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Integrative Medicine: A Clinician's Journal logoLink to Integrative Medicine: A Clinician's Journal
. 2025 Jun;24(3):10–27.

Diagnostic and Therapeutic Challenges in Lyme Disease and Co-Infections: Unraveling Neuropsychiatric and Neurological Complexities—A Comprehensive Case Series Analysis

Kunal Garg 1, Rachael Booth 2, Aiven Cobey 2, Leona Gilbert 1, Aylin Ozdemir 2,
PMCID: PMC12109650  PMID: 40453233

Abstract

Background/Objectives

Lyme disease (LD) and its co-infections present significant diagnostic and treatment challenges due to their complex interplay with neurological symptoms, immune responses, autoimmune reactions, and mental health conditions. Standard two-tier LD testing often fails to detect cases, necessitating expanded serologic and functional testing. Following CARE Guidelines, this case series examines ten clinical narratives of LD, highlighting the limitations of standard diagnostic methods, the potential benefits of specialized testing, and the need for an effective paradigm for LD management.

Methods

A multidisciplinary approach grounded in integrative medicine was adopted. Diagnostic methods included advanced serological panels (e.g., TICKPLEX®), co-infection testing, functional immune markers, Cunningham Panel testing for neuropsychiatric Lyme presentations, and imaging. Treatments included traditional antibiotics, botanical antimicrobials (Cryptolepis, Artemisinin, Biocidin), mitochondrial and neuroprotective support (CoQ10, NAD+, magnesium), nutritional therapies, detox support, immune system support protocols, pulsed electromagnetic field therapy, and methylene blue protocols.

Results

The findings from this case series demonstrate the heterogeneity of LD manifestations across different ages, genders, and backgrounds. Compared to promising specialized testing, standard laboratory tests often misdiagnose LD and its co-infections as Parkinson’s disease, multiple sclerosis, lupus, autism, and psychiatric disorders. Furthermore, integrating diverse treatment modalities, including combination and rotational antibiotic therapy, IV ceftriaxone for neurological cases, detoxification support (glutathione IV, vitamin C IV), and immune modulation with intravenous immunoglobulin, helped manage symptoms. Herxheimer reactions were effectively managed with antioxidant and detox therapies. Patients receiving long-term maintenance therapies, including herbal antimicrobials and gut microbiome support, showed fewer relapses.

Conclusions

This case series advocates for a holistic, patient-centered approach. It emphasizes the necessity of comprehensive diagnostics that consider external factors, including post-vaccine symptom exacerbations, immune dysregulation, personalized treatment strategies, and ongoing research to improve LD management. These findings provide an evidence-based framework for physicians to integrate conventional and natural medicine strategies to optimize LD care.

Introduction

This case series explores ten clinical narratives that showcase the multifaceted and often perplexing nature of Lyme disease (LD) and its co-infections. These cases are drawn from a diverse patient population and highlight the challenges of diagnosing and treating LD and its associated conditions. In this case series, patients of different ages, genders, and backgrounds present with a range of symptoms, from acute demyelinating peripheral neuropathy to cognitive deficits that resemble early dementia. These cases highlight the interplay between infectious agents, neurological symptoms, and the immune response, often complicated by other factors such as autoimmune reactions and mental health conditions. The present case series delves into the diagnosis and treatment of LD, a tick-borne illness primarily caused by the bacterium Borrelia burgdorferi, along with its co-infecting pathogens such as Babesia, Bartonella, Ehrlichia, Rickettsia spp (R. helvetica, R. monacensis), Anaplasma phagocytophilum, tick-borne encephalitis, Powassan viruses, and more.1 These pathogens cause neurological and psychiatric symptoms, challenging conventional diagnostic and treatment methods.2,3 This series examines the diagnostic journey of these patients, some of whom underwent extensive testing with unclear outcomes, resulting in delayed treatment. It highlights the limitations of standard laboratory tests and the potential usefulness of specialized testing in diagnosing infectious causes.4–8

Patients with tick-borne diseases can present a heterogeneous medical history and clinical symptoms,9,10 given the multisystemic nature of the disease.11 Recognizing this heterogeneity of LD is crucial for raising awareness among healthcare providers and other relevant stakeholders in the medical community.9–11 Herein, each case is unique in its clinical presentation and progression, ranging from severe neurological pain and chronic fatigue syndrome to complex autoimmune responses and neuropsychiatric disorders. Several cases feature complications following COVID-19 infection or immunization, raising questions about potential triggers for underlying infections or autoimmune conditions. The treatments used are varied, including traditional antibiotic therapies, intravenous nutritional therapies, detox support, immune system supporting protocols, innovative methods such as pulsed electromagnetic field therapy and the methylene blue protocol. These cases together advocate for a comprehensive approach to LD and its co-infections, integrating specialized testing and a range of treatment modalities. This series of medical case reports follows the CARE Guidelines to ensure they are insightful and scientifically valuable.12

Materials And Methods

Study Design and Ethics

The retrospective case series was conducted at Dr. O Care Clinic, Jacksonville, Florida (USA), a center known for specializing in infectious diseases, focusing on LD and related co-infections (https://www.drocare.com/). The clinic’s multidisciplinary method incorporates a holistic approach with integrative medicine principles, including integrative nutrition, integrative multi-organ system detox support after evaluation, and conventional and functional laboratory testing methods. Patients in this series were chosen for their distinctive clinical features, diagnostic histories, and responses to treatments concerning LD and its co-infections. Symptoms ranged from neurological pain to chronic fatigue, rheumatological conditions, cognitive impairments, and neuropsychiatric disorders (Table 1).

Table 1.

Summary of All Cases with a Focus on Specific Diagnostic Tests and Treatments

Case 1: A 25-year-old male with acute demyelinating peripheral neuropathy and severe neurological pain.
  • Hospitalization at the Mayo Clinic for alcohol delirium and chronic alcoholism.

  • Severe neuropathy pain, multiple axonal neuropathies, and a prognosis of permanent wheelchair dependence.

  • Treatment involved supportive antibiotic therapy and oral antibiotics for six months.

  • Patient’s recovery was remarkable, regaining full mobility and function.

  • Case highlights the complex interplay between LD, co-infections, and alcohol abuse.

Anamnesis Diagnostic Tools and Findings Diagnosis Treatment Final Outcome
The complex interplay between LD, co-infections, and alcohol abuse. TICKPLEX® ELISA (enzyme-linked immunoassay) (Tezted, Finland), Lyme Western Blot IgM/IgG (Igenex, U.S.A.), Bartonella Western Blot (Galaxy labs, U.S.A.), Blood chemistry, blood count, and serological antibody tests* (Quest, U.S.A.)
ELISpot (AID, Germany).
TICKPLEX® positive for LD, Babesia, Bartonella; EMG showed multiple axonal neuropathies; MRI normal; IgG/IgM antibody tests.
LD and co-infections complicated with alcoholism induced length-dependent peripheral neuropathy. Abstinence from alcohol, IV nutritional therapy, and detox support.
Medications: doxycycline hyclate 100 mg (1 capsule x2 per day), coartem 20 mg (4 tablets 2x per day for six days; one course per month for nine months), and Sulfamethoxazole 800 mg- trimethoprim 160 mg (1 tablet 2x per day for nine months).
Supplements: Obtain Health® Vital Stim (1 capsule 2x per day), Obtain Health® Flora Plus (1 capsule at bedtime away from antibiotics and all botanicals), Biocidin Broad Spectrum Liquid Formula (1 drop per 10 lbs of weight per day), Perque Lifeguard multivitamin (2 tablets 1x per day), Obtain Health® Omega-3 (1 capsule per day), and protein shakes daily for elemental nutrition.
Full recovery, regained mobility, no recurrence of symptoms, resumed normal activities; follow-up assessments showed normalized EMG results.
Case 2: A 29-year-old male with chronic fatigue syndrome, neurological and psychiatric symptoms, and Lyme neuroborreliosis and its related strains.
  • Symptoms indicated neuroborreliosis, another strain of Borrelia, and Neuro-Bartonellosis.

  • Treatment began with oral antibiotics, leading to partial improvement until a relapsing fever of Borrelia was detected.

  • Treatment escalated to higher doses of doxycycline for better coverage of tick-borne relapsing fever and LD persisting forms.

  • Post-discharge lab testing revealed persistent forms of Borrelia burgdorferi sensu lato.

  • Patient switched to IM ceftriaxone injections three times weekly.

  • Case highlights the complexity of diagnosing and treating Lyme neuroborreliosis and its variants.

Anamnesis Diagnostic Tools and Findings Diagnosis Treatment Final Outcome
The complexity of diagnosing and treating Lyme Neuroborreliosis and its variants. TICKPLEX® ELISA (Tezted, Finland), Lyme Western Blot IgM/IgG (Igenex, U.S.A.), Bartonella Western Blot (Galaxy labs, U.S.A.) Blood chemistry, blood count, and serological antibody tests* (Quest, U.S.A.), Precision Analytical Inc.: Dutchtest.
Specialty tick-borne disease lab tests detected Borrelia, Bartonella, Babesia, Mycoplasma; IgG/IgM antibodies for Borrelia; TICKPLEX® showed immune response to Borrelia forms.
Chronic Fatigue Syndrome, LD and co-infections, attention deficit/hyperactivity disorder (ADHD), reactive depression and anxiety, and sex addiction. Brain mapping EEG neurofeedback, IV nutritional therapy, and detox support.
Medications: Doxycycline hyclate 100 mg (1 capsule 2x per day), Artemether/lumefantrine 20 mg (2 tablets 2x per day for six days; one course per month for nine months), and Clarithromycin ER 500 mg tablet (2 tablets 1x per day for nine months), ceftriaxone injections 3x per week.
Supplements: Obtain Health® Vital Stim (1 capsule 2x per day), Obtain Health® Flora Plus (1 capsule at bedtime away from antibiotics and all botanicals), Biocidin Broad Spectrum Liquid Formula (1 drop per 10 lbs of weight per day), Perque Lifeguard multivitamin, Obtain Health® Omega-3 (1 capsule per day), and protein shakes daily for elemental nutrition.
Complete recovery; continued periodic evaluations and follow-up testing for persistent Borrelia.
Case 3: A 14-year-old female with severe headaches and chronic fatigue syndrome.
  • Initial treatment suspected to be related to a parasitic illness.

  • Serological and functional laboratory tests indicated past exposure to Borrelia infection.

  • Treatment regimen of ceftriaxone administered intravenously thrice a week, significantly improved energy levels and headaches.

  • Case emphasizes the importance of considering Lyme neuroborreliosis as a potential underlying cause in patients presenting with neurological and psychiatric conditions.

Anamnesis Diagnostic Tools and Findings Diagnosis Treatment Final Outcome
The importance of considering Lyme Neuroborreliosis as a potential underlying cause in patients presenting with neurological and psychiatric conditions. TICKPLEX® ELISA (Tezted, Finland), Lyme Western Blot IgM/IgG (Igenex, U.S.A.), Bartonella IFA IgG (Galaxy labs, U.S.A.), Blood chemistry, blood count, and serological antibody tests* (Quest, U.S.A.).
MRI indicated congenital brain malformation; IgG antibodies against Borrelia; past exposure to Borrelia; standard labs inconclusive; TICKPLEX® showed persistent Borrelia infection.
Tapeworm infection of the brain parenchyma, LD, migraine headaches, and reactive depression. Medications: albendazole 200 mg (2 tablets 2x per day for ten days), Cefdinir 300 mg (1 capsule 2x per day for 6 months- failed treatment).
After Cefdinir- IV Ceftriaxone 2 g (x3 per week for 3 months), and Azithromycin 250 mg (1 tablet 1x per day for six months) Supplements: Obtain Health® Vital Stim (1 capsule 2x per day), Obtain Health® Flora Plus (1 capsule at bedtime away from antibiotics and all botanicals), Biocidin Broad Spectrum Liquid Formula (1 drop per 10 lbs of weight per day), Perque Lifeguard multivitamin, Obtain Health® Omega-3 (1 capsule per day), and protein shakes daily for elemental nutrition.
Complete recovery; no need for long-term therapy; documented improvement using daily pain scores.
Case 4: A 37-year-old male with persistent symptoms of Lyme disease (LD) and Lyme borreliosis.
  • Symptoms included rashes, skin lesions, chronic fatigue, brain fog, joint pain, shortness of breath, headaches, rib cage pain, muscle weakness, and significant weight loss.

  • Symptoms were initially dismissed, leading to a psychiatric referral.

  • A positive antinuclear antibody test suggested an autoimmune response.

  • Immune-supportive treatments included high-dose vitamin B complexes, detox support, anti-inflammatories, and high-dose vitamin C.

  • Symptoms included fatigue and a rash akin to Rickettsia.

  • The patient was prescribed doxycycline for new symptoms suspected to be related to LDM, leading to a severe Herxheimer reaction.

  • The patient was diagnosed with lupus, an autoimmune condition, raising the possibility that the mRNA COVID-19 vaccine might have triggered an autoimmune response.

  • The patient was referred to a New York-based physician who diagnosed him with lupus, an autoimmune condition.

  • The patient is currently under the care of a rheumatologist and a Lyme-literate doctor in Colorado, with periodic follow-ups from the team in Florida.

