New Guidelines Issued for Nervous System Lyme Disease

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New Guidelines Issued for Nervous System Lyme Disease CME/CE

News Author: Susan Jeffrey
CME Author: Désirée Lie, MD, MSEd
Disclosures
Release Date: May 30, 2007; Valid for credit through May 30, 2008 Credits Available

Physicians - maximum of 0.25 AMA PRA Category 1 Credit(s)™ for physicians;
Family Physicians - up to 0.25 AAFP Prescribed credit(s) for physicians;
Nurses - 0.25 nursing contact hours (0.25 contact hours are in the area of pharmacology)




May 30, 2007 — The American Academy of Neurology (AAN) has issued new evidence-based treatment guidelines for nervous system Lyme disease, which endorse conventionally recommended antibiotics for treatment of the disease, both for adults and children. However, they found no compelling evidence of a beneficial effect from the prolonged use of antibiotics in post-Lyme syndrome.

The practice parameter, a report of the AAN's Quality Standards Subcommittee, is published online in the May 23 Expedited E-Pub issue and will appear in the July 3 print issue of Neurology. The document has also been endorsed by the Infectious Diseases Society of America.
Evidence-Based Recommendations

Lyme disease is caused by a tick-borne bacteria Borrelia burgdorferi and affects the nervous system in 10% to 15% of cases, a condition called neuroborreliosis.

Although guidelines exist in the diagnosis and treatment of Lyme disease in general, there is great variability in how neuroborreliosis is treated and little clear guidance is currently available, first author John J. Halperin, MD, from Atlantic Health and Overlook Hospital in Summit, New Jersey, told Medscape. "It's something that causes a lot of consternation both for patients and physicians," he said.

To clarify recommendations for this document, the authors analyzed studies published between 1983 and 2003, using a structured review process to classify the evidence with a focus on answering 3 main questions: which antimicrobial agents are effective, whether some regimens should be preferred over others in different manifestations of nervous system Lyme disease, and, finally, the optimal duration of treatment.

"The first conclusion is that nervous system Lyme disease is very responsive to conventional antibiotics, and that conventional courses which run 2, at most 4 weeks, are quite effective," Dr Halperin said. There was sufficient data to conclude that in both adults and children, neuroborreliosis responds well to penicillin, ceftriaxone, cefotaxime, and doxycycline, the authors write, a level B recommendation.

Dr. Halperin noted that in the United States patients are generally treated using intravenous antibiotics, as are most infections involving the nervous system. Although most of the studies in their review used parenteral antibiotics, they also drew on a "substantial body of literature" from European studies supporting the use of oral doxycycline.

They concluded consequently that, at least in patients with peripheral nervous system Lyme disease or central nervous system Lyme disease without parenchymal involvement, oral doxycycline is "probably a safe and effective treatment," also a level B recommendation.

For Lyme disease with parenchymal involvement, however, "most of us would be nervous using oral antibiotics and in those patients we recommend intravenous antibiotics," Dr. Halperin noted. Intravenous antibiotics are also recommended for patients with other severe neurologic symptomatology or who do not respond to oral regimens.

Finally, for post-Lyme syndrome, in which symptoms linger after there is no longer active infection, the literature indicates that prolonged courses of antibiotics are not effective and carry significant risk for adverse events, a level A recommendation.
Future Research Directions

Their review of the evidence suggests areas where further research is needed, Dr. Halperin noted. The more straightforward question relates to the fact that the oral antibiotic data are entirely from Europe. "Although European Lyme strains are very similar to North American strains, they're not identical, so that work really should be repeated in North America," he said. "One of the things we'd all like to do if we had the time is a randomized trial of oral vs intravenous antibiotics for acute nervous system Lyme disease."

If oral doxycycline were shown to be effective, then assessment of the relative efficacy of other oral agents such as amoxicillin and cefuroxime axetil would also be helpful, the authors write.

A far more challenging area for research is in creating a better understanding of the pathophysiology of post-Lyme syndrome. "It's clear the patients have symptoms that are very distressing and very disruptive to their lives and it's clear it's not infection, but it's not at all clear what it really is, and we need to figure out a way to answer that question," Dr. Halperin concluded.

