Comprehensive Therapeutic Framework for ME/CFS

Clinician Guide: Built from CYNAERA Diagnostic Fingerprints™ + IACCI Terrain Logic + XR/CR Pharmacology Doctrine

Step 1. Diagnostic Fingerprints & Lab Anchors

Order baseline labs to guide phenotype and rule out mimics/emergencies:

• Core Panel: CBC, CMP, ferritin, iron studies, B12, folate, vitamin D, ANA/ENA, CRP, ESR, thyroid panel (TSH, free T3, free T4, antibodies).

• Add-ons by phenotype:

  • Autonomic → orthostatic vitals, norepinephrine supine/upright, aldosterone/renin.

  • Neuroinflammatory → migraine profile if available.

  • Pain-dominant → CK, magnesium, rheum panel.

  • Immune-reactivation → EBV, HHV-6, CMV, immunoglobulin subclasses.

  • MCAS → tryptase, histamine, prostaglandin D2, DAO.

  • Sleep → sleep study, actigraphy.

Step 2. Assign Phenotypes

1. Energy Dysregulation Axis

2. Autonomic & Circulatory Axis

3. Neuro-Immune & Sensory Axis

4. Hormonal & Endocrine Axis

5. Immune, Infection & Reactivation Axis

6. Sleep & Pain Axis

7. Social, Demographic & Access Constrained

Step 3. Universal Pharmacology Doctrine

• Extended-release (XR/CR) formulations preferred wherever possible.

• Start lower than standard minimum dose.

• Titrate slowly: one variable every 7–14 days (longer in severe/MCAS).

• Stop rules: discontinue if PEM worsens >2 weeks, HR <50, new MCAS flare, or intolerable side effects.

• Severe ≠ high dose. The sicker the patient, the slower and lower the approach.

Step 4. Therapeutic Ladders by Phenotype

Tier 1: Foundational (OTC + Supplements)

• Mito Protocol: CoQ10 (100–300 mg XR if available), acetyl-L-carnitine, NAD+, riboflavin, creatine.

• Minerals: magnesium glycinate/threonate, electrolytes, potassium citrate (if renal labs safe).

• Anti-inflammatory nutraceuticals: omega-3s, curcumin, quercetin, resveratrol.

• Stop points: GI upset, bleeding risk, paradoxical insomnia/tachycardia.

Tier 2: PCP-Prescribable Medications

Autonomic (B)

• Beta-blockers (prefer XR/CR): metoprolol succinate XR, propranolol LA. Start 12.5 mg XR daily.

  • Stop if HR <50, symptomatic hypotension, bronchospasm.

• Fludrocortisone: 0.05–0.1 mg daily. Stop if edema, hypertension, hypokalemia.

• Midodrine: 2.5–5 mg TID daytime. Stop if supine hypertension.

• Ivabradine: 2.5 mg BID. Stop if bradycardia <50 or visual phenomena.

Neuroinflammatory (C)

• Migraine prophylaxis (XR/CR): propranolol LA, amitriptyline XR, topiramate XR.

• Neuropathic pain: pregabalin XR (start 25–50 mg nightly).

• Stop points: sedation, paradoxical agitation, cognitive decline.

Immune-reactivation (E)

• Low-Dose Naltrexone (LDN): start 0.5–1.5 mg nightly → titrate 3–4.5 mg.

  • Stop if vivid nightmares >2 weeks, insomnia, liver enzymes rise.

Tier 3: Specialist / Experimental Therapies

Immune / Antiviral

• Valganciclovir, famciclovir, valacyclovir (divided dosing to mimic XR).

  • Stop if neutropenia, LFT elevations, no benefit at 6 months.

IVIG

• 1–2 g/kg monthly. Stop if severe reaction, thrombosis, renal impairment.

Pyridostigmine

• 30–60 mg BID. Stop if intolerable GI, fasciculations, bradycardia.

Emerging Therapies

• Inspiritol (inhaled immunomodulator): investigational; early promise for neuroinflammatory + immune-reactivation phenotypes.

