Bartonella- and Borrelia-Related Disease Presenting as a Neurological Condition Revealing the Need for Better Diagnostics.

The diagnostic tests available to identify vector-borne pathogens have major limitations. Clinicians must consider an assortment of often diverse symptoms to decide what pathogen or pathogens to suspect and test for. Even then, there are limitations to the currently available indirect detection methods, such as serology, or direct detection methods such as molecular tests with or without culture enrichment. Bartonella spp., which are considered stealth pathogens, are particularly difficult to detect and diagnose. We present a case report of a patient who experienced a spider bite followed by myalgia, lymphadenopathy, and trouble sleeping. She did not test positive for Bartonella spp. through clinically available testing. Her symptoms progressed and she was told she needed a double hip replacement. Prior to the surgery, her blood was submitted for novel molecular testing, where Bartonella spp. was confirmed, and a spirochete was also detected. Additional testing using novel methods over a period of five years found Bartonella henselae and Borrelia burgdorferi in her blood. This patient's case is an example of why new diagnostic methods for vector-borne pathogens are urgently needed and why new knowledge of the variable manifestations of Bartonellosis need to be provided to the medical community to inform and heighten their index of suspicion.

Association of Presenting Symptoms With Abnormal Laboratory Values for Vector-Borne Illness - Experience in an Urban Gastroenterology Practice.

PURPOSE: In the clinical setting, it is not common practice to consider a vector bite, such as from a tick or flea, to be a contributing factor to chronic digestive symptoms. This article investigates associations we have observed among symptomatic patients and positive blood tests for vector-borne illness (VBI). METHODS: Patients who visited an urban gastroenterology clinic over a 3-year period were retrospectively reviewed. A total of 270 patients presenting with a constellation of digestive symptoms - and who had no apparent digestive pathology and reported no prior diagnosis or treatments for VBI - were analyzed. Before the initial visit, all patients completed a review of systems medical history form, which comprised 19 gastrointestinal (GI) symptoms and 73 non-GI-related symptoms and conditions. Patients were tested for small intestinal bacterial overgrowth (SIBO) by lactulose breath test. VBI (babesiosis, ehrlichiosis, anaplasmosis, bartonellosis, borreliosis) was established using 1 or more of several blood tests. Odds ratio (OR) analysis determined associations between exposure to VBI, SIBO, and presenting symptoms/conditions. Two age groups (≤35 years and ≥36 years) were studied using Cochran-Mantel-Haenszel stratum-based test. RESULTS: A higher OR (2.03, 95% CI: 1.5-3.6) was found between patients with ≥3 digestive symptoms and positive blood tests for ≥1 VBI. Five of the 19 GI symptoms were independently associated with VBI-positive samples: food intolerance, indigestion, nausea/vomiting, constipation, and heartburn. A similar association in patients with ≥3 non-GI symptoms (OR: 2.83, 95% CI: 1.3-6.4) was observed. Five of the 73 non-GI symptoms/conditions were independently associated with VBI-positive samples: chest pain, shortness of breath, extremity or joint pain, anxiety, and night sweats. Having ≥3 of any digestive or nondigestive symptoms generated significant relative risk of being VBI-positive. Presence of SIBO alone did not identify significant relative risk for a VBI, and age was not a confounder. CONCLUSIONS: Findings revealed an association between positive blood tests for vector-borne illness and chronically symptomatic patients regardless of whether symptoms were digestive or nondigestive. The manifestation of 3 or more gastrointestinal and/or extraintestinal symptoms should raise suspicion for a VBI.

The National Brain Injury Rescue and Rehabilitation Study - a multicenter observational study of hyperbaric oxygen for mild traumatic brain injury with post-concussive symptoms.

