From Kitty Litter to Cortical Recovery

A Naturopathic Case Study on Reversing CIRS-Induced Brain Atrophy

Eric Dorninger ND, LAc

This case study examines a 39-year-old male with severe neurological symptoms linked to Chronic Inflammatory Response Syndrome (CIRS) triggered by endotoxin exposure from a kitty litter box and a water-damaged home. The article explores the pathophysiology of CIRS, effective screening, and diagnostic methods, and how the Shoemaker Protocol successfully reversed brain atrophy and restored health.

What is Chronic Inflammatory Response Syndrome (CIRS)?

Chronic Inflammatory Response Syndrome (CIRS) is a multisystem, multi-symptom illness with many neurological phenomena including, but not limited to, headache, light sensitivity, blurred vision, ice pick pain, memory impairment, decreased assimilation of new knowledge, difficulty concentrating, confusion, tingling, numbness, poor temperature regulation, mood swings, appetite swings, vertigo, metallic taste, and tremors.^1,2   

Like many other inflammatory disorders (RA, Hashimoto’s, psoriatic arthritis, celiac), CIRS has an HLA predisposition.  When exposed to biotoxins, humans with specific HLA for CIRS have enhanced susceptibility for expressing chronic inflammatory responses via the innate immune pathways, resulting in non-sensical, dysregulated cytokine storms (TGFB-1, MMP-9, C4a). 

The unrelenting inflammatory cascades in CIRS result in molecular hypometabolism, proliferative physiology (the Warburg effect), metabolic acidosis, pulmonary hypertension, T-reg cell deficiency, insulin resistance, and neuronal injury.³   

Like Celiac disease needs gluten, CIRS needs a unifying trigger called biotoxins or “nature toxins” to express illness and was initially called “biotoxin illness.” Biotoxins are tiny chemicals produced or derived from microorganisms and can enter the human body through inhalation, ingestion, and injection (bites).  Biotoxins are ionophores or amphipaths/amphiphiles with hydrophilic and hydrophobic properties. They can move from cell to cell (“walk through walls”) due to their tiny size (as small as 1.4 angstroms) and their ability to share electrons.  

Biotoxins are stored in adipose and nerve tissue, where they interact with cellular receptors, including toll 2,4 receptors, mannose, dectin, and C-type lectin receptors, triggering innate immune activation.  Fungi, actinobacteria, gram-negative bacteria (bartonella, endotoxins), recluse spider venom, seafood toxins (ciguatera, pfesteria), cyanobacteria (algae blooms), borrelia burgdorferi (bbtoxin1) and apicomplexans (babesia, sarcocystis, eimneria) are all examples of biotoxin producing organisms.⁴ 

There are three critical stages for discovering, solving, and resolving symptoms caused by Chronic Inflammatory Response Syndrome: 1) Screening, 2) Diagnosi,s and 3) Treatment.

Screening for CIRS: Identifying Patients at Risk:

Why Urinary Mycotoxin Tests Are Inaccurate

Although routinely used with patients, urinary mycotoxins are not a proper screening tool for CIRS, as they simply tell the provider if you have mold exposure. 

Healthy people also have urinary mycotoxins. Multiple studies with over 2500 combined healthy controls show that 60-100% of urine samples showed mycotoxins and metabolites in asymptomatic healthy people.⁵  Unfortunately, no published urinary mycotoxin ranges exist to separate healthy and sick patients.  This is why one spouse with elevated urinary mycotoxin can feel fine in the same building as the sick spouse experiencing CIRS. 

Moreover, urinary mycotoxins and fungal antibody testing are not screening or diagnostic measures for fungal infection.  These tests often result in improper use of herbal and prescription antifungals.  Antifungals can enhance horizontal gene transfer (HGT), a mechanism where microbes spread/share resistance genes, resulting in multiple pathogenic bacteria that are resistant.⁶  Itraconazole has been shown to shut down aerobic metabolism via closure of the VDAC (Voltage Dependent Anion Channel) and has subsequently been patented for use as a potential chemotherapy agent. 

Proper Screening for CIRS is cost-effective and straightforward; it simply requires… 

1) interviewing for biotoxin exposure history    

2) Clustered Symptoms questionnaire (administered by the provider or trained staff)

3) Visual Contrast Sensitivity test (VCS)

Interview for Biotoxin Exposure History:

1. Have you ever lived, worked, worked out, stayed, or vacationed in buildings with water damage? (give examples for the patient to ponder; provide a checklist in your paperwork).

2. Have you ever noticed musty smells or sewer smells? Sulfur smells? 

3. History of spider bites?

4. History of tick bites? Bullseye rash? Pictures?

5. Have you ever been treated for Lyme disease? Where did you grow up?

6. Have you ever had seafood poisoning or eaten reef fish?

7. Have you ever had traveler’s diarrhea or gotten sick while traveling?

8. Name all the continents you’ve traveled to.

9. Have you ever recreated or lived near water with algae bloom? Red tides?

10. Have you ever lived near or had a hobby or local pond?

Clustered Symptoms:

Clustered symptoms are a list of 37 symptoms originating from eight primary categories:  General, Musculoskeletal, Eye, Respiratory, Gastrointestinal, Cognitive, and Hypothalamic. The clustered symptoms are present in at least 30% of patients with CIRS. Hence, a symptom questionnaire cannot sort specific biotoxin exposure but can sort/screen for CIRS.  

