Symptom Clusters and Functional Impairment in Individuals Treated for Lyme Borreliosis.

Context: Persistent fatigue, pain, and neurocognitive impairment are common in individuals following treatment for Lyme borreliosis (LB). Poor sleep, depression, visual disturbance, and sensory neuropathies have also been reported. The cause of these symptoms is unclear, and widely accepted effective treatment strategies are lacking. Objectives: To identify symptom clusters in people with persistent symptoms previously treated for LB and to examine the relationship between symptom severity and perceived disability. Methods: This was a retrospective chart review of individuals with a history of treatment of LB referred to The Dean Center for Tick-Borne Illness at Spaulding Rehabilitation Hospital between 2015 and 2018 (n = 270) because of persistent symptoms. Symptoms and functional impairment were collected using the General Symptom Questionnaire-30 (GSQ-30), and the Sheehan Disability Scale. Clinical tests were conducted to evaluate for tick-borne co-infections and to rule out medical disorders that could mimic LB symptomatology. Exploratory factor analysis was performed to identify symptom clusters. Results: Five symptom clusters were identified. Each cluster was assigned a name to reflect the possible underlying etiology and was based on the majority of the symptoms in the cluster: the neuropathy symptom cluster, sleep-fatigue symptom cluster, migraine symptom cluster, cognitive symptom cluster, and mood symptom cluster. Symptom severity for each symptom cluster was positively associated with global functional impairment (p < 0.001). Conclusion: Identifying the interrelationship between symptoms in post-treatment LB in a cluster can aid in the identification of the etiological basis of these symptoms and could lead to more effective symptom management strategies. Key Message: This article describes symptom clusters in individuals with a history of Lyme borreliosis. Five clusters were identified: sleep-fatigue, neuropathy, migraine-like, cognition, and mood clusters. Identifying the interrelationship between symptoms in each of the identified clusters could aid in more effective symptom management through identifying triggering symptoms or an underlying etiology.

The General Symptom Questionnaire-30 (GSQ-30): A Brief Measure of Multi-System Symptom Burden in Lyme Disease.

Introduction: The multi-system symptoms accompanying acute and post-treatment Lyme disease syndrome pose a challenge for time-limited assessment. The General Symptom Questionnaire (GSQ-30) was developed to fill the need for a brief patient-reported measure of multi-system symptom burden. In this study we assess the psychometric properties and sensitivity to change of the GSQ-30. Materials and Methods: 342 adult participants comprised 4 diagnostic groups: Lyme disease (post-treatment Lyme disease syndrome, n = 124; erythema migrans, n = 94); depression, n = 36; traumatic brain injury, n = 51; healthy, n = 37. Participants were recruited from clinical research facilities in Massachusetts, Maryland, and New York. Validation measures for the GSQ-30 included the Patient Health Questionnaire-4 for depression and anxiety, visual analog scales for fatigue and pain, the Sheehan Disability Scale for functional impairment, and one global health question. To assess sensitivity to change, 53 patients with erythema migrans completed the GSQ-30 before treatment and 6 months after 3 weeks of treatment with doxycycline. Results: The GSQ-30 demonstrated excellent internal consistency (Cronbach α = 0.95). The factor structure reflects four core domains: pain/fatigue, neuropsychiatric, neurologic, and viral-like symptoms. Symptom burden was significantly associated with depression (r s = 0.60), anxiety (r s = 0.55), pain (r s = 0.75), fatigue (r s = 0.77), functional impairment (r s = 0.79), and general health (r s = -0.58). The GSQ-30 detected significant change in symptom burden before and after antibiotic therapy; this change correlated with change in functional impairment. The GSQ-30 total score significantly differed for erythema migrans vs. three other groups (post-treatment Lyme disease syndrome, depression, healthy controls). The GSQ-30 total scores for traumatic brain injury and depression were not significantly different from post-treatment Lyme disease syndrome. Conclusions and Relevance: The GSQ-30 is a valid and reliable instrument to assess symptom burden among patients with acute and post-treatment Lyme disease syndrome and is sensitive in the detection of change after treatment among patients with erythema migrans. The GSQ-30 should prove useful in clinical and research settings to assess multi-system symptom burden and to monitor change over time. The GSQ-30 may also prove useful in future precision medicine studies as a clinical measure to correlate with disease-relevant biomarkers.

Multi-Modal Signatures of Tau Pathology, Neuronal Fiber Integrity, and Functional Connectivity in Traumatic Brain Injury.

