Article under review: Halperin JJ, Shapiro ED, Logigian E, et al. Practice parameter: treatment of nervous system Lyme disease (an evidence-based review): report of the Quality Standards Subcommittee of the American Academy of Neurology. Neurology 2007;69:91-102.
Background: Although there are guidelines for the treatment of Lyme disease in general (Wormser et al 2000), there continues to be controversy over the treatment of Lyme neuroborreliosis. In the United States, parenteral antibiotics are typically used for treatment of Lyme neuroborreliosis, while European studies support the use of oral doxycycline, which achieves adequate levels in the CNS.
The guidelines from the Infectious Diseases Society of America did include specific recommendations for treatment of Lyme neuroborreliosis (Wormser 2000), and 2 members of that panel were subsequently members of the American Academy of Neurology panel that reviewed the treatment of Lyme neuroborreliosis for this practice parameter (ie, Shapiro ED and Wormser GP).
Lyme neuroborreliosis may present in several ways:
The "post-Lyme syndrome" (or "post-treatment Lyme syndrome" or "chronic Lyme disease") is a poorly defined entity that occurs in patients who have had appropriate treatment for Lyme disease, but who have continued vague or nonspecific symptoms, such as fibromyalgia-like musculoskeletal aches (without frank arthritis), paresthesias, headaches, sleep disturbances, chronic fatigue, dysthymia, irritability, self-perceived memory difficulty, difficulty concentrating, and other "neuropsychiatric" symptoms.
Purpose: The purpose of this report is to provide evidence-based recommendations for the treatment of Lyme neuroborreliosis and "post-Lyme syndrome."
Methods: The authors performed a systematic review of studies published in the interval from 1983 to 2003, using a structured review process that rated the quality of the evidence provided. One hundread twelve potentially relevant articles were identified, from which 37 met the inclusion criteria and were included in the analysis.
Table 1: Treatment of Lyme Neuroborreliosis
|Meningitis, or any neurologic syndrome with CSF pleocytosis||Parenteral (particularly if severe), or oral|
|Peripheral or cranial nerve with normal CSF (including radiculopathy, polyneuropathy, and cranial neuropathy)||Oral, or parenteral (if severe or if oral fails)|
|Encephalomyelitis or encephalopathy||Parenteral|
|Post-treatment Lyme syndrome||
Symptomatic management only
(Antibiotics are not indicated, as they do not
improve outcomes and are potentially associated
with adverse effects)
Table 2: Oral and Parenteral Antibiotic Regimens for Treatment of Lyme Neuroborreliosis(1)
|Adult dose||Pediatric dose|
|Doxycycline(2)||100 (-200) mg orally twice a day||
4(-8) mg/kg per day orally in divided doses
(maximum of 200 mg/dose)
|Ceftriaxone(3)||2 g IV daily||
50 to 75 mg/kg per day IV in single dose
(maximum of 2 g/day)
|Cefotaxime(4)||2 g IV every 8 hours||150 to 200 mg/kg per day IV in 3 to 4 divided doses (maximum of 6 g/day)|
|Penicillin G(4)||3 to 4 MU IV every 4 hours||
200,000 to 400,000 unit/kg per day IV in
6 divided doses (ie, every 4 hours) (maximum of 18 to 24 MU/day)
The evaluation and treatment of Lyme disease associated with facial palsy is controversial: some advocate diagnostic lumbar puncture with subsequent parenteral antibiotic treatment of those with identified CSF pleocytosis, while others advocate initial treatment with oral doxycycline without lumbar puncture. Each approach has strengths and weaknesses, and the committee felt that although the first was "reasonable" the latter was also "a safe and valid approach." The role, if any, of corticosteroids in Lyme disease associated with facial palsy is also unclear. Antibiotic treatment does not hasten the resolution of facial palsy in a patient with Lyme disease, but antibiotics are advocated to prevent further sequelae (Wormser et al 2000).
Adverse effects, particularly diarrhea, occurred in a third of patients on prolonged antibiotics, and were life-threatening in 4%.
Comment: There is considerable overlap with the recommendations of the earlier guidelines from the Infectious Diseases Society of America, which is not surprising, particularly given the overlap of some committee members for the 2 sets of guidelines (Wormser et al 2000). Since the earlier set of guidelines, the range of treatment duration has been shortened (from the former maximum of 28 days), the role of oral doxycycline has been expanded, and ceftriaxone is no longer specified as the preferred parenteral agent (ie, it now has relative equivalency to cefotaxime and penicillin G, even if it is more convenient).