Sleep-onset vasomotor myoclonus: Reframing chronic hypnic jerks through a neurovascular lens—informed by case study and group trends

doi:10.21203/rs.3.rs-8309723/v1

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Sleep-onset vasomotor myoclonus: Reframing chronic hypnic jerks through a neurovascular lens—informed by case study and group trends

https://doi.org/10.21203/rs.3.rs-8309723/v1

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Background: Hypnic jerks are considered benign, transient motor events during sleep onset. However, in a subset of individuals, they evolve into chronic, disruptive episodes marked by neurovascular instability, autonomic dysregulation, and impaired sleep continuity. Because these symptoms superficially resemble common benign variants, severe forms remain under-recognized and lack a formal diagnostic classification.

Results: This paper introduces Sleep-Onset Vasomotor Myoclonus (SOVM), a proposed condition defined by myoclonic bursts at sleep transition accompanied by vasomotor delay, impaired baroreflex adaptation, and oscillatory cerebrovascular instability. A 22-year case review synthesizes structural, autonomic, endocrine, immune, and genetic findings into a unified neurovascular framework. Objective data revealed delayed sympathetic vasoconstriction, cervical/CSF flow vulnerability, episodic RAAS underactivity, and neuronal hyperexcitability responsive to ion-channel modulation.

Genomic analyses from the broader patient community add a new dimension: 55 individuals with chronic sleep-onset myoclonus have undergone whole-genome sequencing, and every dataset demonstrates unresolved or atypical structural complexity within the RCCX locus—a multiallelic region containing CYP21A2, TNXB, C4A, and C4B. Among those who underwent targeted CAH testing, all six showed a CYP21A2 duplication, a classic RCCX rearrangement associated with altered steroidogenesis, variable RAAS signaling, connective-tissue fragility, and complement dysregulation. These domains parallel clinical observations in the index case, including low Angiotensin II, cervical mechanical sensitivity, C4/C4a elevation, and blood-brain barrier vulnerability. Taken together, the RCCX signal suggests a shared structural-genetic susceptibility that may amplify neurovascular tone instability at sleep onset.

Conclusions: SOVM may represent a distinct sleep-transition disorder rooted in neurovascular mismatch—a failure to synchronize neuronal and vascular tone during the transition into sleep. Integrating community-level genomic findings, especially RCCX structural variation and CYP21A2 duplication patterns, strengthens the hypothesis of a multifactorial susceptibility spanning RAAS, connective tissue, immune, and autonomic pathways. Recognizing SOVM as a coherent phenotype may facilitate mechanism-based treatment strategies and motivate cross-disciplinary research into cerebrovascular–autonomic dynamics during sleep initiation.

Neurobiology of Disease

sleep-onset myoclonus

hypnic jerks

RCCX locus

CYP21A2 duplication

vasomotor instability

RAAS dysregulation

autonomic dysfunction

ion channelopathy

neurovascular mismatch

cerebrovascular/vascular tone instability

1.1 Hypnic jerks: clinical context and limitations of current models

Hypnic jerks are typically regarded as harmless, transient muscle contractions occurring during sleep onset. However, in rare cases, they appear to evolve into chronic, nightly episodes that resist conventional treatment and severely disrupt sleep—a pattern observed across clinical experience, a global support group, and contributions to the Sanford patient registry. In more severe presentations, the jerking interferes with both sleep initiation and maintenance, triggering repeated sympathetic surges, autonomic dysregulation, and a sustained fight-or-flight state. In some individuals, symptoms gradually subside later in the night, while in others, the jerking remains continuous and can prevent sleep entirely, leaving patients exhausted, confused, and physiologically destabilized.

Patients report both partial and full-body jerking, at times accompanied by explosive head sensations, adrenergic surges, and disturbing internal “shockwave-like” events. In some cases, even the isolated jerking of a single muscle is jarring enough to abruptly wake the patient. These episodes frequently provoke intense fear, disorientation, and a mounting sense of helplessness. The cumulative effect of sleep deprivation and nervous system overactivation can profoundly impair daytime functioning, cognitive clarity, and emotional regulation.

Despite the severity of these cases, patients consistently report being dismissed or misdiagnosed with anxiety, insomnia, or functional neurologic disorders—likely because hypnic jerks are colloquially familiar and typically considered benign. This tendency to attribute symptoms to psychological causes often delays proper investigation into underlying physiologic mechanisms.

Notably, the author’s private support group for individuals experiencing hypnic jerking—now nearing 3,000 members—includes a sizable number of parents of infants and toddlers whose children exhibit persistent jerking at sleep onset. In some cases, symptoms have been present since birth, with a subset of infants classified as failure to thrive due to severe sleep disruption. The presence of such physiologic instability in preverbal children—before the developmental capacity for anxiety or stress perception exists—undermines psychogenic explanations and further challenges the designation of hypnic jerking cases as “functional.” Instead, the early onset and clinical severity point to an underlying mechanism rooted in autonomic or neurodevelopmental dysfunction.

While benign hypnic jerks are acknowledged in the International Classification of Sleep Disorders (ICSD-3-TR) as a normal variant [1], the more severe presentations described in this paper remain unrecognized and lack a diagnostic code. These sleep-onset myoclonic phenomena remain unclassified as a distinct diagnostic entity in either the International Classification of Diseases (ICD-11) or the ICSD-3-TR [2, 1]. This oversight perpetuates patient vulnerability, delays research efforts, and obscures potential treatment strategies.

1.2 Introducing Sleep-Onset Vasomotor Myoclonus (SOVM)

This paper proposes the term Sleep-Onset Vasomotor Myoclonus (SOVM) to describe a distinct syndrome characterized by disruptive myoclonic episodes that emerge during the transition into sleep, alongside evidence of autonomic and cerebrovascular tone instability. In this context, autonomic instability refers to fluctuations or failures in the body’s internal regulation systems, particularly those governing heart rate, respiratory rhythm, and blood pressure. This often results in hypersensitivity to positional changes, environmental stressors, or physiologic and inflammatory shifts, including localized infection.

The pathophysiology underlying these more severe cases remains poorly understood. However, converging observations from clinical experience, patient-reported patterns, and objective findings from the present case review suggest a multifactorial process involving vascular tone instability, delayed baroreflex adaptation, Renin-Angiotensin-Aldosterone System (RAAS) underactivity, and genetic vulnerability affecting ion channel function. These interrelated mechanisms—outlined in the sections that follow—may contribute to the physiologic destabilization during sleep transitions and help explain the chronic, treatment-resistant symptoms observed in this subset of patients.

The baroreflex is a rapid-acting, pressure-sensitive feedback mechanism that helps maintain stable blood pressure by modulating heart rate and vascular tone in response to blood vessel stretch. RAAS is a hormone-regulated pathway responsible for maintaining blood pressure, vascular tone, and fluid balance through the sequential actions of renin, angiotensin, and aldosterone. Given their well-established roles in cardiovascular and autonomic regulation, both the baroreflex and RAAS systems are likely to be implicated in the physiologic instability observed in SOVM.

SOVM hallmark symptoms include sudden shifts in vasomotor tone and myoclonic jerks occurring during N1 sleep—the lightest stage of non-REM sleep, marked by theta wave activity (4–7 Hz) and typically occur during the hypnagogic transition. These early-stage symptoms reflect the underlying physiologic instability, and their recognition is key to distinguishing SOVM from more benign forms of hypnic jerking.

Formal diagnostic recognition is urgently needed. Without a defined category in sleep medicine or neurology, patients with chronic hypnic jerking remain vulnerable to misdiagnosis, overmedication, or medical dismissal. Defining Sleep-Onset Vasomotor Myoclonus (SOVM) anchors this under-recognized phenomenon in neurophysiologic research and clinical awareness—and may help open new therapeutic pathways.

1.3 Classification challenges and overlapping diagnoses

Although hypnic jerks are now commonly referenced in both medical and lay settings, the term itself is colloquial and lacks standardized diagnostic criteria. As previously mentioned, chronic sleep-onset myoclonus—often referred to informally as “hypnic jerking” or “sleep starts”—has not been formally recognized in existing medical taxonomies. This ambiguity leads to frequent misclassification as benign, functional, or idiopathic, despite decades of consistent patient reports and mounting anecdotal evidence.

Patients often describe a “tripwire-like” pattern of symptom recurrence—where symptoms re-emerge suddenly, even after periods of relative stability, and without any identifiable trigger. This unpredictability is profoundly disorienting, leaving patients confused about what went wrong. These fluctuations are often interpreted as psychosomatic or functional in nature, yet they may instead reflect a fragile, threshold-based physiologic system that reacts to minor or invisible internal changes. Even subtle shifts in posture, fluid balance, inflammation, or autonomic tone may be enough to push a destabilized system past a critical tipping point. As a result, interventions that help one day may worsen symptoms the next, deepening both clinical confusion and patient distress—suggesting a threshold-sensitive system where even successful interventions may fail without warning.

Existing literature on myoclonus has largely focused on generalized, cortical, or epileptiform subtypes. However, the sleep-transition–specific, vasomotor-sensitive, and autonomically-influenced variant described here has not been systematically studied. Attempts to document these events with electroencephalogram (EEG) or electromyographic (EMG) likely fail, due to: their timing during early-stage non-REM sleep (N1/N2), subtle or absent muscle activation patterns, and limited focus in neurology on sleep-state vascular regulation [3, 4]. Standard EMG protocols typically lack the sensitivity to detect these subtle bursts, though isolated case reports and specialized studies suggest they may be visible when higher-gain or more targeted settings are applied. EEG studies may likewise miss subclinical electrical activity, particularly in the absence of epileptiform patterns or cortical involvement.

While dismissed as benign, chronic hypnic jerks are sometimes classified under broader and inconsistently defined categories of myoclonus. Propriospinal myoclonus (PSM) and excessive fragmentary myoclonus (EFM) are two of the more frequently cited classifications. PSM, for example, has been described during drowsiness and sleep onset, occasionally mimicking hypnic jerking, and in rare cases may respond to surgical decompression—suggesting a neuroanatomical or mechanical trigger [3, 4]. EFM, identified in the literature by EMG readings during light non-REM sleep, is also considered a benign finding. These classifications may overlap with excessive hypnic jerking, but the connections remain largely unexplored. Interestingly, EFM studies have employed sensitive EMG protocols capable of detecting brief, low-amplitude muscle bursts—typically ≤ 150 milliseconds in duration and ≥ 50 microvolts in amplitude—occurring at a frequency of five or more bursts per minute during at least 20 minutes of NREM sleep [5]. Such parameters offer a model for how subtle motor activity might be physiologically documented, even when not visible or easily detected in standard studies.

