Understanding the clinical overlap between vector-borne infections and pediatric acute-onset neuropsychiatric syndromes—and a systems-based integrative path to healing.

Dr. Myriah Hinchey, ND, FMAPS

Abstract

This article examines the biological overlap between Lyme disease, co-infections, and immune-mediated neuropsychiatric syndromes such as PANS and PANDAS. It explores how chronic infection, cytokine-driven inflammation, gut dysbiosis, and autonomic dysfunction converge—and outlines an integrative, systems-based treatment approach targeting infection, immune regulation, and neuroinflammation.

Introduction

Lyme disease remains one of the most common vector-borne diseases (VBDs) in the United States, with current CDC estimates exceeding 476,000 new diagnoses annually. Surveillance systems likely underestimate the true burden, and epidemiologic analyses suggest actual infection rates may be substantially higher- up to seven times.1 Lyme disease, caused by Borrelia species transmitted primarily through Ixodes ticks, is frequently referred to as “the great imitator” because of its capacity to mimic numerous diseases including neurological, rheumatologic, and psychiatric conditions.

Lyme Disease and the Expanding Vector-Borne Landscape

Clinical complexity increases substantially when Lyme disease occurs alongside additional vector-borne infections, which frequently complicate diagnosis and prolong illness. These infections may also precipitate immune-mediated neurological syndromes such as Pediatric Acute-Onset Neuropsychiatric Syndrome (PANS) and Pediatric Autoimmune Neuropsychiatric Disorder Associated with Streptococcal infection (PANDAS).5,6 Increasingly, clinicians also recognize that environmental and post-viral immune stressors—including mold and mycotoxin exposure and persistent immune dysregulation following viral infections such as SARS-CoV-2 as well as damage from spike protein—may further amplify immune dysfunction in susceptible individuals.8

These seemingly distinct conditions converge through shared biological mechanisms involving chronic immune activation, cytokine-driven inflammation, neuroinflammation, and disruption of autonomic nervous system regulation. Many patients develop symptoms consistent with dysautonomia, including fatigue, orthostatic intolerance, tachycardia, exercise intolerance, gastrointestinal dysmotility, temperature dysregulation, and cognitive impairment. Emerging research suggests inflammatory signaling and alterations affecting cholinergic pathways, including potential effects on nicotinic acetylcholine receptor signaling, may contribute to autonomic instability in chronic inflammatory states. For many patients, restoration of autonomic nervous system balance becomes central to recovery, and effective treatment therefore requires addressing infection, immune dysregulation, and autonomic dysfunction simultaneously.

Vector-borne infections extend well beyond Lyme disease alone. Although Lyme disease is most commonly attributed to Borrelia burgdorferi, multiple Borrelia species may cause infection, and additional transmission routes, including possible vertical transmission, have been described though remain incompletely characterized.3 Ticks and other vectors frequently transmit additional pathogens such as Bartonella, Babesia, Anaplasma, Ehrlichia, Rickettsia, Mycoplasma, and viral organisms including Powassan virus. These organisms often coexist, intensifying immune activation and complicating recovery.

Clinical manifestations may involve nearly every organ system. Patients frequently report profound fatigue and post-exertional malaise, migratory musculoskeletal pain, neuropathy, cognitive dysfunction, headaches, neck stiffness, gastrointestinal disturbance, mood and sleep disruption, and autonomic symptoms such as dizziness or palpitations. Cardiac, respiratory, and neurological complications—including encephalopathy and neuroborreliosis—may also occur in more severe cases. One of the primary challenges in treatment is pathogen persistence. Organisms such as Borrelia and Bartonella employ immune-evasive strategies including intracellular localization, antigenic variation, immune modulation, and biofilm formation, allowing survival despite immune response and treatment while sustaining inflammatory signaling. Consequently, patients may continue to experience symptoms following antibiotic therapy due to ongoing immune dysregulation and inflammatory injury rather than simple infection alone (although one study showed chronic Borrelia infection was s seen in >41% of PTLDS using Nanotrap technology).2,4

Chronic Infection and Immune Dysregulation

Under normal circumstances, the immune system eliminates pathogens through coordinated innate and adaptive responses. However, persistent infection can distort immune signaling. Chronic infection promotes sustained production of proinflammatory cytokines, including IL-6, IL-1β, TNF-α, and interferon-gamma. These molecules are essential during acute infection but become harmful when persistently elevated, contributing to fatigue, pain syndromes, cognitive dysfunction, mood disturbance, and sleep disruption. Simultaneously, immune competence may decline through immune exhaustion, altered T-cell regulation, dysregulated antibody responses, impaired natural killer cell activity, and reduced pathogen clearance. The immune system thus becomes simultaneously overactive and ineffective, sustaining inflammation without successfully eliminating infection.

