NEW YORK (Reuters Health) – There is no evidence of central nervous system (CNS) infection in patients with neurobehavioral symptoms of Lyme disease, researchers report.
“The cognitive, memory, and concentration difficulties often attributed to Lyme disease are not caused by brain infection or immune activation within the nervous system, nor do they appear to be specific to Lyme disease,” Dr. John J. Halperin from Overlook Medical Center, Atlantic Health System, Summit, New Jersey, told Reuters Health by email. “There may be systemic immune activation (i.e., not related to the nervous system) causing these symptoms; understanding this better may lead to insights and useful therapeutic interventions.”
Lyme encephalopathy manifests as objective cognitive abnormalities on mental status testing, but it remains unclear what mechanisms underlie this phenomenon.
Dr. Halperin’s team performed multiplex immunoassays to measure cytokines and chemokines in cerebrospinal fluid (CSF) samples from 74 patients who underwent lumbar puncture for possible Lyme neuroborreliosis (LNB).
Several inflammatory markers were elevated in the CSF of patients with definite LNB and non-Lyme neuroinflammation, but not in patients with Lyme or non-Lyme encephalopathy.
CSF CXCL13 proved to be a sensitive and specific marker of LNB in patients with specific intrathecal antibodies to Borrelia burgdorferi, according to the January 11 online report in Clinical Infectious Diseases.
“This is important, first, because it has been proposed as a useful marker of active CNS infection, one that drops after successful treatment,” Dr. Halperin said. “Second, it’s reassuring to find that mechanisms of disease are similar in U.S. and European patients, as the responsible spirochetes are slightly different. Knowing that mechanisms are the same enhances our ability to apply lessons learned in Europe as we try to understand mechanisms of disease in U.S. patients.”
Serum levels of the T-cell growth factor IL-7 were elevated in patients experiencing neurobehavioral symptoms, regardless of their history of Lyme disease.
Moreover, encephalopathy and headache patients, with or without a history of Lyme disease, showed elevations in serum cytokine levels indicative of a Th17-type immune response.
None of the cytokines analyzed in the study was elevated in CSF of patients with headache or encephalopathy, compared with measurements from 50 control patients with non-neuroinflammatory disorders.
These findings “should be reassuring to patients and their physicians – the presence of this symptom complex in no way implies there is a difficult-to-eradicate brain infection,” Dr. Halperin said. “Intriguingly it suggests that this state may, regardless of the specific circumstances, reflect a particular pattern of ongoing immune activation – having nothing to do with the nervous system, or for that matter Lyme disease per se. Understanding this better could lead to better therapeutic interventions in these patients, for many of whom the symptoms are quite disabling.”
SOURCE: http://bit.ly/2DLNiNS
Clin Infect Dis 2018.
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