Drug-induced myoclonus further complicates classification, with known mechanisms including serotonin modulation, glutamate excitotoxicity, and ion channel interference [6]. The absence of clear diagnostic boundaries, corroborative literature, or consistent physiologic criteria across these categories reflects a fragmented and often arbitrary use of terminology.

These overlaps highlight the potential for the sleep-onset component (SOVM) to reside within a broader spectrum of physiologically triggered, context-dependent movement disorders—rooted in shared neurovascular and autonomic mechanisms rather than traditional taxonomic boundaries. Many reported triggers—whether pharmacologic, structural, inflammatory, or hormonal—may not reflect true causative pathology, but rather the final stressor in a system already operating near a physiologic threshold. In this model, skeletal compression, CSF outflow restriction, or drug sensitivity may act as the proverbial “straw that broke the camel’s back,” unmasking a deeper instability in vascular or autonomic tone. Given this diagnostic ambiguity, a clearer and more mechanistically grounded classification is warranted.

1.4 Rationale for diagnostic advancement

This paper supports the need for:

A formal diagnostic label for sleep-onset myoclonus with neurovascular-autonomic features
Inclusion in the ICD to enable formal classification, research funding, and proper insurance coding
An expansion of classification frameworks to consider cerebrovascular tone (the brain’s ability to regulate blood vessel constriction and dilation) and autonomic reactivity during sleep transitions

1.5 Emerging glial and genetic mechanisms

Amid these classification challenges, recent discoveries in sleep neuroscience have revealed molecular and glial contributors that may underlie this physiologic instability. Emerging neurobiological insights have implicated glial activity in the regulation of sleep onset. Astrocytic calcium signaling is increasingly recognized as a central mechanism in sleep initiation and stability. Findings from Bojarskaite et al. demonstrate that astrocytes exhibit increased calcium activity during transitions between wakefulness and sleep, suggesting a regulatory role in modulating neuronal circuits during this period. They further found that disrupting astrocytic calcium signaling impairs slow-wave sleep and increases arousals, indicating that calcium misregulation in glial cells may destabilize the neural environment at sleep onset [7].

Disruptions in these glial mechanisms may compound existing genetic susceptibilities, particularly those impacting ion channel regulation. Genetic variants may further contribute to physiologic instability, forming an emerging ion framework. The link between oxidative stress and ion channel dysfunction—a factor in various neurodegenerative disorders—further reinforces this model [8]. Variants in genes seen in this case review—CACNA1H, KCNAB2, SCN1A, and EPAS1—may contribute to neurophysiologic instability through diverse mechanisms. CACNA1H, encoding a T-type calcium channel, has been shown to increase excitability in sensory neurons after injury, potentially mimicking the effects of chronic neuroinflammation or subclinical injury [9]. KCNAB2, a potassium channel subunit, regulates dopamine neuron firing and is linked to seizure susceptibility through its modulation of Kv1 channel activity [10]. SCN1A, a sodium channel gene associated with epilepsy, contributes to abnormal neuronal firing, while EPAS1, a hypoxia-inducible transcription factor, influences sympathetic tone and vasomotor adaptation. Together, these gene pathways suggest that ion channel vulnerability and neuroinflammation may amplify neural instability underlying SOVM.

1.6 Structural and mechanical contributions

Structural and mechanical influences have also been noted, with clinical parallels drawn from similar neurologic conditions. Mechanical interference in vascular or nerve structures has also been linked to neurologic dysfunction. In one case, Eagle’s syndrome (elongated styloid process) was implicated in seizure-like activity in an elderly patient, demonstrating how anatomic variants can produce episodic cortical hyperexcitability [11]. This mirrors the present case review, in which enlarged styloid processes and atlas instability were identified and addressed (see case review section).

1.6.1 RCCX locus structural variation across cohort suggests shared susceptibility architecture

Across the SOVM community, early genomic data indicates that structural variation within the RCCX locus may represent a shared susceptibility architecture linking endocrine regulation, autonomic tone, connective tissue mechanics, and neurovascular stability during sleep onset. Among 55 individuals who have undergone whole-genome sequencing (WGS), every dataset demonstrates unresolved or atypical structural complexity in the RCCX region—a multiallelic block containing CYP21A2, TNXB, C4A, and C4B, all of which interface with physiological systems implicated in SOVM.

Although short-read WGS cannot fully resolve this region, the consistent recurrence of RCCX complexity across independent individuals with the same rare sleep-transition phenotype suggests a non-random genomic pattern worthy of focused attention. Notably, six members of the cohort underwent a dedicated congenital adrenal hyperplasia (CAH) gene panel, and all six displayed a CYP21A2 duplication, a classic RCCX structural rearrangement. CYP21A2 duplications are associated with altered steroidogenesis, variable cortisol/aldosterone signaling, and shifts in RAAS dynamics—mechanisms that align closely with observed SOVM features such as:

Low Angiotensin II levels,
Delayed vasoconstrictive response during sleep onset,
Salt-wasting or fluid-regulation instability,
Episodes resembling autonomic crises, and
Sensitivity to medications affecting vascular tone.

In parallel, variation involving TNXB—also embedded within the RCCX locus—has mechanistic relevance for connective-tissue integrity and cranio-cervical stability, both of which influence CSF flow and mechanical triggers for neurovascular dysregulation. Complement components C4A/C4B, likewise housed in the RCCX block, intersect with immune activation and endothelial permeability, consistent with findings of elevated C4/C4a and a compromised blood–brain barrier in the index case.

Taken together, these parallel findings across endocrine, autonomic, connective-tissue, and immune domains point toward RCCX structural variation as a unifying genomic hub, potentially amplifying susceptibility to the neurovascular mismatch seen in SOVM. While preliminary, the reproducibility of RCCX signals across unrelated individuals underscores the need for targeted long-read sequencing to clarify breakpoints, chimeric configurations (such as CAH-X–like fusions), and shared structural motifs.

This section presents both an in-depth individual case review and patterns reported by a broader patient community, followed by early AI-based model testing.

2.1 Case review

The patient is a 51-year-old woman with a 22-year history of chronic, treatment-resistant sleep-onset myoclonic jerking, with significant stabilization after year 16. Symptoms began abruptly in 2002, following a convergence of physiological and environmental stressors. She had recently abruptly discontinued a 1.5-year course of low-dose dexamethasone (0.25 mg), which had been prescribed following a misdiagnosis. In the months that followed, she had contracted the flu, discovered mold exposure and was living directly across the water from lower Manhattan at the time of the World Trade Center collapse. This raised concerns about possible exposure to multiple environmental toxins.

The jerking began suddenly one night while sleeping in a position without adequate neck support, shortly after what appeared to be an adrenal crisis that required intravenous SoluCortef. This convergence of biomechanical strain and acute neurohormonal stress may have acted as the initiating event. What started as brief, localized jolts quickly progressed into nightly, full-body myoclonic events that triggered sympathetic surges and severe sleep disruption. Over time, the symptoms became entrenched and debilitating, with standard sleep studies, EEGs and EMGs all failing to identify abnormalities. No adjustments to EEG or EMG sensitivity thresholds were made during clinical testing in this case, which may have contributed to the absence of observable abnormalities.

Despite consulting with hundreds of physicians across multiple specialties, no definitive diagnosis or mechanistic explanation emerged. To manage the assaults of sleep-onset jerking, many providers offered nightly benzodiazepine prescriptions—as a default intervention, without investigation into underlying causes. While these medications occasionally enabled sleep, they appeared to worsen excitatory instability over time. As tolerance developed, the patient was forced to rotate among different agents to sustain any therapeutic effect. This trajectory underscored the need for mechanism-driven treatment strategies rather than symptomatic suppression.

Repeated attempts at evaluation led to inconsistent explanations, despite a reproducible pattern and growing physiologic evidence. Findings included autonomic instability, reactions to agents that rapidly alter vascular tone, intolerance to anticholinergic substances, nocturnal blood pressure and heart rate surges, intermittent nocturnal polyuria, and genetic and laboratory evidence of RAAS underactivity.

Objective monitoring—both at home and during clinical visits—captured episodic blood pressure and heart rate elevations upon transitioning from lying to sitting, with systolic increases > 20 mmHg, diastolic increases over 15 mmHg, and heart rate surges exceeding 25 bpm. These exaggerated responses suggest intermittent baroreflex impairment and heightened sympathetic activation, particularly during sleep-wake or positional transitions. However, such changes were not consistently reproducible across all settings or times of day, and the pattern does not meet diagnostic criteria for Postural Orthostatic Tachycardia Syndrome (POTS)—there was no sustained tachycardia or upright intolerance. Rather, the findings reflect a state-dependent autonomic vulnerability, supporting the broader hypothesis of episodic tone dysregulation during sleep transitions.

In addition, the patient experienced episodes of throat closure when lying face-down (e.g., on a massage table) near the sleep-wake threshold. These episodes were positional and consistently reproducible, suggesting possible airway vulnerability or autonomic reflex involvement during prone, near-sleep states.

In the two years preceding hypnic jerking onset, the patient experienced several episodic illnesses characterized by acute dehydration, weakness, and gastrointestinal loss—often in the setting of viral infection, medication exposure, or physiologic stress. These episodes were notable for their abrupt onset and reproducible resolution following low-dose hydrocortisone, despite normal aldosterone levels, suggesting functional RAAS underactivity. Urinary testing was obtained during one of the episodes, yielding a chloride level of 178 mmol/L, consistent with renal salt-wasting physiology. The jerking onset occurred in the aftermath of this suspected adrenal crisis and SoluCortef administration, likely compounded by biomechanical strain during sleep. The patient later experienced symptom flares triggered by medications affecting vascular tone or central excitability (e.g., duloxetine, chelation therapy), with chronic symptoms ultimately emerging in the context of persistent immune activation. While these episodic crises diminished after 2005—likely due to increased physiologic awareness, trigger avoidance, and strategic use of low-dose hydrocortisone—the nighttime myoclonic jerking perhaps persisted as a chronic, patterned manifestation of underlying neurovascular instability.