Autonomic Dysfunction and the Inflammatory Loop

Persistent cytokine signaling also alters autonomic nervous system balance by disrupting vagal and sympathetic regulation. This contributes to dysautonomia, manifesting clinically as orthostatic intolerance, tachycardia, gastrointestinal dysmotility, temperature dysregulation, cognitive dysfunction, and exercise intolerance. These autonomic disturbances further perpetuate inflammatory stress and functional impairment, creating a self-reinforcing cycle that prolongs illness.

PANS and PANDAS: Infection-Triggered Neuropsychiatric Syndromes

PANS and PANDAS represent immune-mediated neuropsychiatric syndromes characterized by abrupt onset behavioral and psychiatric symptoms following infection. PANDAS is associated specifically with Group A Streptococcal infection, while PANS encompasses multiple infectious triggers, including Lyme disease and co-infections. Clinical features commonly include sudden obsessive-compulsive behaviors, severe anxiety or separation anxiety, emotional lability or aggression, motor or vocal tics, cognitive regression or academic decline, sleep disturbance, urinary symptoms, and sensory or food restriction issues.5,6

Current models suggest infections trigger antibody production that cross-reacts with neuronal tissue, particularly within the basal ganglia, disrupting motor and emotional regulation. Concurrent cytokine activation further alters neurotransmitter signaling, including dopaminergic pathways, producing the abrupt neuropsychiatric symptoms observed clinically. These conditions therefore represent immune-mediated brain inflammation rather than primary psychiatric disease, and treatment must address the underlying immune and infectious drivers.

Lyme disease, co-infections, mold-related illness, and post-viral immune syndromes converge through shared mechanisms involving persistent immune activation, chronic cytokine signaling, neuroinflammation, autonomic dysregulation, neurotransmitter disruption, and subsequent behavioral and cognitive symptoms.9 Certain organisms, particularly Borrelia and Bartonella, display neurotropic tendencies, affecting nervous system tissue and vascular structures supplying the brain. Symptoms are frequently misattributed to primary psychiatric disorders when they instead reflect infection-driven neuroinflammation and immune dysfunction, underscoring the need for careful clinical evaluation.

The Gut-Immune-Brain Axis in Chronic Inflammatory Illness

Immune regulation is also strongly influenced by gut health. Approximately seventy percent of immune activity resides within gut-associated lymphoid tissue, and the gut microbiome plays a central role in regulating immune signaling, inflammatory balance, and intestinal barrier integrity. Antibiotics, infections, environmental toxins, and chronic stress may disrupt microbial balance, resulting in dysbiosis and increased intestinal permeability. Compromised gut barriers allow inflammatory molecules and microbial fragments to enter circulation, sustaining immune activation and systemic inflammation. Gut dysfunction therefore contributes significantly to persistent inflammatory states seen in Lyme disease and PANS/PANDAS, and restoration of gut integrity is often necessary to normalize immune responses and support neurological recovery.7

A central treatment challenge lies in reducing infectious burden while restoring immune competence. Antimicrobial therapy may decrease pathogen load but does not necessarily repair immune dysregulation or inflammatory injury, and prolonged antibiotic use may further disrupt gut microbiota. Effective treatment strategies must therefore address infection, immune imbalance, neuroinflammation, gut dysfunction, metabolic stress, and autonomic nervous system regulation concurrently.

Integrative Treatment Strategies: Botanical and Systems-Based Approaches

Botanical medicine plays an important role in this context because many plants exert antimicrobial, anti-inflammatory, and immune-modulating effects simultaneously. Japanese Knotweed (Polygonum cuspidatum) contains resveratrol and related polyphenols that modulate inflammatory signaling pathways, reduce oxidative stress, and support vascular and neurological integrity, potentially mitigating cytokine-driven tissue injury. Cat’s Claw (Uncaria tomentosa) contains oxindole alkaloids that influence immune signaling pathways and help regulate inflammatory responses while supporting immune competence. Astragalus membranaceus contains polysaccharides and saponins that influence immune regulation and support host resistance, particularly useful in immune support and earlier stages of disease.10

Other botanicals frequently incorporated into protocols include Cryptolepis sanguinolenta, which demonstrates antimicrobial properties in laboratory studies and is often used clinically against persistent infections resembling Babesia species.11 Houttuynia cordata and Sida acuta are commonly utilized in botanical protocols targeting intracellular organisms such as Bartonella, demonstrating antimicrobial and anti-inflammatory properties while supporting immune responses. These botanicals often exert overlapping actions, including antimicrobial effects, immune modulation, inflammatory regulation, and vascular and neurological support, allowing simultaneous targeting of infection while assisting restoration of immune balance.