  • Stop if airway irritation, MCAS flares.

• Tollovid (3CL protease inhibitor nutraceutical): considered in immune-reactivation phenotype, viral serology-positive patients.

  • Stop if GI upset, CYP drug interactions, cost burden.

Step 5. Environment & Flare Logic

• Heat/humidity: prioritize autonomic treatments (XR beta-blockers, fludrocortisone, electrolytes).

• Cold: support circulation (compression, fludrocortisone if safe).

• Poor air quality / smoke: MCAS supports (antihistamines, cromolyn, filters).

• Mold/home triggers: consider MCAS ladder, cholestyramine, environmental remediation.

• Light/noise sensitivity: neuroimmune stabilizers (lamotrigine, memantine, riluzole).

Step 6. Abuse/Trauma Overlay

• Screen all patients: care interference, environmental sabotage, med tampering.

• If risk band ≥3:

  • XR/CR formulations preferred for steady coverage.

  • Pharmacy blister packs, direct delivery.

  • Single-variable titration every 7–14 days.

  • Private note segmentation in EHR.

Step 7. Stop Rules (Cross-Cutting)

• Therapy-induced PEM: treat as dose-too-high, not drug failure.

• New MCAS symptoms: pause, add H1/H2 support.

• One change at a time. No polytrialing.

• Objective check-ins: repeat CBC, CMP, ferritin, CRP, ESR after major drug changes.

Step 8. Escalation Boundaries

• Advance to higher tiers only when:

  1. Lower tier exhausted/tolerated.

  2. Labs and phenotype support escalation.

  3. Patient consent and monitoring in place.

• Severe/bedbound patients should never be escalated aggressively.

Disclaimer

This framework is decision support only. It integrates CYNAERA Diagnostic Fingerprints™, Phenotyping, IACCI terrain logic, XR/CR pharmacology doctrine, and patient safety overlays. Final prescribing authority rests with the treating clinician.

Author’s Note:

All insights, frameworks, and recommendations in this white paper reflect the author's independent analysis and synthesis. References to researchers, clinicians, and advocacy organizations acknowledge their contributions to the field but do not imply endorsement of the specific frameworks, conclusions, or policy models proposed herein. This information is not medical guidance.

Applied Infrastructure Models Supporting This Analysis

Several standardized diagnostic and forecasting models developed through CYNAERA were utilized or referenced in the construction of this white paper. These tools support real-time surveillance, economic forecasting, and symptom stabilization planning for infection-associated chronic conditions (IACCs).

Note: These models were developed to bridge critical infrastructure gaps in early diagnosis, stabilization tracking, and economic impact modeling. Select academic and public health partnerships may access these modules under non-commercial terms to accelerate independent research and system modernization efforts.

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Learn More: https://www.cynaera.com/systems

About the Author 

Cynthia Adinig is an internationally recognized systems strategist, health policy advisor, and the founder of CYNAERA, an AI-powered intelligence platform advancing diagnostic reform, clinical trial simulation, and real-world modeling for infection-associated chronic conditions (IACCs). She has developed 400+ Core AI Frameworks, 1 Billion + Dynamic AI Modules. including the IACC Progression Continuum™, US-CCUC™, and RAEMI™, which reveal hidden prevalence, map disease pathways, and close gaps in access to early diagnosis and treatment.

Her clinical trial simulator, powered by over 675 million synthesized individual profiles, offers unmatched modeling of intervention outcomes for researchers and clinicians.

Cynthia has served as a trusted advisor to the U.S. Department of Health and Human Services, collaborated with experts at Yale and Mount Sinai, and influenced multiple pieces of federal legislation related to Long COVID and chronic illness. 

She has been featured in TIME, Bloomberg, USA Today, and other leading publications. Through CYNAERA, she develops modular AI platforms that operate across 32+ sectors and 180+ countries, with a local commitment to resilience in the Northern Virginia and Washington, D.C. region.head.