Using cluster analysis, subjective symptoms are systematically converted into objective data through statistical methods, enabling the development of a scoring system.  If a patient answers yes to one or more symptoms in a cluster, that counts as a point. A positive Cluster analysis is eight or more of 13 clusters (6 of 13 for pediatrics; <11 constitutes “pediatric” for clustered symptoms).  If an adult patient has eight or more clusters of symptoms, the likelihood of CIRS exceeds 95%. When combined with VCS deficits, symptom clusters can yield an accuracy in diagnosis of 98.5%.⁸

VISUAL CONTRAST SENSITIVITY (VCS)

Contrast sensitivity (CS) is perceiving sharp and clear outlines of tiny objects. It is also defined as identifying minute differences in the shadings and patterns. CS helps detect objects without a clear outline and distinguish them from their background contrast.⁹

Biotoxin Illness reduces the ability to see contrast via inflammatory cytokine effects on the retinal artery (measured by the Heidelberg retinal blood flow meter).  Healthy controls demonstrated 400 units of retinal blood flow with a 5% VCS fail rate. In contrast, patients with CIRS post-biotoxin exposure demonstrated a marked retinal blood flow reduction (200 units) and a high VCS fail rate (50-92%, depending on the clinic data set).¹⁰ Treatment with the Shoemaker protocol restored retinal blood flow and allowed for contrast visualization to similar levels of healthy controls. 

Logistics of VCS Screening:

There are two current validated versions of the VCS test available on survivingmold.com.  One is handheld in the office, and the other is online for patients at home or in a potentially clean/contaminated building (computer screen on full brightness, well-lit room with 18” string to account for screen distance).

Visual conditions affect VCS, including, but not limited to, cataracts, glaucoma, LASIK, retinopathy, and dry eye.  At approximately 7 years of age, pediatric patients can conceptualize and execute the VCS.

Diagnosis 

Although clustered symptoms and a failed VCS test can be used as an alternative means to CIRS diagnosis, this approach is suggestive of natural disasters, severe financial constraints, and large populations in crisis and to validate illness that cannot see response to treatment if stuck in a concerning building.

The diagnostic confirmation for CIRS utilizes the multiple inflammatory and neuroendocrine peptides and hormones that differ in CIRS patients from healthy controls.¹¹ Published data shows high confidence in CIRS diagnosis when 5 of 10 or more of the original biomarkers differ from the range of healthy controls. In contrast, healthy controls never showed more than 3 of 10 biomarkers positive.  The original CIRS research reference ranges were set on averaging healthy controls laboratory analysis. A healthy control was defined as a human with three or less of the 37 clustered symptoms.  There are now 52 objective biomarkers to aid in the diagnosis, prognosis, and treatment of CIRS, including more laboratory biomarkers, brain MRI with Neuroquant, nasopharyngeal culture, skin culture transcriptomic testing (GENIE), echocardiogram (PASP) and PFT’s. 

Treating CIRS: The Shoemaker Protocol

The 12-Step Shoemaker Protocol

A peer-reviewed, reproducible, published sequential twelve-step protocol known as the Shoemaker (see diagram 1) solves and resolves CIRS when applied in earnest.¹²   Although the first three steps are arduous and involve dramatic improvements, the last step, “VIP” (vasoactive intestinal peptide), has been published to safely restore atrophic gray matter nuclei in patients with brain atrophy secondary to CIRS^13,14. Moreover, VIP has also been published to help normalize immune dysregulation and innate immune responses.¹⁵ 

CIRS in practice: 

Case Study: a 39-year-old male with multiple nuclear atrophy secondary to CIRS-WDB and CIRS-Endotoxin.

Patient Presentation

A 39-year-old male presented with 34 out of 37 clustered symptoms, including severe reflux.  Overnight oximetry revealed sleep apnea as part of the underlying cause of reflux, and four tsp. of DGL powder per quart of warm water was prescribed to drink throughout the day to dampen reflux and tonify gastric lining while referral for C-PAP was in progress.  4200 mg of EPA/DHA fish oil was administered to modulate the immune system’s pre-bile acid sequestrant and to support a healthy Omega-3 index. 

The Shoemaker protocol was started (4 grams cholestyramine tid-qid), and home testing through envirobiomics.com was ordered for patient-administered testing. A microfiber dust cloth collected ERMI, actinobacteria, and endotoxin from the basement and subsequent floors (one #8 kit per floor).  Building testing revealed astronomically elevated endotoxin on the main and upstairs bedroom floors.  HERTSMI-2 mold scores were also elevated. A follow-up inspection elucidated that a kitty litter box in the utility closet was the source of endotoxin, which spread through the house via HVAC.  In addition, multiple water-damaged areas were elucidated and addressed with various rounds of remediation.  Brain MRI with Neuroquant revealed multiple (four) very age-inappropriate nuclear atrophy relative to age-matched controls, including cortical gray, hippocampus, caudate, and pallidum.  Neuroquant also revealed the specific causation pattern of endotoxin exposure (cortical gray atrophy, plus at least two more nuclear atrophy). 

