Manual cervical therapy and vestibular migraine: A case series

Background: Vestibular migraine (VM) is a relatively new diagnostic entity with incomplete knowledge regarding pathophysiological mechanisms and therapeutic guidelines. By reporting the effect of manual cervical therapy (MCT) on people with VM, we suggest a possible role for upper cervical afferents in VM treatment and/or pathogenesis. The objective was to describe the change in clinical presentation and self-reported symptoms of VM corresponding to MCT and followed up to six months. Methods: A nonrandomised *ABA design was utilised to consecutively and prospectively evaluate selected patients with diagnosed VM. Symptom characteristics (frequency and intensity) were recorded along with standardised patient-reported outcomes (PROs) to document the response to MCT. Results: Three patients were recruited who met the diagnostic criteria for VM. All three patients demonstrated improvement in both migraine attack and interictal symptom frequency. These improvements mirrored changes in PROs and were sustained over a six-month follow-up period. Conclusions: The improvement that coincided with the intervention including MCT was rapid, observable and sustained. This suggests that the upper cervical spine could be a therapeutic target in VM and may have implications for future research into the pathogenesis of VM.


Introduction
Vestibular migraine (VM) is a disorder characterised by episodes of specific vestibular symptoms, at least half of which are accompanied by features consistent with migraine (Lempert et al., 2012), and is considered to be the most frequent cause of episodic vertigo (Dieterich et al., 2016).
The diagnostic criteria for VM were formalised jointly by the Committee for Classification of Vestibular Disorders of the Bárány Society and the International Headache Society in 2012 (Lempert et al., 2012); hence, as a relatively new diagnostic entity, information regarding epidemiology is limited, with the one-year prevalence of VM (including 'probable' VM) estimated to be between 1.98% (Neuhauser et al., 2006) and 2.7% (Formeister et al., 2018).
Vertigo is a cardinal symptom for diagnosis of VM (Lempert et al., 2012), and therefore the ability of the cervical spine to cause vertigo as a symptom is central to any discussion regarding the upper cervical spine and VM.Some authors state overtly that 'vertigo is not a symptom arising from the cervical spine' (Reiley et al., 2017, p.2), whilst others consider vertigo a rare manifestation of traumatic neck pain, such that it is considered a useful symptom to differentiate from non-cervical causes of sensorimotor disturbance (Treleaven, 2017) The lack of established clinical evidence for upper cervical afferent contribution to vertigo may explain why it is not considered amongst the hypotheses for disorders contributing to the pathophysiological mechanisms underpinning VM, which currently include abnormal thalamic function, calcitonin gene-related peptide release into the inner ear and/or brainstem and/or cerebellum, genetic factors, abnormal processing of shared vestibular and nociceptive pathways, and cortical spreading depression (Furman et al., 2013).This appears discordant with clinical evidence indicating 25% of people with whiplash associated disorder report spinning as a symptom despite a lack of positive otoneurological findings (Treleaven et al., 2003).Similarly, case reports of what the authors termed 'cervical vertigo' (Brandt & Huppert, 2016), describe remission of vertiginous symptoms with resolution of neck pain.Clinical evidence is contingent on the presence of neck pain, however experimental evidence suggest non-painful afferents may also play a role in producing vertigo.Blocking afferents by injecting anaesthetic unilaterally in the upper cervical spine induced vertigo (sense of titling and falling) ipsilaterally (de Jong et al., 1977), whilst mimicking activation of cervical muscle spindles with vibratory stimulation results in both the visual environment moving contralaterally to the vibration (Jamal et al., 2020), and the sense of self-motion being either doubled (activated ipsilateral to side of rotation) or annulled (activated contralateral to side of rotation) (Panichi et al., 2011).Both clinical and experimental evidence suggest it is possible for upper cervical afferents (painful or non-painful) to contribute to vertigo as a symptom.
The widely accepted model describing neural integration of afferent inflow from the vestibular, visual and proprioceptive systems was first proposed by von Holst and Mittelstaedt (von Holst & Mittelstaedt, 1950), whereby an 'efference copy' of the intended movement is subtracted from the feedback from self-generated movement or 'reafference'.A perfect match results in sensory inflow from the vestibular system being cancelled (Figure 1a).Brooks and Cullen (Brooks & Cullen, 2014) demonstrated that aberrant feedback from upper cervical muscles failed to cancel vestibular reafference, leading to a summation of vestibular signals (Figure 1b) and resulting in vestibular symptoms.
Additional upper cervical afferents project to CNS regions believed to be involved in the pathophysiology of migraine.These include the trigeminocervical complex (Piovesan et al., 2003), hypothalamus (Malick et al., 2000), locus coeruleus (Cedarbaum & Aghajanian, 1978) and vestibular nuclei (Fredrickson et al., 1966) along with centres involved in autonomic regulation (nucleus tractus solitarius (Menétrey & Basbaum, 1987)), providing a compelling anatomical and physiological case for upper cervical afferent contribution to the symptomatic manifestation of VM. found for one therapy over another (Byun et al., 2021).Whilst no manual therapy trials have been reported for VM, a systematic review and meta-analysis in migraine indicates similar effect between different modalities (physical therapy, relaxation biofeedback, chiropractic spinal manipulative therapy -CSMT) and prophylactic medication (topiramate, propranolol, amitriptyline), however a lack of control groups lowered the clinical utility of the results (Chaibi et al., 2011).This was further emphasised with a single-blinded placebo-controlled trial into CSMT in migraine finding equivocal improvement in the treatment and placebo groups ( (Chaibi et al., 2017).Despite attempts to identify 'gaps' in knowledge (Mallampalli et al., 2022) and the body of research linking upper cervical afferents to the production of vestibular symptoms in clinical, experimental and anatomical studies, their potential contribution to the pathophysiology of VM is consistently omitted, and MCT is not currently considered a therapeutic option.
The aim of this case series is to demonstrate the effect of a novel MCT approach on the clinical presentation and self-reported symptoms of VM.The approach described by Watson (Watson, 1997), involves assessment of asymmetrical resistance to transverse pressure (TP) at C2 spinous process (SP), which is treated using sustained digital 'postero-anterior' (PA) pressure to the C3 SP, but validation as a treatment technique in a clinical population is lacking.This study aims to provide preliminary evidence in support of a novel MCT approach as a plausible modality for the treatment of VM and a basis for further research examining the role of upper cervical afferents in VM pathophysiology.

Methods
This study protocol was developed in line with the CARE guidelines for reporting on case reports (Gagnier et al., 2013) and the CENT guidelines for reporting on N-of-1 trials (Vohra et al., 2015) in an attempt to minimise bias.Ethics approval was granted by the University of South Australia Human Research Ethics Committee (protocol number: 202637).