The National Brain Injury Rescue and Rehabilitation Project was established as a preliminary study to test the safety and practicality of multi-center hyperbaric oxygen administration for the post-concussive symptoms of chronic mild traumatic brain injury as a precursor to a pivotal, independent, multi-center, controlled clinical trial. This report presents the results for 32 subjects who completed a preliminary trial of hyperbaric oxygen several years before the passage of the 21 st Century Cures Act. This study anticipated the Act and its reassessment of clinical research. Subjects received 40-82 one-hour treatments at 1.5 atmospheres absolute 100% oxygen. Outcome measures included repeated self-assessment measures and automated neurocognitive tests. The subjects demonstrated improvement in 21 of 25 neurocognitive test measures observed. The objective neurocognitive test components showed improvement in 13 of 17 measures. Earlier administration of hyperbaric oxygen post injury, younger age at the time of injury and hyperbaric oxygen administration, military status, and increased number of hyperbaric oxygen administrations were characteristics associated with improved outcomes. There were no adverse events. Hyperbaric oxygen was found to be safe, inexpensive and worthy of clinical application in the 21 st Century model of facile data collection provided by recent research regulatory shifts in medicine. The study was approved by the ethics review committee of the Western Institutional Review Board (WIRB; Protocol #20090761).

Bartonella henselae Bloodstream Infection in a Boy With Pediatric Acute-Onset Neuropsychiatric Syndrome.

BACKGROUND: With the advent of more sensitive culture and molecular diagnostic testing modalities, Bartonella spp. infections have been documented in blood and/or cerebrospinal fluid specimens from patients with diverse neurological symptoms. Pediatric acute-onset neuropsychiatric syndrome (PANS) is characterized by an unusually abrupt onset of cognitive, behavioral, or neurological symptoms. Between October 2015 and January 2017, a 14-year-old boy underwent evaluation by multiple specialists for sudden-onset psychotic behavior (hallucinations, delusions, suicidal and homicidal ideation). METHODS: In March 2017, Bartonella spp. serology (indirect fluorescent antibody assays) and polymerase chain reaction (PCR) amplification, DNA sequencing, and Bartonella enrichment blood culture were used on a research basis to assess Bartonella spp. exposure and bloodstream infection, respectively. PCR assays targeting other vector-borne infections were performed to assess potential co-infections. RESULTS: For 18 months, the boy remained psychotic despite 4 hospitalizations, therapeutic trials involving multiple psychiatric medication combinations, and immunosuppressive treatment for autoimmune encephalitis. Neurobartonellosis was diagnosed after cutaneous lesions developed. Subsequently, despite nearly 2 consecutive months of doxycycline administration, Bartonella henselae DNA was PCR amplified and sequenced from the patient's blood, and from Bartonella alphaproteobacteria growth medium enrichment blood cultures. B henselae serology was negative. During treatment with combination antimicrobial chemotherapy, he experienced a gradual progressive decrease in neuropsychiatric symptoms, cessation of psychiatric drugs, resolution of Bartonella-associated cutaneous lesions, and a return to all pre-illness activities. CONCLUSIONS: This case report suggests that B henselae bloodstream infection may contribute to progressive, recalcitrant neuropsychiatric symptoms consistent with PANS in a subset of patients.

Infection with hemotropic Mycoplasma species in patients with or without extensive arthropod or animal contact.

PCR amplification targeting the 16S rRNA gene was used to test individuals with and without extensive arthropod and animal contact for the possibility of hemotropic mycoplasma infection. The prevalence of hemotropic mycoplasma infection (4.7%) was significantly greater in previously reported cohorts of veterinarians, veterinary technicians, spouses of veterinary professionals, and others with extensive arthropod exposure and/or frequent animal contact than in a previously reported cohort of patients examined by a rheumatologist because of chronic joint pain or evidence of small-vessel disease (0.7%). Based upon DNA sequence analysis, a Mycoplasma ovis-like species was the most prevalent organism detected; however, infection with "Candidatus Mycoplasma haematoparvum" and a potentially novel, but incompletely characterized, hemotropic Mycoplasma species was also documented. Historical exposure to animals and arthropod vectors that can harbor hemotropic Mycoplasma spp. should be considered during epidemiological investigations and in the evaluation of individual patients.