  • This case underscores the importance of considering differential diagnoses like LD and co-infections, especially in patients with lupus-like symptoms post-doxycycline treatment, where Herxheimer reactions may mimic lupus reactivation.

Anamnesis Diagnostic Tools and Findings Diagnosis Treatment Final Outcome
The importance of considering differential diagnoses like LD and co-infections, especially in patients with lupus-like symptoms post-doxycycline treatment, where Herxheimer reactions may mimic lupus reactivation. TICKPLEX® ELISA (Tezted, Finland), Lyme Western Blot IgM/IgG (Igenex, U.S.A.), Bartonella IFA IgG (Galaxy labs, U.S.A.), Blood chemistry, blood count, and serological antibody tests* (Quest, U.S.A.).
Positive ANA test, TICKPLEX® positive for Borrelia spp. and Ehrlichia; diagnosed with Rocky Mountain spotted fever; positive IgG for Rickettsia; serology panel confirmed.
LD, co-infections, and SLE were further complicated during LD treatment. Medications: Doxycycline hyclate 100 mg (1 capsule 2x per day) and Rifampin 300 mg (1 capsule 2x per day), both discontinued within one week due to lupus-like syndrome, Malarone (atovaquone and proguanil), Prednisone 10 mg (1 tablet 1x per day).
Supplements: Obtain Health® Vital Stim (1 capsule 2x per day), Obtain Health® Flora Plus (1 capsule at bedtime away from antibiotics and all botanicals), Biocidin Broad Spectrum Liquid Formula (1 drop per 10 lbs of weight per day), Perque Lifeguard multivitamin, Obtain Health® Omega-3 (1 capsule per day), and protein shakes daily for elemental nutrition.
Patient is stable on low-dose steroid maintenance for SLE; improvement in clearing rashes, lesions, and serositis; regular follow-ups.
Case 5: A 52-year-old male with a complex medical history characterized by severe neuropathy in the left thigh, chronic pain, fatigue, sleep disorders, headaches, sinus and nasal congestion, and anosmia.
  • Serological tests revealed positive results for Borrelia burgdorferi sensu lato and Bartonella.

  • The patient’s symptoms intensified following the COVID-19 vaccinations, prompting further investigation into his underlying conditions.

  • A comprehensive treatment plan focused on nutritional therapy, antioxidants, detoxification support, and targeted oral antibiotics for Borrelia and Bartonella infections.

  • The patient experienced complete resolution of neuropathy, chronic fatigue syndrome, sinusitis, anosmia, and sleep disorders.

  • The case emphasizes potential diagnoses of Lyme and peripheral neuropathy in unexplained neurological and systemic symptoms, that chronic sinus infections may indicate chronic Bartonellosis, and the case raises awareness about the possible exacerbation of underlying stealth infections post-COVID-19 vaccinations.

Anamnesis Diagnostic Tools and Findings Diagnosis Treatment Final Outcome
Potential diagnosis of LD and peripheral neuropathy in unexplained neurological and systemic symptoms that illnesses like chronic sinus infections may indicate chronic Bartonella illness, and the case raises awareness about the potential exacerbation of underlying stealth infections post-COVID-19 vaccinations. TICKPLEX® ELISA (Tezted, Finland), Lyme Western Blot IgM/IgG (Igenex, U.S.A.), Bartonella IFA IgG (Galaxy labs, U.S.A.), Blood chemistry, blood count, and serological antibody tests* (Quest, U.S.A.).
TICKPLEX® positive for Borrelia burgdorferi sensu lato and Bartonella; history of chronic pain and sinusitis; post-vaccination symptoms deterioration.
LD and co-infections, peripheral neuropathy, chronic sinusitis, COVID-19 long-hauler syndrome, reactive depression, and sleep disorders. PEMF 3x per week during the last three months of treatment, IV nutritional therapy, and detox support.
Medications: Doxycycline hyclate 100 mg (1 capsule 2x per day for 1 year), low dose naltrexone (LDN) 4.5 mg (1 tablet 1x per day for 1 year), Sulfamethoxazole 800 mg- Trimethoprim 160 mg (1 tablet x2 per day for 1 year), Tinidazole 500 mg (1 tablet 2x per day before meals).
Supplements: Obtain Health® Vital Stim (1 capsule 2x per day), Obtain Health® Flora Plus (1 capsule at bedtime away from antibiotics and all botanicals), Biocidin Broad Spectrum Liquid Formula (1 drop per 10 lbs of weight per day), Perque Lifeguard multivitamin, Obtain Health® Omega-3 (1 capsule per day), and protein shakes daily for elemental nutrition.
Complete resolution of neuropathy, chronic fatigue, and sinusitis; regular follow-up assessments documented complete recovery.
Case 6: A 17-year-old Caucasian male with severe muscle spasms characterized by intense stiffness and excruciating pain upon muscle contraction.
  • Initial tests were negative, but a subsequent antibiotic challenge yielded a positive result for Babesia.

  • The patient underwent a versatile treatment regimen, including IV anti-inflammatory and antioxidant treatments, specialized IV infusion therapies, and oral administration of antioxidants and antimicrobial botanicals.

  • The patient showed remarkable recovery, with complete remission of pain and muscle stiffness after five months of treatment.

  • The patient has fully recovered and is actively pursuing his aspirations, including attending medical school and engaging in social activities.

  • This case highlights the importance of an integrative approach in diagnosing and treating LD and its co-infections.

Anamnesis Diagnostic Tools and Findings Diagnosis Treatment Final Outcome
Importance of an integrative medicine approach in diagnosing and treating LD and its co-infections. TICKPLEX® ELISA (Tezted, Finland), Lyme and Babesiosis Western Blot IgM/IgG (Igenex, U.S.A.), Bartonella Western Blot (Galaxy labs, U.S.A.), Blood chemistry, blood count, and serological antibody tests* (Quest, U.S.A.), ELISpot (AID, Germany).
Positive 83-93 bands for Borrelia; initial negative tests for Bartonella turned positive after antibiotic challenge; comprehensive serological workup.
LD, mycoplasma infection and babesiosis, peripheral muscle weakness, and pain syndrome. IV nutritional therapy and detox support
Medications: Doxycycline hyclate 100 mg (1 capsule 2x per day for 1 year), Artemether/lumefantrine 20 mg (2 tablets 2x per day for six days; one course per month for one year), azithromycin 250 mg (1 tablet daily for one year).
Supplements: Obtain Health® Vital Stim (1 capsule 2x per day), Obtain Health® Flora Plus (1 capsule at bedtime away from antibiotics and all botanicals), Biocidin Broad Spectrum Liquid Formula (1 drop per 10 lbs of weight per day), Perque Lifeguard multivitamin, Obtain Health® Omega-3 (1 capsule per day), and protein shakes daily for elemental nutrition.
Complete remission of symptoms; ongoing treatment until nine months post-symptom cessation; monitored pain assessments and functional gains.
Case 7: A 55-year-old woman with dementia symptoms, including brain fog, difficulty with word recall, and memory lapses, was included in a study for further evaluation.
  • Despite initial lab tests showing no LD indicators, one Ig band was positive, suggesting a potential link to LD.

  • The patient opted for a natural treatment route, focusing on enhancing cognitive and mitochondrial functions.

  • The methylene blue protocol was introduced, significantly improving cognitive function and work capacity.

  • The case was the first to utilize methylene blue for a patient with latent LD symptoms, providing new insights into alternative treatment approaches.

Anamnesis Diagnostic Tools and Findings Diagnosis Treatment Final Outcome
First to utilize methylene blue (MB) for a patient with latent LD symptoms and E. Coli UTI, providing new insights into integrative treatment approaches. TICKPLEX® ELISA (Tezted, Finland), Lyme and Babesiosis Western Blot IgM/IgG (Igenex, U.S.A.), Bartonella Western Blot (Galaxy labs, U.S.A.), Blood chemistry, blood count, and serological antibody tests* (Quest, U.S.A.), ELISpot (AID, Germany).
TICKPLEX® negative, but positive IgG band (58); confirmed E. coli UTI; gut workup showed high methane score; serology showed multiple IgG responses.
LD, Babesiosis, Bartonellosis, mold exposure, Candida, E. Coli UTI, short-term memory loss, confusion, and fatigue. CZTL labs MB Cure 1% weight by volume solution; mix 1g of methylene blue with 100 ml of water to make a 1% solution. Administered based on the weight of the patient (1 ml of CZTL labs MB 1% weight by volume solution per 0.1 kilogram of weight). Full recovery from dementia-like symptoms and UTI; improvement in cognitive function; regular monitoring showed normalization of serology and urine cultures.
Case 8: Pediatric Acute-onset Neuropsychiatric Syndrome (PANS) and PANDAS (Pediatric Autoimmune Neuropsychiatric Disorders Associated with Streptococcal Infections)
  • A 15-year-old male with PANS and PANDAS symptoms exhibited severe depression, anxiety, and social withdrawal.

  • Initial evaluations pointed towards PANS and PANDAS, and several rounds of antibiotics were administered.

  • The patient’s family consulted a neurology team, who administered an immunomodulatory dose of Intravenous Immunoglobulin (IVIG) once a month for three months.

  • A relapse occurred, and the patient developed aseptic meningitis during another round of IVIG, requiring hospitalization.

  • The patient was brought to a clinic in Jacksonville, where a combined approach included antibiotics and immunomodulatory doses of IVIG.

  • A significant breakthrough was achieved by addressing the patient’s low blood pressure, leading to an improvement in mood and a decrease in depression, anxiety, and chronic fatigue.

Anamnesis Diagnostic Tools and Findings Diagnosis Treatment Final Outcome
A significant breakthrough was achieved by addressing the patient’s low blood pressure, leading to an improvement in mood and a decrease in depression, anxiety, and chronic fatigue. This case helped us understand that vagus nerve dysregulation in LD patients, needs support and treatment as well as in LD. TICKPLEX® ELISA (Tezted, Finland), Lyme Western Blot IgM/IgG (Igenex, U.S.A.), Blood chemistry, blood count, and serological antibody tests* (Quest, U.S.A.), ELISpot (AID, Germany), Cunningham Panel (Moleculera Biosciences, U.S.A.).
Cunningham Panel testing confirmed PANS/PANDAS; TICKPLEX® positive for multiple Borrelia strains, Babesia microti, Ehrlichia chaffeensis; additional tests negative or borderline.
LD, co-infections, mold exposure, POTS, Reactive Depression, and PANS/PANDAS. IV nutritional therapy and prolonged detox protocols for mold detoxification for 3 months, aggressive POTS management with electrolytes and hydration therapy.
Medications: Doxycycline hyclate 100 mg (1 capsule 2x per day for thirty days), and Rifampin 150 mg (1 capsule 2x per day for thirty days).
Supplements: Obtain Health® Vital Stim (1 capsule 2x per day), Obtain Health® Flora Plus (1 capsule at bedtime away from antibiotics and all botanicals), Biocidin Broad Spectrum Liquid Formula (1 drop per 10 lbs of weight per day), Perque Lifeguard multivitamin, Obtain Health® Omega-3 (1 capsule per day), and protein shakes daily for elemental nutrition.
Complete recovery from PANS, depression, anxiety, and POTS; no need for further antibiotics or IVIG; documented through symptom checklists and regular follow-ups.
Case 9: Early-onset Parkinson’s Disease
  • The patient, who had an active childhood, began to experience tremors and weakness in her hands, progressing to anxiety and other central nervous system symptoms.

  • After exhausting all Parkinson’s treatments, she sought LD testing, revealing positive results for Borrelia burgdorferi and Bartonella.

  • The patient’s history of outdoor activities and subsequent neurological symptoms prompted the consideration of LD and co-infections in the diagnostic process.

  • The patient was initially treated with a three-week doxycycline trial followed by pulsed electromagnetic field therapy, the ALS protocol known as the Deanna Protocol and Align World, and various supplements and vitamins tailored to her needs.

  • Plans are underway to combine the Deanna Protocol with IV ceftriaxone and oral Bartonella coverage.

  • This case highlights the importance of a thorough diagnostic approach, which should include testing for LD (Lyme disease) and co-infections in patients who exhibit neurological symptoms such as Parkinson’s disease, multiple sclerosis (MS), and amyotrophic lateral sclerosis (ALS).