Trial design
A case-series methodology (Vohra et al., 2015) was employed with a nonrandomised *ABA design, mimicking that of an N-of-1 study.Period '*A' (i.e., run-in) was 'usual care' and varied in length based on the clinic waiting list and participant availability to commence treatment.The duration of period *A and the nature of 'usual care' were not standardised for ethical reasons, as this would have involved delaying treatment.Period 'B' was MCT.As is standard in physiotherapy practice, the nature, frequency and timing of the interventions were not standardised and were based on participant availability and treatment response in concert with an individual's unique VM presentation.Period 'A' was postintervention.Participants did not commence any new interventions or change medications that could influence their VM symptoms throughout the data collection period (*ABA).

Eligibility criteria
Three participants (two females aged 26 and 48, a male aged 43) who were diagnosed with VM by a neurologist and met the Bárány Society criteria for VM (Lempert et al., 2012) sought  A systematic review and meta-analysis for treatment of VM indicates improvement in vertigo frequency and patient-reported perceived handicap (measured by dizziness handicap inventory) with pharmacological treatment (antiepileptic drugs, calcium channel blockers, tricyclic antidepressants, beta-blockers, serotonin and noradrenaline reuptake inhibitors), diet modification and physical therapy vestibular rehabilitation (VRT).There were no double-blinded, randomised placebocontrolled trials available for this analysis and given the low quality of evidence and similar outcomes, no preference was treatment from the participating physiotherapist (RO).Participants were excluded from the study if they had a history of previous neck surgery or traumatic brain injury, recently started or changed medication or other treatment with the potential to influence VM (i.e., antidepressant medication, anxiolytics, analgesics, vestibular suppressants, VRT), had recently started or changed MCT to the cervical spine, or were diagnosed with another chronic pain condition (i.e., fibromyalgia, complex regional pain syndrome).Any potential participants who were unable to read the information sheet or demonstrate understanding of the study information presented if read to them or had insufficient cognitive capacity to provide voluntary written informed consent or impaired capacity to communicate verbally (i.e., aphasia) were excluded.

Study setting and recruitment
The study took place at a private physiotherapy clinic in Australia.Participants were prospectively identified at the time of booking their initial consultation.Administration or clinical staff screened each patient against the Bárány Society criteria for VM (Lempert et al., 2012) and the study criteria.All potential participants were treated as study recruits; however, to avoid perceived coercion, individuals were not formally invited to participate until the end of period B. To avoid reporting bias, after period B, all prospectively identified individuals were invited to participate regardless of treatment response.

Outcomes and analysis
The primary outcome measures were symptom severity and frequency, and the use of pharmaceutical intervention, recorded in a diary tracking the presence and intensity of symptoms in period A* and the last 4 weeks of each subsequent review in period A, and therapist notes in period B. A 50% or greater change in symptom frequency over a 28-day period was considered significant (Tassorelli et al., 2018).The symptom diary was recorded in paper form, and represented each symptom experienced by the participant on a particular day, approximate duration and intensity of each symptom, and amount of medication used if required.Diaries were presented on review and verified by the clinician with the participant during which time symptoms were classified in accordance with diagnostic criteria for VM (Lempert et al., 2012).Accordingly, a migraine day was defined as a day during which the participant experienced vestibular symptoms (typically vertigo) lasting at least 5 minutes and up to 72 hours, at least half (in frequency) of which were accompanied by at least 1 migraine feature (migrainous headache, photophobia and/or phonophobia or visual aura).Any vertiginous episodes were recorded separately under internal vertigo (false sense of self motion) or external vertigo (false sense that the visual surround is spinning or flowing).Headaches, fatigue, and nausea were reported independently (Lempert et al., 2012).Assigning a day as a 'migraine day' did not exclude it being counted as a vertigo or headache day, and as such the categories are not mutually exclusive.As such, a vertigo day may, or may not, have also been included as a migraine day, depending on the presence of other diagnostic features.Patient-reported outcomes (PROs) were used as secondary outcome measures and included the Headache Impact Test-6 (HIT-6), Dizziness Handicap Inventory (DHI), and the Depression Anxiety Stress Scale (DASS-21).
The impact of headache on daily life was assessed using the HIT-6, which is a validated six-item questionnaire generating total scores from 36 to 78, with scores ≥ 60 indicating severe impact (for full scoring see (Yang et al., 2011)).In people with migraine, the within-person clinically meaningful change in the HIT-6 score over 12 weeks is estimated to be between -2.5 (mean change approach) and -6 points (ROC curve approach) (Smelt et al., 2014).We have used the more conservative six-point change to indicate improvement.
The DHI (Jacobson & Newman, 1990) is a validated 25-item scale developed to assess the handicap caused by dizziness, with total scores ranging from 0 to 100.Total scores are divided into three handicap categories from mild (0-30) to moderate (31-60) and severe (61-100) (Whitney et al., 2004).There is a standard error for test-retest indicating a minimal important change of 18 points from pre-to postintervention and three points using the ROC curve approach (Friscia et al., 2014).
The DASS-21 is a valid and reliable measure used to detect symptoms of depression, anxiety and stress (Antony et al., 1998), with subscales having independent cut-off scores (reported in (Lovibond & Lovibond, 1995)) for symptom severity that can be averaged to produce a composite measure.Minimum detectable change has been reported for each subscale as 3.86 (depression), 3.85 (anxiety) and 4.9 (stress) (Ronk et al., 2013).
Clinical records were audited at the conclusion of each participant's intervention period.Primary and secondary outcome measure data were extracted and input into Excel© (Microsoft, USA) along with details of the intervention delivered.Changes in VM attack features (frequency, severity and medication use) and impact (HIT-6, DHI and DASS-21) are presented descriptively as a series of cases using measures of 'clinically meaningful change' (Jacobson & Newman, 1990;Ronk et al., 2013;Smelt et al., 2014).

