Low risk	All participants returned to follow‐up at 1 year or longer.
Selective reporting (reporting bias)	Unclear risk	No evidence that all outcomes were prespecified; the pre‐study protocol was not available for review, and the study was not registered prior to initiation.
Other bias	Low risk	No other identified