Anamnesis Diagnostic Tools and Findings Diagnosis Treatment Final Outcome
The importance of a thorough diagnostic approach, which should include testing for LD (Lyme Disease) and co-infections in patients who exhibit neurological symptoms such as Parkinson’s Disease (PD), Multiple sclerosis (MS), and amyotrophic lateral sclerosis (ALS). TICKPLEX® ELISA (Tezted, Finland), Lyme Western Blot IgM/IgG (Igenex, U.S.A.), Bartonella IFA IgG (Galaxy labs, U.S.A.), Everlywell home Lyme disease test (U.S.A.), Blood chemistry, blood count, and serological antibody tests* (Quest, U.S.A.).
TICKPLEX® positive for Borrelia burgdorferi and Bartonella; Everlywell home test suggested Lyme Disease exposure; initially tested negative using conventional methods.
Early-Onset Parkinson’s Disease manifested in the late 30s or early 40s. LD, co-infections (Bartonellosis), MTHFR mutation (Heterozygous Compound with Homozygous COMT Mutation), and Reactive Depression. IV nutritional therapy and prolonged detox protocols, including a high dose of 6000 mg glutathione, seven weeks of seven days a week PEMF-ELI technology (extreme low intensity pulsed electromagnetic field therapy) for Parkinson’s Disease support frequency.
Medications: doxycycline hyclate 100 mg 2x per day for three weeks caused immediate improvement of Parkinson’s symptoms, which eventually returned; then, the patient was given IV ceftriaxone up to 750 mg, maximum dose 3x per week for four weeks.
Supplements: Obtain Health® Vital Stim (1 capsule 2x per day), obtain Health® Flora Plus (1 capsule at bedtime away from antibiotics and all botanicals), long-term botanical coverage, and Greenman Gardens cryptolepis (½ teaspoon = 2.5 ml 2x per day). continued for maintenance. Bartonellosis has not been fully addressed due to multiple botanical tolerance issues.
Almost complete resolution of Parkinson’s disease symptoms with a complete gain of function, such as the patient being able to feed, bathe, do household chores, and drive independently; maintenance therapy with targeted botanicals and supplements.
Case 10: 24-year-old female with a long-standing history of immune deficiency, recurrent infections, neuro-atypical behavior, PANS, and PANDAS, treated with IVIG over sixteen years.
  • Her stealth infection workup elicited LD with multiple co-infections, opportunistic candidiasis, and group B strep colonization.

  • With treatment, her infectious burden decreased, allowing her immune system to fully recover, produce antibody responses, and grow out of her CVID diagnosis. She also gained significant cognitive abilities following infection-induced encephalopathy treatment; she no longer presents with neuro-atypical behaviors.

  • Patient’s infection-induced encephalopathy improved along with neurotypical growth and development.

  • This case highlights that all stealth infections and infection-induced encephalopathy must be ruled out before any regressive autism diagnosis is given.

Anamnesis Diagnostic Tools and Findings Diagnosis Treatment Final Outcome
The importance of diagnosing multiple stealth infections in a case presentation of a neuro-atypical child with clinical presentation of regressive autism, PANS/PANDAS, and CVID. TICKPLEX® ELISA (Tezted, Finland), Lyme Western Blot IgM/IgG (Igenex, U.S.A.), Blood chemistry, blood count, and serological antibody tests* (Quest, U.S.A.), ELISpot (AID, Germany).
Low IgG levels confirmed CVID; stealth infection workup showed positive for LD, Bartonellosis, Babesiosis, Candida; serology indicated persistent infections.
Speculated congenital LD, co-infections, CVID, Heterozygous Compound MTHFR Mutation, Autism, PANS/PANDAS. Immune deficiency dose of IVIG (500 mg per kg per infusion- treatment failed), dose increased to immunomodulatory dose (1g-2g per kg per infusion), which provided partial improvement of PANS/PANDAS symptoms up until her stealth infections were diagnosed and treated with doxycycline hyclate 100 mg (1 capsule 2x per day), Rifampin 150 mg (1 capsule 2x per day), and azithromycin 250 mg (1 tablet per day for 2 years). After the infections were treated, she underwent IV nutritional therapy and detox protocols for mold detoxification for six weeks, including PK protocol (Cell Membrane Medicine). Full recovery from neuro-atypical behaviors and infections; patient tested negative for all co-infections, discontinued IVIG, and is attending college full-time.

Inclusion criteria for patient selection were: (1) a history of chronic symptoms suggestive of LD and co-infections for at least six months, (2) positive serological tests for LD or co-infections, (3) previous unsuccessful treatment attempts in conventional medical settings, and (4) consent to participate in the study. Exclusion criteria were: (1) patients with a history of autoimmune diseases not related to infections, (2) patients receiving treatment for other chronic illnesses that could confound the results, and (3) lack of consent to use their medical data.

Diagnostic Tests

Extensive testing was pivotal for diagnosis, encompassing serological tests for IgG and IgM antibodies (targeting pathogens like Borrelia burgdorferi, Bartonella henselae, and Babesia microti), functional labs, and advanced imaging. The TICKPLEX® test provided deeper insights.7,8 TICKPLEX® is a CE-marked in-vitro diagnostics (CE-IVD) registered enzyme-linked immunosorbent assay (ELISA) and COFEPRIS-approved test manufactured under ISO 13485:2016, an industry standard for all clinical diagnostic tests. All the patients had been sick for an average of ten years, necessitating specific serological tests to guide treatment decisions, particularly in selecting antibiotics. TICKPLEX® was the only test demonstrating positive results for many patients, enabling targeted antimicrobial treatments that led to significant improvements and recoveries.

Additionally, neurological assessments, including electromyography (EMG) and magnetic resonance imaging (MRI), were performed.13,14 Standard two-tier Lyme disease testing15 was performed, followed by a Western blot from IGeneX (USA). Patients were also tested for Bartonella through Galaxy Diagnostics (USA) and ELISpot (Germany), along with other blood counts, blood chemistry, and serological tests conducted by Quest Diagnostics (USA). Cases with initially inconclusive or negative results that later turned positive, often post-antibiotic challenge, were also documented. Borderline test results indicated evidence of infection exposure, and patients were treated accordingly.

Treatment Interventions and Follow-up Procedures

Tailored oral and intravenous antibiotics were central to treatment, addressing specific diagnoses such as LD, Bartonellosis, and Babesiosis. Complementary therapies included IV detox, nutritional therapy, neurofeedback, and pulsed electromagnetic field therapy. Innovative approaches like the methylene blue and Deanna Protocols were also utilized. The sequence of interventions typically began with a baseline assessment, followed by initiation of antimicrobial treatment based on serological and functional lab results. Follow-up procedures included periodic reassessment of symptoms, repeat serological testing to monitor infection status, and adjustments to treatment protocols as needed. Patients were monitored through regular clinical visits, phone consultations, and review of laboratory results to ensure optimal management of their condition. The efficacy of these treatments was monitored through periodic follow-ups, focusing on symptom improvement, infection resolution, and overall quality of life enhancement. Data was retrospectively gathered from patients’ records, covering demographics, medical history, clinical presentations, diagnostic tests, physical exams, and treatment details. Consent was obtained for the use of this medical data. The study adhered to ethical guidelines and the Helsinki Declaration,16 with a strict emphasis on patient confidentiality.17

Tools for Processing Retrospective Data

We utilized several software tools to analyze data and create a well-structured case series. To facilitate our analysis, Microsoft Word (Microsoft Office 365) was used to transcribe audio medical notes about each patient into written form, leveraging the audio-to-text transcription feature. Microsoft Excel version 16.8 was utilized to organize, categorize, and analyze patient symptoms and laboratory test results. OpenAI’s ChatGPT (GPT-4, www.chat.openai.com) was instrumental in refining the case series following CARE guidelines.12 Quillbot (www.quillbot.com) and Grammarly (www.grammarly.com) were used to improve the clarity and grammatical accuracy of the case series. The manuscript underwent multiple review processes amongst the authors to ensure accuracy and integrity.

Results

The following sections provide a comprehensive overview of ten patient cases, including their backgrounds, diagnostic tests, treatments, and outcomes. Table 1 summarizes these cases, highlighting the diagnostic tests and treatment protocols used. Tables S1 to S10 in the supplementary Excel file also offer an in-depth breakdown of the various therapies administered in each case study.

Table S1.

Prescription Drug Therapy, Oral Nutritional Therapy, and IV Nutritional Therapy for Case 1

Case 1: A complex interplay between Lyme disease, co-infections, and alcohol abuse
Prescription drug therapy
Medication Dosage and Frequency Duration/Notes
Doxycycline hyclate 100 mg capsule, 2 times a day by mouth 6 months
Artemether/lumefantrine 20 mg-120 mg, 4 tablets 2 times a day by mouth 6 months
Gabapentin 400 mg capsule, 3 capsules every 8 hours
Start with 50 mg capsule every two days until
9 months (then tapered off and switched to Pregabalin)
Pregabalin reaching 150 mg, 3 times a day After tapering off Gabapentin
Oral nutritional therapy
Supplement Dosage and Instructions Duration/Notes
OH* Vital-Nervease 1 capsule, 2 times a day by mouth for neuropathy support 6 months
OH* SBI Shield 1 scoop, 2 times a day on an empty stomach (before breakfast and dinner) Continued for maintanence during the course of antibiotics
OH* L-glutamine 1 capsule before breakfast daily Continued for maintanence during the course of antibiotics
OH* Metabolic Balance Protein 2 scoops in 12 oz almond milk or ripple milk with 1 cup frozen strawberries and chia or flax seeds. Mix in blender and take with breakfast. Continued for maintanence during the course of antibiotics
OH* Vital Binder Capsules taken at least 2 hours away from other supplements, 1-2 times daily on Mondays, Wednesdays, and Fridays 90 days
OH* Pediaflora 2 scoops in a drink at bedtime, at least 2 hours away from SBI Shield, Vital Binder, L-Glutathione Continued for maintanence during the course of antibiotics
Utah Sea Minerals 2 teaspoons, twice a day in water or juice by mouth 3 months
Life Guard (Perque) 2-3 tablets, twice daily with meals (Alternative dosing based on stress level) 3 months
Omega 3-6-9 (NOW Foods) 2 soft gels every morning by mouth 3 months
OH* Flora Plus 1 capsule by mouth at bedtime Continued for maintanence during the course of antibiotics
IV nutritional therapy
Week IV Components
Week 1 B complex 2 mL, Ascorbic acid IV 5 gm, Chloride combo IV 2 mL, Zinc chloride 10 mg, Magnesium chloride 2000 mg, Methyl B12 5000 mcg, Glutathione IV 2000 mg
Week 2 B complex 2 mL, Ascorbic acid IV 5 gm, Chloride combo IV 2 mL, Zinc chloride 10 mg, Magnesium chloride 1600 mg, Methyl B12 5000 mcg, Glutathione IV 2000 mg, Acetylcysteine IV 400 mg
Week 3 B complex 2 mL, Ascorbic acid IV 5 gm, Chloride combo IV 2 mL, Zinc chloride 10 mg, Magnesium chloride 2000 mg, Methyl B-12 5000 mcg, Glutathione IV 2000 mg
Week 4 B complex 2 mL, Ascorbic acid IV 5 gm, Chloride combo IV 2 mL, Magnesium chloride 2000 mg, Methyl B-12 5000 mcg, Glutathione IV 2000 mg
Week 5 B complex 2 mL, Ascorbic acid IV 5 gm, Chloride combo IV 2 mL, Magnesium chloride 1600 mg, Quercetin 200 mg, Glutathione IV 2000 mg, Methyl B-12 5000 mcg
Week 6 B complex 2 mL, Chloride combo IV 2 mL, Magnesium chloride 2000 mg, Acetylcysteine IV 400 mg, Hydroxy B-12 5000 mcg, Quercetin 200 mg
Week 7 B complex 2 mL, Chloride combo IV 2 mL, Magnesium chloride 2000 mg, Quercetin 200 mg, Acetylcysteine IV 400 mg, Methyl B-12 5000 mcg
Week 8 Glutathione IV 2000 mg, Chloride combo IV 2 mL, Magnesium chloride 2000 mg, Zinc chloride 10 mg, Methyl B-12 5000 mcg, B complex 2 mL Vitamin C 9 gm, Chloride combo IV 2 mL, Magnesium chloride 1300 mg,
Week 9 Acetylcysteine IV 400 mg, Methyl B-12 5000 mcg B complex 2 mL, Chloride combo IV 2 mL, Magnesium sulfate chloride 2000 mg,
Week 10 Acetylcysteine IV 400 mg, Methyl B-12 5000 mcg, Quercetin 200 mg, Zinc chloride 10 mg

Table S2.

Prescription Drug Therapy, Oral Nutritional Therapy, and IV Nutritional Therapy for Case 2

Case 2: The complexity of diagnosing and treating Lyme Neuroborreliosis and its variants
Prescription drug therapy
Medication Dosage and Frequency Duration/Notes
Doxycycline hyclate 100 mg capsule, 2 times a day by mouth 9 months
Clarithromycin ER 500 mg tablet, extended release 24 hr, 2 tablets by mouth every day before meals 12 months
Artemether/lumefantrine 20 mg-120 mg, 4 tablets, 2 times a day by mouth 9 months
Ceftriaxone 2 gm IV on Wednesday, Thursday, Friday 12 weeks
Tinidazole 250 mg tablet, 2 tablets before a meal, 2 times a day, to be taken Friday, Saturday, and Sunday 4 weeks
     
Oral nutritional therapy
Supplement Dosage and Instructions Duration/Notes
UltraInflamX Plus 360®, Mango (Metagenics) 2 scoops, twice a day (Mix in 8 ounces of fluid) 2 months
HPA Adapt (Integrative Therapeutics) 2-4 capsules, once a day (on an empty stomach) Continued for maintanence during the course of antibiotics
Nighttime HPA (Gaia PRO) 2 capsules, every night Continued for maintanence during the course of antibiotics
Liposomal Melatonin Spray (Readisorb) Shake and spray once or more under the tongue, or as recommended by healthcare professional.
Hold in mouth for 20 seconds before swallowing.
Continued for maintanence during the course of antibiotics
Utah Sea Minerals (Trace Minerals Research) 2 teaspoons, twice a day in water or juice by mouth 3 months
Life Guard (Perque) 2-3 tablets, twice daily with meals (Alternative daily doses based on stress level) 3 months
Omega 3-6-9 1000mg (NOW Foods) 2 gels, every morning by mouth 3 months
Cal/Mag Plus w/ Vit D and K-2 (Metabolic Maintenance) 2 capsules, three times a day 3 months
Power Greens Berry (NuMedica) 1 scoop, every morning 3 months
Cryptolepis (Ortho Molecular Products) Mix 1 full dropper (0.7 mL or approximately 25-30 drops) with 2 fluid ounces of water, twice per day or as recommended by healthcare professional. Continued for maintanence after antibiotics stopped
Seriously Delicious Orange Creme Total Omega (Barlean’s Organic Oils) 1 tablespoon, every morning (straight or mixed into juice, yogurt, oatmeal, cottage cheese, or blended beverages) 6 months
OH* Flora Plus 1 capsule by mouth at bedtime Continued for maintanence during the course of antibiotics
     
IV nutritional therapy
Week IV Components
Weeks 1-12 B complex 2 mL, Ascorbic acid IV 5 gm-25 gm, Chloride combo IV 2 mL, Zinc chloride 10 mg-20 mg, Magnesium chloride 2000 mg, Methyl B12 (total cobalamin) 5000 mcg, Glutathione IV 2000 mg, Quercetin 200 mg, Acetylcysteine 400 mg

Table S3.

