+1 Neuroinflammation

+3 Cerebral Cortex

+3 Comorbid Mental Health Conditions

+3 Neurological Dysfunction

+3b Neuroimmune and neuroendocrine processes

1a Decreases in Sphingolipid, glycosphingolipid, phospholipid, purine, microbiome aromatic amino acid and branch chain amino acid metabolites, as well as in flavine adenine nucleotide (FAD) and lathosterol

1a Hypermobility ehlers-danlos syndrome

1 Abnormalities in bioenergetic function

1 Brain Regions and Specific Classes/Systems

1 Circulatory Impairment, Disease and Irregularities

1 pTBI-CF, TBI

2 Dysfunction Cycles Syndrome theory

2 Treatment for Circulatory System, Blood Volume and Blood Pressure Signaling Effect Abnormalities

3 Alterations in normal energy metabolic processes and abnormalities in cellular bioenergetics

3 Cofactors (Common)

3 Common and Uncommon Causes and Cofactors

3 DNA and Genetic/Epigenetic Factors

4 Common Comorbid Diseases (Common) and Uncommon Causal Diseases (Uncommon)

4 Endocrine system (and alterations to system)

4 Metabolic Dysfunction

4 Non Allopathic Treatments of Interest

4 ph Levels

5 Gastroenterology, Digestive and Urological

5 Sympathetic Dominance/Hyperactivity

6 Cytokine Abnormalities

6 Immune System

6 Metabolism

7 Lymphatic System

7 Patient Tests

7 Systems Model

8 Chronic Immune Activation

8 Musculoskeletal System

9 Cellular

9 Disrupted Th1 - Th2 homeostasis (Th2 dominance)

9 Hypometabolic state (as evident in plasma and serum metabolomics)

10 Nervous System

10 Peptides and Neuropeptides

11b Half of CFS patients (appear to) have a previously undiagnosed medical condition, most often diabetes, CVD and thyroid diseases

11 Sleep

14 reported deficiencies in the urea and the TCA cycles, (ornithine/citrulline and pyruvate/isocitrate ratios)

19 Steroidogenic Pathways

A Molecular Neurobiological Approach to Understanding the Aetiology of Chronic Fatigue Syndrome (Myalgic Encephalomyelitis or Systemic Exertion Intolerance Disease) with Treatment Implications

Abnormalities in Cerebral Perfusion

Abnormalities in CFS (listing of 1,000 studies in Fourty Five Catagories)

Abnormalities in Cortico-basal Ganglia-thalamo-cortical Loops

Abnormalities in lymphocyte function in CFS

Abnormalities of AMPK activation and glucose uptake

Abnormalities of Gene Expression in the Blood

Abnormalities of stress system activation have been shown in inflammatory diseases such as rheumatoid arthritis, as well as behavioural syndromes such as melancholic depression

ACTH

Anosmia (loss of smell)

Autoimmune and Metabolic Pathway Abnormalities

Basal Hypocortisolism

Blood Brain Barrier and disorders

Brain

Brain Fog, Confusion, Sensory overstimulation, memory difficulties, pseudopsychopathy, High Effort in processing Planning Administrative Executive Function Planning Anxiety Stress Passive vs Proactive Shy Withdrawn Uncertain w social self esteem and anxiety etc Dysthymia etc

Brain Zaps

Cardiac abnormalities

Central nervous system and hormone abnormalities

Cerebral Blood Flow is Decreased in CFS

Channelopathies

Cognitive Dysfunction

Compensated Idiopathic Cardiomyopathy (A Model)

Cortical Glutathione and Reductions in the levels of cortical GSH

Cortisol Levels

Decrease in White matter, Grey Matter (and lesions?)

Default State

DHEA

Dizziness

Dysregulation of acetylcholine and adrenergic signalling

Dysregulation of Protein Kinase Gene Expression in NK Cells from Chronic Fatigue Syndrome/Myalgic Encephalomyelitis Patients

Ehlers–Danlos syndrome

Enzymes

Excessive sweating, Fatigue, Frequent nighttime urination and Night sweats

GH-IGF-I axis abnormalities

Granular Anuloma

Grey matter abnormalities

Headrush

Homeostasis is Dynamic Equilibrium within and without Internal and Environment

Hyperventilation

Hypochlorhydria + Dysbiosis + Chronic inflammation = Acquired Mitochondrial Damage

Hypocortisolemia, Hypocortisolism

Hypopituitarism

Immune suppression with active opportunistic infections

Impaired ACh-Mediated Vasodilatation and Endothelial Dysfunction

Impaired Activation of the Hypothalamic-Pituitary-Adrenal Axis

Infection-triggered disease onset, chronic immune activation and autonomic dysregulation in CFS point to an autoimmune disease directed against neurotransmitter receptors.

irritable bowel syndrome (IBS)

Jittery leg

Key Terms

Kindling and Oxidative Stress

Kindling Theory

Low Blood Volume (Hypovolemia)

Low NK Cell Activity

Medial prefrontal cortex deficits and unrefreshing sleep

Medical Hypothesis

Metabolomics

Mitochondrial Inhibition, Damage and Hypometabolism

Mitral Valve Prolapse

Most Effective Treatments

Myalgic Encephalomyelitis/Chronic Fatigue Syndrome as Disturbed Homeostasis due to Focal Inflammation in the Hypothalamus

Neuro-immune Model

Neuroanatomical Model of Fatigue

Neurotransmitters and Neurotransmitter Systems

NK Cells

OCD

Onset, Patient History of Illness and Triggers

Other Therapies

Overexpending for task Drain on resources

Overview of the current understanding of the associations between ME/CFS and metabolic disease by Erifili Hatziagelaki, MD, PhD, Maria Adamaki, PhD, Irene Tsilioni, PhD, George Dimitriadis, MD, Theoharis C. Theoharides, MS, MPhil, PhD, MD

Patient Model

Patient Specific

Post Exertional Malaise

Postural orthostatic tachycardia syndrome

Pseudo Neurological Damage (Pre Existing and/or Causal to CFS)

Raynaud’s phenomenon

RCCX Hypothesis

reduced adrenal responsiveness to ACTH

Reduced Absolute Cortical Blood Flow in CFS

Reduction of serotonin transporters of patients with chronic fatigue syndrome

Routine cognitive processes are experienced as unduly effortful and Brain Fog

Signaling

Sleep Disturbances, CFS as sleep disorder

Spinal Fluid Abnormalities in Patients with Chronic Fatigue Syndrome

Stimulation of Hypothalamic Mast Cells by Environmental Neuroimmune Pathogenic And stress triggers activates microglia leading to focal inflammation in the brain

Stress

Structural brain abnormalities and Neuroimaging Abnormalities

Sympathetic/Autonomic/HPA Axis/Immune/Gastroenterology Model

The stress response and the hypothalamic‐pituitary‐adrenal axis: from molecule to melancholia

Thyroid hormones

Treatment for TBI

Vestibular Disorders

Vivid dreams and talking in sleep

What it feels like and how to explain to family and friends

White matter abnormalities