Interventions
No manipulative (localised, high-velocity thrust, low amplitude) techniques were applied.During period B, participants received an MCT intervention from a physiotherapist registered in Australia.In accordance with a specific protocol described in the introduction, manual assessment of the cervical spine determined the presence of asymmetrical response of C2 SP to TP with hypomobility typically present unilaterally.To restore a symmetrical response to TP palpation of C2 SP the therapist applied sustained digital PA pressure to the C3 SP (Watson, 1997).The direction and depth of pressure and the number and duration of sustained 'holds' were unique to each individual and appropriate for the participants' presentations (determined by manual assessment of the neck).
During the initial assessment education was also provided regarding the nature of the disorder (VM) and the potential role for upper cervical afferents, including a description of the manual assessment to follow.Subsequent treatments included demonstration of cervical retraction as a sustained stretch (20 seconds) repeated 4 times, to be done as a home exercise program up to 4 times per day (i.e.maximum 4 x 20 seconds x 4 times per day).
Due to the nature of a case series, data analysis was not conducted.However, to provide a description of change in self-reported measures pre-and postintervention, we used Hedges g effect size analysis (Shadish et al., 2015) with the magnitude of change interpreted using Cohen's d recommendations of trivial (<0.2), small (0.2-0.49), medium (0.5-0.79) and large (>0.8) (Cohen, 1988).All collated data and effect size calculations are provided in Supplementary file 1.

Cases and eligibility
Initially, four individuals were enrolled.However, one individual was excluded from the study prior to assessment due to the presence of comorbid fibromyalgia.Three eligible individuals reported having had at least five attacks, and all reported headache and visual and vestibular symptoms as features of their migraine presentation (see Table 1, Table 2, Table 3).The possibility of comorbid cervicogenic dizziness was excluded in all three participants as none demonstrated, neck pain and/or painful restriction of cervical range of motion (ROM) (Reiley et al., 2017).All participants tolerated the intervention, and no contraindications or adverse events related to the intervention were reported.
Participant 01 (P1) Participant profile.P1 was a 26-year-old female with a three-year history of vestibular symptoms after contracting a viral illness while recovering from surgery.Initially, diagnosed with vestibular neuritis, P1 experienced frequent headache, suboccipital tension (without neck pain), orthostatic and head motion-induced dizziness, spontaneous vertigo, 'slow, unclear and fuzzy' vision, and nausea.Subsequently, diagnosed with anxiety, treatment with a psychologist was unsuccessful.Venlafaxine was prescribed after a neurologist diagnosed VM, resulting in a decrease in symptoms (reported as 70-80%), but P1 was still prone to acute exacerbations with triggers.
Venlafaxine was weaned after two years with symptoms stable for six to eight weeks before returning with daily interictal symptoms.Migraine prophylaxis with topiramate (not tolerated well and ceased after two weeks) and propranolol (80 mg) was recommenced seven months prior to assessment (start of period 'B') without improvement.Venlafaxine was reintroduced four months before assessment, with slight improvement in dizziness intensity but otherwise no obvious improvement in other symptoms.P1 suffered comorbid anxiety and depression and reported improvement in these symptoms with propranolol and venlafaxine.
Migraine attacks began with paraesthesia in both feet, progressing proximally through the legs and body, subsequently resolving to be replaced by vertigo, headache (NRS 8/10) and nausea.Attacks lasted from one to three days, easing to milder chronic daily headache (NRS 5/10) with vestibular symptoms, including spontaneous and orthostatic dizziness and sound-induced vertigo, every second day (see Table 1).Key findings of manual assessment: Full, pain free cervical ROM.VBI testing comprised 10 seconds sustained end of range rotation and was asymptomatic; returning to midline produced a 'visual spotting/white blotches' lasting a few seconds.Standing balance -tandem stance, eyes closed (TSEC) was unremarkable.Palpation of the spinous process of C2 demonstrated deviation to the left of the midline.Transverse pressure on the C2 spinous process was asymmetrical with significantly more resistance to manual pressure from left to right when compared with right to left.
Intervention.Manual cervical therapy as described in Methods was provided.P1 had seven treatments over five weeks starting in September 2020, with two three-month nontreatment periods concluding in April 2021.A reassessment was conducted at the end of each nontreatment period.
Outcomes.Raw data are presented in Table 1, indicating improvement across all primary and secondary outcome measures.After initial treatment returning to neutral from sustained right cervical rotation produced no symptoms.P1 reported improvement in attack frequency from six migraine days per month (28 days) to no migraine days in the six-month nontreatment (follow-up) period.Interictal symptoms also showed improvement, with no symptom-free days in the run-in period changing to 21 symptom-free days (every 28 days) during the follow-up period.
Secondary outcome measures all showed clinically meaningful improvements during the treatment phase and continued to improve after the first four weeks of the nontreatment phase.After reporting increased feelings of anxiety and depression with significant life events during the nontreatment period, all scores regressed slightly for a short time before showing sustained improvement at the six-month follow-up.Dosage of propranolol and venlafaxine also increased at this time, however improvement in primary outcome measures had already occurred during Period B.
Participant 02 (P2) Participant profile.P2 was a 48-year-old female with a 14-year history of recurrent vertigo and head motion-induced dizziness triggering migraine attacks following surgery on a pituitary cyst.A bout of persistent motion sickness at age 14 was closely followed by a fall from a horse, resulting in low back pain (no head or neck trauma was reported).Recurrent headache and nausea developed twelve months later, progressively worsening over a three-year period, which included the onset of menstrual-related migraine without aura (age16 years).At this time, nausea was constant, and multiple diagnoses from reflux to anorexia were given after losing 30 kg in weight over a four-year period.
Migraine attacks increased intensity and frequency after the birth of her last child, and after surgery on a pituitary cyst P2 was diagnosed with VM by a neuro-otologist in July 2019 and prescribed amitriptyline, which was not tolerated well.P2 preferred meditation and manual therapy (chiropractic) for the daily headaches and low back pain, which would provide a reduction of symptoms for one to two days at best.
Migraine attacks began with intensification of interictal symptoms (nausea, dizziness and lethargy) and infrequently a scintillating scotoma.The scotoma gave way to suboccipital tightness and intense pressure in the retro-orbital regions and paroxysmal sharp 'ice pick' pain around the right orbit.Acute attacks lasted between three and five days, easing to interictal symptoms of chronic daily headache (NRS 5/10), nausea (5/10), dizziness and/or vertigo (4/10) and lethargy (6/10).
Key findings of manual assessment: Full, pain free cervical ROM.VBI testing comprised 10 seconds sustained end of range rotation.Increased anxiety while in left rotation eased on return to neutral but was followed immediately by vertigo -a sense of the body being pulled to the right.No symptoms to the right or on return to neutral.Standing balance -tandem stance, eyes closed (TSEC) was unable to be maintained > 10 seconds.Palpation of the spinous process of C2 demonstrated deviation to the right of the midline.Transverse pressure on the C2 spinous process was asymmetrical with increased resistance to manual pressure from right to left when compared to left to right.
Intervention.Manual treatment as described in Methods was provided.P2 had seven treatments starting in September 2020.
The first five appointments were in the first two weeks, with the remaining two appointments over a two-and four-week period.A symptom diary and outcome measures (PRO) were recorded after successive three-month nontreatment periods concluding in March 2021.
Outcomes.Raw data are presented in Table 2, indicating improvement across all primary and secondary outcome Rx (Treatment) I NRS (Numerical Rating Scale for pain) I *clinically meaningful change | (ES) Extremely severe, (S) -severe, (Mo) moderate, (Mi) mild, (N) normal measures.After initial treatment, P2 reported an immediate improvement with standing balance (TSEC) stable for 25 seconds and no feeling of anxiety or vertigo with return from sustained left rotation.Migraine attack frequency improved from 16 migraine days per month (per 28 days) to one migraine day during the treatment period and no migraine days in the eight months to the end of data collection.This is despite being admitted to the hospital with colitis during the first three-month nontreatment period, which is reflected in some of the outcome measures worsening during this period.Interictal symptoms also showed improvement with four symptom-free days in the run-in period, with three of these occurring immediately after two chiropractic appointments to an average of 17 symptom-free days in the last month of each treatment-free period.
Secondary outcome measures showed clinically meaningful improvements during the treatment phase and continued to improve after the first four weeks of the follow-up phase.An episode of colitis caused an increase in nausea frequency, with a minimal increase in dizziness episodes; however, the perceived disability from dizziness worsened slightly.Intervention.Manual treatment as described in Methods was provided.P3 was a fly-in fly-out oil rig engineer, and as such treatments were grouped initially according to his availability.After his initial consultation in September 2020 the next four treatments occurred during October before a two-week, and then a four-week review concluded in December 2020, with the first seven appointments occurring in the first five weeks.Symptom diary and outcome measures (PROs) were collected four weeks after the end of the last treatment and then again after two successive three-month nontreatment periods.
Outcomes.Raw data are presented in Table 3, indicating improvement across all primary and secondary outcome measures.After initial treatment, visual lag was absent on retesting return to neutral from sustained right cervical rotation.P3 reported improvement in attack frequency from two migraine days per month to no migraine days after treatment began, including during a six-month follow-up phase.Interictal symptoms also showed improvement, with P3 reporting no symptom-free days in the run-in period and averaging 18 days per month symptom-free in the last month of each three-month follow-up phase, which included 10 dizziness days after P3 had fallen off a roof.This was reinforced by a reduction in medication use, with only one maxalt taken as a preventive 'insurance' before an important interview, rather than due to symptoms/migraine attack.
Secondary outcome measures showed no change during treatment.During the first four weeks of the follow-up phase, secondary outcome measures improved dramatically; however, they showed some regression with the mild increase in dizziness after a fall from a ladder, reflected in the outcome measures at three months.