Prescription Drug therapy, Oral Nutritional Therapy, and IV Nutritional Therapy for Case 3

Case 3: The importance of considering Lyme Neuroborreliosis as a potential underlying cause in patients presenting with neurological and psychiatric conditions
Prescription drug therapy
Medication Dosage and Frequency Duration/Notes
Ceftriaxone 2 gm IV on Wednesday, Thursday, Friday 12 weeks (started after oral antibiotics failed)
Cefdinir 250/5ml, 5 ml by mouth, 2 times a day 6 months
Albendazole 200 mg, 2 tablets by mouth, 2 times a day 10 days
Ivermectin 12.5 mg by mouth, once daily 5 days
Doxycycline Hyclate 100 mg by mouth, 2 times a day 6 months
Zithromax 250 mg by mouth, 1 time a day 6 months
Artemether/lumefantrine 20 mg-120 mg, 4 tablets, 2 times a day by mouth 6 months
     
Oral nutritional therapy
Supplement Dosage and Instructions Duration/Notes
OH* Vital Binder 1 capsule, 1-2 times a day, at least 2 hours away from everything every other day Continued for maintanence during the course of antibiotics
OH* Vital Stim 1 capsule, 1-2 times a day Continued for maintanence during the course of antibiotics
Obtain Health* EFA’s OR OH* Flora Powder 1 tsp with breakfast OR 1 scoop at bedtime, 2 hours away from everything Continued for maintanence during the course of antibiotics
Biocidin Broad Spectrum Liquid Formula (Biocidin Botanicals) 5 drops, three times a day (take on an empty stomach, gradually increase to 5 drops three times daily; mix with water, swish in mouth, and swallow) 8 weeks then stop and start the antibiotics
Biocidin LSF Liposomal Formula Liquid (Biocidin Botanicals) 3 sprays, three times a day (3 drops three times daily with or without food) 8 weeks then stop and start the antibiotics
Pediatric Custom Multivitamin Base Powder (Metabolic Maintenance) 3 scoops, every morning 3 months
Hydroxo B12 with Folinic Acid (Seeking Health) 1 lozenge, every morning 3 months
     
IV nutritional therapy
Week IV Components
Weekly basis B complex 2 mL, Ascorbic acid IV 5 gm-25 gm, Chloride combo IV 2 mL, Zinc chloride 10 mg-20 mg, Magnesium chloride 2000 mg, Methyl B12 5000 mcg, Glutathione IV 2000 mg, Quercetin 200 mg, Acetylcysteine 400 mg

Table S4.

Prescription Drug Therapy, Oral Nutritional Therapy, and IV Nutritional Therapy for Case 4

Case 4: Herxheimer reactions may resemble lupus reactivation in patients with lupus-like symptoms post-doxycycline treatment
Prescription drug therapy
Medication Dosage and Frequency Duration/Notes
Rifampin 300 mg by mouth, 2 times a day 4 weeks
Doxycycline 150 mg by mouth, 2 times a day 4 weeks
Metronidazole 500 mg by mouth, 3 times a day on Fridays, Saturdays, and Sundays 3 months
Prednisone Started with 80 mg, tapered to 10 mg maintenance dose over 2 weeks 60 mg for 10 days then maintenance dose of 10 mg daily ongoing
Atovaquone 250 mg by mouth (anti-babesia drug) Continued for maintanence during the course of prednisone
Proguanil Hydrochloride 100 mg by mouth Continued for maintanence during the course of antibiotics
Cryptolepis For Lyme disease support Continued for maintanence after rifampin and doxycycline stopped
     
Oral nutritional therapy
Supplement Dosage and Instructions Duration/Notes
Biocidin Broad Spectrum Liquid Formula (Biocidin Botanicals) 5 drops, three times a day ongoing (Take on an empty stomach. Gradually increase dosage to 5 drops three times daily; mix with water, swish in mouth, and swallow) 8 weeks then stop and start the antibiotics
OH* Vital Stim 1 capsule with meals, 2 times a day Continued for maintanence during the course of antibiotics
OH* Flora Plus 1 capsule at bedtime Continued for maintanence during the course of antibiotics
OH* Tur-vital 1 capsule with breakfast Continued for maintanence during the course of antibiotics
Seriously Delicious Pomegranate Blueberry Smoothie Total Omega Vegan (Barlean’s Organic Oils) 1 tablespoon by mouth daily Continued for maintanence during the course of antibiotics
Power Greens Premium Berry (NuMedica) 1 serving, once a day (May mix with ice chip water, frozen berries) Continued for maintanence during the course of antibiotics
     
IV nutritional therapy
Week IV Components
Weekly basis B complex 2 mL, Ascorbic acid IV 5 gm-25 gm, Chloride combo IV 2 mL, Zinc chloride 10 mg-20 mg, Magnesium chloride 2000 mg, Methyl B12 5000 mcg, Glutathione IV 2000 mg, Quercetin 200 mg, Acetylcysteine 400 mg

Table S5.

Prescription Drug Therapy, Oral Nutritional Therapy, and IV Nutritional Therapy for Case 5

Case 5: Chronic sinus infections may indicate chronic Bartonella illness in Lyme and peripheral neuropathy patients with unexplained neurological and systemic symptoms
Prescription drug therapy
Medication Dosage and Frequency Duration/Notes
Doxycycline 150 mg by mouth, 2 times a day Not specified
Trimethoprim/Sulfamethoxazole DS 1 tablet by mouth, 2 times a day 90 days, one month off, then repeat for another 90 days
Tinidazole 500 mg by mouth, 2 times a day on Fridays, Saturdays, and Sundays Last month of the antibiotic course for 4 weeks
     
Oral nutritional therapy
Supplement Dosage and Instructions Duration/Notes
OH* Vital Stim 1 capsule, 2 times a day Continued for maintanence during the course of antibiotics
OH* Flora Plus and OH* Vital Spore Taken at dinner time, at least 2 hours away from Biocidin 8 weeks then stop and start Flora Plus 1 capsule at bed time
OH* Seasonal Support 1-2 chews, 2-3 times a day Continued for maintanence during the course of antibiotics
Nasal irrigation protocol Continue daily Continued for maintanence during the course of antibiotics
Biocidin Broad Spectrum Liquid Formula (Biocidin Botanicals) 5 drops, three times a day ongoing (Take on an empty stomach. Gradually increase to 5 drops three times daily; mix with water, swish in mouth, and swallow) 8 weeks then stop and start the antibiotics
     
IV nutritional therapy
Week IV Components
Weekly basis B complex 2 mL, Ascorbic acid IV 5 gm-25 gm, Chloride combo IV 2 mL, Zinc chloride 10 mg-20 mg, Magnesium chloride 2000 mg, Methyl B12 5000 mcg, Glutathione IV 2000 mg, Quercetin 200 mg, Acetylcysteine 400 mg

Table S6.

Prescription Drug Therapy, Oral Nutritional Therapy, and IV Nutritional Therapy for Case 6

Case 6: Importance of an integrative medicine approach in diagnosing and treating Lyme disease and its co-infections
Prescription drug therapy
Medication Dosage and Frequency Duration/Notes
Doxycycline 100 mg by mouth, 2 times a day 6 months
Zithromax 250 mg by mouth, once daily 3 months of the last 3 months of doxycycline
Artemether/lumefantrine 20 mg-120 mg, 4 tablets, 2 times a day by mouth 6 months
     
Oral nutritional therapy
Supplement Dosage and Instructions Duration/Notes
LifeGuard (Perque) 2 tablets, every morning (Take with breakfast) 3 months
Utah Sea Minerals (Trace Minerals Research) 2 teaspoons, four times a day 1 month
Inositol (Powder) (Pure Encapsulations) 2 scoops, once a day (with or between meals) Continued for maintanence during the course of antibiotics
Biocidin Broad Spectrum Liquid Formula (Biocidin Botanicals) 5 drops, three times a day ongoing (Take on an empty stomach. Gradually increase to 5 drops three times daily; mix with water, swish in mouth, and swallow) 8 weeks then stop and start the antibiotics
Biocidin LSF Liposomal Formula Liquid (Biocidin Botanicals) 3 sprays, three times a day (3 drops three times daily) Continued for maintanence during the course of antibiotics
Proflora4R Restorative Probiotic Combination (Biocidin Botanicals) 1 capsule, once a day 8 weeks then stop and start Flora Plus 1 capsule at bed time
Liposomal Glutathione (Pure Encapsulations) 1 capsule, once a day ongoing (in divided doses, with meals) Continued for maintanence during the course of antibiotics
Greens First PRO Berry (Greens First) 1 scoop, once a day Continued for maintanence during the course of antibiotics
Flora Plus 1 capsule at bed time Continued for maintanence during the course of antibiotics
     
IV nutritional therapy
Week IV Components
Weekly basis B complex 2 mL, Ascorbic acid IV 5 gm-25 gm, Chloride combo IV 2 mL, Zinc chloride 10 mg-20 mg, Magnesium chloride 2000 mg, Methyl B12 5000 mcg, Glutathione IV 2000 mg, Quercetin 200 mg, Acetylcysteine 400 mg

Table S7.

Prescription Drug Therapy, Oral Nutritional Therapy, and IV Nutritional Therapy for Case 7

Case 7: Methylene blue (MB) for a patient with latent Lyme disease symptoms, providing new insights into integrative treatment approaches
 
Product Preparation Instructions Administration Instructions Duration/Notes
CZTL Labs MB Cure 1% Solution Mix 1g of methylene blue with 100 ml of water to make a 1% weight by volume solution Administer 1 ml of CZTL Labs MB 1% solution per 0.1 kilogram of the patient’s weight 2 weeks for E coli UTI support. Continued mitochondrial support for post Lyme Diease maintance

Table S8.

Prescription Drug Therapy, Oral Nutritional Therapy, and IV Nutritional Therapy for Case 8

Case 8: Addressing low blood pressure resulted in an improvement in mood and a decrease in depression, anxiety, and chronic fatigue in a patient with PANS and PANDAS
Prescription drug therapy
Medication Dosage and Frequency Duration/Notes
Doxycycline hyclate 100 mg (1 capsule, 2 times per day) 30 days
Rifampin 150 mg (1 capsule, 2 times per day) 30 days
IVIG (Intravenous Immunoglobulin) 2 gm/kg per infusion over 4 days, once monthly 3 months
     
Oral nutritional therapy
Supplement Dosage and Instructions Duration/Notes
OH* Mitoboost 1 capsule by mouth in the morning (AM) Continued for maintanence during the course of antibiotics
OH* Omega-3 1 capsule by mouth in the morning (AM) Continued for maintanence during the course of antibiotics
OH* Flora Plus 1 capsule at bedtime, 2 hours away from all antibiotics Continued for maintanence during the course of antibiotics
     
IV nutritional therapy
Week IV Components
Weekly basis B complex 2 mL, Ascorbic acid IV 5 gm-25 gm, Chloride combo IV 2 mL, Zinc chloride 10 mg-20 mg, Magnesium chloride 2000 mg, Methyl B12 (total cobalamin) 5000 mcg, Glutathione IV 2000 mg, Quercetin 200 mg, Acetylcysteine 400 mg

Table S9.

