A generation of young, previously healthy people are deteriorating with severe acquired brain dysfunction. Labeling this as “brain fog” erases severity, obscures biology, and delays recognition of true neurologic injury.
This warrants attention and reposting for awareness 🧵 I believe this injury is reversible because I witness recovery - but it is profoundly unrecognized across medicine. Without recognition, patients are dismissed, under-investigated, and told they are fine while cognitive function and quality of life continue to decline.

MCAS: When “Trying Everything” Fails

Most refractory MCAS patients have not truly failed treatment as they’ve likely been treated within a narrow framework.

Antihistamines and stabilizers often fail when you never ask the question - why mast cells are activated at all 🧵 The real questions are upstream:
🔷Why is the baseline activation set so high?
🔷What is the state of the autonomic & limbic nervous system?
🔷Which metabolic conditions lower the degranulation threshold?
🔷What sensory inputs are interpreted as threat?

🔷After treating thousands of patients with chronic illness, here’s the real reason most never get better:

The medical system isn’t designed to produce recovery.
It’s designed to maximize throughput.

Once you see that, everything clicks. Let me explain 🧵 Throughput medicine rewards:
🔷short visits
🔷clear diagnoses
🔷protocol compliance
🔷symptom control

Chronic illness requires:
🔷time
🔷iteration
🔷pattern recognition
🔷systems thinking

These are structurally incompatible.

Medical PTSD: when "care" causes lasting damage

For many living with ME/CFS or Long COVID, trauma from medical encounters is not uncommon. Being dismissed, disbelieved, or mismanaged in clinical settings can lead to lasting psychological injury alongside physical illness. 🧵 Medical PTSD may show up as intense anxiety before appointments, avoidance of care, emotional numbing, or physiological distress during routine exams. Triggers can include specific language, environments, or clinician behavior.

Neuromodulators in ME/CFS and Long COVID

Amantadine, memantine, low-dose aripiprazole, and lamotrigine are used to modulate neuroinflammation and excitatory signaling in ME/CFS and Long COVID.

These are brain problems - let’s dive into unique brain medications 🧵 Memantine reduces glutamatergic excitotoxicity and dampens neuroinflammatory signaling. In ME/CFS and Long COVID, it improves cognitive steadiness, reduces sensory hypersensitivity, and increases threshold for mental exertion.

Management of severe and very severe ME/CFS and Long COVID demands a fundamentally distinct clinical approach, centered on profound autonomic dysregulation, intractable post-exertional malaise and extreme multisystem sensitivity - especially to medications. These patients often present with severe orthostatic intolerance, paradoxical drug reactions, and hypersensitivities that limit even supportive interventions. Standard protocols frequently provoke deterioration and conventional care models are insufficient and risky.

"I am Jack's...headache"

Headache is one of the most common and disabling symptoms in ME/CFS and Long COVID. Many patients have a prior history of migraine, but post-viral headaches often have distinct features. Accurate classification is critical to guide treatment. 🧵 In ME/CFS and Long COVID, headaches may resemble migraine but can also reflect intracranial pressure disturbances, autonomic dysfunction, or cervical instability. History and exam must assess positional changes, visual symptoms, and response to previous migraine therapy.

You’ve been told it’s anxiety.
Or IBS. Or just “post-viral fatigue.”
But what if it’s actually a collagen disorder affecting your entire body - from your heart rate to your gut to your brain?
Long COVID is revealing what was missed for decades.
🧵 Many post-COVID patients with fatigue, cognitive issues, GI symptoms, or multi-system complaints likely have an underlying connective tissue disorder.
Hypermobile Ehlers-Danlos syndrome (hEDS), often alongside MCAS, POTS, and ME/CFS, remains widely underdiagnosed.

The Limbic System in ME/CFS and Long COVID

In ME/CFS and Long COVID, growing evidence implicates persistent dysfunction of the limbic system -particularly the amygdala, hippocampus, and hypothalamus - as a core driver of autonomic, neuroimmune, and endocrine imbalance. This dysfunction may lead to HPA axis disruption, chronic sympathetic activation, and impaired homeostatic recovery. Clinically, this may present as fatigue, orthostatic intolerance, cognitive dysfunction, and post-exertional malaise.

A recent review highlights neuroimmune drivers of Long COVID: glial activation, BBB dysfunction, endothelial injury, neurotransmitter imbalance, and neuro-degeneration.

Beyond antivirals and MABs, here are a few pharmacologic tools I utilize to manage neurologic phenotypes. 🧵 For neuroinflammation and perfusion - pressure, cognitive lag, sensory overload - pentoxifylline (TNF-α, microvascular support) and PDE3 inhibitor cilostazol (cAMP modulation, antiplatelet effect). LDN - when it works - can enhance glial signaling; minocycline in short courses.