The authors have disclosed no relevant financial relationships.

Neurology. Published online May 23, 2007.

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Clinical Context

According to the authors of the current review, Lyme disease is a multisystem disease caused by a tick-borne bacteria B burgdorferi and can affect the nervous system, a condition called neuroborreliosis; however, there is considerable controversy about the approach to treatment of neuroborreliosis. In the United States, Lyme disease affecting the nervous system is generally treated with parenteral therapy, whereas in Europe comparable efficacy has been shown with oral doxycycline. Optimal duration of treatment has not been established, according to the authors.

This is a literature review of studies on nervous system Lyme disease to identify best management strategies for antibiotics and optimal duration of therapy and to outline approaches to post-Lyme syndrome. It was conducted by the Quality Standards Subcommittee of the AAN.
Study Highlights
37 articles were selected by independent reviewers on the panel after a search of MEDLINE, PubMed, and EMBASE databases using keywords identified 112 articles.
Excluded were articles that were not peer reviewed, did not address treatment of neuroborreliosis, or were solely review articles.
Studies were divided into areas of adult Lyme disease, pediatric disease, and post-Lyme syndrome.
4 studies were of class I; 4, class II; 4, class III; and the remainder, class IV evidence.
Effects of Lyme disease on the nervous system were categorized as meningitis, cranial neuritis, and radiculoneuritis; parenchymal inflammation of brain and spinal cord; mild radiculoneuropathy and encephalopathy.
Post-Lyme syndrome has been defined as a combination of chronic symptoms of fatigue, musculoskeletal pain, and neuropsychiatric symptoms in the absence of laboratory or clinical evidence of focal or inflammatory nervous system involvement.
The data are sufficient to conclude that in adults and children, Lyme disease involving the nervous system responds well to penicillin, ceftriaxone, cefotaxime, and doxycycline.
Ceftriaxone at a dosage of 2 g/day for periods varying from 7 to 30 days has been shown to be as effective as 4 g/day for Lyme meningoradiculitis and Lyme disease encephalopathy.
None of the follow-up studies on efficacy included control patients.
Good evidence supports the use of oral doxycycline at a dosage of 200 mg daily for 9 to 17 days for nonparenchymal nervous system Lyme disease as comparable to intravenous antibiotic regimens because of the excellent cerebrospinal fluid penetration achieved by doxycycline.
There is a low probability of neurologic sequelae after doxycycline treatment of Lyme disease.
For parenchymal involvement, severe neurologic symptoms, or failure to respond to oral therapy, parenteral antibiotic regimens may be associated with better outcomes than oral regimens.
Some recommend routine cerebrospinal fluid examination of patients with Lyme disease who develop facial nerve palsy.
There is no clear beneficial or harmful effect of using corticosteroids in patients with neuroborreliosis who are treated with appropriate antibiotics.
In children, nervous system manifestations of Lyme disease include cranial neuropathies, headache, seizures, meningitis, meningoencephalitis, encephalopathy, focal neurologic signs, ataxia, vertigo, chorea, and transverse myelitis.
Facial nerve palsy and meningitis are the most common manifestations.
Treatment with either intravenous penicillin G or ceftriaxone has been shown to be effective.
The etiology of post-Lyme syndrome remains uncertain, and persistent B burgdorferi infection is unlikely in patients who have been adequately treated with antibiotics.
Antibiotics are not effective with respect to overall quality of life, depression, fatigue, and cognitive symptoms in double-blind placebo-controlled studies.
Post-Lyme syndrome does not respond to prolonged courses of antibiotics and because such treatment may be associated with adverse effects, it is not recommended.
Pearls for Practice
Lyme disease involving the nervous system responds well to penicillin, ceftriaxone, cefotaxime, and doxycycline in adults and children.
The current literature review concluded that post-Lyme syndrome does not respond to prolonged courses of antibiotics and that because such treatment may be associated with adverse effects it is not recommended.

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