[18F]AV-1451 (aka 18F-Flortaucipir, [18F]T807) was developed for positron-emission tomography (PET) imaging of paired helical filaments of hyperphosphorylated tau, which are of interest in a range of neuropathologies, including traumatic brain injury (TBI). Magnetic resonance imaging (MRI) techniques like diffusion tensor imaging (DTI) and resting state functional connectivity assess structural and functional characteristics of the brain, complementing the molecular information that can be obtained by PET. The goal herein was to explore the utility of such multi-modal imaging in a case series based on a population of TBI subjects. This study probes the interrelationship between tau deposition, white matter integrity, and gray matter functional connectivity across the spectrum of TBI. Nineteen subjects (11 controls, five former contact sports athletes, one automotive accident, and two with military-related injury) underwent [18F]AV-1451 PET and magnetic resonance scanning procedures. [18F]AV-1451 distribution volume ratio (DVR) was estimated using the Logan method and the cerebellum as a reference region. Diffusion tractography images and fractional anisotropy (FA) images were generated using diffusion toolkit and FSL. Resting-state functional MRI (fMRI) analysis was based on a graph theory metric, namely weighted degree centrality. TBI subjects showed greater heterogeneity in [18F]AV-1451 DVR when compared with control subjects. In a subset of TBI subjects, areas with high [18F]AV-1451 binding corresponded with increased FA and diminished white matter tract density in DTI. Functional MRI results exhibited an increase in functional connectivity, particularly among local connections, in the areas where tau aggregates were more prevalent. In a case series of a diverse group of TBI subjects, brain regions with elevated tau burden exhibited increased functional connectivity as well as decreased white matter integrity. These findings portray molecular, microstructural, and functional corollaries of TBI that spatially coincide and can be measured in the living human brain using noninvasive neuroimaging techniques.

Association of small fiber neuropathy and post treatment Lyme disease syndrome.

OBJECTIVES: To examine whether post-treatment Lyme disease syndrome (PTLDS) defined by fatigue, cognitive complaints and widespread pain following the treatment of Lyme disease is associated with small fiber neuropathy (SFN) manifesting as autonomic and sensory dysfunction. METHODS: This single center, retrospective study evaluated subjects with PTLDS. Skin biopsies for assessment of epidermal nerve fiber density (ENFD), sweat gland nerve fiber density (SGNFD) and functional autonomic testing (deep breathing, Valsalva maneuver and tilt test) were performed to assess SFN, severity of dysautonomia and cerebral blood flow abnormalities. Heart rate, end tidal CO2, blood pressure, and cerebral blood flow velocity (CBFv) from middle cerebral artery using transcranial Doppler were monitored. RESULTS: 10 participants, 5/5 women/men, age 51.3 ± 14.7 years, BMI 27.6 ± 7.3 were analyzed. All participants were positive for Lyme infection by CDC criteria. At least one skin biopsy was abnormal in all ten participants. Abnormal ENFD was found in 9 participants, abnormal SGNFD in 5 participants, and both abnormal ENFD and SGNFD were detected in 4 participants. Parasympathetic failure was found in 7 participants and mild or moderate sympathetic adrenergic failure in all participants. Abnormal total CBFv score was found in all ten participants. Low orthostatic CBFv was found in 7 participants, three additional participants had abnormally reduced supine CBFv. CONCLUSIONS: SFN appears to be associated with PTLDS and may be responsible for certain sensory symptoms. In addition, dysautonomia related to SFN and abnormal CBFv also seem to be linked to PTLDS. Reduced orthostatic CBFv can be associated with cerebral hypoperfusion and may lead to cognitive dysfunction. Autonomic failure detected in PTLDS is mild to moderate. SFN evaluation may be useful in PTLDS.

Selective Essential Oils from Spice or Culinary Herbs Have High Activity against Stationary Phase and Biofilm Borrelia burgdorferi.

Although the majority of patients with acute Lyme disease can be cured with the standard 2-4 week antibiotic treatment, about 10-20% of patients continue suffering from chronic symptoms described as posttreatment Lyme disease syndrome. While the cause for this is debated, one possibility is that persister bacteria are not killed by the current Lyme antibiotics and remain active in the system. It has been reported that essential oils have antimicrobial activities and some have been used by patients with persisting Lyme disease symptoms. However, the activity of essential oils against the causative agent Borrelia burgdorferi (B. burgdorferi) has not been well studied. Here, we evaluated the activity of 34 essential oils against B. burgdorferi stationary phase culture as a model for persister bacteria. We found that not all essential oils had activity against the B. burgdorferi stationary phase culture, with top five essential oils (oregano, cinnamon bark, clove bud, citronella, and wintergreen) at a low concentration of 0.25% showing high anti-persister activity that is more active than the known persister drug daptomycin. Interestingly, some highly active essential oils were found to have excellent anti-biofilm ability as shown by their ability to dissolve the aggregated biofilm-like structures. The top three hits, oregano, cinnamon bark, and clove bud completely eradicated all viable cells without any regrowth in subculture in fresh medium, whereas but not citronella and wintergreen did not have this effect. Carvacrol was found to be the most active ingredient of oregano oil showing excellent activity against B. burgdorferi stationary phase cells, while other ingredients of oregano oil p-cymene and α-terpinene had no apparent activity. Future studies are needed to characterize and optimize the active essential oils in drug combination studies in vitro and in vivo and to address their safety and pharmacokinetic properties before they can be considered as a novel treatment of persistent Lyme disease.