Do supplements work in complex chronic medical conditions such as ME/CFS, Long COVID, and MCAS?

While I'm an allopathic MD who treats very sick patients who've tried everything, here are three supplements that can offer meaningful benefits in my experience. 🧵 Phosphatidylcholine supports cellular membrane integrity and mitochondrial repair, aiding in cognitive function and energy metabolism disrupted in ME/CFS and Long COVID as well as mast cell degranulation in MCAS.

ACE2 and Long COVID

Beyond initial SARS-CoV-2 infection, the potential involvement of ACE2 extends to facilitation of long term viral presence, disruption of the renin-angiotensin system, autonomic dysfunction, and neuroinflammation. 1. The ACE2 receptor, expressed in multiple organs, may harbor viral persistence, triggering inflammatory and immune responses.
2. ACE2 dysregulation may trigger endothelial dysfunction resulting in poor blood flow, low oxygen delivery, and increased risk of clotting.

HEAD PRESSURE in Long COVID

Head pressure, often described as a dull and constant fullness, is one of the most common symptoms I encounter in my LC populous.

It is commonly described as worse at the base of the brain and often exacerbated by physical or mental exertion. Possible mechanisms of disease include:
1. Neuroinflammation secondary to viral persistence and/or spike protein
2. Autonomic nervous system (ANS) dysfunction leading to deleterious changes in intracranial pressure and perfusion

GASTROINTESTINAL DISEASE in LC and ME/CFS

Disruption of the gut-brain axis may lead to impaired signaling pathways - hormonal, neural, immune - resulting in dysmotility, dysbiosis, and additional GI sequelae. Clinical manifestations include however are not limited to:
1. Abdominal pain and bloating
2. Diarrhea and/or constipation
3. Chronic nausea
4. Loss of appetite
5. Gastroparesis and lower GI dysmotility
6. Weight loss or weight gain
7. Food intolerance and sensitivities

The BLOOD POOLING of Long COVID

Blood pooling in LC refers to the abnormal accumulation of blood in veins of the dependent extremities.
This common LC phenomenon oft observed in young, healthy patients may be due to autonomic nervous system (ANS) dysfunction (ie., POTS). Patients commonly describe edema, darkening, hyperemia and/or mottling of the extremities - most commonly the legs - amidst a setting of orthostatic intolerance, fatigue and weakness. Actions such as meal preparation or showering may seem insurmountable due to orthostasis.

The INTERNAL TREMOR of Long COVID

The oft described internal tremor of LC is likely related to autonomic nervous system (ANS) dysfunction however additional biologically plausible mechanisms include neuroinflammation and dysregulation of micro-vascular circulation. Patients often describe the internal tremor as a sensation of vibration or buzzing occurring internally as opposed to external. Patients have additionally described an internal "shuddering" or "wobbling" sensation most pronounced in the chest, abdomen, or extremities.

Skin changes in Long COVID - look familiar?

Acrocyanosis - bluish discoloration of the skin, most commonly affecting the fingers and toes Livedo reticularis - net-like pattern of discoloration that can appear as purplish or bluish patches

Triggers in Mast Cell Activation Syndrome (MCAS)

Multiple triggers provoke the activation and the inappropriate degranulation of mast cells, leading to release of histamine and other proteases, resulting in a variety of symptoms affecting multiple organ systems. Common triggers for MCAS include (feel free to contribute your unique triggers if not included below)
1. Allergens - pollen, dust mites, mold exposure, pet dander, food and drink 🐈
2. Infections - bacterial, viral, fungal and parasitic infections of any organ system 🦠

Causation and risk factors in Mast Cell Activation Syndrome (MCAS) are likely a combination of genetic, environmental, and immunological influences. Genetic factors in MCAS
1. Mutations in mast cell-relevant genes that regulate mast cell receptors or enzymes involved in degranulation ie., KIT 🧬
2. Family history of conditions such as asthma and eczema or mast cell disorders ie., SM

Clinical presentation of Mast Cell Activation Syndrome (MCAS) with no organ system or structure spared.

In the additional posts of this 🧵a comprehensive summation of clinical sequelae of MCAS are listed - comment as to any additional you have experienced. Nasal-ocular - congestion and eye watering and itching
Respiratory - sore throat, hoarseness, wheezing, dyspnea, airway edema
Cardiovascular - chest pain, hypotension, tachycardia, syncope
Gastrointestinal - bloating, cramping, GERD, diarrhea, constipation, dumping syndrome

Hypoxia and reduced oxygen supply in neurocognitive disease in ME/CFS and LC

Reduction of oxygenation to brain parenchyma secondary to mitochondrial dysfunction and autonomic dysfunction may be key factors contributing to cognitive disease. Mitochondrial dysfunction deleteriously affecting cellular energy production may lead to reduced delivery of oxygen and nutrients to the brain resulting in cognitive impairment.