BackgroundThe increased incidence and geographic expansion of Lyme disease has made it the most common vector-borne infection in North America. Posttreatment Lyme disease syndrome (PTLDS) represents a subset of patients who remain ill following standard antibiotic therapy for Lyme disease. The spectrum of symptoms and their impact on quality of life remain largely unexplored among patients with well-documented PTLDS.ObjectiveTo characterize a case series of patients with well-documented PTLDS compared to a sample of healthy controls.MethodsSixty-one participants met the proposed case definition for PTLDS. Twenty-six healthy controls had neither a clinical history of Lyme disease nor current antibodies to Borrelia burgdorferi. Participants with PTLDS and controls were evaluated by physical exam, clinical laboratory testing, standardized questionnaires, and a 36-item current symptom list.ResultsCompared to controls, participants with PTLDS reported significantly greater fatigue, pain, sleep disturbance, and depression (Fatigue Severity Scale: 50.0 ± 10.6 vs. 19.8 ± 8.6; Short-Form McGill Pain Questionnaire: 13.7 ± 8.3 vs. 0.8 ± 1.9; Pittsburgh Sleep Quality Index: 10.1 ± 4.7 vs. 4.1 ± 2.1; Beck Depression Inventory-II: 15.1 ± 7.7 vs. 2.2 ± 3.2; p < 0.001 for each), and significantly lower quality of life (SF-36 Physical Component Score: 33.9 ± 9.7 vs. 55.1 ± 6.2; Mental Component Score: 42.9 ± 10.1 vs. 54.2 ± 5.4; p < 0.001 for each). Nineteen non-PTLDS-defining symptoms were found to be significantly more severe among participants with PTLDS than controls, including sleep difficultly and visual complaints. Initial delayed or misdiagnosis was characterized in 59.0% of participants with PTLDS, and 32.2% had abnormal vibratory sense.ConclusionAlthough physical exam and clinical laboratory tests showed few objective abnormalities, standardized symptom questionnaires revealed that patients with PTLDS are highly and clinically significantly symptomatic, with poor health-related quality of life. PTLDS patients exhibited levels of fatigue, musculoskeletal pain, sleep disturbance, and depression which were both clinically relevant and statistically significantly higher than controls. Our study shows that PTLDS can be successfully identified using a systematic approach to diagnosis and symptom measurement. As the prevalence of PTLDS continues to rise, there will be an increased need for physician education to more effectively identify and manage PTLDS as part of integrated patient care.

d Approximately 10% to 20% of patients optimally treated for early Lyme disease develop persistent symptoms of unknown pathophysiology termed posttreatment Lyme disease syndrome (PTLDS). The objective of this study was to investigate associations between PTLDS and immune mediator levels during acute illness and at several time points following treatment. Seventy-six participants with physician-documented erythema migrans and 26 healthy controls with no history of Lyme disease were enrolled. Sixty-four cytokines, chemokines, and inflammatory markers were measured at each visit for a total of 6 visits over 1 year. An operationalized definition of PTLDS incorporating symptoms and functional impact was applied at 6 months and 1 year following treatment completion, and clinical outcome groups were defined as the return-to-health, symptoms-only, and PTLDS groups. Significance analysis of microarrays identified 7 of the 64 immune mediators to be differentially regulated by group. Generalized logit regressions controlling for potential confounders identified posttreatment levels of the T-cell chemokine CCL19 to be independently associated with clinical outcome group. Receiver operating characteristic analysis identified a CCL19 cutoff of >111.67 pg/ml at 1 month following treatment completion to be 82% sensitive and 83% specific for later PTLDS. We speculate that persistently elevated CCL19 levels among participants with PTLDS may reflect ongoing, immune-driven reactions at sites distal to secondary lymphoid tissue. Our findings suggest the relevance of CCL19 both during acute infection and as an immunologic risk factor for PTLDS during the posttreatment phase. Identification of a potential biomarker predictor for PTLDS provides the opportunity to better understand its pathophysiology and to develop early interventions in the context of appropriate and specific clinical information.

Objective: Major depression is the most common psychiatric sequela of traumatic brain injury (TBI), but effective treatment continues to be a challenge, with few studies providing guidance.Methods: In a pilot study, the authors evaluated the effect size of low-frequency right-sided (LFR) repetitive transcranial magnetic stimulation (rTMS), compared with sham treatment, over the right dorsolateral prefrontal cortex (DLPFC) in patients (N=30) with TBI depression and co-occurring neuropsychiatric symptoms, including suicidal thoughts, anxiety, posttraumatic stress disorder, sleep disturbance, behavioral problems, and cognitive dysfunction. Exploratory analyses of diffusion tensor imaging pre-and postintervention were performed to determine the effect size of LFR rTMS on white matter integrity.Results: Small (Hedge's g=0.19) and highly variable effects of LRF rTMS over right DLPFC in TBI depression were observed. Similarly, the effect of LFR rTMS for treatment of comorbid neuropsychiatric symptoms varied from small to moderate.Conclusions: These findings suggest that the observed effects of LFR rTMS over the right DLPFC in TBI depression and co-occurring neuropsychiatric symptoms are small, at best, and, preliminarily, that low-frequency right DLPFC stimulation has limited potential in this patient population. However, studies employing different rTMS parameters (e.g., type, location, frequency, duration) or other participant characteristics (e.g., TBI severity, chronicity, comorbidity, concurrent treatment) may potentially yield different responses