Prescription Drug Therapy, Oral Nutritional Therapy, and IV Nutritional Therapy for Case 9

Case 9: The diagnostic approach for patients with neurological symptoms such as Parkinson’s Disease (PD), Multiple sclerosis (MS), and amyotrophic lateral sclerosis (ALS) should include testing for Lyme disease and co-infections
Prescription drug therapy
Medication Dosage and Frequency Duration/Notes
Doxycycline 100 mg by mouth, 2 times a day 3 weeks
Ceftriaxone 750 mg (maximum tolerable dose) on Mondays, Wednesdays, and Fridays (3 days per week) 4 weeks
     
Oral nutritional therapy
Supplement Dosage and Instructions Duration/Notes
Greenman Gardens Cryptolepis ½ teaspoon (2.5 ml), 2 times a day Continued for maintenance during the course of antibiotics
BRT-Nutramedix 15-30 drops daily Continued for maintenance during the course of antibiotics
OH* Mitoboost 1 capsule by mouth in the morning (AM) Continued for maintenance during the course of antibiotics
OH* Omega-3 1 capsule by mouth in the morning (AM) Continued for maintenance during the course of antibiotics
OH* Flora Plus 1 capsule at bedtime, 2 hours away from all antibiotics Continued for maintenance during the course of antibiotics
     
IV nutritional therapy
Week IV Components
Weekly basis B complex 2 mL, Ascorbic acid IV 5 gm-25 gm, Chloride combo IV 2 mL, Zinc chloride 10 mg-20 mg, Magnesium chloride 2000 mg, Methyl B12 (total cobalamin) 5000 mcg, Glutathione IV 2000 mg, Quercetin 200 mg, Acetylcysteine 400 mg

Table S10.

Prescription Drug Therapy, Oral Nutritional Therapy, and IV Nutritional Therapy for Case 10

Case 10: The importance of diagnosing multiple stealth infections in a case presentation of a neuro-atypical child with clinical presentation of autism and PANS/PANDAS
Prescription drug therapy
Medication Dosage and Frequency Duration/Notes
Doxycycline 50 mg by mouth, 2 times a day 12 months
Rifampin 150 mg by mouth, 2 times a day 12 months
Tinidazole 500 mg by mouth on Fridays, Saturdays, and Sundays 12 months
Phosphatidylcholine Post-antibiotic completion 5 vials per day 4 weeks
     
Oral nutritional therapy
Supplement Dosage and Instructions Duration/Notes
OH* Mitoboost 1 capsule by mouth in the morning (AM) Continued for maintenance during the course of antibiotics
OH* Omega-3 1 capsule by mouth in the morning (AM) Continued for maintenance during the course of antibiotics
OH* Flora Plus 1 capsule at bedtime, 2 hours away from all antibiotics Continued for maintenance during the course of antibiotics
     
IV nutritional therapy
Week IV Components
Weekly basis B complex 2 mL, Ascorbic acid IV 5 gm-25 gm, Chloride combo IV 2 mL, Zinc chloride 10 mg-20 mg, Magnesium chloride 2000 mg, Methyl B12 (total cobalamin) 5000 mcg, Glutathione IV 2000 mg, Quercetin 200 mg, Acetylcysteine 400 mg

Case 1: A Complex Interplay Between Lyme Disease, Co-Infections, and Alcohol Abuse

The patient is a 25-year-old male who presented with acute demyelinating peripheral neuropathy and severe neurological pain. He had used a wheelchair for several months before the accurate diagnosis was established. His medical history included chronic alcohol ingestion over the past year, leading to hospitalization at the Mayo Clinic in Jacksonville, Florida, for alcohol delirium and chronic alcoholism. The patient experienced extreme neuropathy and pain with no resolution after all medications during his 23 days of hospitalization. EMG and neurological workup confirmed multiple axonal neuropathies, rendering him unable to walk or use his hands and feet. Initially, the prognosis was grim, with expectations of permanent wheelchair dependence. The patient underwent a three-week hospitalization, focusing on alcohol delirium and alcohol-related neuropsychiatric support. After transferring to our clinic, he underwent comprehensive testing for chronic active infections known to cause chronic inflammatory demyelinating polyradiculoneuropathy (CIDP).

The criteria for diagnosing CIDP in this patient included symptoms, such as difficulty walking, problems using the arms, hands, legs, or feet, absence of reflexes in deep tendons, and severe pain in all four extremities, persisting for at least eight weeks. The patient also reported sensory changes like numbness, decreased sensation, pain, burning, or tingling. He exhibited a progressive or relapsing-remitting disease course, characterized by symmetric muscle weakness in both upper and lower limbs, along with sensory involvement in at least two limbs. Electrodiagnostic studies provided evidence of peripheral nerve demyelination. Blood tests confirmed a diagnosis of Babesia, Bartonella, and LD. We then focused on alcohol detoxification and nutritional therapy, along with neurological support and treatment for the patient, including pain management, mobility training, physical therapy, and pulsed electromagnetic field therapy (PEMF). Treatment involved a six-week course of supportive antibiotic therapy for the infections, followed by six months of oral antibiotics to address all three co-infections simultaneously. Specific information regarding the treatment can be found in Table S1.

Notably, the patient’s recovery was remarkable as he regained full mobility and function, overturning the initial prognosis of lifelong wheelchair dependence. Six months post-therapy, the patient returned to his usual state of health, free from chronic demyelinating polyneuropathy or nerve pain. IV nutritional therapies, antioxidant and detox protocols, and comprehensive infection treatment facilitated his full recovery over six months. Following our treatment based on TICKPLEX® serological test results for LD and co-infections, the patient, who was wheelchair-bound for over three months, returned to a normal state of health and is currently working at his father’s construction company as a construction worker. His MRI showed no abnormalities at the Mayo Clinic. Due to extreme chronic pain, he did not undergo a spinal tap.

The patient’s rehabilitation program included specific physical therapy and mobility exercises, starting with Active Release Techniques (ART) physical therapy three times a week, which was gradually reduced to once weekly, and then on an as-needed basis. PEMF was incorporated into the regimen with one 60-minute session for lymphatic drainage using Lenyo Systems’ Extreme Low-Intensity (ELI) pulsed electromagnetic therapy. Follow-up assessments to monitor the patient’s progress showed normalized EMG results and a total return to function, allowing for strenuous daily physical activity. No long-term follow-up was needed, as no recurrence of symptoms or new complications was observed.

This case underscores the complex interplay between LD, co-infections, and alcohol abuse. The patient’s alcohol consumption was a form of self-treatment, potentially exacerbating peripheral neuropathy and acute axonal damage. It highlights the critical need to consider substance use as a secondary coping mechanism in chronic neuropathy cases. The successful recovery of this patient demonstrates the importance of thorough diagnostic assessments and the efficacy of integrated treatment approaches in managing complex cases of LD and alcohol-related complications. It serves as a pivotal reminder for healthcare professionals to consider underlying infections in cases of unexplained neuropathy, especially in the context of substance abuse.

Case 2: The Complexity of Diagnosing and Treating Lyme Neuroborreliosis and its Variants

A 29-year-old male having a complex medical journey with a focus on chronic fatigue syndrome, various neurological and psychiatric symptoms, and a range of infectious diseases, particularly Lyme neuroborreliosis and its related strains. Initially, the patient presented with symptoms including chronic fatigue, depression, anxiety, and severe obsessive-compulsive disorder (OCD), mainly manifested in pleasure-seeking behaviors. These symptoms indicated neuroborreliosis, another strain of Borrelia, and neuro-bartonellosis. Standard laboratory tests failed to show significant findings. However, specialty tick-borne disease laboratory tests detected Borrelia, which causes relapsing fever, LD, Bartonella, Babesia, and Mycoplasma. Serological tests confirmed the presence of IgG and IgM antibodies for Borrelia burgdorferi sensu lato, Bartonella, and Babesia. The patient’s treatment journey began with oral antibiotics, leading to partial improvement until a relapsing fever of Borrelia was detected.

Consequently, the treatment was escalated to higher doses of doxycycline, 200 mg by mouth twice daily, for better coverage of tick-borne relapsing fever and LD persistent forms. Additional treatments included IV detox, nutritional therapy, neurofeedback, and pulsed electromagnetic field therapy. Details regarding the specific therapies used are available in Table S2. Neurofeedback therapy, specifically neurofeedback/biofeedback Low Energy Neurofeedback System (LENS), helped improve the patient’s focus and mood. Following 18 months of this regimen, the patient showed significant improvement and was discharged from the clinic. However, post-discharge lab testing using TICKPLEX® revealed an immune response towards the persistent Borrelia burgdorferi sensu lato forms. Despite the absence of significant clinical illness, the patient continued to experience fatigue, which led to a switch in treatment to IV ceftriaxone injections three times weekly. The decision to transition to IV ceftriaxone was due to the inadequate response to oral antibiotics. The IV ceftriaxone regimen consisted of 2 g, administered thrice weekly. Remarkable improvement in fatigue and recovery from sleep and headache disorders, which previously affected daily functioning, was observed within three weeks of starting the injections.

This case highlights the complexity of diagnosing and treating Lyme neuroborreliosis and its variants. It underscores the importance of considering multiple strains of Borrelia in diagnosis, mainly when patients test negative for Borrelia burgdorferi but continue to exhibit symptoms. The case also illustrates the efficacy of changing antibiotic delivery methods and the potential benefits of parenteral antibiotics in treating central nervous system infections. Follow-up protocols to monitor for persistent symptoms or new infections included IGeneX lab’s immunoblot and Galaxy lab’s IgG serology testing. Additional recommendations post-discharge include in-office clinical evaluations every 90 days. In summary, Case 2 is a vivid example of the multifaceted nature of Lyme neuroborreliosis and its co-infections, challenging diagnostic processes, and the necessity of tailored therapeutic interventions for successful outcomes.

Case 3: The Importance of Considering Lyme Neuroborreliosis as a Potential Underlying Cause in Patients Presenting with Neurological and Psychiatric Conditions

The patient is a 14-year-old female admitted to the hospital presenting with severe headaches and chronic fatigue syndrome. An MRI indicated a congenital brain malformation, but this did not explain her chronic symptoms. Standard laboratory examinations were largely unremarkable, except for the MRI findings. Initially, the patient’s condition was suspected to be related to a parasitic illness, and she was treated with albendazole, an antiparasitic medication, for possible tapeworm infection in her brain. However, this treatment did not alleviate her symptoms. Our group was then consulted for a more thorough evaluation. Serological and functional laboratory tests indicated past exposure to Borrelia infection, with IgG antibodies against Borrelia burgdorferi sensu lato but no IgM antibody response. Patients like Case 3 had presented in our clinic after receiving comprehensive evaluations in multiple tertiary care centers, leading to heightened medical anxiety and a history of numerous trials and tribulations. MRI and spinal tap were performed for cases with chronic headaches, as in Case 3. LD was not tested in her spinal tap because it was not suspected in conventional healthcare institutions. The MRI lesion cleared after antibiotic and antiparasitic use, but the spinal tap was not repeated due to extreme headaches and chronic medical anxiety.

The patient began a treatment regimen of ceftriaxone, administered intravenously three times a week. The ceftriaxone regimen was detailed, with specific dosages and administration schedules provided over a 12-week course, during which a complete blood count and metabolic profile were monitored weekly. Remarkably, within three weeks, her energy levels and headaches improved significantly. Six weeks into the treatment, her overall health and quality of life had notably improved. She completed a three-month course, receiving 2 g doses of IV ceftriaxone three days a week. Details of the adjunctive treatments provided alongside ceftriaxone can be found in Table S3. A significant improvement in her condition following the ceftriaxone treatment highlights the importance of considering Lyme neuroborreliosis as a potential underlying cause in patients presenting with neurological and psychiatric conditions like chronic fatigue syndrome and chronic migraines. The patient’s improvements were measured and documented using daily pain scores and clinical improvements in her symptoms, such as headache and fatigue. Long-term or maintenance therapies were not needed. This case emphasizes the complexity of diagnosing conditions like Lyme neuroborreliosis and the necessity for comprehensive evaluation and personalized treatment approaches. The optimal duration and protocols for IV antibiotic therapy in central nervous system infections due to Lyme borreliosis and chronic fatigue syndrome remain to be fully defined.

Case 4: Herxheimer Reactions May Resemble Lupus Reactivation in Patients with Lupus-Like Symptoms Post-Doxycycline Treatment

The patient, a 37-year-old white male, presented with a perplexing array of symptoms persisting for two years. These included unexplained rashes, painful skin lesions, chronic fatigue, brain fog, joint pain, shortness of breath, headaches, rib cage pain, muscle weakness, and significant weight loss. His condition notably deteriorated following two doses of the mRNA COVID-19 vaccine, received on February 5 and February 26, 2021. Despite repeated consultations with various doctors, his symptoms were initially dismissed, leading to a psychiatric referral. However, in November 2022, his condition was reevaluated, including blood tests and specimens. These investigations revealed a positive antinuclear antibody (ANA) test, suggesting an autoimmune response. Initially, the patient’s symptoms were dismissed, including mild manifestations such as painful rashes on his hands and toes, low-grade fevers, fatigue, and headaches. While awaiting a rheumatology consultation, which took three months due to scheduling delays, we commenced immune-supportive treatments, including high-dose vitamin B complexes, detox support, anti-inflammatories, and high-dose vitamin C. Although these interventions initially alleviated some symptoms, the patient subsequently developed fatigue and a rash akin to Rickettsia. We based our diagnosis on TICKPLEX® results, showing positive IgG for Borrelia spp. and Ehrlichia chaffeensis. The patient also tested positive for Rickettsia before coming to our office and clinically presented with a typical Rickettsia rash with fever, leading to a diagnosis of Rocky Mountain spotted fever. He became afebrile after doxycycline treatment.