Discussion
The results of this case series demonstrate medium to large effects (Hedges' g) of MCT on the clinical features (frequency, intensity, medication use) and self-reported symptoms (HIT-6, DHI, DASS-21) of VM in three consecutive and prospectively selected participants (see Supplementary file 1).Furthermore, no adverse reactions to treatment were reported.Reductions in all symptoms (migraine attacks and interictal symptoms) as well as PROs maintained medium to large effects over successive three-month nontreatment periods.Improvements in both the frequency of VM episodes and the interictal symptoms suggest a common underlying cause that was influenced by treatment including MCT.
Any attempt to explain why the clinical presentation of the participants in this study improved demands a cautious approach, not only because of the limitations inherent in case study design but also because the pathophysiology of VM remains uncertain (Mallampalli et al., 2022).It is this uncertainty that instigated a panel of experts to call for collaboration to elucidate the pathophysiological mechanisms underlying VM (Mallampalli et al., 2022) and provide the conditions for which case study research is well suited.That is, to contribute to the broader scientific discussion around the potential pathophysiology of a disease, particularly when the view may be seen as counterintuitive or contrarian (Vandenbroucke, 2001).Speculation regarding the possible reason for effects observed with our three participants serves to propose novel directions for future investigation.
The focus of our hypothesis centres around a key finding in all our participants: palpable malalignment of the C2 spinous process in combination with increased resistance to transverse pressure (compared to the opposite side) on the spinous process of C2.These findings were clinically interpreted to represent hypertonicity of the ipsilateral obliquus capitis inferior (OCI).Subtle rotations of the odontoid peg and lateral mass of C1 have been described using radiographic assessment in cervical dizziness patients (Zamysłowska-Szmytke et al., 2019), however the reliability of manually palpating the position of the C2 spinous process with respect to midline, and comparing resistance to transverse pressure on the C2 SP from left compared to right has not been assessed and remains an important area for future investigation.Equally, the attribution of any asymmetrical resistance to pressure and/or malalignment of C2 SP to the presence of increased activity within OCI is another hypothesis requiring validation.Accepting these limitations, if the assessment is assumed to reflect hypertonic OCI activity, by what mechanism would a central PA on C3 impact this activity, and could this explain the changes observed in the clinical presentation of our three participants?The ligamento-spinal reflex describes the response of paraspinal muscles to increasing  mechanoreceptor activity in ligaments to prevent damage (Stubbs et al., 1998).Electrical and mechanical stress on a lumbar supraspinous ligament produced contraction of the multifidus muscle at the same segment, and two segments rostral and caudal to the stimulation (Solomonow et al., 1998).
Similarly, saline injected into the annulus of lumbar disc (Indahl et al., 1997) activates lumbar multifidus, while saline injected into cervical interspinous ligaments alters cervical kinematics (Qu et al., 2019).As the C2-3 interspinous ligament shares an attachment site at the C2 spinous process with OCI, this may be an upper cervical analogue of those stress induced reactions observed in the lumbar spine.It is then plausible that sustained PA pressure on the C3 SP may have a modulating and/or inhibitory effect on this reflex.
Of the many CNS regions that are potentially affected by this purported muscle dysfunction, it is interesting to note that the locus coeruleus (LC) has been shown to be sensitive to small asymmetries in trigeminal muscle afferent input (De Cicco et al., 2014), the correction of which has a demonstrable impact on cognitive function (De Cicco et al., 2016).Beyond cognition, the LC has been linked to numerous aspects of migraine pathophysiology, including cortical spreading depression (purported to underpin migraine aura (Goadsby et al., 2017)) and pain modulation (Vila- Pueyo et al., 2019), plays a role in anxiety and depression (Poe et al., 2020), and has been linked to the comorbidity of anxiety with vestibular disorders (Balaban et al., 2011).In this light, it is interesting to note that the asymmetries and resistance noted at C2 were resolved during treatment with sustained pressures on the spinous process of C3.All participants demonstrated complete resolution of symptoms associated with sustained end of range cervical rotation immediately after resolution of asymmetry to resistance to transverse pressure at C2. Non-VBI symptoms have been reported in subjects with persistent post-traumatic headache during more prolonged (60 second) sustained neck rotation testing (Hammerle et al., 2023a), which were subsequently correlated with sub-occipital muscle pressure sub pain thresholds (Hammerle et al., 2023b), providing some support to our hypothesis regarding OCI.
In addition, resolution of asymmetry to TP at C2 coincided with changes in our participants' primary and/or secondary outcome measures, providing a direction for further research.That all participants continued to report some residual symptoms underscores the complexity of migraine, and whilst the interventions provided had a significant impact it appears to be a partial rather than complete solution in these three cases.
While it is clear that the participants in this case series improved (see Table 1-Table 3 and Supplementary file 1), it is impossible to attribute improvement to a specific aspect of treatment.The 'real world' nature of these treatments encompass a multimodal approach, where MCT is provided in conjunction with education and a single stretching exercise.It has been demonstrated that education can enhance the effectiveness of manual therapy (Meise et al., 2023), and therefore, if the intervention was effective (beyond placebo and/or natural history) it is likely that these modalities in concert, rather than MCT alone, is responsible for the changes observed.Indeed, participant 1 was using migraine prophylaxis (venlafaxine and propranolol) and had these dosages increased in the follow-up period A, after a significant reduction in symptoms had already occurred during period B.
As a case series, we are limited by the lack of a control group and sample size power and are open to the potential confounding factors associated with selection bias (Nissen & Wynn, 2014).We have attempted to minimise bias by recruiting participants consecutively and prospectively, conducting this study in accordance with the CARE guidelines for reporting case studies and the CENT guidelines for reporting on N-of-1 trials (Gagnier et al., 2013;Vohra et al., 2015).Previously, the natural history of VM was reported in an observational study of 61 patients followed up over nine years.Recurrent vertigo was observed in 87% of patients with 44% unchanged or worse and with 56% with some reduction in frequency (Radtke et al., 2012).While not impossible, spontaneous remission in three participants with long histories of symptoms seems highly implausible.Expectation of a positive outcome is crucial to a placebo response (Benedetti, 2013).While it is well accepted that manual therapy (MT) provides a placebo effect (Bialosky et al., 2017), these effects have been assessed in conditions that would traditionally be treated with MT.As none of our participants experienced neck pain or restricted ROM supporting a 'cervicogenic dizziness' diagnosis and MCT is not considered a treatment for VM (Byun et al., 2021;Mallampalli et al., 2022), it seems unlikely that these individuals had a 'strong' expectation of a positive result, however, as they sought treatment as paying customers, they would reasonably have 'some' expectation that the treatment might help, introducing selection bias further reducing the generalisability of findings.The exception is participant P2, who had undergone chiropractic MT for many years for lower back problems.This included treatment of the neck, which provided relief for one to two days, possibly giving some belief that the neck was implicated.