After the first three steps of the Shoemaker protocol, the clustered symptoms dropped from 34 to 14.  After implementing intranasal vasoactive intestinal peptide, symptoms dropped from 14 > 4> 1, and the patient reported still having some fatigue that he felt “could only restore in the gym.” Despite previous exercise intolerance, the patient could return to the gym, slowly ramp up workouts, and restore pre-CIRS energy and athletic levels. 

Conclusion: Recognizing and Treating CIRS in Clinical Practice

Water-damaged building molds are well published in the literature as a cause of multisystem, multi-symptom illness.  However, bacteria (gram-positive actinobacteria and LPS/endotoxin-forming gram-negative bacteria) need to become a regular part of our differential when striving to identify and treat the underlying cause.

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References

1. Cartwright, M. J., Martin, S. E., & Donta, S. T. (1999, May). A novel neurotoxin (Bbtox1) of Borrelia burgdorferi. Meeting of the American Society of Microbiology, Chicago.
2. Head, S., Shi, W., Zhao, L., Gorshkov, K., Pasunooti, K., et al. (2015). Antifungal drug itraconazole targets VCAC1 to modulate the AMPK/mTOR signaling axis in endothelial cells. Proceedings of the National Academy of Sciences, 112, E2726-E7285.
3. Kaur, K., & Gurnani, B. (2023, June 11). Contrast Sensitivity. In StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing. Available from: https://www.ncbi.nlm.nih.gov/books/NBK580542/
4. McMahon, S. W. (2017). An evaluation of alternate means to diagnose chronic inflammatory response syndrome and determine prevalence. Medical Research Archives, 5(3). https://doi.org/10.18103/mra.v5i3.1000
5. Ryan, J., & Shoemaker, R. (2017). RNA-Seq on patients with chronic inflammatory response syndrome (CIRS) treated with vasoactive intestinal peptide (VIP) shows a shift in metabolic state and innate immune functions that coincide with healing. Medical Research Archives, 4, 1.
6. Shoemaker, R. (2003, September). Use of visual contrast sensitivity and cholestyramine in diagnosis and treatment of indoor air acquired, chronic, neurotoxin-mediated illness. Conference peer review. Available from: https://www.survivingmold.com/docs/Use_of_visual_contrast_sensitivity.PDF
7. Shoemaker, R. (2020). Metabolism, molecular hypometabolism, and inflammation: Complications of proliferative physiology include metabolic acidosis, pulmonary hypertension, T reg cell deficiency, insulin resistance, and neuronal injury. Trends in Diabetes & Metabolism, 3, 1-15.
8. Shoemaker, R., Heyman, A., & Lark, D. (2023). Transcriptomics and brain volumetrics define the causes of cognitive impairment in patients with CIRS and support the use of VIP in treatment. Medical Research Archives, 11(2).
9. Shoemaker, R., House, D., & Ryan, J. (2013). Vasoactive intestinal polypeptide (VIP) corrects chronic inflammatory response syndrome (CIRS) acquired following exposure to water-damaged buildings. Health, 5(3), 396-401.
10. Shoemaker, R., Johnson, K., Jim, L., Berry, Y., Dooley, M., Ryan, J., & McMahon, S. (2018). Diagnostic process for chronic inflammatory response syndrome (CIRS): A consensus statement report of the Consensus Committee of Surviving Mold. International Medical Review, 4(5), 1-47.
11. Shoemaker, R., Katz, D., McMahon, S., & Ryan, J. (2017). Intranasal VIP safely restores atrophic grey matter nuclei in patients with CIRS. Internal Medicine Review, 3(4), 1-14.
12. Shoemaker, R., & Ritchie, M. D. (2019, October). Urinary mycotoxins: A review of contaminated buildings and food in search of a biomarker separating sick patients from controls. Internal Medicine Review.
13. U.S. Centers for Disease Control and Prevention. (n.d.). About antimicrobial resistance. Retrieved from https://www.cdc.gov/antimicrobial-resistance/about/index.html
14. ​​​​Shoemaker, R., Heyman, A., & Lark, D. (2023). Transcriptomics and brain volumetrics define the causes of cognitive impairment in patients with CIRS and support the use of VIP in treatment. Medical Research Archives, 11(2). https://doi.org/10.18103/mra.v11i2
15. Ryan, J., & Shoemaker, R. (2017). RNA-Seq on patients with chronic inflammatory response syndrome (CIRS) treated with vasoactive intestinal peptide (VIP) shows a shift in metabolic state and innate immune functions that coincide with healing. Medical Research Archives, 4(1).