Further autonomic testing revealed a moderate Phase II Valsalva decline with partial recovery and a small Phase IV overshoot—indicating impaired sympathetic vasoconstriction despite normal parasympathetic tone and tilt-table findings. This was further supported by abnormal fractional exhaled nitric oxide (FeNO) testing, conducted in a pulmonology setting using the NIOX system. The test initially failed due to poor exhalation force but normalized after a single puff of albuterol. This response suggests functional sympathetic underactivation affecting airway tone.

In 2006, additional infectious workup revealed elevated Lyme disease titers— likely reflecting a chronic, previously undiagnosed case, as well as positive Bartonella titers. These findings further highlight a complex immune landscape and may have contributed to neurovascular instability. Evidence suggests that Lyme disease and Bartonella can impact the nervous system and potentially contribute to neurophysiological instability. Glial sensitization, where glial cells like astrocytes and microglia become more reactive and contribute to neuroinflammation, may play a role, as research on the neuro-glial-vascular unit shows the importance of glial-vascular interactions in maintaining brain homeostasis [12]. Furthermore, Bartonella species are known to infect endothelial cells, potentially causing endothelial stress and contributing to vascular dysfunction. While more speculative, these infections could also indirectly influence systems like the Renin-Angiotensin-Aldosterone System (RAAS) which is crucial for cardiovascular regulation, potentially contributing to neurovascular instability [13]. Collectively, these infections may exacerbate neurophysiological instability through various mechanisms, including glial sensitization, endothelial stress, and potential indirect effects on systems like the RAAS. These case findings point to three interwoven contributors: structural, immune, and autonomic instability. These are summarized in the following subsections.

2.1.1 Case-specific structural stress indicators

Cerebrospinal Fluid (CSF) flow MRI showed reduced flow anterior to the cervical cord and posterior to the mid/lower cervical cord, with significant improvement after atlas adjustment
MR Venography (MRV) demonstrated moderate right-side transverse sinus stenosis
MRI of the Brain revealed an empty sella suggestive of chronic CSF pooling
Ophthalmologic exam indicated chronic dry eye with abnormal tear film metrics and reduced tear break-up time (TBUT)
Cervical instability was documented, with improvement following Atlas Orthogonal care and styloidectomy

2.1.2 Case-specific immune markers and glial sensitization

C4a persistently elevated across 2 decades, with a peak >23,000 ng/mL
C4 was elevated up to 64 mg/dL
High-sensitivity C-reactive protein (hs-CRP) remained chronically elevated (e.g., 16.74 mg/L) over the 22-year span
ANA was positive beginning year 18 (2+; homogeneous/fine speckled) without specific autoantibodies (e.g., dsDNA, SSA, SSB), suggestive of non-specific immune activation rather than classic autoimmunity

2.1.3 Case-specific autonomic and vascular findings

Autonomic testing showed a Phase II decline on Valsalva (impaired sympathetic activation) and a small Phase IV overshoot (incomplete baroreflex compensation)
Pulmonary function testing (FeNO via NIOX device) was initially incomplete due to impaired exhalation and normalized following albuterol administration, suggesting airway tone dysregulation and possible sympathetic underactivation.
RAAS underactivity was supported by below-range angiotensin II, low-normal angiotensin I, a historical low ACE level (later normalized), delayed ADH recovery, and persistently undetectable serum ADH despite low-normal osmolality
Small fiber neuropathy was supported by positive skin biopsies in 2006 and 2018, though a three-site biopsy was negative in 2025 after perineural therapy
Genetic findings included variants in AGT, ACE (angiotensin/bradykinin regulation), EPAS1 (oxygen-sensitive vascular tone), CACNA1H, KCNAB2, SCN1A (ion channels), RELN (synaptic signaling), and F2 (prothrombotic risk)

Together, these findings suggest broader upstream neurohormonal underactivation involving both the renin-angiotensin and ADH axes. Clinically low angiotensin II levels with angiotensin I in the low-normal range—coupled with delayed vasopressin recovery, support the hypothesis of impaired vascular tone regulation during sleep transitions.

These findings converge on a multifactorial explanation for the patient’s condition. The following framework synthesizes the observed physiologic, structural, and genetic contributors into a unified model of disease pathogenesis.

2.1.4 Case-specific pathophysiologic framework

The patient’s symptom profile is consistent with a multifactorial neurovascular disorder characterized by impaired vascular tone regulation, disrupted fluid balance, and excitatory instability during sleep onset. Table 1 summarizes the key diagnostic domains identified in this case review, offering a foundation for structured investigation in other individuals presenting with chronic sleep-onset jerking.

[insert Table 1 here]

Key contributing mechanisms include:

Neurovascular instability during sleep initiation may be driven by impaired vasomotor tone regulation and parasympathetic overactivity at the sleep–wake transition. This is supported both by peripheral findings linking distal vasodilation to sleep-onset latency [14] and by central models implicating brainstem and diencephalic structures in the initiation of sleep and vascular tone modulation [15].
Delayed baroreflex adaptation and blunted RAAS-sympathetic activation, supported by low angiotensin II levels and poor vasopressin recovery, potentially contributing to abrupt BP and HR surges during sleep transitions. RAAS plays a key role in blood pressure regulation, and its interaction with the baroreflex is important for maintaining cardiovascular homeostasis [16]. During sleep transitions, disruptions in these mechanisms may lead to periods of instability.
Suspected bradykinin accumulation, potentially amplifying excitatory and inflammatory cascades due to impaired degradation and RAAS underactivity, may contribute to heightened sensitivity during sleep transitions. ACE (angiotensin-converting enzyme), which is part of the RAAS (renin-angiotensin-aldosterone system), plays a key role in bradykinin degradation. ACE inhibitors, used to manage hypertension, can increase bradykinin levels by inhibiting this degradation. Impaired bradykinin degradation can lead to amplified inflammation. Disruptions in the kinin-kallikrein system, which generates bradykinin, may be involved in regulating sleep and stress responses, though the exact link to sleep transitions and heightened sensitivity requires further research. Further supporting the role of bradykinin receptors in neurovascular processes, studies using a bradykinin B2 receptor agonist have demonstrated a transient disruption of the blood-brain barrier [17].
Confirmed genetic variants across RAAS, ion channel, coagulation, and neurodevelopmental pathways include mutations in SCN1A [18], CACNA1H [19], KCNAB2 [10], RELN [20], ACE [21,22], AGT [21,23], EPAS1 (via hypoxia-induced response) [24], and F2 [25]—collectively contributing to vulnerability in neural excitability, perfusion instability, fluid imbalance, and tone dysregulation during sleep transitions.
Functional HPA axis sluggishness, evidenced by the reliable resolution of episodic flares with low-dose hydrocortisone (5 mg), suggestive of impaired stress-response capacity [26].
Chronic autonomic features, including childhood oliguria (resolved with dexamethasone), lifelong hypohidrosis, and persistently dry skin

These interwoven mechanisms are visually represented in Figure 1. Impaired conversion of angiotensin I to angiotensin II—evidenced by clinically low angiotensin II levels and low-normal angiotensin I—may result from genetic factors (e.g., homozygous ACE deletion), chronic infection (e.g., Actinomyces), or autoimmune influence (e.g., Parvovirus B19 exposure). This disruption leads to reduced vasoconstrictive signaling and accumulation of bradykinin, an inflammatory peptide that increases vascular permeability and dilation. When bradykinin is not adequately degraded, it may enhance neural excitability, promote neuroinflammation, and contribute to osmotic instability. Evidence suggests that sleep disturbance itself can induce neuroinflammation [27]. Furthermore, water homeostasis in the brain is critical, and osmotic instability, potentially leading to intracellular swelling, can destabilize brain regions, including those critical for sleep initiation [28]. These effects, particularly under conditions of plasma dilution or impaired chloride handling, can lead to intracellular swelling and destabilization of brain regions critical for sleep initiation.

[insert Figure 1 here]

Building on this mechanistic framework, the patient’s confirmed genetic findings (Table 2) converge across three major physiologic domains: RAAS-driven vascular tone regulation, neuronal ion channel excitability, and neurovascular coupling integrity. A homozygous ACE deletion and heterozygous AGT variant suggest a compromised renin-angiotensin axis, reducing angiotensin II bioavailability while elevating bradykinin, thereby impairing vascular responsiveness and chloride transport. Concomitant variants in SCN1A, CACNA1H, and KCNAB2 may further lower neuronal firing thresholds and disrupt ionic homeostasis. These excitability shifts are particularly destabilizing at sleep onset—a neurophysiological state requiring finely tuned vascular and synaptic transitions, including thalamocortical oscillatory synchronization and autonomic downshifting.

[insert Table 2 here]

The genetic constellation shown in Table 2 helps explain this threshold-based fragility. The system’s tendency to relapse in response to minor or even imperceptible shifts—such as changes in posture, inflammation, hydration, or electrolyte balance—suggests a fragile, threshold-based physiology. This is characteristic of ion channelopathies, where small deviations in membrane potential can trigger disproportionate neuronal firing. In such cases, symptom recurrence may reflect electrical hypersensitivity rather than functional reactivity, helping explain why patients often struggle to identify consistent triggers, and why symptom patterns may appear erratic despite a biologic basis. Collectively, these findings converge on a novel, multifactorial framework of sleep-onset vasomotor myoclonus (SOVM), in which dysregulated neurogenic and vascular systems fail to synchronize appropriately during the critical transition from wakefulness to sleep.

2.1.5 Case-specific fluid flow and drainage dysfunction

Repeated MRIs of the brain demonstrate an empty sella, consistent with chronic CSF pooling and pituitary flattening. During nighttime symptom flares, the patient has experienced a sensation of fluid “draining” from her head upon sitting upright. This pattern also emerged after chiropractic neck adjustments and Atlas Orthogonal care, echoing a childhood episode in which severe chronic allergies abruptly resolved following cervical manipulation, accompanied by the same sense of drainage.

Enlarged cervical lymph nodes, removed intraoperatively during styloidectomy, further support the presence of regional immune or lymphatic congestion. Patient’s tear film has replenished with external facial pressure, suggesting mechanical or autonomic obstruction of lacrimal gland function. The patient also experienced a several year phase of severe, sudden-onset oral parching, exclusively at sleep onset. This symptom was markedly improved after a brief protocol of early morning high-salt water intake, suggesting a reversible shift in fluid distribution or RAAS-related tone underactivity.