Conclusion
This case series demonstrates an observable, rapid and sustained impact on the clinical presentation and medium to large effects in self-reported symptoms of VM in three prospectively and consecutively recruited patients.VM is a relatively new diagnostic category with currently unclear pathophysiology and treatment pathways.It is therefore important that all hypotheses regarding pathophysiology be considered and tested and that novel treatment options be considered.Despite the known pathoanatomical and pathophysiological pathways linking the upper cervical spine to regions explaining symptom behaviour, the upper cervical spine is not readily considered in current pathophysiological explanations for VM.The challenge of proposing a hypothesis involving the upper cervical spine for conditions involving migraine and vertigo is not lost on the authors.In light of this, we echo the sentiments of May (May, 2020), urging readers to remain open to all possible mechanisms associated with migraine and vertigo to inform a broader approach to managing these patients.
In conclusion, this case series suggests that this MCT approach may represent a safe, well-tolerated and affordable option with the potential for rapid and sustained relief of symptoms in some patients with VM and advocates a legitimate avenue of scientific enquiry for treatment and pathophysiological mechanisms of VM.

Extended data
Open Science Framework: Manual Cervical Therapy and Vestibular Migraine, https://doi.org/10.17605/OSF.IO/23MNJ (O'Toole, 2023).This project contains the following underlying data: The discussion now highlights the resolution of symptoms with upper cervical intervention and attempts to relate this to existing literature relevant to sub-occipital muscles.However I feel that more detailed explanation needs to be given on how pressure to C3 spinous process alone might alter sub-occipital muscle activation.The authors quote Watson & Drummond (2014) to support the application of pressure to C3 but in that paper pressure was not just applied to C3. Pain or Vestibular migraine is clearly a complex issue.Can this complexity really be explained by changes to these small muscles alone by the application of force to a single vertebra?Its important to be as clear as possible in the explanation of potential effects.More evidence is clearly required and as the authors point out, very little can be taken from a case series other than to inform on future research.
I also have some concerns, in line with the first reviewer's comment, about the recognition of potential bias of the participants in their very likely positive expectation for a positive outcome from treatment they expected to receive attending a specialist clinic.

Are enough details provided of any physical examination and diagnostic tests, treatment given and outcomes? Partly
Is sufficient discussion included of the importance of the findings and their relevance to future understanding of disease processes, diagnosis or treatment?Yes

Is the conclusion balanced and justified on the basis of the findings? Yes
Competing Interests: No competing interests were disclosed.
Reviewer Expertise: Manual examination.Diagnostic accuracy.Manual therapy.Cervicogenic headache I confirm that I have read this submission and believe that I have an appropriate level of expertise to confirm that it is of an acceptable scientific standard, however I have significant reservations, as outlined above.
Author Response 14 Aug 2023