Bartonella henselae infection in a family experiencing neurological and neurocognitive abnormalities after woodlouse hunter spider bites.

BACKGROUND: Bartonella species comprise a group of zoonotic pathogens that are usually acquired by vector transmission or by animal bites or scratches. METHODS: PCR targeting the Bartonella 16S-23S intergenic spacer (ITS) region was used in conjunction with BAPGM (Bartonella alpha Proteobacteria growth medium) enrichment blood culture to determine the infection status of the family members and to amplify DNA from spiders and woodlice. Antibody titers to B. vinsonii subsp. berkhoffii (Bvb) genotypes I-III, B. henselae (Bh) and B. koehlerae (Bk) were determined using an IFA test. Management of the medical problems reported by these patients was provided by their respective physicians. RESULTS: In this investigation, immediately prior to the onset of symptoms two children in a family experienced puncture-like skin lesions after exposure to and presumptive bites from woodlouse hunter spiders. Shortly thereafter, the mother and both children developed hive-like lesions. Over the ensuing months, the youngest son was diagnosed with Guillain-Barre (GBS) syndrome followed by Chronic Inflammatory Demyelinating Polyradiculoneuropathy (CIDP). The older son developed intermittent disorientation and irritability, and the mother experienced fatigue, headaches, joint pain and memory loss. When tested approximately three years after the woodlouse hunter spider infestation, all three family members were Bartonella henselae seroreactive and B. henselae DNA was amplified and sequenced from blood, serum or Bartonella alpha-proteobacteria (BAPGM) enrichment blood cultures from the mother and oldest son. Also, B. henselae DNA was PCR amplified and sequenced from a woodlouse and from woodlouse hunter spiders collected adjacent to the family's home. CONCLUSIONS: Although it was not possible to determine whether the family's B. henselae infections were acquired by spider bites or whether the spiders and woodlice were merely accidental hosts, physicians should consider the possibility that B. henselae represents an antecedent infection for GBS, CIDP, and non-specific neurocognitive abnormalities.

Bartonella spp. bacteremia and rheumatic symptoms in patients from Lyme disease-endemic region.

Bartonella spp. infection has been reported in association with an expanding spectrum of symptoms and lesions. Among 296 patients examined by a rheumatologist, prevalence of antibodies against Bartonella henselae, B. koehlerae, or B. vinsonii subsp. berkhoffii (185 [62%]) and Bartonella spp. bacteremia (122 [41.1%]) was high. Conditions diagnosed before referral included Lyme disease (46.6%), arthralgia/arthritis (20.6%), chronic fatigue (19.6%), and fibromyalgia (6.1%). B. henselae bacteremia was significantly associated with prior referral to a neurologist, most often for blurred vision, subcortical neurologic deficits, or numbness in the extremities, whereas B. koehlerae bacteremia was associated with examination by an infectious disease physician. This cross-sectional study cannot establish a causal link between Bartonella spp. infection and the high frequency of neurologic symptoms, myalgia, joint pain, or progressive arthropathy in this population; however, the contribution of Bartonella spp. infection, if any, to these symptoms should be systematically investigated.

Bartonella spp. bacteremia in high-risk immunocompetent patients.

Serum and blood samples from 192 patients, who reported animal exposure (100.0%) and recent animal bites or scratches (88.0%), were screened for antibodies by indirect immunofluorescence assays and for bacteremia using the BAPGM (Bartonella alpha Proteobacteria growth medium) platform. Predominant symptoms included fatigue (79.2%), sleeplessness (64.1%), joint pain (64.1%), and muscle pain (63.0%). Bartonella spp. seroreactivity or bacteremia was documented in 49.5% (n = 95) and 23.9% (n = 46) of the patients, respectively; however, indirect immunofluorescence antibodies were not detected in 30.4% (n = 14) of bacteremic patients. Regarding components of the BAPGM platform, Bartonella DNA was amplified from 7.5% of blood (n = 21), 8.7% of serum (n = 25), and 10.3% of enrichment culture samples (n = 29). Polymerase chain reaction (PCR) on only extracted blood would not have detected Bartonella infection in 34.7% (16/46) of bacteremic patients. Serology, in conjunction with blood, serum, and BAPGM enrichment culture PCR, facilitates the diagnosis of Bartonella spp. bacteremia in immunocompetent patients.