These structural and dynamic patterns, taken together, reinforce the hypothesis that SOVM may involve systemic tone instability and impaired fluid clearance, manifesting across cranial, lymphatic, and exocrine pathways. This closely parallels the neurovascular and fluid-regulatory dysregulation described earlier.

2.1.6 Case-specific treatment responses

Significant improvement following chiropractic neck adjustment, atlas orthogonal care, styloidectomy, and low-dose acetazolamide
Interventions helpful during flares: 5% topical liposomal lidocaine cream, charcoal, cholestyramine, hydrocortisone (5 mg), head/leg elevation, alkalinizing agents
Jerking exacerbations were noted following intake of substances known to disrupt vascular tone, including anticholinergic agents (e.g., Benadryl), vasoactive peptides (e.g., VIP), GABAergic compounds (e.g., Xyrem), and certain nutrients (e.g., vitamin B6, magnesium).

2.1.7 Case-specific outcome and current status

Symptom stabilization emerged gradually through a multi-pronged management approach introduced around the 16-year mark, with key improvements observed following incidental interventions. Notably, on two separate occasions, the removal of occult dental infections accompanied by sinus inflammation—identified via CT imaging—was associated with improved sleep, suggesting a role for inflammatory resolution or sinus drainage. These findings support the possibility that subclinical craniofacial inflammation, or impaired sinus outflow may contribute to sleep-state instability in SOVM, particularly when adjacent to vascular or lymphatic pathways involved in cranial fluid clearance. Core management strategies—including low-dose acetazolamide and cervical alignment intervention—led to more sustained improvement. While mild jerking can occasionally recur in the setting of systemic inflammation, injury, or excessive salt intake, baseline sleep has improved.

Supplementation with allithiamine, a fat-soluble thiamine derivative known to support neurovascular metabolism, appeared to contribute to symptom stabilization in this case. Additionally, improving ferritin levels through heme iron supplementation appeared to further reduce hypnic jerking. While no formal studies have examined this relationship, parallels may be drawn from established links between iron deficiency and movement-related sleep disorders such as restless legs syndrome and periodic limb movements.

Additionally, at times the patient observed improved sleep quality and reduced hypnic jerking when sleep onset occurred earlier in the night—typically before 10:30pm, with the most notable improvements closer to 9:30pm. On those nights, sleep scores recorded by the Oura Ring (a sleep wearable) were often improved across multiple domains, including readiness, nighttime arousals, and overall score. This leads us to wonder whether aligning sleep with circadian melatonin and thermoregulatory cycles may help stabilize neurovascular transitions and mitigate symptom severity. This observation differs from conventional Cognitive Behavioral Therapy for Insomnia (CBT-I), which often encourages delaying bedtime to consolidate sleep. In this case, earlier sleep timing may play a role in stabilizing neurovascular transitions and reducing arousals, pointing to a potentially distinct, timing-sensitive mechanism in SOVM.

The outcomes above suggest that, in select cases, targeting neurovascular tone, fluid balance, and inflammatory load may help reduce symptom burden—even in long-standing presentations—though further study is needed to assess broader applicability. Patterns seen in this case are echoed across a broader patient community, pointing to a potentially shared mechanism.

2.2 Community review

2.2.1 Community-based patterns

The hypnic jerking support group, co-founded and moderated by the author, has been active for eight years. This continuity has enabled long-term observation of symptom progression, treatment responses, and demographic shifts. Since early 2020, membership has grown rapidly—and now averages about 50 new members worldwide, per month. While multiple factors may contribute to this trend, the increase aligns with rising reports of post-viral autonomic and neurovascular symptoms, suggesting a growing clinical relevance for the SOVM framework.

Group members consistently report similar symptom patterns, triggers, and physiologic responses—observations also reflected in registry data from the Sanford Institute, raising the possibility of shared underlying mechanisms. Commonly reported features include intolerance to anticholinergic agents, responsiveness to 5% topical liposomal lidocaine cream, vivid dreaming, and intermittent nocturnal polyuria. A frequently cited trigger is major hormonal change—including pregnancy, postpartum, menopause, adjustments to hormone therapy, and states of hormone deficiency (e.g., low estrogen, progesterone, or testosterone). These shifts are known to affect vascular tone, fluid balance, and neural excitability—all key elements in the SOVM framework—and appear relevant across individuals with diverse hormone profiles. Evening exercise is another common trigger, often followed by symptom flares that same night. While not formally studied, one possible explanation involves impaired sympathetic recovery following exercise-induced vasodilation, which may increase physiologic vulnerability during sleep transitions. Many members also describe symptomatic relief with levetiracetam (Keppra) and brivaracetam (Briviact)—antiepileptic medications that reduce synaptic excitability—supporting a role for ion channel instability and central excitatory dysregulation in SOVM.

While often labeled a psychological confounder, anxiety may itself act as a physiologic amplifier in patients with SOVM. Emotional stress has been shown to elevate sympathetic tone and delay baroreflex adaptation [29]. Research also suggests that anxiety-induced changes in respiration can influence cerebral blood flow [30]. Stress-induced breathing changes and CO₂ fluctuations may also transiently shift intracranial pressure and CSF dynamics, further destabilizing neurovascular tone during the transition to sleep.

This reframes anxiety not as a root cause, but as a relevant contributing factor in those with underlying vascular or autonomic vulnerability. Additionally, hormonal fluctuations—frequently reported as SOVM triggers—can both disrupt vascular-autonomic stability and amplify anxiety symptoms through shared neurophysiologic pathways, further compounding sleep transition vulnerability across individuals with diverse hormonal profiles.

Building on this theme of sympathetic vulnerability, one proposed explanation for patients’ intermittent nocturnal polyuria involves fluid loss during early sleep transitions—consistent with patterns of nocturnal polyuria and natriuresis described in prior research [31]. Nocturnal polyuria is defined as nighttime urine production exceeding a certain percentage of the total daily volume, often 20% in younger individuals or 33% in the elderly [32]. While the exact mechanisms underlying this fluid shift are complex and may involve impaired sympathetic tone and delayed vasoconstriction leading to venous pooling, atrial stretch, and compensatory ANP release, further research is needed to fully clarify these processes. This systemic fluid shift during vulnerable sleep phases may further compromise cerebral perfusion, particularly in a setting of already blunted RAAS compensation and vascular tone instability.

In addition to the autonomic irregularities described above, several other symptoms are occasionally reported by members of the hypnic jerking support group—likely reflecting downstream effects of chronic sleep disruption rather than primary features of the condition. These include hypnagogic and hypnopompic hallucinations, often auditory, which are traditionally associated with severe sleep deprivation. While less common, they have been described by group members and also appear in registry data from the Sanford Institute. This overlap raises the possibility that such episodes may reflect transient cortical dysregulation or cerebral perfusion instability during sleep–wake transitions, particularly in individuals with prolonged or severe sleep disturbance. Exaggerated startle responses have similarly been noted, typically emerging during periods of heightened symptom flare or cumulative sleep loss.

In a similar vein, patients often describe hypersensitivity to sound, touch, or movement, sometimes reacting with full-body jolts to minor stimuli. This may reflect a primed sympathetic system, lowered sensory thresholds, or brainstem hyperexcitability. In addition to peripheral autonomic effects, the amygdala—central to processing fear and threat—may play a role in amplifying sympathetic tone during sleep transitions. Heightened amygdalar activity has been linked to poor sleep continuity and exaggerated cardiovascular reactivity, particularly in individuals with underlying autonomic vulnerability [33,34].

Though these symptoms often emerge later in the course of illness, they are frequently dismissed as secondary or psychological. However, they may offer important clinical clues—pointing to dysregulation across central vascular, sensory, and sleep-state regulatory systems. Recognizing this broader constellation of features may aid in identifying cases of SOVM and distinguishing them from more benign or transient forms of sleep myoclonus.

2.2.2 Community-based hypothesis testing

In addition to retrospective group analysis, early beta testing of the SOVM manuscript was conducted exclusively using ChatGPT, selected for its ability to retain context over time and to apply clinical reasoning across multisystem inputs. Twenty individuals uploaded and contextualized the full SOVM manuscript within their ChatGPT sessions, alongside whatever personal health data they had available—such as genetic variants, laboratory results, imaging reports, symptom patterns, medication and supplement responses, sleep positioning details, or outcomes from mechanical interventions. While the scope and completeness of data varied across participants, each was encouraged to include as much relevant context as possible for their individual case.

Participants then asked ChatGPT a structured set of questions:

1. Is there crossover between this SOVM theory and my hypnic jerking condition?

2. What would my next steps be based on this new framework?

3. How might this specifically inform my use of supplements and medications?

4. What evaluations would you recommended in light of this proposed framework?

5. Which types of doctors or specialists should I consult based on these insights?

The individualized responses shared with the author revealed a notable degree of alignment between the SOVM framework and the users’ clinical histories. In particular, participants’ genetic variants, neuroimaging findings, symptom trajectories, and medication/supplement responses frequently mapped onto key elements of the SOVM framework. Users expressed appreciation for the utility of the exercise, reporting that the framework provided not only conceptual clarity but also a practical lens through which to interpret their complex, multisystem symptoms. Additionally, users reported having next steps for follow-up. This emergent pattern suggests that the framework is both internally coherent and adaptable across a variety of individualized presentations.

While not a formal clinical trial, this ChatGPT-based engagement represents a novel mode of real-time, patient-led hypothesis testing. It offers an early glimpse of the framework’s generalizability and translational potential. As an informal form of AI-assisted beta testing, it highlights the evolving role of participatory medicine and feedback loops in accelerating rare disease theorization and refinement. Future directions may include structured clinical validation of the SOVM framework, alongside ongoing community-based evolution using AI platforms as adaptive testing tools. This hybrid approach would allow the framework to evolve responsively while assessing its predictive utility across diverse, real-world patient cohorts.

As mentioned above, the term Sleep-Onset Vasomotor Myoclonus (SOVM) is proposed to describe this syndrome—a distinct pattern of sleep-onset myoclonus associated with neurovascular instability. While initially described as a syndrome, emerging evidence suggests that SOVM may represent a discrete disorder involving impaired cerebrovascular tone regulation, delayed baroreflex adaptation, and blunted RAAS-sympathetic activation.