Roger O'Toole
This is an interesting and generally well written paper which has improved in its second version.The authors have responded to the reviewer's comments in the main.There is now some modification to the introduction with an expanded section on current treatment for vestibular migraine and a discussion on manual therapy for migraine.Thank you for your time.We greatly appreciate the time taken to review this article and your feedback to improve its quality.
Assessment information for each participant has been included more comprehensively, although I would like to see more information on the test used to identify suitable patients for this treatment.Thank you for your clarifying question.Participants were selected prior to manual (or any other) clinical assessment based on their diagnosis and absence of exclusion criteria as indicated in Eligibility criteria.
That is the transverse pressure of the C2 spinous process.Mainly in the interests of future research on this approach.What is the reliability of this test?What is actually an "asymmetrical response".Is it pain and stiffness?Or both?To the best of our knowledge transverse pressure has not been tested as an assessment tool.The palpation of bony position of C2 spinous process and resistance to transverse pressure from left, compared to right have not been formally tested for reliability and validated as relating to OCI hypertonicity.Whilst the lack of validation was mentioned in the discussion the absence of formally tested reliability was not and is an omission that has been corrected.The discussion now reflects this as an area of interest for the next stages of research.Asymmetry is described only in terms of resistance to transverse pressure.Pain on palpation is not described and not necessary for assessment, as the aim is to determine the side of OCI hypertonicity.
The discussion now highlights the resolution of symptoms with upper cervical intervention and attempts to relate this to existing literature relevant to sub-occipital muscles.However I feel that more detailed explanation needs to be given on how pressure to C3 spinous process alone might alter sub-occipital muscle activation.Thank you for sharing reviewer 1's interest in our hypothesis regarding the possible mechanism by which C2-3 may cause, and be implicated in the treatment of dysfunction relating to OCI.We have expanded the discussion to further highlight our hypothesis in this regard.
The authors quote Watson & Drummond (2014) to support the application of pressure to C3 but in that paper pressure was not just applied to C3. Thank you for seeking clarification.Pain or Vestibular migraine is clearly a complex issue.Can this complexity really be explained by changes to these small muscles alone by the application of force to a single vertebra?Its important to be as clear as possible in the explanation of potential effects.More evidence is clearly required and as the authors point out, very little can be taken from a case series other than to inform on future research.Thank you for your question.Firstly, pain and migraine in any manifestation is a complex issue, and this is reflected in the incomplete resolution of symptoms in all three participants.This is not being presented as a 'simple neck issue', but moreso an important and overlooked cog in a complex wheel.Secondly, we have yet to prove that these changes occurred due to the application of pressure to C3, as this was a multimodal therapy.I have no doubt, as reviewer 2 has indicated, that education and a single stretch played a role in achieving the response we have reported, but we also have acknowledged potential confounders with natural history and placebo.Your disbelief at the potential impact of a minimalist intervention is mirrored by and exceeded on a daily basis by the people we treat.The introduction and discussion adequately highlight the possible networks disturbed by dysfunction affecting OCI connecting it to all possible symptomatic manifestations of VM.The aim of a case series is to raise questions rather than provide answers, and I am excited at the interest that three well credentialled reviewers have shown in this paper and look forward to sharing the next steps of the research journey to demonstrate how impactful small changes in the suboccipital region can be.
I also have some concerns, in line with the first reviewer's comment, about the recognition of potential bias of the participants in their very likely positive expectation for a positive outcome from treatment they expected to receive attending a specialist clinic.Thank you for sharing reviewer 1's input.We agree that there is certainly a selection bias impacting generalisability of results and this will also reflect an underlying belief the

Are enough details provided of any physical examination and diagnostic tests, treatment given and outcomes? Partly
Is sufficient discussion included of the importance of the findings and their relevance to future understanding of disease processes, diagnosis or treatment?Yes

Is the conclusion balanced and justified on the basis of the findings? Yes
Competing Interests: No competing interests were disclosed.
Reviewer Expertise: Physiotherapy, pain, migraine I confirm that I have read this submission and believe that I have an appropriate level of expertise to confirm that it is of an acceptable scientific standard, however I have significant reservations, as outlined above.
Author Response 14 Aug 2023

Roger O'Toole
Thank you very much for reporting these three interesting cases of vestibular migraine.All three have complex clinical presentations combining long disease histories and comorbidities with traumatic events and psychiatric diagnoses.All three cases improved after sustained manual techniques.The manuscript is well written and provides sufficient detail about patient cases and interventions.The discussion is appropriately worded for a case series.The authors acknowledge that 3 cases cannot provide evidence for the effect of the intervention and that future research is required to investigate whether manual therapy can effectively reduce vestibular migraine symptoms.Thank you for your time.We greatly appreciate the time taken to review this article and your feedback to improve its quality.I have only one comment which I believe should find a place in the discussion section: the treatment did not only provide sustained pressure on C3 but also education about the disease and a self-management program.Both are extremely relevant treatment components.We just showed, that simply explaining the pathophysiology of migraine when provided additionally to manual therapy enhanced the effectiveness of the treatment (Meise et al. 2023)1.And from other chronic pain diseases we know, that regaining control over symptoms by being provided with a home exercise program contributes to symptom and disability reduction.I would love to see this discussed more in depth.Thank you for seeking clarification regarding the multimodal nature of the intervention, and providing further resources to support this.We had acknowledged that as a real-world intervention it was multi-modal with education and a single exercise complementing the manual therapy.We have expanded and reworded the discussion to incorporate your finding, that education can enhance the effectiveness of manual therapy and to emphasise that it is more likely a combination of modalities (MT + education + stretch) than manual therapy alone that has had a beneficial impact.Something should be mentioned about how the treatment of C3 pressure might effect the IO muscle given its attachments.The discussion centres around the fact that I/O muscle is likely implicated but the potential effect of the treatment should be mentioned.

1.
Bias of the participants-it should still be stated that the participants were attending and paying for private physiotherapy so presumably they had some belief the treatment might work.

2.
Both of these should be addressed in the next version.

Are enough details provided of any physical examination and diagnostic tests, treatment given and outcomes? Yes
Is sufficient discussion included of the importance of the findings and their relevance to future understanding of disease processes, diagnosis or treatment?Yes

Is the conclusion balanced and justified on the basis of the findings? Yes
Competing Interests: No competing interests were disclosed.
I confirm that I have read this submission and believe that I have an appropriate level of expertise to confirm that it is of an acceptable scientific standard, however I have significant reservations, as outlined above.

Version 1
Reviewer Report 09 June 2023 https://doi.org/10.21956/healthopenres.14403.r27221 Overall, the introduction contains a lot of information that is likely irrelevant to the topic and certainly doesn't match the possible hypothesis of the discussion.I suggest that it is rewritten to reflect this.
Second paragraph -co-morbidity doesn't equal causality.Might be better to rephrase to suggest that only many migraine patients suffer from dizziness that might also be a spectrum of VM and thus the incidence could be higher.
Third paragraph need to first establish the diagnostic criteria of VM and then show the similarity to whiplash.Cervical vertigo is not a suitable term, only 25 % of the whiplash patients reported vertigo.
Fourth paragraph -greater MSK is not supported by a recent SR-Liang et al 2019.(Liang, Galea et al. 2019) 1 .This sentence is not needed to make the point from previous paragraph supporting cervical afferents for contributing to the cause of dizziness.Suggest remove the first sentence.
Could also suggest a possible trigger for migraine, rather than a direct cause of the symptoms e.g.(Malhotra, Pace et al. 2020) 2 .Could also refer to recent articles suggesting a possible autonomic trigger from the upper cervical region.(Hammerle, Lu et al. 2022, Hammerle, Thomas et al. 2022) 3,  4 .
Paragraph 7 -need to discuss current treatment evidence for VM (Byun, Levy et al. 2021) 5 as well as current evidence for manual therapy for usual migraine as well.There have been some trials e.g.(Chaibi, Tuchin et al. 2011, Herranz-Gómez, García-Pascual et al. 2021, Varangot-Reille, Suso-Martí et al. 2022) 6,7,8 .Thus the aim of the study is to demonstrate effect of this specific MCT in VM.Need to also discuss this particular technique and approach and how it is different.