Cerebrovascular dynamics and vascular endothelial growth factor in acute mountain sickness.

OBJECTIVE: To determine if serum vascular endothelial growth factor (VEGF) and ultrasonic monitoring of vascular dynamics with dynamic vascular analysis at sea level and high altitude correlate with acute mountain sickness symptoms. METHODS: Nine volunteers participated in a staged ascent from sea level to 4300 m undergoing complete transcranial Doppler studies with dynamic vascular analysis. Serum VEGF levels, Lake Louise scores, Spielberger-1 scores, Subjective Exercise Experiences Scale positive scores, and Symptom Checklist-90 surveys were collected after 24 hours at each altitude. RESULTS: Symptom scores, index of pulsatility, and dynamic flow index differentiated the subjects into 2 distinct groups. Symptomatic subjects had increased VEGF levels at sea level but decreased levels at 4300 m. The dynamic flow index increased in symptomatic subjects at 4300 m compared with the asymptomatic subjects. The mean flow velocity increased in both groups and could not be used to differentiate the subjects. CONCLUSIONS: Altered vascular physiology is associated with acute mountain sickness. Increased vascular permeability increases vascular capacitance, with an increase in dynamic flow index to meet these demands. Altered vascular dynamics were associated with high-altitude cerebral edema in 1 subject. Dynamic vascular analysis demonstrated altered vascular pathophysiology associated with acute mountain sickness. Changes in VEGF were meaningful when interpreted with the dynamic vascular analysis findings. These physiological findings may help explain the vascular changes associated with hypocarbic hypoxemia at altitude.

Differentiating vascular pathophysiological states by objective analysis of flow dynamics.

BACKGROUND AND PURPOSE: There is an unmet need to classify cerebrovascular conditions physiologically and to assess cerebrovascular system performance. The authors hypothesized that by simultaneously considering the dynamic parameters of flow velocity, acceleration, and pulsatility index (PI) (impedance) in individual Doppler spectrum waveforms, they could develop an objective method to elucidate the pathophysiology of vascular conditions and classify cerebrovascular disorders. This method, dynamic vascular analysis (DVA), is described. METHODS: First, a theoretical model was developed to determine how any vascular segment and the ensemble of intracranial vascular segments could be defined according to its dynamic physiological characteristics. Next, the DVA method was applied to 847 anonymous serial complete clinical transcranial Doppler (TCD) studies of patients without regard for their diagnosis to ascertain actual reference ranges and the normality of the distribution curves for each dimension of the 3-parameter nomogram. The authors applied DVA to 2 clinical cases to see if they could track the changes in vascular performance of 2 known progressive diseases. RESULTS: The theoretical analysis identified 295,245 possible vascular states for the ensemble of vascular segments in the cerebral circulation. When applied to clinical TCD data, DVA revealed continuous, normally distributed data for the velocity, PI, and logarithm of the acceleration. CONCLUSIONS: DVA is proposed as a method for monitoring the physiological state of each cerebral artery segment individually and in ensemble. DVA evaluates the relationship among acceleration (force or pressure), velocity, and PI and provides an objective means to evaluate intracranial vascular segments using the paradigm of the well-described pressure-perfusion autoregulation relationship. DVA may be used to study cerebrovascular pathophysiology and to classify, evaluate, and monitor cerebrovascular disorders or systemic disorders with cerebrovascular effects.