Pharmacokinetic Evaluation of the Tau PET Radiotracer 18F-T807 (18F-AV-1451) in Human Subjects.

18F-T807 is a PET radiotracer developed for imaging tau protein aggregates, which are implicated in neurologic disorders including Alzheimer disease and traumatic brain injury (TBI). The current study characterizes 18F-T807 pharmacokinetics in human subjects using dynamic PET imaging and metabolite-corrected arterial input functions. Methods: Nine subjects (4 controls, 3 with a history of TBI, 2 with mild cognitive impairment due to suspected Alzheimer disease) underwent dynamic PET imaging for up to 120 min after bolus injection of 18F-T807 with arterial blood sampling. Total volume of distribution (VT) was estimated using compartmental modeling (1- and 2-tissue configurations) and graphical analysis techniques (Logan and multilinear analysis 1 [MA1] regression methods). Reference region-based methods of quantification were explored including Logan distribution volume ratio (DVR) and static SUV ratio (SUVR) using the cerebellum as a reference tissue. Results: The percentage of unmetabolized 18F-T807 in plasma followed a single exponential with a half-life of 17.0 ± 4.2 min. Metabolite-corrected plasma radioactivity concentration fit a biexponential (half-lives, 18.1 ± 5.8 and 2.4 ± 0.5 min). 18F-T807 in gray matter peaked quickly (SUV > 2 at ∼5 min). Compartmental modeling resulted in good fits, and the 2-tissue model with estimated blood volume correction (2Tv) performed best, particularly in regions with elevated binding. VT was greater in mild cognitive impairment subjects than controls in the occipital, parietal, and temporal cortices as well as the posterior cingulate gyrus, precuneus, and mesial temporal cortex. High focal uptake was found in the posterior corpus callosum of a TBI subject. Plots from Logan and MA1 graphical methods became linear by 30 min, yielding regional estimates of VT in excellent agreement with compartmental analysis and providing high-quality parametric maps when applied in voxelwise fashion. Reference region-based approaches including Logan DVR (t* = 55 min) and SUVR (80- to 100-min interval) were highly correlated with DVR estimated using 2Tv (R2 = 0.97, P < 0.0001). Conclusion:18F-T807 showed rapid clearance from plasma and properties suitable for tau quantification with PET. Furthermore, simplified approaches using DVR (t* = 55 min) and static SUVR (80-100 min) with cerebellar reference tissue were found to correlate highly with compartmental modeling outcomes.

Healthcare Hackathons Provide Educational and Innovation Opportunities: A Case Study and Best Practice Recommendations.

Physicians and other healthcare professionals are often the end users of medical innovation; however, they are rarely involved in the beginning design stages. This often results in ineffective healthcare solutions with poor adoption rates. At the early design stage, innovation would benefit from input from healthcare professionals. This report describes the first-ever rehabilitation hackathon-an interdisciplinary and competitive team event aimed at accelerating and improving healthcare solutions and providing an educational experience for participants. Hackathons are gaining traction as a way to accelerate innovation by bringing together a diverse group of interdisciplinary professionals from different industries who work collaboratively in teams and learn from each other, focus on a specific problem ("pain point"), develop a solution using design thinking techniques, pitch the solution to participants, gather fast feedback and quickly alter the prototype design ("pivoting"). 102 hackers including 19 (18.6 %) physicians and other professionals participated, and over the course of 2 days worked in teams, pitched ideas and developed design prototypes. Three awards were given for prototypes that may improve function in persons with disabilities. 43 hackers were women (42.2 %) and 59 men (57.8 %); they ranged in age from 16 to 79 years old; and, of the 75 hackers who reported their age, 63 (84 %) were less than 40 years old and 12 (16 %) were 40 years or older. This report contributes to the emerging literature on healthcare hackathons as a means of providing interdisciplinary education and training and supporting innovation.