The clinical turn took a dramatic shift when the patient was prescribed doxycycline for the new symptoms suspected to be related to LD, which led to a severe Herxheimer reaction, necessitating hospitalization. During this hospital stay, he received multiple antibiotics and achieved a fever-free state within 72 hours. The complexity of his case heightened when the hospital questioned the LD diagnosis. Seeking further expertise, we consulted a New York-based physician who diagnosed him with lupus, an autoimmune condition. The diagnostic approach involved distinguishing between lupus and LD with co-infections by comparing specific serological tests for LD and associated co-infections against the established Lupus Diagnostic Criteria, which includes the 11 hallmark symptoms of systemic lupus erythematosus (SLE).18 This diagnosis, juxtaposed with the previous suspicion of LD and co-infections, raised the possibility that the mRNA COVID-19 vaccine might have triggered an autoimmune response, particularly lupus, against a backdrop of underlying LD. Given the patient’s annual summer stays in Colorado, we facilitated his connection with a local physician specializing in rheumatology and LD. The treatment regimen was adjusted to Malarone to include adequate hydroxychloroquine for anti-inflammatory properties alongside low-dose hydrocortisone steroid, which showed promising results. Table S4 summarizes high-dose vitamin B complexes, detox support, anti-inflammatories, Malarone, and other medications for treating LD and its co-infections.

Currently, the patient is under the diligent care of a rheumatologist and a Lyme expert doctor in Colorado, with periodic follow-ups from our team in Florida. Following the adjustment of the treatment regimen, the patient showed improvements in clearing malar rash, hand, and foot lesions, serositis, non-erosive arthritis, oral ulcers, photosensitivity, electrolyte imbalance, and symptoms of anxiety and depression. Continued care involves ongoing low-dose steroid therapy for maintenance. This case underscores the importance of considering differential diagnoses like LD and co-infections, especially in patients with lupus-like symptoms post-doxycycline treatment, where Herxheimer reactions may mimic lupus reactivation.

Case 5: Chronic Sinus Infections May Indicate Chronic Bartonella Illness in Lyme and Peripheral Neuropathy Patients with Unexplained Neurological and Systemic Symptoms

A 52-year-old male patient presented with a complex medical history characterized by severe neuropathy in the left thigh, chronic pain, fatigue, sleep disorders, headaches, sinus and nasal congestion, and anosmia (loss of smell). His symptoms persisted for over a decade, during which he underwent extensive testing at the Mayo Clinic, but no conclusive diagnosis or relief was obtained. The patient reported a noticeable and rapid worsening of symptoms following the second COVID-19 vaccination two months before his initial consultation at our clinic. Upon presenting to our clinic, serological tests revealed positive results for Borrelia burgdorferi sensu lato and Bartonella, which cause infectious diseases that are often challenging to diagnose. The patient’s demographics and history of receiving COVID-19 mRNA vaccines (first dose on March 3, 2021, second dose on April 20, 2021, and third dose on October 26, 2021) were noted. This patient had a Centers for Disease Control and Prevention (CDC)-positive LD diagnosis and was treated with conventional antibiotics longer than the recommended CDC protocol for LD and co-infections. Integrative approaches and supportive natural medicine modalities complemented the evidence-based treatments.

Interestingly, the patient’s symptoms following the COVID-19 vaccinations prompted further investigation into his underlying conditions. The comprehensive treatment plan included specific antibiotics, supported by a combination of oral and intravenous nutritional therapies (Table S5). Nutritional support, antioxidants, and detoxification strategies were integrated with standard antibiotic treatments for LD and co-infections to enhance the therapeutic effects (Table S5). This holistic approach led to a significant improvement in his health. The patient experienced complete resolution of neuropathy, chronic fatigue syndrome, sinusitis, anosmia, and sleep disorders. Integrative approaches and supportive natural medicine modalities should not undermine our treatments, as they are based on evidence-based approaches.19,20 It is crucial to support phase 1, phase 2, and all detox pathways while treating a substantial infectious burden at the cellular level to prevent unbearable Herxheimer reactions and mast cell activation responses. Symptom improvement was thoroughly documented through regular assessments using pain score charts, which demonstrated a marked reduction and eventual complete resolution of neuropathy after a decade of suffering. Follow-up care involved monthly evaluations, with continuous monitoring of neuropathy and quality of life metrics, including activity levels, sleep quality, and functional lifestyle assessments.

This case highlights the complexities in diagnosing conditions like Lyme borreliosis and Bartonellosis, which can manifest as a spectrum of symptoms, including chronic fatigue, neuropathy, sleep disorders, and psychiatric conditions. Conventional medical settings often face challenges in diagnosing these complex symptoms. However, with accurate diagnosis and timely antibiotic treatment, a drastic improvement in the quality of life can be achieved. In summary, this patient’s case underscores the importance of considering LD and peripheral neuropathy as potential diagnoses in patients with unexplained neurological and systemic symptoms. Additionally, it suggests that chronic sinus infections might indicate chronic Bartonellosis. The case also raises awareness about the potential exacerbation of underlying stealth infections following COVID-19 vaccinations, necessitating a thorough investigation in similar cases.

Case 6: Importance of an Integrative Medicine Approach in Diagnosing and Treating Lyme Disease and its Co-Infections

The subject of this case is a 17-year-old Caucasian male who recently moved from the shores of New Jersey to Jacksonville in the summer of 2022. Upon relocation, the patient experienced severe muscle spasms characterized by intense stiffness and excruciating pain upon muscle contraction. Prior consultations at the Children’s Hospital in Philadelphia and with a neurologist in Jacksonville yielded no conclusive diagnosis. Initial tests, including EMG and EEG, were negative. The patient was initially referred to psychiatry under the assumption of a pain augmentation syndrome. However, further examination by our team revealed positive 83-93 bands, indicative of a Borrelia burgdorferi sensu lato infection. These bands are known as the longest-lasting markers of the disease. Initial tests for Bartonella were also negative, but a subsequent antibiotic challenge yielded a positive result for Babesia.

The patient underwent a versatile treatment regimen, starting with a three-month course for LD, followed by treatment for Babesia, which included IV antiinflammatory and antioxidant treatments, specialized IV infusion therapies, and oral administration of antioxidants and antimicrobial botanicals like cryptolepis and artemisinin. The symptoms initially prompting referral to psychiatry were addiction, depression, and OCD. Details of the treatment regimen for LD and Babesia, including specific therapies and their administration methods, are provided in Table S6. Pain management was addressed through pulsed electromagnetic field therapy, hyperbaric oxygen therapy, and microcurrent therapies. The pain management protocols, such as PEMF and hyperbaric oxygen therapy, included using a home-based hyperbaric oxygen chamber, delivering 90-minute sessions at a minimum of 1.4 ppm oxygen, at least five days per week for 40 sessions. As of May 2023, the patient showed remarkable recovery, with complete remission of pain and muscle stiffness after five months of treatment. Notably, treatment for Babesia typically continues for at least nine months post-symptom cessation. The patient achieved three months without symptoms by May, leading to the plan for ongoing treatment until the end of August 2023.

This case highlights the importance of an integrative approach in diagnosing and treating LD and its co-infections. The patient’s journey from misdiagnosis to full recovery underscores the need for a thorough investigation and the effectiveness of combining various treatment modalities. Specific metrics used to evaluate the patient’s recovery included pain assessments and functional gains, such as the ability to walk and exercise daily. The ongoing treatment plan was adjusted in response to the patient’s progress, evidenced by reduced pain levels and improved physical endurance, allowing for daily activities without fatigue. The patient has fully recovered and is actively pursuing his aspirations, including attending medical school and engaging in social activities.

Case 7: Methylene Blue (MB) for a Patient with Latent Lyme Disease Symptoms, Providing New Insights into Integrative Treatment Approaches

The patient, a 55-year-old white female and mother of two children, presented with symptoms resembling early signs of dementia, including brain fog, difficulty with word recall, and memory lapses. She is a fitness and personal trainer. The patient experienced significant forgetfulness and struggled to grasp or understand certain concepts. Given her family history, where both her sons tested positive for LD, she was included in a study for further evaluation. Initial lab tests showed she tested negative for most LD indicators. However, one of the IgG bands (58) was positive, suggesting a potential link to LD. This finding necessitated a thorough review for a definitive conclusion. Despite the uncertainty surrounding her diagnosis, the patient opted for a natural treatment route. She chose not to use botanicals or antibiotics but focused on enhancing cognitive and mitochondrial functions. She was introduced to the MB protocol, which she followed diligently. Details of the MB protocol followed by the patient can be found in Table S7.

Before starting the MB treatment, the patient developed cystitis symptoms, a type of urinary tract infection (UTI). Lab tests confirmed an E. coli UTI that had progressed to an upper tract infection, with over 100 000 E. coli bacteria present. Despite the severity of her UTI, she declined antibiotics in favor of continuing the MB protocol. Remarkably, after two weeks on the MB protocol, a repeat urine culture showed no traces of E. coli. Additionally, her word recall, short-term memory, and overall cognitive function improved significantly. After completing the MB protocol, all symptoms were resolved, and testing for TICKPLEX® IgG response was negative. Additional lab results showed multiple IgG responses for Babesia, Bartonella, Aspergillus, and Candida. Her attached gut workup revealed a high methane score with elevated IgA and low short-chain fatty acids, consistent with small intestinal bacterial overgrowth (SIBO). Our clinic interpreted these results as indicating the presence of the organisms mentioned above in her intestinal lining.

Consequently, not only were her short-term memory loss and word recall problems resolved, but also her SIBO symptoms and all gut-related complaints, including bloating, diarrhea, and food intolerances. As a fitness and personal training professional, she noticed a 100% increase in her work capacity and productivity. After two months of using the protocol, she fully recovered. The patient’s success led to further research into the efficacy of MB against E. coli UTIs, revealing its effectiveness even against resistant strains. The improvements in cognitive function and overall health included enhanced short-term memory, better word recall, resolution of brain fog, and reduced frustration with daily tasks. Post-treatment follow-up and monitoring included repeat urine cultures and LD serology panels, both of which normalized. This case was the first to utilize MB for a patient with latent LD symptoms and has provided new insights into alternative treatment approaches. This case highlights the importance of considering alternative treatments21 in complex cases, where traditional methods may not be viable or preferred by the patient. In this case, the successful use of the MB protocol opens avenues for further research and application in similar clinical scenarios.

Case 8: Addressing Low Blood Pressure Resulted in an Improvement in Mood and a Decrease in Depression, Anxiety, and Chronic Fatigue in a Patient with PANS and PANDAS

The patient is a 15-year-old male with a unique medical case involving central nervous system infections, specifically PANS (Pediatric Acute-onset Neuropsychiatric Syndrome) and PANDAS (Pediatric Autoimmune Neuropsychiatric Disorders Associated with Streptococcal Infections). These conditions manifested in acute neuropsychiatric symptoms, potentially related to strep infections, LD, and its co-infections. Initially, at the age of nine, the patient exhibited severe depression, anxiety, and social withdrawal. His behavior was notably atypical, feeling out of place even among peers, leading to reluctance to attend school or socialize, which was accompanied by panic attacks and bouts of depression. The initial symptoms and their progression involved resolving episodes of depression, panic attacks, and suicidal ideation, with a corresponding improvement in school performance. Initial evaluations pointed towards PANS and PANDAS, and several rounds of antibiotics were administered. However, the infections became latent despite a partial response to the treatment. The diagnosis of PANS and PANDAS was confirmed by Cunningham Panel testing,22,23 which provided vital diagnostic markers. The patient’s family then consulted a neurology team, including Lyme neurologists, who administered an immunomodulatory dose of intravenous immunoglobulin (IVIG) monthly once, for three months. This treatment led to marked improvement. Unfortunately, a relapse occurred, and the patient developed aseptic meningitis during another round of IVIG, which resulted in a critical condition requiring hospitalization at a hospital in New York, USA.

Afterward, the patient was brought to our clinic in Jacksonville, where a reactivation of his infections was discovered. Our combined approach included antibiotics alongside immunomodulatory doses of IVIG, aiming for better penetration across the blood-brain barrier and reducing complications in the central nervous system. A significant breakthrough was achieved by addressing the patient’s low blood pressure. Stabilizing it led to an improvement in mood and a decrease in depression, anxiety, and chronic fatigue. The immunomodulatory dose of IVIG administered was 2 g/kg over four days, and the management of low blood pressure and Postural Orthostatic Tachycardia Syndrome (POTS) was supported with IV nutritional therapy (Table S8). It was observed that if the central nervous system cannot regulate low blood pressure and patients receive IVIG, there is an increased risk of developing aseptic meningitis. Therefore, patients with untreated POTS should be cautiously treated with high-dose IVIG, especially if administered rapidly. Our treatment plan strongly emphasizes managing the patient’s POTS before proceeding, which is crucial as a rapid increase in blood pressure in the brain due to a high dose of IVIG, combined with an inability to regulate peripheral blood pressure, can create an imbalance leading to complications in POTS patients. Following our Intravenous (IV) protocols and a strict oral rehydration regimen, including increased salt, electrolyte, and fluid intake, the patient made a remarkable recovery.

The patient is now thriving without the need for antibiotics or IVIG, overcoming his PANS, depression, anxiety, and POTS. The patient’s improvements were measured and documented through improved depression and anxiety scores, as well as a resolution of near-fainting episodes and panic attacks. The long-term or maintenance therapies included depression, anxiety, and POTS symptom checklists every 90 days. The lab results further substantiated this case, indicating positive responses for Borrelia burgdorferi, Borrelia afzelii, Borrelia garinii (related to LD), Babesia microti, and Ehrlichia chaffeensis. At the same time, other tests for infections like Bartonella henselae, Rickettsia akari, and Epstein-Barr virus were negative or borderline. This comprehensive approach underscores the efficacy of combined IV and nutritional therapy with fluid management for POTS patients in an outpatient setting, presenting a successful case after years of challenging treatments.