This dysregulation becomes especially relevant during sleep onset, a time when cerebral blood vessels normally widen to accommodate increased brain perfusion or blood flow to the head. Vasodilation facilitates the shift into sleep, but it must be followed by a subtle sympathetic and RAAS-mediated vasoconstriction to stabilize perfusion pressure. In individuals with SOVM, this compensatory response appears to be delayed or insufficient—resulting in unchecked vasodilation, reduced cerebral perfusion, and triggering of hypnic jerks.

Supporting this idea, studies in male mice have demonstrated distinct cerebrovascular dynamics across sleep stages, including slow, large-amplitude vessel oscillations during NREM sleep, vasodilation in REM sleep, and vasoconstriction upon awakening [35]. Research also indicates that distal vasodilation plays a functional role in sleep initiation [14]. These vascular shifts—when poorly buffered by the autonomic and RAAS systems—may destabilize neurovascular tone during transitions and contribute to the characteristic jerking of SOVM.

As detailed in Fig. 1, the patient exhibits multiple markers of RAAS underactivity and impaired angiotensin II signaling—factors that amplify bradykinin accumulation and disrupt vascular tone stability during sleep transitions. These include clinically low angiotensin II, low-normal angiotensin I, a transiently low serum ACE level, a homozygous ACE gene deletion, and delayed vasopressin recovery on water deprivation testing. This constellation of findings reinforces the core mechanistic framework proposed in SOVM.

Historical infections may also contribute. Endoscopic biopsy confirmed prior exposure to Actinomyces, and medical records indicate past Parvovirus B19 infection. Though not formally studied in SOVM, both have been implicated in ACE degradation or autoantibody-mediated disruption of RAAS signaling in other contexts. Such interference could plausibly reduce angiotensin II availability, contributing to delayed vasoconstriction and insufficient baroreflex adaptation seen in this case.

Furthermore, the patient’s immune profile reflects a chronic, low-grade inflammatory state. Complement component C4a levels have remained persistently elevated, peaking above 12,000 ng/mL. Intermittent increases in C3 (up to 227 mg/dL) and persistent elevations in C4 (up to 64 mg/dL) were noted. High-sensitivity C-reactive protein (hs-CRP), a marker of systemic inflammation and endothelial stress, has remained elevated over two decades, with values such as 16.74 mg/L. ANA testing was recently positive (2+) with homogeneous and fine discrete speckled patterns, though disease-specific antibodies (e.g., anti-dsDNA, SSA, SSB) were negative. Collectively, these findings suggest non-specific immune activation contributing to endothelial dysfunction, blood-brain barrier vulnerability, and excitatory neural signaling. These immune-inflammatory effects likely intersect with the RAAS profile and genetic predispositions to destabilize cerebrovascular tone during sleep transitions.

Interestingly, the patient experienced episodic symptom relief through interventions targeting neurovascular tone, inflammation, and CSF dynamics. These included alkalinizing agents, bile acid sequestrants like cholestyramine, activated charcoal, and at times positional strategies—like elevating both the head and feet of the bed. Notably, 5% topical liposomal lidocaine cream reliably provides relief from hypnic jerks. Lidocaine, a voltage-gated sodium channel blocker traditionally used as a local anesthetic, has also been reported by group members to reduce symptoms when administered topically, intravenously, or during dental procedures. This suggests a potential central neuromodulatory effect warranting further investigation (see Section 5).

Further supporting the vascular tone hypothesis, research by Bojarskaite et al. demonstrates that rhythmic pulsations of cerebral blood vessels are essential for cerebrospinal fluid clearance and solute transport via perivascular pathways [35]. Their findings suggest that reduced vascular dynamics during specific sleep cycles can impair glymphatic flow, reinforcing the hypothesis that tone dysregulation—as seen in SOVM—may contribute not only to impaired perfusion, but also to metabolic congestion and excitatory instability at sleep onset. This highlights a plausible downstream consequence of RAAS underactivity and insufficient baroreflex adaptation in the present case.

Finally, autonomic dysfunction may extend beyond the cerebrovascular system. As previously mentioned, the patient was unable to complete a NIOX (FeNO) airway tone test prior to albuterol administration. This may reflect dysregulation of airway tone under autonomic control, aligning with her Valsalva findings of sluggish sympathetic vasoconstriction. Both tests suggest a broader tone instability across vascular and respiratory systems, particularly under stress or transition states.

3.1 Clarifications on sleep transition timing and naming

Clinically, symptoms of SOVM typically begin during sleep onset (the hypnagogic transition), often presenting as jerks during the initial descent into sleep. Over time—and particularly with increasing physiologic stress or inflammation—these symptoms may also emerge to during transitions out of sleep—most commonly in early-morning or intra-sleep arousals. Many individuals with SOVM eventually become unable to remain asleep for more than a few hours at a time—most commonly waking after 3 to 4 hours—despite falling asleep with relative ease. This disruption in sleep maintenance further amplifies physiologic stress and destabilizes downstream systems.

The pattern suggests a broader dysregulation of vascular tone during light (theta-dominant) N1 sleep, extending beyond sleep onset alone. While the name 'Sleep-Onset Vasomotor Myoclonus' reflects the condition’s initial presentation, growing evidence indicates that its physiologic vulnerability spans multiple transitions within light sleep. The term SOVM is retained for clarity, while acknowledging its broader applicability.

3.2 Expanded pathophysiologic considerations

In the same patient described earlier, additional symptoms emerged several years later—including intermittent jaw pain and sudden head throbbing described as a "strangled" sensation. Imaging and surgical evaluation revealed bilaterally thickened and mildly elongated styloid processes, one of which lay adjacent to the internal carotid artery, glossopharyngeal nerve (CN IX), vagus nerve (CN X), and accessory nerve (CN XI). Resection of the styloid processes—performed to a level above the lateral process of C1—fully alleviated the discomfort. Although not part of the initial diagnostic work-up, these findings illustrate how structural or compressive factors may amplify or perpetuate symptoms in SOVM. The patient continues to experience intermittent tenderness on the scalp and ears, which may reflect lingering regional imbalances in intracranial pressure or dysregulated cranial nerve signaling—consistent with altered neurovascular tone.

Similar reports of cranial tenderness, mechanical sensitivity, or postural symptom flares have also been shared by members of the hypnic jerking support group. These converging patterns suggest that structural contributors may play a broader, underrecognized role within the SOVM framework, particularly when situated near vascular or autonomic pathways.

3.2.1 Electrical vs vascular instability

While traditional frameworks often attribute myoclonic jerks to cortical or subcortical electrical instability, the present case suggests that these events may emerge from transient dysregulation of neurovascular tone. Genetic variants affecting ion channels (e.g., CACNA1H, KCNAB2, SCN1A) and vasomotor regulators (e.g., EPAS1) may contribute to heightened neuronal excitability, yet the clinical pattern—especially the sleep-onset timing, the response to acetazolamide, and the exacerbation of symptoms by vasoactive agents—points to a primary vulnerability in vascular regulation. Rather than being seizure-driven, the jerks in this case appear to reflect an electrically sensitive system reacting to abrupt shifts in cerebral blood flow, intracranial pressure, or perfusion gradients. This interplay suggests that neuronal hyperexcitability may not be the initiating cause but rather a downstream amplifier of vasomotor instability at the moment of sleep transition.

In this context, even external interventions—such as bodywork—may exert opposing effects depending on how they interact with vascular versus electrical sensitivity. Gentle, targeted manual therapies like craniosacral therapy, osteopathy, or Atlas Orthogonal chiropractic may support cerebrovascular tone, CSF flow, and autonomic regulation without provoking excess excitability. However, deeper or more forceful techniques may trigger sudden shifts in blood flow or intracranial pressure, inadvertently amplifying symptoms through reflexive neuronal responses.

Notably, the patient’s small fiber neuropathy, confirmed by skin biopsy in 2006 and 2018, resolved following a course of perineural injection therapy. This therapeutic response—accompanied by improved sleep stability and reduced hypnic jerking—suggests that peripheral C-fiber dysfunction may amplify neurovascular tone instability at the sleep–wake transition. While typically classified as a sensory neuropathy, small fiber dysfunction also impacts autonomic tone and vascular regulation, implicating it as a plausible contributor to the impaired baroreflex and vasomotor lability observed in SOVM. In addition, approximately 20 members of the patient-led support group have confirmed small fiber neuropathy diagnoses, reinforcing its potential relevance across similarly affected individuals. These findings support the hypothesis that peripheral sensitization may play a role in the excitatory threshold instability central to SOVM.

These observations further underscore the distinction between primary vascular instability and secondary electrical reactivity, reinforcing the need to tailor interventions accordingly.

3.3 Barriers to recognition, diagnosis, and treatment implementation

In addition to its clinical and physiologic ambiguity, SOVM may be overlooked due to its partial overlap with Restless Leg Syndrome (RLS). RLS is typically limited to the lower extremities and is characterized by a voluntary (awareness of the) urge to move, often occurring before sleep onset. In contrast, SOVM involves full-body, involuntary jerks that occur during N1 sleep, without any conscious sensation or urge to move.

There are several reasons why hypnic jerking remains poorly researched and clinically misunderstood:

Episodes occur at the edge of sleep, when cognition and memory formation are diminished, making them difficult for patients to describe clearly.
Mild hypnic jerks are common, obscuring recognition of more severe, chronic variants.
These severe presentations are often misattributed to stress, anxiety, or psychiatric causes.
Standard EEG and EMG studies typically fail to capture abnormalities. More broadly, symptoms lack visible pathology or clear biomarkers, and abnormalities are rarely identified through standard diagnostic panels.
Multiple contributors—such as ion channelopathies and CSF flow restriction—complicate classification and discourage investigation, particularly given that SOVM represents a newly emerging framework not yet reflected in existing diagnostic models.

At the time of writing, the author’s private support group includes nearly 3,000 members from around the world. The volume and consistency of symptom descriptions shared in this forum point to a potentially underrecognized clinical pattern. These shared experiences not only reinforce the recurring features described in this case but also highlight common trajectories in misdiagnosis and management.

