Meeting #1: It begins (with Tracy and Dr. Jay)

Dr. Jay Lombard, DO https://cmbm.org/team/team-member/jay-lombard/

Kickoff Meeting #1 – Summary, Agenda and Notes July 18, 2025

Attendees: Tracy Hans, Dr. Jay Lombard, Jackie deVries

Research Launch Underway!

Summary: We had our first official meeting with Dr. Jay Lombard, and it went incredibly well. We’ve officially kicked off our collaborative research into SOVM, and Dr. Lombard is on board with helping us refine the manuscript, expand to a 10–12 person case series, and identify the most promising genetic and clinical patterns. We discussed journal strategy, registry data access, potential collaborators, and the importance of your continued input through polls, registry and case documentation. This is a huge step forward

Agenda:

1. Logistical Items

·       Finalize weekly meeting day/time and location that works for us

2. Manuscript Strategy

·       What needs to happen before submission is viable?

·       Considering feedback from Orphanet Journal of Rare Diseases, should we:

ü  Increase case number and convert to a case series?

ü  Keep it a concept/theory paper and submit to Medical Hypotheses?

ü  Strengthen group data (e.g., registry data or retrospective summaries)?

·       Target Journal Selection: preference is for Impact factor ≥2 and PubMed indexing

ü  Orphanet recs: Discover Magazine, Egyptian Journal of Neurology/P/N, Sleep Science and Practice, Sleep and Biological Rhythms, Sleep and Vigilance, Cureus

·       Discuss preprint option of Research Square

3. Refining Case-Studies

·       Current case: plan for editing

·       Discuss any potential collaborators for case contributions

·       How many additional cases?

ü  Criteria for inclusion? Use Q&A to select?

4. Jay’s Supplemental Material Suggestions

·       Supplemental Table 1, create a Genetics Flowchart

·       Supplemental Table 2, Clarify the additional row mentioned

5. Conceptual Refinement

·       Condition Naming & Paper Naming

·       Subtypes & Mechanisms

·       Review the "onion model" to triage for treatment

·       Reference chart and literature summary

6. Literature Integration

·       Go over summary of external articles and their relevance to SOVM

·       What other literature should be cited or analyzed?

7. Thematic Expansion

·       Inflammation Section

·       Should we expand the manuscript with a section on Inflammation management?

·       Detoxification approaches?

8. Medication-Specific

·       Review Supp Table 2 and Diamox Struggles: Maintaining alkalinity—along with nutritional and pharmacologic approaches

Why retain the “SOVM” Title?

1. It’s Not a Generic Myoclonus — It’s a Neurovascular-Autonomic Syndrome

·       “Sleep-onset myoclonus” is already a broad, non-specific term in the literature and is often treated as a symptom, not a distinct pathological process.

·       New theory names a distinct mechanism involving:

ü  Impaired vasomotor tone regulation at sleep onset

ü  Likely involvement of autonomic dysfunction

ü  Possible vascular, channelopathy, or CSF flow abnormalities

·       These mechanisms are not present in classic myoclonus syndromes — this is what makes the model novel and clinically actionable. We are proposing a new diagnostic framework.

2. “Vasomotor” Is the Crux of Our Hypothesis

·       “Vasomotor” emphasizes the central thesis: that this disorder arises from instability in vascular tone, which regulates nerves and hormones. particularly at the neurovascular-autonomic intersection during sleep-wake transitions,

·       Removing that term downplays the core insight we’re trying to introduce to the field.

3. Diagnostic Precision & Pathophysiological Specificity

·       “SOVM” implies a specific diagnostic entity — not a vague phenomenon.

·       Like “Restless Legs Syndrome” or “Orthostatic Tremor,” it gives doctors and patients a precise label for what is currently a misunderstood or misdiagnosed condition.

4. Journal Strategy: Novel Terminology Stands Out

·       Journals like Medical Hypotheses or Frontiers appreciate cohesive new frameworks with compelling, novel terminology.

·       “SOVM” tells reviewers this is a unified condition, not a scattered collection of symptoms. That helps frame the paper as hypothesis-generating, not just anecdotal.

5. SOVM model goes further than any other research on the condition by connecting:

·       Vascular tone instability

·       Autonomic dysregulation (e.g., delayed vasoconstriction)

·       CSF dynamics

·       Electrolyte & ion channelopathy contributions (including inflammatory/toxin mediated)

POTS isn’t just called “standing tachycardia”, it points to a specific pattern of autonomic dysfunction.

RLS isn’t called “leg myoclonus at night”

‘sleep-onset myoclonus’ is the more familiar clinical term — but that’s exactly why it doesn’t serve this condition well. It describes a symptom, not a mechanism. With all the similar symptom names being used colloquially, new recognition is more likely to stick with a new descriptive name. The proposal is a new, pathophysiologically distinct syndrome. The vasomotor component isn’t just an add-on — it’s the key to understanding the underlying neurovascular instability.

‘Sleep-Onset Vasomotor Myoclonus’ lets us advance the field by identifying a novel mechanism, not just labeling a movement pattern. If we use only the generic term, we risk the paper being overlooked or misclassified under well-studied, unrelated conditions like benign myoclonus of infancy, REM behavior disorder, or even periodic limb movement disorder — none of which fit this clinical picture.

Exploring personalized medicine Why Briviact helps me: Genetic Mechanism Match for SOVM-

1. My Ion Channelopathy-Related Genes

Gene	Effect	Why Briviact Helps
CACNA1H	T-type calcium channel variant → ↑ bursting, especially at sleep-wake transition	Reduces overactive firing from thalamic neurons; eases sleep entry
KCNAB2	Potassium channel variant → altered repolarization	Stabilizes membranes by reducing presynaptic neurotransmitter overload
SCN1A	Sodium channel variant → potential for neuronal overactivation	SV2A modulation dampens downstream sodium channel overdrive indirectly

2. My Neurotransmitter Regulation Genes

Gene	Effect	Why Briviact Helps
COMT (Val158Met)	Slower breakdown of dopamine and norepinephrine → over-arousal	Tones down presynaptic signaling to counterbalance overactivation
SLC6A4 (5-HTTLPR S/S)	Reduced serotonin transporter → fragile serotonergic tone	SV2A calming effect supports serotonin balance
MAO-A (R297R)	Homozygous mutation → increased stress sensitivity	Avoids overwhelming monoamine systems (unlike SSRIs)

3. My Structural & Vascular Sensitivity

Gene	Effect	Why Briviact Helps
ACE (Del16), AGT, EPAS1	RAAS dysfunction → erratic vascular tone	Does not exacerbate vasodilation; supports vasomotor stability
RELN	Affects structural brain development & cerebellar signaling	Calms looping activity in vulnerable circuits

Review Oura Ring Improvements

Metric	Why It Improves with Briviact
Sleep latency	Reduced thalamocortical excitability at sleep onset
HRV stability	Fewer autonomic swings during sleep
Reduced arousals	Fewer jerks from hyperexcitable firing
Deep sleep time	Stabilized sleep architecture via ion modulation