Case 9: The Diagnostic Approach for Patients with Neurological Symptoms such as Parkinson’s Disease (PD), Multiple Sclerosis (MS), and Amyotrophic Lateral Sclerosis (ALS) Should Include Testing for Lyme Disease and Co-Infections

The patient (51-year-old female), who enjoyed an active childhood with frequent camping and playing in the woods, remained healthy until her early 40s. At this time, she began to experience tremors and weakness in her hands, which progressed to anxiety and other central nervous system symptoms. The patient’s initial symptoms included tremors, difficulty walking steadily, inability to drive long distances, inability to feed herself, and drooling. Over time, these symptoms showed substantial improvement, leaving only mild residual effects. Diagnosed with early-onset Parkinson’s disease at 42, her condition deteriorated over time. A decade later, after exhausting all Parkinson’s treatments, she sought LD testing. Initially skeptical, the patient eventually underwent LD testing, revealing positive results for Borrelia burgdorferi and Bartonella. The diagnosis was challenging due to the overlap of symptoms with Parkinson’s disease and other neurological conditions. The patient’s history of outdoor activities and subsequent neurological symptoms prompted the consideration of LD and co-infections in the diagnostic process. The patient initially tested negative for LD using the conventional two-tier testing method. However, a home test called Everlywell suggested LD exposure. This was later confirmed by the TICKPLEX® test, which identified LD and associated co-infections.

Parkinson’s patients are supported with many electromagnetic modalities, and the Deanna Protocol is used for neurological complications of these stealth infections. The patient responded significantly to doxycycline, achieving complete resolution of tremors not seen with any other drug. The initial doxycycline regimen remarkably improved her motor function, but progress plateaued after three weeks. She was then switched to intravenous ceftriaxone, with a maximum dose of 750 mg administered thrice weekly for four weeks. Her remaining tremor is now well-controlled, allowing her to fully function following the botanical protocol outlined below (Table S9). Subsequent treatments included pulsed electromagnetic field therapy, the ALS protocol known as the Deanna Protocol and Align World, and various supplements and vitamins tailored to her needs, especially considering her methylenetetrahydrofolate reductase (MTHFR) mutation. Subsequent treatments, including the Deanna Protocol, involved multiple oral supplements and intravenous administration of ceftriaxone. These interventions led to significant improvements in her symptoms.

While the patient experienced a marked improvement in her tremors and muscle aches, her Bartonellosis co-infection was managed with BRT-Nutramedix at 15-30 drops daily, as tolerated, in combination with Greenman Gardens Cryptolepis (½ teaspoon or 2.5 ml, twice daily), which provided broader support for LD and Babesia (Table S9). Despite her improvements, she continued to experience occasional tremors and shakiness, particularly under emotional stress. The patient’s improvements were assessed and documented based on her neurological performance and daily functioning. She regained the ability to perform household chores such as changing bed linens, washing dishes, washing her hair independently, gardening, and falling asleep without her muscles becoming tired and sore from constant tremors. Long-term maintenance therapies included Greenman Gardens Cryptolepis (½ teaspoon or 2.5 ml, twice daily) and BRT-Nutramedix (15-30 drops daily). This case underscores the need for a comprehensive diagnostic approach, including testing for LD and co-infections, in patients presenting with neurological symptoms like diseases like Parkinson’s, MS, and ALS. This approach helps prevent misdiagnosis, avoids unnecessary treatments, and ensures appropriate care. In such cases, the positive response to targeted therapy for LD and co-infections advocates for their inclusion in standard diagnostic and treatment protocols for these neurological conditions.

Case 10: The Importance of Diagnosing Multiple Stealth Infections in a Case Presentation of a Neuro-Atypical Child with Clinical Presentation of Autism and PANS/PANDAS

A twenty-four-year-old female with a long-standing history of immune deficiency, recurrent infections, neuroatypical behavior, PANS, and PANDAS was treated with IVIG for sixteen years. The patient was diagnosed with CVID (Common Variable Immune Deficiency) at the age of twenty-six months by Duke Medical Center in Raleigh, North Carolina, USA. After the failure of the immune deficiency dose of IVIG, evidenced by breakthrough infections, the patient’s IVIG was increased to the immunomodulator dose of IVIG. Despite minimal improvement with an immunomodulatory dose of IVIG, the patient continued to develop breakthrough infections with cyclic fevers every four to six weeks. After she reached puberty, her cyclic fevers coincided with her menstrual cycles.

The initial symptoms included unexplained skin rashes, recurrent fevers, multiple episodes of food anaphylaxis, and frequent bacterial infections, all of which progressed over time. The diagnosis of CVID and other infections was confirmed by a total IgG level below 500 (her levels were in the low 300s), with no detectable antibodies to tetanus, diphtheria, and pneumococcal vaccines. Stealth infection workup showed LD, Bartonellosis, Babesiosis, Candida, and group B colonization. During her journey to full recovery, the patient received various integrative treatments, including IV nutritional therapy, detox support for Herxheimer reactions, PEMF (pulsed electromagnetic field therapy), and the phosphatidylcholine protocol (PK protocol). The detailed list of antibiotics and integrative approach used and their administration schedule can be found in Table S10.

The patient underwent a two-year course of antibiotics, such as doxycycline, rifampin, and azithromycin. She continued receiving an immunomodulatory IVIG dose throughout the antibiotic treatment. This approach resolved her recurrent fever pattern and significantly improved her recurrent infections. The Babesia infection, which had contributed to her underdeveloped lung function, was associated with persistent reactive airway disease and small airway disease with restrictive patterns. Her improvements were systematically tracked and documented during her recovery by resolving recurrent fevers, bacterial infections, and unexplained rashes. Long-term or maintenance therapies included both oral and IV nutritional therapies as well as regular sessions of the phosphatidylcholine protocol. The patient tested negative for LD and all co-infections and discontinued IVIG infusions. She also experienced a full recovery from neuro-atypical behaviors and was no longer diagnosed with ASD (autism spectrum disorder), PANS/PANDAS, or CVID. The patient is now attending college full-time and shows no signs of immune deficiencies or stealth infections.

Discussion

This series of ten patient cases illustrates the complexity, variability, and challenges in diagnosing and treating conditions such as LD, co-infections, and related neurological and psychiatric disorders. The cases, ranging from acute peripheral neuropathy exacerbated by alcohol abuse (Case 1) to stealth infections aggravating PANS/PANDAS (Case 10), underscore the multifaceted nature of these illnesses and highlight several key themes and lessons learned.

For example, in Case 1, we observe a complex interaction between substance misuse and neurological conditions. The patient’s long-term alcohol usage not only concealed an existing polyneuropathy but may have also aggravated it. This case underscores the intricate relationship between substance abuse and neurological disorders, a topic of growing concern in medical research.24 Substance use disorders are significantly correlated with a higher incidence of infectious diseases, a relationship that is complicated and critical.24 Contributing factors include behaviors associated with drug use, such as needle sharing and engaging in risky activities, along with drug contaminants.24 These behaviors often suppress the immune system and increase infection vulnerability.24 Moreover, socioeconomic challenges like poverty and homelessness compound this risk. The comorbidity of infectious diseases and drug use is associated with substantial morbidity, mortality, and healthcare expenditures.24,25

Particularly noteworthy is the connection between infectious diseases and neurological disorders like epilepsy.26 Infections are a significant contributor to epilepsy, especially in areas such as Sub-Saharan Africa.26 Various infectious agents, including neurocysticercosis, tuberculosis, HIV, and cerebral malaria, can lead to epilepsy.26 These infections create structural brain changes that result in persistent seizures, even after infection treatment.27 Recent progress in neuroimaging technology has significantly enhanced our understanding of the relationship between substance abuse and neurological disorders, such as polyneuropathy. Tools like functional MRI, positron emission tomography (PET), single-photon emission computed tomography (SPECT), and magnetic resonance spectroscopy have crucially uncovered the effects of substance misuse on brain functions related to executive functioning, reward processing, memory, and stress response.27 This improved insight facilitates more accurate diagnoses and the development of personalized treatment plans for patients with substance use disorders. The first case in our series emphasizes the importance of recognizing substance abuse as a factor complicating the diagnosis and treatment of neurological disorders. Case 1 is particularly unique as it showcases the interplay between substance abuse and neurological disorders in the context of tick-borne diseases, a connection not extensively documented before.

Cases 2, 5, and 9 in this medical case series highlight the intricate diagnostic processes of identifying LD and associated co-infections. These cases presented a diverse array of symptoms, ranging from psychiatric issues to severe physical impairments, leading to initial misdiagnoses or a lack of diagnosis. The necessity for thorough and specialized laboratory testing is evident in managing such complex cases. Recent scientific studies underscore the significant challenges in diagnosing LD and its co-infections.28,29 A notable concern is the regional variability in Borrelia species, particularly between North America and Europe. In North America, Borrelia burgdorferi sensu stricto (Bbss) is prevalent, with some cases of B. bissettii and B. mayonii.30 However, in Europe, the serology is more complex due to the presence of multiple Borrelia species such as B. afzelii, B. garinii, B. bavarensis, B. burgdorferi ss, B. spielmani, B. valaisiana, and B. lusitaniae.31 This complexity may necessitate using recombinant antigens and multilocus chimeric proteins.32 The reliability of existing diagnostic methods.4,5,28,29 The standard two-tier serology test, revised with the modified two-tier test frequently used for diagnosing Lyme borreliosis, provides superior sensitivity and specificity.33–35 However, false negative test results can occur in the early stages of LD, and false positives can occur due to cross-reactivity with other illnesses, like viral infections.36,37 Researchers are investigating improved diagnostic techniques, such as applying peptides from linear B cell epitope mapping and testing for the pleomorphic forms of Borrelia, to increase the specificity and sensitivity of the LD test.7,38–41

Moreover, the inadequacies of current molecular and serologic assays complicate the diagnosis of tick-borne co-infections.28,29 Considering that at least nineteen tick-borne pathogens have been identified in the United States, predominantly spread by just two tick species, there is a high risk of polymicrobial transmission.1,42 However, commercial diagnostic methods often fail to detect multiple agents simultaneously in a single test, which is crucial to effective diagnosis of co-infections.43,44 Numerous case studies further highlight the diagnostic challenges and the implications of severe misdiagnosis.45–47 There have been instances where symptoms of LD were mistakenly attributed to other ailments, leading to incorrect treatments and additional health complications.46 For example, a 25-year-old woman initially presented with symptoms suggestive of temporomandibular disorder was later accurately diagnosed with LD.46 These cases emphasize the critical need for precise diagnosis and the dangers of overdiagnosis and misdiagnosis. Investigations have shown that co-infections in ticks are common,43,48 underscoring the need for more extensive surveillance and improved diagnostic strategies to better comprehend and manage these complex medical cases.

This case series also highlights the need for personalized, comprehensive treatment strategies in medicine. Case 3, for instance, saw significant health improvements with a custom intravenous antibiotic regimen designed for specific medical needs. Similarly, Case 6’s recovery, aided by a combination of antimicrobial, anti-inflammatory, and physiotherapy, showcases the success of diversified treatment plans. The trend towards individualized antibiotic therapy is critical for saving lives, preventing infection complications, and effective antibiotic use, which involves considering factors like specific pathogens, antibiotic resistance patterns, and the patient’s health, including immune and organ function.49 Personalizing treatment also means accounting for the patient’s drug metabolism, travel history, and unique challenges, such as biofilm infections.49 Johns Hopkins Medicine’s study on optimizing antibiotic therapy, especially for gram-negative bloodstream infections, is notable.50 It will examine the efficacy of transitioning from IV to oral antibiotics early in treatment, aiming to reduce risks associated with prolonged IV therapy, which is crucial for patients with chronic conditions prone to these infections.50

Furthermore, we witnessed the interaction between external factors, such as vaccinations, and the worsening of latent health conditions, focusing on the COVID-19 vaccine. Cases 4 and 5 represent this phenomenon, where vaccination likely aggravated existing symptoms. This observation suggests a potential reactivation or amplification of dormant health issues following external stimuli, such as vaccination. Current research delves into the complex dynamics between COVID-19 and the emergence or magnification of health complications.51,52 Notably, studies have shed light on autoimmune disorders potentially triggered or worsened by COVID-19 infection.52 For instance, a retrospective cohort study from England has identified a notable link between SARS-CoV-2 infection and an increased incidence of autoimmune diseases, including type 1 diabetes, inflammatory bowel disease, and psoriasis.53 Thus, the symptomatology of post-acute sequelae of COVID-19 (PASC) has also been a focal point of research.51,54,55

Patients affected by PASC exhibit many symptoms involving multiple body systems.51 These symptoms range from physical impairments, often associated with myopathy, neuropathy, and cardio-respiratory issues, to chronic manifestations indicative of multi-organ damage.51 These persistent symptoms bear similarities to chronic fatigue syndrome and fibromyalgia syndrome, suggesting a complex interaction involving viral presence and immune response irregularities, among other factors.55 Additionally, there is growing concern about rare autoimmune diseases potentially linked to post-COVID-19 vaccination, including autoimmune glomerulonephritis, autoimmune rheumatic diseases, and autoimmune hepatitis.56–58 Despite these concerns, accurately assessing the incidence of such autoimmune diseases post-vaccination is challenging, as only some cases are reported.