Among support group members and registry participants, benzodiazepines are commonly prescribed as a first-line treatment, often in the absence of investigation into underlying autonomic, neurovascular, or inflammatory mechanisms. While these agents can temporarily suppress symptoms, members frequently report that long-term use worsens sleep quality and contributes to greater physiologic instability over time. In many cases, physiologic dependence develops, and attempts to discontinue the medication may trigger symptom rebound or exacerbation of hypnic jerking. This aligns with published research showing that chronic benzodiazepine use may impair adaptive sleep mechanisms and disrupt restorative sleep architecture [36, 37].

Moreover, when symptoms are suppressed in this way, the urgency to investigate underlying drivers often disappears—delaying or preventing root-cause exploration. In practice, this creates a double barrier: physicians stop searching for explanations, and patients become biochemically unable to pursue other options. Many group members report that once they are prescribed nightly benzodiazepines, they are unable to trial non-pharmacologic interventions—including supplements targeting neurovascular tone or excitability—until they undergo a gradual taper. This taper process can take months or even years, significantly delaying access to potentially stabilizing therapies. In this way, benzodiazepine use not only obscures the diagnostic picture but also directly impedes progress once patients begin seeking more mechanism-based care.

In the case under review, despite consultation with hundreds of physicians, this same class of medication was repeatedly prescribed. Clinicians only investigated vascular or autonomic factors after the patient’s repeated requests. This pattern is echoed across the global support group, underscoring a widespread reliance on symptom suppression over root-cause exploration. The result is a persistent diagnostic blind spot in chronic sleep-onset movement disorders.

Yet in this case, clear and reproducible physiologic patterns were observed across multiple domains—including improved exhalation metrics following beta-agonist administration and mild autonomic irregularities on standardized testing. However, these findings were still frequently minimized or deemed clinically insignificant, simply because they failed to align with conventional diagnostic criteria.

Even when patients are equipped with clear plans—whether developed through AI-assisted health tools, self-research, or clinician collaboration—implementation often proves difficult. Many in the support group report that, despite having a beta-tested list of actionable next steps, access to appropriate testing, imaging, or therapeutic trials is frequently blocked by physician skepticism, limited regional resources, or the absence of defined specialist pathways.

These limitations reflect a broader pattern of diagnostic inertia, in which atypical or cross-disciplinary symptoms are dismissed for failing to conform to established diagnostic frameworks. This paper highlights a critical gap in current medical paradigms: when vascular, neurologic, and autonomic dysregulation converge outside recognized diagnostic categories, patients are often left without meaningful interpretation or clinical support. This disconnect highlights a deeper issue: the fragmentation of care across specialties. The need for a more integrative, systems-level approach is especially urgent in cases like this, where symptom reproducibility exists, but institutional recognition does not.

SOVM may reflect a spectrum disorder rooted in early-stage baroreflex adaptation delay and RAAS underactivity. These impairments may be amplified and even driven by genetic channel vulnerability, hormonal fluctuation or deficiency, and mechanical CSF/venous outflow compromise. Sleep-transition physiology and perfusion timing warrant deeper investigation as clinical entry points for identifying early cerebrovascular-autonomic syndromes. In this case review, earlier sleep onset—typically before 10:30pm and occasionally as early as 9:30pm—has been associated with reduced hypnic jerking and higher sleep scores, suggesting that circadian alignment may help stabilize neurovascular tone at sleep onset. This observation underscores the need for dynamic, context-specific testing beyond standard in-office evaluations.

The recognition of SOVM challenges existing frameworks by suggesting that subtle neurovascular imbalances during vulnerable sleep transitions—including both initial sleep-onset and intra-sleep arousals—may underlie not only movement phenomena, but a broader range of unexplained sleep-state disturbances. This case review illustrates that even longstanding, treatment-resistant symptoms can improve with carefully targeted interventions. Drawing on both an individual case and group-level patterns, this paper offers a proof-of-concept for others with similar presentations.

As a newly defined entity, SOVM exposes a critical gap in current sleep and neurological taxonomies. Formal inclusion in rare disease classifications could enhance diagnostic precision, guide treatment innovation, and bring visibility to a distinct yet under-recognized patient population. Future research should focus on early detection of vasomotor, cerebrovascular, and autonomic vulnerabilities to prevent chronic sleep-state disruption.

In summary, this review introduces a unified framework linking hypnic jerks with vascular-autonomic instability during vulnerable sleep transitions, including both sleep-onset and intra-sleep arousals. While hypotheses remain preliminary, reframing chronic jerking as a marker of subclinical cerebrovascular tone dysregulation opens the door to diagnostic clarity and therapeutic development.

This section outlines six priority areas for future investigation that may help refine diagnostic frameworks and therapeutic strategies for incessant hypnic jerking or SOVM. These include mechanistic contributors—such as neurovascular dysregulation, fluid imbalance, immune activation, and genetic variation—as well as emerging diagnostic tools and integrated research models aimed at capturing the multisystem nature of this condition.

5.1 Genetic contributors to bradykinin clearance

Future investigations into SOVM and related syndromes could explore whether genetic or acquired impairment in bradykinin-degrading enzymes contributes to neurovascular instability, inflammatory sensitization, and sleep-state dysregulation. These enzymes include angiotensin-converting enzyme (ACE), aminopeptidase P (APP), and carboxypeptidase N (CPN), which collectively regulate the clearance of bradykinin—a potent vasodilator and blood–brain barrier disruptor. Research on bradykinin metabolism highlights the central role these enzymes play in breaking it down and preventing its accumulation. Reduced activity of these enzymes—whether due to genetic variation, post-infectious injury, or microbial interference (e.g., Actinomyces species)—could plausibly result in sustained bradykinin elevation and downstream effects such as increased vascular permeability, fluid shifts, and central sensitization. For example, studies show that inhibitors of ACE, a key bradykinin-degrading enzyme, can lead to increased bradykinin levels and angioedema through this mechanism [38]. Furthermore, studies using a bradykinin B2 receptor agonist have demonstrated a transient disruption of the blood-brain barrier [17].

Genetic screening for RAAS-related and bradykinin-degrading polymorphisms, such as ACE Del/Del, AGT, or APP variants, may help identify shared susceptibilities in patients with chronic hypnic jerks or autonomic instability. While these specific genes have not yet been systematically studied in the context of hypnic jerking, prior literature has linked ACE I/D polymorphisms to systemic inflammatory states [22] and APP mutations to early-onset Alzheimer’s disease [39], suggesting broader neurovascular involvement.

5.2 Genetic contributors to electrical and fluid balance

In parallel with enzymatic pathways, underlying ion channel dysfunction has also emerged as a potential contributor to SOVM and related syndromes. Across individuals reporting similar symptom profiles—particularly those with chronic sleep-onset myoclonus, intermittent nocturnal polyuria, and sensitivity to fluid or electrolyte shifts—a pattern of ion channel variants has begun to surface. Multiple members of a patient support group, including the subject of this case, have tested positive for channelopathies identified through epilepsy or seizure gene panels, most commonly involving potassium and calcium channels. These mutations may amplify neuronal excitability while disrupting vascular tone regulation and renal electrolyte handling, together contributing to cortical hyperexcitability and homeostatic instability during the sleep transition. In some cases, clinicians have observed synergistic effects between potassium and calcium channel variants, amplifying vulnerability during sleep-state transitions. This pattern aligns with findings that astrocytic calcium signaling, which plays a key role in regulating slow-wave sleep, is reduced during sleep itself [7]. Such observations further implicate central ion channel dysregulation in the pathogenesis of SOVM. Future studies may also explore the reported clinical benefit of synaptic excitability modulators such as levetiracetam and brivaracetam in patients with SOVM-like presentations. Genetic screening using seizure panels and whole-exome or whole-genome sequencing should be prioritized, with expanded focus on AQP2, AVPR2, and other genes involved in vasopressin signaling and renal water transport, to better characterize the genetic architecture of this syndrome and its overlap with autonomic–fluid dysregulation.

The convergence of RAAS (ACE, AGT), ion channel (SCN1A, CACNA1H, KCNAB2), coagulation (F2), and hypoxia-sensitive vasomotor regulators (EPAS1) in this case highlights genetic constellations worthy of further investigation. These ion channel genes have been previously implicated in excitability and sleep-state transition physiology [10, 18, 19, 24, 25]. Although a single case cannot establish causality, the presence of multi-systemic variants affecting vascular tone, neuronal excitability, and perfusion regulation underscores the value of future multi-gene screening efforts. Each variant was interpreted in the context of its known or suspected role in neurovascular regulation, osmoregulatory function, or excitability pathways— mechanisms central to the proposed SOVM framework.

Assembling these findings required five distinct genetic samples, processed at five separate laboratories spanning clinical, research, and third-party settings over multiple time points. This multi-platform approach was essential to capturing the full spectrum of relevant variants, spanning pathogenic, modifier, risk factor, and VUS classifications. The need for cross-laboratory analysis underscores the diagnostic complexity of SOVM and highlights the current limitations of relying on single-platform sequencing for rare, multifactorial conditions.

To support future genetic investigation, a broader list of candidate genes is provided in Supplemental Table 1. These include genes involved in ion transport, vascular regulation, bradykinin signaling, osmoregulation, and neuroinflammatory processes, with known or suspected relevance to sleep-state physiology. Although no additional clinically significant variants in these pathways were identified in this case review, their biological relevance to state-transition stability and neurovascular homeostasis warrants further exploration in larger cohorts. Notably, several of the framework-driven candidate genes listed have also appeared in support group members’ genetic testing results, suggesting emerging areas of overlap that merit further study.

5.3 Mechanical and neuroimmune contributors

It is possible, based on the case presentation, that mechanical compression of blood vessels or nerves may contribute to persistent immune activation and vascular instability in SOVM. Stagnant venous flow and endothelial stress may contribute to IL-6 and CRP elevation, as has been proposed in inflammatory and mechanical stress contexts. Similarly, nerve compression can stimulate local release of inflammatory mediators and complement proteins, amplifying systemic immune responses.

These mechanisms may help explain how structural abnormalities such as cervical instability or venous outflow restriction, contribute to the chronic elevations in hs-CRP, C4 and C4a observed in this patient. Future research should investigate the role of mechanical stress in driving immune dysregulation and vascular tone instability in sleep-onset vasomotor disorders.

