I am transitioning off a waitlist and gearing up for big news! Stay tuned and please direct virtual and in office consultation requests to drmichaelscoma@gmail.com and they will be answered in the order in which they are received. #MECFS #LongCovid #MCAS #LymeDisease

The Triad That Traps: PEM, Orthostatic Intolerance, and Brain Fog. In ME/CFS and Long COVID, these domains drive the greatest morbidity. Mechanistically distinct from fatigue or pain, they better predict loss of function and treatment failure if not directly addressed.

The limbic system integrates threat detection, autonomic control, and immune signaling. When dysregulated, it may perpetuate the chronic, multisystem symptoms of ME/CFS and Long COVID. Therapeutically targeting it may be key to interrupting this cycle.

Therapies may include clonidine to reduce central sympathetic activation, low-dose lamotrigine to modulate glutamatergic signaling, and intranasal ketamine to stabilize limbic circuits involved in stress integration, autonomic tone, and neuroimmune regulation.

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.

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.

Had an excellent discussion with @microbeminded2 and @PutrinoLab. Looking forward to a meaningful collaboration aimed at advancing understanding and proactive care in Long COVID and related chronic disease states. Excited for what lies ahead. #LongCOVIDTreatments.

I occasionally utilize dextromethorphan to attenuate PEM intensity, particularly when dosed intermittently around periods of expected symptom exacerbation. Clinical response suggests a reduction in severity rather than duration, making it a useful symptomatic intervention.

CNS Hyperreactivity Modulation:.By targeting NMDA and sigma-1 pathways, dextromethorphan may stabilize central nervous system reactivity, dampen overactive stress responses, and buffer against sensory overload and exertional crashes in neuroimmune conditions.

Sigma-1 Receptor Agonism:.As a sigma-1 receptor agonist, dextromethorphan may modulate ER stress, enhance mitochondrial resilience, and regulate neuroimmune signaling - supporting energy metabolism and reducing neuroinflammation in ME/CFS and Long COVID.

Dextromethorphan in PEM: Potential Mitigation?. NMDA Receptor Antagonism:.Dextromethorphan blocks NMDA receptors, reducing glutamate-mediated excitotoxicity. This may blunt CNS overactivation, lowering the severity of post-exertional symptom exacerbation in ME/CFS and Long COVID.

We need immunophenotyping pre/post IL-15 agonism: granzyme B+ CD8+ TEMRA, NK CD56, IFN-γ signatures, and reservoir burden (cfDNA, sgRNA). Is the Long Covid immune landscape primed - or contraindicated - for this approach?.

Long Covid pathogenesis implicates persistent antigen, clonal T cell dysregulation, and SARS-CoV-2 persistence. IL-15 signaling may restore cytotoxic effector function and lymphoid architecture. But what immune phenotype would best predict response?.

Anktiva, an IL-15 superagonist, drives memory CD8+ T and NK cell proliferation. Approved in NMIBC, its mechanism raises questions for Long Covid. Could it reverse immune exhaustion or clear viral reservoirs? @DrPatSoonShiong - worth investigating?

Off-label use is guided by motoric PEM phenotype and parallels data from MS-related fatigue, where functional gains have been documented.

In some patients, fampridine may reduce motor post-exertional malaise and enhance physical function by improving central motor signals. Some patients report reduced limb heaviness and earlier return to baseline following activity.

Fampridine is used off-label in ME/CFS and Long COVID patients with post-exertion-induced motor fatigue. As a voltage-gated potassium channel blocker, it improves axonal conduction and neuromuscular transmission in demyelinating or slowed pathways.

I am unclear as to the mystique surrounding Pemgarda as this beacon of unattainability. Approval is straightforward - I’ve done it for 30+ patients, ~10 more pending. It’s the eye of the tiger. Private practice equates to freedom to be proactive and do what’s best for patients.

Synapsin is administered at bedtime or as needed in the setting of cognitive post-exertional malaise and is utilized in my clinical practice for ME/CFS and Long COVID patients with encouraging effect, particularly in the setting of "feeling concussed.".

RG3, a metabolite of ginsenoside Rg1, has been shown to suppress microglial activation and downregulate proinflammatory cytokine expression. Nicotinamide riboside acts as a precursor to NAD+, supporting mitochondrial function and activating sirtuin pathways.

Synapsin (intranasal RG3 + nicotinamide riboside) is often effective for post-exertional symptom exacerbation in ME/CFS and Long COVID. Intranasal delivery enables direct CNS penetrance and enhanced bioavailability in neuroinflammation.