Clinical Implications and a Path Toward Recovery

Ultimately, Lyme disease, co-infections, PANS/PANDAS, mold-related illness, and post-viral immune syndromes represent complex conditions driven by infection-induced immune dysregulation and chronic inflammation affecting both body and brain.8,9 Recovery depends not solely on reduction of infectious burden but also on restoration of immune competence and autonomic nervous system stability. Chronic inflammatory signaling—whether driven by vector-borne infections, environmental exposures such as mold and mycotoxins, or post-viral immune dysregulation—frequently disrupts autonomic regulation, perpetuating fatigue, cognitive dysfunction, and multisystem symptoms.

Clinical improvement often requires a comprehensive approach addressing infection, immune balance, gut health, and autonomic regulation. When these factors are systematically corrected, many patients experience meaningful functional recovery and restoration of quality of life.

Dr. Myriah Hinchey’s mission is to educate and empower patients to heal from infection-driven inflammatory illnesses through naturopathic medicine by restoring immune competence, improving the internal terrain that allows chronic infections to persist, and helping patients identify underlying infectious contributors to chronic disease. In support of this mission, she founded LymeBytes™, a multimedia platform dedicated to educating patients and practitioners and connecting communities with resources that support lasting healing and recovery. She also created LymeCore Botanicals™ to provide clean, effective herbal formulas for Lyme disease and other tick-borne infections and remains actively involved in sourcing and producing botanical formulations used in clinical practice. Dr. Hinchey serves as adjunct faculty and lectures nationally at several medical conferences, including MAPS, ILADS, A4M, IHS, and her own educational conference, The LymeBytes Symposium. In addition, she treats adult and pediatric patients with complex infection-driven conditions at her clinic, TAO, in Connecticut.

References

1. Kugeler KJ, Schwartz AM, Delorey MJ, Mead PS, Hinckley AF. Estimating the frequency of Lyme disease diagnoses, United States, 2010–2018. Emerg Infect Dis. 2021;27(2):616–619.
2. Magni R, Espina BH, Shah K, et al. Application of Nanotrap technology for high sensitivity measurement of urinary outer surface protein A carboxyl-terminus domain in early stage Lyme borreliosis. J Transl Med. 2015;13:346. doi:10.1186/s12967-015-0701-0.
3. Steere AC, Strle F, Wormser GP, et al. Lyme borreliosis. Nat Rev Dis Primers. 2016;2:16090.
4. Fallon BA, Pavlicova M, Coffino SW, Brenner LA. A comparison of Lyme disease serologic test results from four laboratories in patients with persistent symptoms after antibiotic treatment. Clin Infect Dis. 2014;59(12):1705–1710.
5. Swedo SE, Leckman JF, Rose NR. From research subgroup to clinical syndrome: modifying the PANDAS criteria to describe PANS. Pediatr Ther. 2012;2(2).
6. Frankovich J, Swedo S, Murphy T, et al. Clinical management of pediatric acute-onset neuropsychiatric syndrome. J Child Adolesc Psychopharmacol. 2017;27(7):566–573.
7. Cryan JF, O’Riordan KJ, Cowan CSM, et al. The microbiota-gut-brain axis. Physiol Rev. 2019;99(4):1877–2013.
8. Proal AD, VanElzakker MB. Long COVID or post-acute sequelae of COVID-19 (PASC). Front Microbiol. 2021;12:698169.
9. Shoemaker RC, Ryan JC. Structural brain abnormalities in inflammatory illness acquired following exposure to water-damaged buildings. Neurotoxicol Teratol. 2017;59:44–52.
10. Feng J, Leone J, Schweig S and Zhang Y (2020) Evaluation of Natural and Botanical Medicines for Activity Against Growing and Non-growing Forms of B. burgdorferi. Front. Med. 7:6. doi: 10.3389/fmed.2020.00006
11. Zhang Y, Alvarez-Manzo H, Leone J, Schweig S and Zhang Y (2021) Botanical Medicines Cryptolepis sanguinolenta, Artemisia annua, Scutellaria baicalensis, Polygonum cuspidatum, and Alchornea cordifolia Demonstrate Inhibitory Activity Against Babesia duncani. Front. Cell. Infect. Microbiol. 11:624745. doi:10.3389/fcimb.2021.624745