5.4 Vascular-autonomic tone contributors

Beyond ion transport mechanisms, disruptions across fluid-regulatory, inflammatory, and autonomic systems—including RAAS, vasopressin signaling, bradykinin pathways, and neurosensory feedback loops—may further destabilize vascular tone, renal handling of fluid, and sleep-state homeostasis in SOVM. For example, aberrations in RAAS—whether through reduced ACE activity, altered angiotensin II signaling, or genetic polymorphisms in RAAS components (e.g., REN, AGT, AGTR1)—could impair kidney responses to volume shifts and potentiate nocturnal fluid loss [21]. Similarly, genetic or functional impairments in vasopressin-mediated water balance—through abnormalities in AQP2 water channels, AVPR2 receptors, and associated regulatory proteins—may underlie cases of intermittent nocturnal polyuria and dehydration tendencies observed in this patient population [40]. These pathways have been implicated in disorders of salt wasting and nocturnal diuresis, though their role in SOVM remains speculative.

Investigating both RAAS and vasopressin signaling genes, alongside clinical correlates such as salt wasting, nocturnal diuresis, and blood pressure instability, could reveal critical mechanistic links between autonomic dysfunction, vascular permeability, and sleep-state disturbance in SOVM and related syndromes.

5.5 Emerging diagnostic methodologies

Based on the mechanistic hypotheses raised by this case, several diagnostic tools warrant systematic inclusion in future clinical evaluations and research protocols involving patients with chronic sleep-onset vasomotor symptoms. Recommended assessments include: baroreflex sensitivity testing (BRS) to evaluate autonomic reflex integrity; supine and upright plasma renin, aldosterone, and angiotensin levels to assess RAAS function and fluid-regulatory tone; and 24-hour ambulatory blood pressure monitoring to detect positional or nocturnal instability often missed during office visits. Functional brain perfusion studies, such as single-photon emission computed tomography (SPECT) or arterial spin labeling (ASL), may offer insight into cerebrovascular tone, while autoimmune panels—particularly testing for angiotensin II type 1 receptor antibodies (AT1-AA)—may help identify inflammatory or molecular mimicry-based contributors.

In addition, future research should incorporate high-sensitivity EMG protocols during overnight polysomnography (PSG), modeled after EFM criteria [5], to improve detection of subtle or segmental myoclonus. This includes multi-channel EMG targeting relevant muscle groups with thresholds sensitive to bursts ≤ 150 ms and ≥ 50 µV in amplitude. Collectively, these modalities offer a framework for targeted, cross-disciplinary investigation into the neurovascular, immune, and fluid-regulatory underpinnings of this emerging syndrome.

While high-sensitivity EMG can occasionally capture muscle bursts consistent with myoclonus, these events are rarely associated with epileptiform discharges on EEG. Among a cohort of nearly 3,000 affected individuals, only a small handful have demonstrated EEG abnormalities. This suggests a mechanism involving non-epileptic cortical or subcortical hyperexcitability that evades conventional EEG thresholds. Future studies should explore whether modifying EEG parameters—such as increasing gain, adjusting montage configurations, or employing sleep-state-specific protocols—could improve detection of subclinical electrical instability during sleep transitions in this population.

Beyond conventional instrumentation, certain interventions may themselves serve diagnostic value by revealing physiological responsiveness within specific pathways. While this paper does not propose a formal treatment protocol, the framework outlined here highlights several physiologically grounded targets for further investigation, including cerebrospinal fluid regulation, neuronal excitability, neurogenic inflammation, cerebrovascular tone regulation, and bradykinin reduction. Of particular interest is therapeutic targeting of the bradykinin pathway (e.g., B2 receptor antagonists), which remains a plausible avenue for study. Mechanisms such as mast cell activation and release of neuroinflammatory peptides (e.g., substance P) may also contribute to excitability and pain sensitivity at sleep onset and deserve further exploration within the neurogenic inflammation domain. A conceptual summary of these mechanistic domains and candidate therapies is provided in Supplemental Table 2.

One example is lidocaine, referenced in the second row of Supplemental Table 2, which modulates central excitability and alters pain thresholds through sodium channel regulation [41–42]. By stabilizing membrane potentials and reducing synaptic overactivation, lidocaine may help restore neuronal balance. Even in the absence of sodium channel gene variants, secondary upregulation of sodium currents may occur in chronic ion channelopathy states, amplifying excitatory signaling. In such cases, dampening sodium activity may interrupt abnormal neurovascular feedback loops. These effects support a systemic ion channel instability framework, consistent with the calcium and potassium channel variants identified in this case. This adds further support to the theory of dynamic physiologic instability driving the jerking episodes.

Another agent of interest, listed in the fourth row of Supplemental Table 2, is clonidine, a centrally acting alpha-2 adrenergic agonist. Some patients with hypnic jerking report that clonidine facilitates return to sleep following middle-of-the-night awakenings, particularly during episodes of heightened excitability or neurovascular instability. These episodes are often described in visceral terms—such as a rushing sensation in the head, pounding or pulsing before sleep, feeling flushed or agitated, or waking with head pressure and a racing heart—reflecting the physiologic instability clonidine may help modulate. Its known effects include reducing sympathetic outflow, lowering circulating norepinephrine, and stabilizing blood pressure, making it well suited to address the autonomic dysregulation hypothesized in SOVM. By dampening noradrenergic arousal and modulating vascular tone, clonidine may interrupt the feedback loop contributing to sleep-onset jerking. These observed effects position clonidine as both a therapeutic and potentially diagnostic tool within the SOVM neurovascular framework.

In addition to pharmacologic and procedural approaches, a recent community trend has drawn attention to the use of pre-sleep vibration plates as a promising adjunctive strategy. Multiple group members report marked reductions in hypnic jerking following consistent use of vibration plates before bedtime. While the mechanism remains unclear, potential pathways include modulation of cerebrovascular tone, autonomic stabilization, enhanced lymphatic or glymphatic flow, and somatosensory recalibration. Though anecdotal, this trend warrants systematic evaluation, ideally using physiologic monitoring of vascular, lymphatic, or autonomic responses.

In parallel, many group members have reported that behavioral techniques such as gargling, humming, or singing produce mild dampening of jerking episodes. These techniques likely enhance vagal tone and support autonomic balance. As emerging non-invasive approaches, they warrant structured investigation to clarify their role within the broader SOVM framework.

5.6 Integrated systems approach

Although no unified research framework currently exists for investigating chronic sleep-onset myoclonus or its associated vascular and fluid regulatory abnormalities, this case review illustrates a replicable, systems-level approach. Table 1 provides a practical summary of the domains most affected in this patient and may serve as a foundation for structured evaluation in future cases and inform future cross-disciplinary investigation. By mapping converging evidence across imaging, immune function, autonomic testing, genetic analysis, and sleep-state physiology, this framework offers a starting point for collaborative, cross-disciplinary research aimed at illuminating the mechanisms of SOVM and identifying actionable biomarkers.

5.7 Toward ICSD recognition and improved physiologic capture

Growing interdisciplinary interest supports next-step efforts toward the formal recognition of SOVM within the International Classification of Sleep Disorders (ICSD). A collaborative sleep research team is currently reviewing the emerging phenotype, proposed diagnostic criteria, and neurovascular framework described in this manuscript. Their goal is to determine whether SOVM demonstrates the degree of consistency and clinical utility required for consideration in a future ICSD revision. Such inclusion requires reproducible clinical features, clearly defined diagnostic criteria, and supportive case-series or cohort-level evidence—benchmarks that early SOVM data appear increasingly able to meet.

In parallel, work is underway to determine how SOVM can be more reliably identified during standard clinical sleep studies. Conventional polysomnography (PSG), EEG, and EMG often fail to capture the rapid neurovascular oscillations, micro-vasomotor shifts, and autonomic-phase transitions that define the disorder at sleep onset. Pilot efforts are now exploring modified physiologic parameters, including: high-resolution multi-channel EMG, beat-to-beat blood-flow and vascular-tone metrics, cerebrovascular perfusion indices, autonomic-phase tracking, and sleep-state-transition–specific signal processing. These approaches may yield objective markers of the oscillatory vasomotor instability hypothesized to underlie SOVM.

Together, these developments underscore both the clinical need and the research momentum behind establishing SOVM as a sleep-transition disorder within formal nosology. Improved physiologic capture is essential not only for diagnostic accuracy, but also for advancing mechanistic research, enabling interventional trials, and helping clinicians distinguish SOVM from epileptic, parasomnic, or anxiety-related sleep-onset phenomena. Continued refinement of classification criteria and sleep-study methodology will be crucial for moving this condition toward broad clinical recognition.

A1 – Angiotensin I

A2 – Angiotensin II

ACE – Angiotensin-Converting Enzyme

ADH – Antidiuretic Hormone

ANP – Atrial Natriuretic Peptide

APP – Amyloid Precursor Protein

BBB – Blood–Brain Barrier

C3, C4 – Complement components 3 and 4

CGRP – Calcitonin Gene-Related Peptide

CPN – Carboxypeptidase N

CSF – Cerebrospinal Fluid

EFM – Excessive Fragmentary Myoclonus

FeNO – Fractional exhaled Nitric Oxide

HPA – Hypothalamic–Pituitary–Adrenal

HRV – Heart Rate Variability

IIH – Idiopathic Intracranial Hypertension

INP – Intermittent Nocturnal Polyuria

NO – Nitric Oxide

PEA – Palmitoylethanolamide

POTS – Postural Orthostatic Tachycardia Syndrome

PSM – Propriospinal Myoclonus

RAAS – Renin–Angiotensin–Aldosterone System

SFN – Small Fiber Neuropathy

SOVM – Sleep-Onset Vasomotor Myoclonus

SPM – Specialized Pro-Resolving Mediator

VIP – Vasoactive Intestinal Peptide

WES – Whole Exome Sequencing

Ethics approval and consent to participate

Not applicable.

Consent for publication

The author confirms that she is the subject of this case study and has provided full informed consent for the publication of all personal, clinical, and genetic data contained within the manuscript.

Availability of data and materials

All data supporting the conclusions of this article are included in the manuscript.

Competing interests

The authors declare that they have no competing interests.

Funding

Not applicable.

Authors’ contributions

The author researched and gathered information for the case report and group findings, including the literature review, clinical synthesis, and proposed diagnostic framework. She compiled all supporting documentation, coordinated expert review and incorporated personal patient data spanning over two decades of observation.