Ethical clearance required?
This sentence does not make sense -please clarify."Subsequently, absence of neck pain and/or limitation of cervical ROM in all three participants eliminated concurrent 'cervicogenic dizziness' as an alternate or comorbid diagnosis (Reiley et al., 2017)." Need reference for 50% reduction in frequency.
Is the hit 6 most suitable for VM-headache?
Need more information re: the diary.How collated etc.
Intervention-should state all that was done here included stretches etc.
The manual technique is a form of MT and should also be introduced in the introduction.
Not clear what the difference between migraine, headaches, internal and external vertigo.These measures need to be described in the methods.

RESULTS -
P1-was there a history of normal migraine prior?
Table 1 -need to be clear about what all these are e.g. is headache number of headaches in the 28 days?Also ensure all relating to clinically meaningful change is depicted in the tables as well.
Interventions state it was PA pressure at C3 but in patient 1 it was transverse pressure to C2-or is that just assessment findings?
Also dose of propranolol significantly increased during that time as well.Why was this done?This should be mentioned in the results.
P2.Why was sustained neck rotation done?Was this also done in P1? Reference this test?
P3 had a hit to the back of the head would that be exclusion?(Participants were excluded from the study if they had a history of previous neck surgery or traumatic head injury".Perhaps state why this was an exclusion criteria in the first place or refine the statement?
Tables should be uniform.Perhaps put primary outcome measures first and then secondary outcome measures.
Present summary of effect sizes as well in results.

DISCUSSION -
Discussion is better description of possible relationships between the neck and VM in these patients than the introduction.This further highlights that a lot of the introduction is not necessary as it doesn't relate to the discussion.Could also refer to sustained cervical rotation and these articles (Hammerle, Lu et al. 2022, Hammerle, Thomas et al. 2022) to help your point in the introduction and revisit in the discussion 3,4 .
Need to sate why Patient 1 increased dose of medication.
"it seems unlikely that these individuals had a 'strong' if any expectation of a positive result."-buthow were the patents referred to the clinic?They sought and paid for treatment so there was likely some belief that it would work.
Perhaps stress in the conclusion it might only be some patients, some bias in selection of VM patients.Reviewer Expertise: neck pain, dizziness, headache, concussion.I am not an expert at n of 1 trials.

References
I confirm that I have read this submission and believe that I have an appropriate level of expertise to confirm that it is of an acceptable scientific standard, however I have significant reservations, as outlined above.
spectrum of VM and thus the incidence could be higher.Thank you for your comment.As a symptom, dizziness is almost entirely excluded (other than when associated with head movement and nausea) from the classification of VM.The reporting of the comorbidity between dizziness and migraine was not intended to suggest causality, but more to extend the understanding of the relationship beyond the reported prevalence of VM.While I agree these probably represent a spectrum, I also agree that it doesn't add to the hypothesis of this paper and have duly been omitted.
Third paragraph need to first establish the diagnostic criteria of VM and then show the similarity to whiplash.Cervical vertigo is not a suitable term, only 25 % of the whiplash patients reported vertigo.Need to also discuss this particular technique and approach and how it is different.Thank you for your suggestion.We have expanded the current treatment evidence for VM and included a review of manual therapy for migraine.We have also included a description of the manual therapy used in this study.

METHODS -Ethical clearance required?
This sentence does not make sense -please clarify."Subsequently, absence of neck pain and/or limitation of cervical ROM in all three participants eliminated concurrent 'cervicogenic dizziness' as an alternate or comorbid diagnosis (Reiley et al., 2017)."Thank you for your feedback.We have revised the sentence for clarity.
Need reference for 50% reduction in frequency.Thank you for pointing out this omission.A reference to the guidelines for reporting clinical trials has been added.
Is the hit 6 most suitable for VM-headache?Thank you for your question.All participants had significant headache interictally, with headache recorded 20, 17 and 23 days per 28 days respectively.This justifies the use of a headache specific PRO and the HIT-6 is a valid and reliable tool for assessing the impact of headache symptoms.However, with each patient exhibiting multiple interictal symptoms it is likely that the specificity of attribution of impact to headache may not be valid.This is highlighted by Participant 1's HIT-6 increasing to 'severe impact' in the 4 weeks from 2-3 months post treatment, despite only recording 1 headache for the period with the same intensity as the previous period (NRS 2/10).That other life events impacted during this period is reported, as reflected in the DASS-21 indicating the headache, despite being less frequent and just as intense, was more impactful.Future research will incorporate more objective measures to compliment clinical outcomes and PRO's.
Need more information re: the diary.How collated etc. Thank you for highlighting this.
We have added further detail on the collating and confirmation of diary data in the methods section.I ntervention-should state all that was done here included stretches etc. Thank you for your suggestion.We have added further detail in the Interventions section regarding the stretch and education.
Not clear what the difference between migraine, headaches, internal and external vertigo.These measures need to be described in the methods.Thank you for your question.We have added further detail on the definition of each symptom in the methods section.
The manual technique is a form of MT and should also be introduced in the introduction.Thank you for your suggestion.We have added further detail in the introduction and methods on the technique used.

