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Brian A. Fallon, MD; Richard B. Lipkin, BA; Kathy M. Corbera, MD; Shan Yu, PhD; Mitchell S. Nobler, MD; John G. Keilp, PhD; Eva Petkova, PhD; Sarah H. Lisanby, MD; James R. Moeller, PhD; Iordan Slavov, PhD; Ronald Van Heertum, MD; Brett D. Mensh, MD, PhD; Harold A. Sackeim, PhD

Arch Gen Psychiatry. 2009;66(5):554-563.

Context  There is controversy regarding whether objective neurobiological abnormalities exist after intensive antibiotic treatment for Lyme disease.

Objectives  To determine whether patients with a history of well-characterized Lyme disease and persistent cognitive deficit show abnormalities in global or topographic distributions of regional cerebral blood flow (rCBF) or cerebral metabolic rate (rCMR).

Design  Case-controlled study.

Setting  A university medical center.

Participants  A total of 35 patients and 17 healthy volunteers (controls). Patients had well-documented prior Lyme disease, a currently reactive IgG Western blot, prior treatment with at least 3 weeks of intravenous cephalosporin, and objective memory impairment.

Main Outcome Measures  Patients with persistent Lyme encephalopathy were compared with age-, sex-, and education-matched controls. Fully quantified assessments of rCBF and rCMR for glucose were obtained while subjects were medication-free using positron emission tomography. The CBF was assessed in 2 resting room air conditions (without snorkel and with snorkel) and 1 challenge condition (room air enhanced with carbon dioxide, ie, hypercapnia).

Results  Statistical parametric mapping analyses revealed regional abnormalities in all rCBF and rCMR measurements that were consistent in location across imaging methods and primarily reflected hypoactivity. Deficits were noted in bilateral gray and white matter regions, primarily in the temporal, parietal, and limbic areas. Although diminished global hypercapnic CBF reactivity (P < .02) was suggestive of a component of vascular compromise, the close coupling between CBF and CMR suggests that the regional abnormalities are primarily metabolically driven. Patients did not differ from controls on global resting CBF and CMR measurements.

Conclusions  Patients with persistent Lyme encephalopathy have objectively quantifiable topographic abnormalities in functional brain activity. These CBF and CMR reductions were observed in all measurement conditions. Future research should address whether this pattern is also seen in acute neurologic Lyme disease.

Author Affiliations: Departments of Psychiatry (Drs Fallon, Corbera, Yu, Keilp, Petkova, Lisanby, Moeller, Slavov, Mensh, and Sackeim), Radiology (Drs Van Heertum and Sackeim), and Biostatistics (Dr Petkova), College of Physicians and Surgeons of Columbia University, New York, New York; the New York State Psychiatric Institute, New York (Drs Fallon, Corbera, Yu, Nobler, Keilp, Petkova, Lisanby, Moeller, Slavov, Mensh, and Sackeim); the Department of Neural and Behavioral Science, State University of New York at Downstate, New York (Mr Lipkin); and the Department of Psychiatry and Behavioral Sciences, New York Medical College, New York (Dr Nobler).

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