Acknowledgements

The author thanks Sheryl Leventhal, MD, for her medical insight, validation, and ongoing support in the investigation of this condition. She also wishes to acknowledge Scott Bender, DC and Denna Dashti, DC for their critical chiropractic insight and for contributing essential structural and flow-related data that informed this case. Special thanks to Jacqueline DeVries, MS, whose collaborative research, tireless exploration, and investigative partnership helped shape many of the insights presented in this report. The author also wishes to express heartfelt gratitude to the members of the Hypnic Jerking Support Group whose shared experiences, insights, and resilience have been instrumental in shaping the clinical understanding and validation of this condition. She further thanks Austin Letcher of Engage Health, for lending his expertise and supportive ear.

Portions of this manuscript were developed using an AI-based writing and editing tool (OpenAI ChatGPT), under the full direction and oversight of the author. Whole-exome sequencing was performed in collaboration with the Manton Center for Orphan Disease Research at Boston Children’s Hospital.

Authors’ information

Tracy Hans, LPC, ACS, is the founder of the Therapeutic Alliance Group, Paramus, New Jersey, USA. She is a licensed psychotherapist, patient-researcher, and advocate who has lived with chronic hypnic jerking for over two decades. In 2017, she co-founded the first global support community dedicated to this condition, which now includes nearly 3,000 members. In 2018, she created the first hypnic jerking patient registry in collaboration with Sanford Research. The following year, she helped organize a study of 10 affected individuals and their relatives in partnership with the Manton Center for Orphan Disease Research at Boston Children’s Hospital. In 2020 she launched hypnicjerking.com, the first website focused on research, education, and awareness for sleep-onset movement disorders.

Tracy has previously contributed to research related to her profession and published a meta-analysis on locus of control in the Journal of Contemporary Psychotherapy.

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Table 1. Multidimensional screening domains based on case findings

Domain	Finding in case	Proposed screening method in future studies
Neurovascular tone and flow	CSF flow restriction (cervical MRI), transverse sinus stenosis, and vascular tone shifts; EPAS1 variant (rs7557402) may impair oxygen-sensitive sympathetic regulation	Flexion/extension cervical MRI; MR (Angiography, Venography) of the brain and cervical vasculature; CSF flow MRI; exome analysis including EPAS1 and related genes.
Ion channel function	CACNA1H, SCN1A and KCNAB2 variants (calcium, sodium and potassium channels)	Genetic epilepsy/seizure panels; ion channel gene analysis
RAAS underactivity	ACE I/D polymorphism (Del/Del) and AGT variant (rs699) suggest reduced RAAS function. Clinically low levels of ACE and angiotensin II along with low normal angiotensin I.	Exome analysis for RAAS genes (ACE, REN, AGT, AGTR1), and blood testing for angiotensin I and II to evaluate upstream RAAS tone
Bradykinin pathway disruption, impaired degradation	ACE level gene variant identified via WES	Analysis of ACE, APP (XPNPEP2), and CPN (CPN1/CPN2) genes
Immune activation	Persistent elevation of complement C4a (ranging 3000–24,000 over two decades); chronic hs-CRP elevation (15–16 mg/L); mild C4 elevation; positive ANA without specific antibodies	Blood markers of chronic immune activation (complement system—C4 and C4a), hs-CRP and ANA levels
Autonomic instability	Moderate phase II decline on Valsalva, with delayed sympathetic recovery and small phase IV overshoot reflects sluggish vasoconstriction BP and HR spikes noted during sleep-wake transitions suggest state-dependent baroreflex impairment Incomplete NIOX (FeNO) test until post-albuterol; suggests airway tone instability	Formal autonomic testing (tilt-table, Valsalva maneuver); overnight or positional blood pressure monitoring to identify transition-state surges. NIOX (FeNO) testing to explore airway tone dysregulation.
Renal water balance	Salt-wasting episodes, delayed ADH recovery after water deprivation test; persistently undetectable serum ADH (< .8 pg/mL) with low-normal osmolality (284 mOsm/kg) suggesting impaired ADH response	Serum/urine electrolytes; urine osmolality; water deprivation testing, repeat plasma ADH.
Structural compression	Styloid elongation, chronic atlas misalignment	MR (Venography) or CT (Venography), ruling out Eagle syndrome, Thoracic outlet syndrome and cervical instability
Sleep transition disruption	Hypnic jerking linked to vascular/sympathetic shifts	Sleep study with cardiorespiratory and autonomic monitoring
Sleep timing alignment	Occasional improvements in sleep scores and reduced hypnic jerking when sleep onset occurs early (before 10:30pm), possibly due to circadian alignment and reduced vasomotor stress	Sleep diary or wearable sleep tracker (e.g., Oura Ring) to assess timing-dependent symptom changes; trial of earlier sleep onset to evaluate response.
Medication sensitivity profiles	Hypersensitivity to substances that cause abrupt changes in vascular tone (e.g., magnesium, VIP, Benadryl, Naratriptan).	Structured medication provocation history

Notes:

Summary of diagnostic categories identified through clinical evaluation, imaging, laboratory testing, and genetic analysis in a patient with chronic, treatment-resistant sleep-onset myoclonus.

This table summarizes diagnostic categories identified through clinical evaluation, imaging, laboratory testing, and genetic analysis in a patient with chronic, treatment-resistant sleep-onset myoclonus. These domains reflect key areas of physiologic disruption and may offer a pragmatic framework for evaluating patients with chronic sleep-onset myoclonus or suspected SOVM. Suggested screening methods are included to support mechanism-based diagnostic approaches.

Table 2. Confirmed genetic variants

Gene	Zygosity	Pathogenicity	Clinical relevance	Source/Testing method
RAAS & Vascular tone modulators
ACE
Del/Del (Alu 287bp)	Homozygous	Functional modifier	Associated with reduced ACE activity, lower angiotensin II levels, and impaired bradykinin degradation; contributes to RAAS underactivity and vascular tone instability	Methylation pathway analysis (holistic health international)
AGT
c.803T>C (p.Met268Thr, rs699)	Heterozygous	Risk factor	May increase angiotensinogen expression; in the context of ACE deletion, may exacerbate RAAS underactivity and fluid regulation abnormalities	Sequencing.com; genetic genie interpretation of 23andMe data
EPAS1
c.580G>A (p.Ala194Thr, rs7557402)	Heterozygous	Risk factor/VUS	Regulates oxygen-sensitive vasomotor tone, vasopressin release, and renin expression; may impair sleep-state adaptation	Sequencing.com (WES based analysis)
Coagulation
F2
G20210A (rs1799963)	Heterozygous	Pathogenic	Increased risk of clotting events	LabCorp clinical test; 23andMe; Sequencing.com
Neurodevelopmental/Synaptic coupling
RELN
c.8056G>A (rs754635743)	Heterozygous	VUS	Variant of uncertain significance, previously linked to neurodevelopmental disorders	Fulgent genetic epilepsy panel
Ion channelopathy/Excitability genes
CACNA1H
c.4790G>A (p.Arg1597Gln,rs200579402)	Heterozygous	VUS	Voltage-gated calcium channel involved in neuronal firing, reflecting altered calcium channel functioning	fulgent genetic epilepsy panel (WES based analysis)
c.3958G>A (p.Glu1320Lys, rs370079169)	Heterozygous	VUS
KCNAB2
c.910C>T (p.Pro304Ser)	Heterozygous	VUS	Regulates potassium currents; may modulate excitability	Fulgent genetic epilepsy panel
SCN1A
c.3184A>G (P.Thr1067Ala, rs3812718)	Heterozygous	Risk factor	Linked to increased risk of seizure reaction; sodium channel mutation	Sequencing.com (WES based analysis)

Notes:

This table outlines confirmed genetic variants identified in the patient that align with key domains of the SOVM framework, including vascular tone, fluid balance, and autonomic regulation. These variants may help guide targeted screening and inform mechanism-based interpretation in patients with similar symptom profiles. Pathogenicity designations are based on variant classification systems from ClinVar, testing laboratory reports (LabCorp, Fulgent), and third-party genomic interpretation (Sequencing.com).

The authors declare no competing interests.

SupplementalTable1SOVMCandidateGenes.docx
Title of data: Supplemental Table 1: Candidate genes aligned with the SOVM framework Description of data: This table lists candidate genes grouped by functional domain for consideration in genetic review. These genes have been selected based on known or proposed relevance to neuronal excitability, vascular tone regulation, osmoregulation, bradykinin signaling, and sleep-state transition physiology. They include both confirmed and hypothesized contributors drawn from this case and broader pathophysiological frameworks.
SupplementalTable2SOVMCandidateTherapies.docx
Title of data: Supplemental Table 2: Candidate therapies aligned with the SOVM framework Description of data: This table depicts conceptual mapping of candidate intervention categories aligned with five proposed mechanistic domains of Sleep-Onset Vasomotor Myoclonus (SOVM). These include CSF regulation, neural excitability, neurogenic inflammation, cerebrovascular tone, and bradykinin signaling. The table is intended to guide future research by outlining therapeutic targets derived from the case findings and neurovascular-autonomic framework described in this paper. No formal treatment recommendations are made.

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Sleep-onset vasomotor myoclonus: Reframing chronic hypnic jerks through a neurovascular lens—informed by case study and group trends

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Abstract

Figures

1 Background

1.1 Hypnic jerks: clinical context and limitations of current models

1.2 Introducing Sleep-Onset Vasomotor Myoclonus (SOVM)

1.3 Classification challenges and overlapping diagnoses

1.4 Rationale for diagnostic advancement

1.5 Emerging glial and genetic mechanisms

1.6 Structural and mechanical contributions

1.6.1 RCCX locus structural variation across cohort suggests shared susceptibility architecture

2 Case and community review

3 Discussion

3.1 Clarifications on sleep transition timing and naming

3.2 Expanded pathophysiologic considerations

3.2.1 Electrical vs vascular instability

3.3 Barriers to recognition, diagnosis, and treatment implementation

4 Conclusion

5 Areas for further research

5.1 Genetic contributors to bradykinin clearance

5.2 Genetic contributors to electrical and fluid balance

5.3 Mechanical and neuroimmune contributors

5.4 Vascular-autonomic tone contributors

5.5 Emerging diagnostic methodologies

5.6 Integrated systems approach

5.7 Toward ICSD recognition and improved physiologic capture

Abbreviations

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Tables

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