Further research is needed to clarify the causal relationship between COVID-19 vaccines and autoimmune diseases. Notably, our intention is not to detract from the importance of vaccines; rather, our objective is to bring attention to potential risks associated with COVID-19 vaccination while emphasizing our strong belief in the overwhelming benefits of immunization.

Case 7 introduces a new treatment approach with MB, showcasing its potential efficacy in combating latent symptoms of LD and UTIs caused by E. coli. First synthesized in 1876, MB, a synthetic dye, was initially employed as an antimalarial agent.59 Its antimicrobial properties are well-documented, and it is generally considered gentler on the gastrointestinal system than conventional antibiotics. As an evolving therapeutic option for LD, MB shows promise but necessitates further rigorous research supported by peer-reviewed studies. Feng et al. have underscored its capacity to eliminate stationary-phase Borrelia in their in vitro research.60

Similarly, Zheng et al. revealed that MB can effectively eliminate persistent Bartonella infections in vitro when combined with azithromycin or rifampin.61 However, the lack of in vivo studies underscores the need for caution. Patients must use this medication strictly under medical supervision due to potential drug interactions, notably with antidepressants, and its possible risks to individuals with liver or kidney conditions. Typical side effects include blue-tinted urine, tooth or mouth staining, headaches, dizziness, altered taste perception, limb pain, sweating, and nausea. More serious adverse reactions, such as allergic responses, sudden fever, yellowing of the skin, weakness, confusion, breathing difficulties, chest pain, and cyanosis of hands or feet, may also occur.59

Cases 8 and 10 presented a unique challenge in treating neuropsychiatric disorders like PANS and PANDAS, particularly when associated with infections like LD. In such cases, the treatment involves a holistic approach that addresses various aspects of these complex conditions. For example, Cross et al. report a case of a 7-year-old girl who initially exhibited sudden neuropsychiatric symptoms, leading to the diagnosis of PANDAS and LD.23 Her treatment journey was comprehensive, involving a variety of antibiotics such as amoxicillin, clindamycin, and ceftriaxone, along with other medications like cefdinir, azithromycin, and tinidazole to tackle the infections and their symptoms; and, intravenous immunoglobulin (IVIg) to address the autoimmune aspects of her condition.23 Regular monitoring through an LD checklist and various lab tests informed the adjustments in her treatment plan.23 The thorough and adaptive approach resulted in significant improvements, culminating in her recovery and return to normal activities and academic success.23 Cross et al. and our Case 8 highlight the importance of a detailed and responsive treatment strategy in managing complex pediatric conditions involving infectious and autoimmune elements.23

The persistence of LD symptoms and co-infections is complex, involving immune dysregulation, latent infections, and bacterial remnants causing inflammation.62 Case 4 illustrates a Herxheimer reaction resembling lupus reactivation after antibiotics, underscoring the need to distinguish infection-induced symptoms from autoimmune responses. Positive ANA tests suggest LD-triggered autoimmunity. Case 9 highlights the importance of considering LD in neurological diagnoses to avoid misdiagnosis. Latent infections, where pathogens reactivate under certain conditions, are crucial for understanding persistent symptoms. Case 10 involves recurrent infections leading to chronic immune activation, initially misdiagnosed as CVID. Treating stealth infections eliminated the need for long-term IVIG infusions, prompting a re-evaluation of the CVID diagnosis. Cases 2 and 6 show the complexity of Lyme neuroborreliosis treatment, with relapses despite initial therapy. Switching to intramuscular ceftriaxone and using intravenous interventions like high-dose antibiotics and IV nutritional therapies improved outcomes, emphasizing personalized treatment.

Persistent symptoms can also stem from ongoing inflammation due to bacterial remnants like peptidoglycan or DNA.62 Case 5 describes improved chronic sinus infections and systemic symptoms after targeted antibiotic treatment, implicating bacterial components in sustained inflammation. Interleukin-26 (IL-26) perpetuates this inflammation due to the continuous presence of Borrelia DNA.63 In Case 1, a patient with severe neurological symptoms and a history of alcohol abuse recovered after comprehensive infection treatment, including IV therapies and antioxidants, highlighting the need to support pathophysiology and detox pathways for healing chronic ailments. Serological responses, including IgG, may indicate active infection when dealing with slow-growing, latent infectious agents. Patient clinical responses have supported the IgG hypothesis, with all ten patients experiencing significant improvements following specific protocols that conventional interventions had not achieved.

While modest in scale, our study provides valuable insights into LD and its co-infections. We embraced a retrospective case series approach,64 which allowed us to analyze real-world data. Although this method has constraints like historical data limitations and the absence of a control group, it offers a unique view into patient experiences and treatment responses. While not broadly representative, our study’s small sample size of ten cases highlights specific, detailed case studies that contribute meaningfully to the existing knowledge. We acknowledge the possibility of selection bias due to the unique clinical features of our chosen cases.65 However, this approach has enabled us to delve deeply into each case, providing a detailed understanding of the various treatment responses. Establishing causation and generalizability is challenging in such a setup, yet the insights gained could become invaluable stepping stones for future research. There is significant potential for more extensive and diverse studies. Prospective studies with control groups, standardized treatment protocols, and long-term follow-up will significantly enhance our understanding. There is immense value in including socioeconomic and geographic diversity in future research. The validation of specialized diagnostic tests in broader clinical settings and conducting rigorous clinical trials for innovative treatments will undoubtedly enhance our understanding and management of LD and its co-infections.

Recommendations For Medical Professionals

Description of the Pathogenesis and Clinical Signs of Lyme Inflammation

LD is a multi-systemic and extremely complicated infectious disease that has a range of clinical manifestations, frequently defying accepted diagnostic frameworks. Prolonged inflammatory responses and immunological dysregulation, the immune-evasive mechanisms of Borrelia species and related co-infections, or the intricate interactions between neurological, psychiatric, and systemic diseases contribute to this complexity. Clinicians must use a differentiated diagnostic approach to account for LD in patients with persistent, multi-systemic symptoms that cannot be explained, especially when such patients do not respond to traditional treatment measures. This is because LD is a changeable condition.

Key Clinical Markers for Diagnosing Lyme Disease

The symptoms of LD and associated co-infections vary from patient to patient. Some examples of landmark indicators are: (i)Systemic flu-like illness, migratory arthralgia, and erythema migrans rash are early warning signals. (ii) Neurological adverse effects include peripheral neuropathy, obsessive-compulsive behaviors, severe depressive illness, generalized anxiety disorder, episodic psychosis, and cognitive impairment (executive dysfunction, “brain fog”). (iii) Autoimmune-like signs include symptoms like fibromyalgia, chronic fatigue syndrome, and inflammatory arthropathies that resemble rheumatoid arthritis or systemic lupus erythematosus. (iv) Palpitations, postural orthostatic tachycardia syndrome (POTS), and Lyme carditis are examples of cardiovascular dysautonomia. (v) Recurrent infections like Epstein-Barr virus (EBV) reactivations, persistent sinus infections, or co-infections such as Babesia, Bartonella, and Mycoplasma add to the complexity of clinical diagnosis.

Evidence-Based on Cases

Case 3 shows how the neurocognitive symptoms of LD, originally misdiagnosed, were alleviated after antibiotic treatment. As seen in Case 9, patients who present with neurodegenerative-like symptoms (e.g., Parkinsonian tremors) require screening for LD and co-infections.

Diagnostic Approaches Grounded in Evidence

Suggested Testing Methodology

(i) According to CDC recommendations, the first-line tests are the standard or modified two-tiered LD tests with a high specificity but a low sensitivity for chronic or early-stage presentations. (ii) Advanced tests like TICKPLEX® multiplex ELISA are used to identify broad-spectrum pathogens. Polymerase chain reaction (PCR) can also be used to identify Borrelia species directly. Other specialized co-infection tests include Bartonella immunoblots or Babesia PCR. (iii) Lymphocyte transformation assays (ELISpot) can identify immune responses specific to antigens. Inflammatory cytokine profiling can help understand chronic immune activation.

Methods of Interpretation

(i) A positive IgM/IgG test indicates an ongoing or previous infection; this needs clinical correlation. (ii) Serologic testing after an antibiotic challenge for seronegative LD should be repeated if there is significant clinical suspicion.

Evidence-Based on Cases

Advanced testing revealed the etiology of Bartonella in Case 5, which was first misdiagnosed as allergic rhinitis. In instance 6, multiplex testing was used to correct false-negative serologic results that led to a delay in LD diagnosis.

Integrated Therapeutic Approaches

Conventional Treatments

(i) Antibiotics include minocycline (CNS penetration) for Borrelia, ceftriaxone (IV for neuroborreliosis), and doxycycline. (ii) Quinolones for Bartonella, azithromycin, and rifampin. (iii) Azithromycin and atovaquone/proguanil for Babesia. (iv) Corticosteroids are used as adjuvant medication in certain situations of autoimmune disorders (such as neuroinflammation and lupus-like flare-ups).

Adjunctive Integrative Modalities

(i) Phytotherapeutics include berberine, artemisinin, and cryptolepis for synergistic antibacterial action. (ii) Antiinflammatory and neuroprotective substances include phosphatidylcholine, glutathione, quercetin, and omega-3 fatty acids. (iii) IV vitamin C, methylated B-complex, and antioxidant treatment for mitigating Herxheimer reactions are detoxification and biochemical support examples. (iv) Regenerative and bioenergetic therapies include mitochondrial support (CoQ10, NAD+ precursors), hyperbaric oxygen therapy (HBOT), and pulsed electromagnetic field therapy (PEMF).

Evidence-Based on Cases

Case 7 demonstrated the effectiveness of MB in reducing cognitive impairment linked to a chronic Borrelia infection. A young neuro-atypical kid whose PANS/PANDAS symptomatology improved with a multimodal integrative regimen was the focus of Case 10.

More Complex Clinical Perspectives and Issues Mistakes in Diagnosis and Treatment

(i) Reliance on traditional two-tier LD testing alone might result in incorrect or underdiagnosis. (ii) Symptomatic treatment should not ignore the underlying microbial load. (iii) Mistaking Herxheimer reactions for an intolerance to antibiotics.

The Framework for Strategic Management

(i) Examining co-infections systematically: Customized antibiotic regimens are necessary for most individuals with polymicrobial illnesses. (ii) Phased treatment sequencing: In phased therapy sequencing, initial microbial eradication is followed by immune regulation and organ system restoration. (iii) Monitoring clinical outcomes: Serologic normalization is not as crucial as functional symptom reduction when evaluating the effectiveness of treatment.

Evidence-Based on Cases

Case 4’s misinterpretation of the Herxheimer response as a lupus flare highlights the need for differentiated diagnosis in immunological dysregulation. Interventions aimed at dysautonomia markedly reduced the neuropsychiatric symptoms of PANS/PANDAS in Case 8.

Synopsis and Clinical Incorporation

Clinicians who treat patients with chronic, multi-systemic disease should be especially vigilant about LD. Beyond traditional serologies, diagnostic techniques should include multiplex panels and functional immune testing. Antimicrobial, immunomodulatory, and adjuvant medicines must be integrated into a comprehensive, multimodal therapy plan. Clinical symptomatology should be prioritized over laboratory seroconversion while holistically tracking a patient’s development. Actively educating patients about Herxheimer responses and anticipated treatment durations is essential. This structured paradigm offers an evidence-based yet flexible approach that maximizes patient outcomes through precision-based medicine for doctors involved in diagnosing and treating Lyme disease and its co-infections.

Conclusions

This case series serves as a vital reminder of the intricate and often overlapping nature of LD, its co-infections, and related neurological and psychiatric disorders. It emphasizes the need for comprehensive diagnostic approaches, the importance of considering external factors such as substance abuse and vaccinations, and the efficacy of personalized and integrative treatment strategies. Furthermore, it underscores the need for continuous research and innovation in diagnostic methods and treatment protocols to better understand and manage these complex conditions.

Acknowledgments

Eyes will not see what the mind does not know. Once you know, you cannot unknow. Dr. Charles Ray Jones said this when I was ready to give up enduring the crucible of chronic Lyme disease.

Footnotes

Funding

This research received no external funding.

Institutional Review Board Statement

This case series study followed the ethical standards outlined in the Declaration of Helsinki. The study involved a retrospective evaluation and audit of patient records. All necessary precautions were taken to ensure the confidentiality and privacy of patient data. Data was collected using anonymized records, and no identifiable personal information was included in the analysis or publication. An ethics review was waived because the study did not involve any prospective data collection or patient intervention. Instead, it was a retrospective analysis of existing records, and all data were handled in a manner compliant with applicable data protection laws and institutional policies.

Data Availability Statement

All data produced or examined in this investigation are available in this published publication and by reasonable request.

Author Disclosure Statement

Informed consent was obtained from all subjects involved in the study for additional sera testing on leftover and de-identified samples. Written informed consent was not obtained from the patient(s) to publish this paper as the patient information was de-identified for retrospective analysis.

Supplementary Materials

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