RESULTS -
P1-was there a history of normal migraine prior?Thank you for your question.No, there was no past history of migraine in participant 1.
Table 1 -need to be clear about what all these are e.g. is headache number of headaches in the 28 days?Also ensure all relating to clinically meaningful change is depicted in the tables as well.Thank you for your observation.The formatting of the tables with alternating highlights may be confusing and the headings not standing out as well as desired.We have requested an amenedment to better emphasise the heading for each section.
Interventions state it was PA pressure at C3 but in patient 1 it was transverse pressure to C2-or is that just assessment findings?A key part of the assessment is bony position of the C2 spinous process and asymmetrical resistance with transverse pressure at C2. Clinically this is interpreted as increased tone of OCI unilaterally and is explained in paragraph 3 of the discussion.The intervention to treat or correct this is a PA pressure on the spinous process of C3.An explanation of the assessment of C2 will be added to the introduction and methods section describing the technique.
Also dose of propranolol significantly increased during that time as well.Why was this done?This should be mentioned in the results.Thank you for this observation, as not commenting on this is an oversight.Participant 1 suffered from comorbid anxiety and depression (omitted), which were exacerbated with events surrounding COVID lockdown.Originally prescribed propranolol and effexor for her VM, when she resumed taking them seven months prior to assessment (described in the results under P1), they did not help her VM symptoms, but were helping manage her anxiety.She was self titrating effexor beads (hence the variable dose) and increased prorpanolol when her anxiety increased.As the table of results indicates significant change across all outcomes measures except for nausea before the increase in dose of either medication we did not expand on the explanation, but in reflection this was an oversight that will be revised.
P2.Why was sustained neck rotation done?Was this also done in P1? Reference this test?For clarification we have amneded the assessment section for each participant, as some data realting to testing in all 3 was omitted.This represents part of VBI screening.Data regarding findings for this test have been added to the results for each participant.
P3 had a hit to the back of the head would that be exclusion?(Participants were excluded from the study if they had a history of previous neck surgery or traumatic head injury".Perhaps state why this was an exclusion criteria in the first place or refine the statement?Thank you for your observation.The error is with the wording of the exclusion criteria which should read traumatic brain injury.P3's head hit a branch whilst straightening from leaning under it.It was offerred as an event based on a momentary feeling of 'strain' in the neck P3 though tmight be relevant to the neck assessment, rather than an impact to the head.There were no symptoms beyond the initial neck strain feeling, relating either to the head or neck.In a short time after he had a viral illness.On rereading the temporal relationship of this episode is not as clear as it could be and we will revise the description for P3, but are confident that the incident did not reflect a concussion/mTBI and therefore warrant exclusion.
Tables should be uniform.Perhaps put primary outcome measures first and then secondary outcome measures.Thank you for your comments on the table.Being a case sewries we tried to reflect the variability amonst patient symptom intensity and frequency, and medication use as uniformly as possible.These are listed as our primary outcome measures with the PRO's as secondary outcomes, listed at the bottom of each table.
Present summary of effect sizes as well in results.Access to the full data set is available under Extended data at the end of the manuscript.

DISCUSSION -
Discussion is better description of possible relationships between the neck and VM in these patients than the introduction.This further highlights that a lot of the introduction is not necessary as it doesn't relate to the discussion.Could also refer to sustained cervical rotation and these articles (Hammerle, Lu et al. 2022, Hammerle, Thomas et al. 2022) to help your point in the introduction and revisit in the discussion3,4.Thank you for highlighting this recent evidence.We have included them in the expanded discussion on the response of symptoms in sustained cervical rotation to treatment.
Need to sate why Patient 1 increased dose of medication.See prev comments.
"it seems unlikely that these individuals had a 'strong' if any expectation of a positive result."-buthow were the patents referred to the clinic?They sought and paid for treatment so there was likely some belief that it would work.I can understand how this might seem incongruous, and ultimately the question of placebo will require suitable trial conditions to prove or disprove, rather than our interpretation of expectations.That said, the current medical model says that vertigo is not a symptom produced by the upper cervical spine, and that migraine is a neurological disorder best treated by neurologists and doctors with medications.We see people in whom these approaches have failed, often multiple times over many years.My own opinion and clinical experience is that 'high hopes' the treatment will help is a long way from 'strong expectation of positive benefit'.P2 is a great example (refer to her client impact statement).Decades of misdiagnosis and mistreatment built a significant distrust of the medical system, and previous manual therapy failure to improve her symptoms may in fact argue for a 'nocebo' effect.As indicated she may have had some expectation of positive benefit, but equally, we could make a case for her having an expectation of short term benefit as that had been her experience with manual therapy prior.Equally P1 could have had strong beleifs that effexor (venlafaxine) would help, as it had done so previously, yet it failed to improve her symptoms.A more robust design is required to elucidate the relative contribution of placebo, manual therapy, education and natural history to any changes observed.Our puropse was simply to have upper cervical manual assessmen included in that disucssion.
Perhaps stress in the conclusion it might only be some patients, some bias in selection of VM patients.Yes a cautious tone has been foremost in our thoughts given the position Case Series occupy in the hierarchy of evidence.The final paragraph in the discussion acknowledges possible counfounding factors associated with selection bias, natural history, and placebo.The final paragraph of the conclusion does state 'in some patients with VM' which we believe adequately understate our findings.

Figure 1a .
Figure 1a.Sensory inflow from the vestibular system cancelled by normal and expected proprioceptive inputs.

Figure 1b .
Figure 1b.Noxious afferent feedback from upper cervical muscles fails to cancel sensory inflow from the vestibular system.Vestibular symptoms are experienced.
) I NRS (Numerical Rating Scale for pain) I *clinically meaningful change | (ES) Extremely severe, (S) -severe, (Mo) moderate, (Mi) mild, (N) normal The introduction has been modified to remove reference to the techniques described by Watson and Drummond (2014) which aimed to reproduce familiar headpain.The last paragraph now reflects the description under interventions for the technique for central PA pressure on C3 is cited in both sections as Watson, 1997 referring to the training manual for learning the technique.This is the first published description of that aspect of the treatment approach.

Reviewer Report 19
July 2023 https://doi.org/10.21956/healthopenres.14448.r27386© 2023 Treleaven J.This is an open access peer review report distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.Julia Treleaven 1 Neck and Head Research Unit, The School of Health and Rehabilitation Sciences, The University of Queensland, Saint Lucia, Queensland, Australia 2 Neck and Head Research Unit, The School of Health and Rehabilitation Sciences, The University of Queensland, Saint Lucia, Queensland, Australia I am happy with most of the corrections.I have a couple of comments that should be addressed before approval.
Is the background of the cases' history and progression described in sufficient detail?Partly Are enough details provided of any physical examination and diagnostic tests, treatment given and outcomes?Partly Is sufficient discussion included of the importance of the findings and their relevance to future understanding of disease processes, diagnosis or treatment?Partly Is the conclusion balanced and justified on the basis of the findings?Partly Competing Interests: No competing interests were disclosed.

Table 2 . Participant 2 Symptom features pre- and postMCT.
with scanning, all of which were rarely absent.Rolling in bed, looking down at his phone, pushing his daughter in a pram or swing would induce vertigo and migraine attacks.
neck, head or other symptoms.Approximately one week later following the commencement of a new job, disrupted sleep with a newborn and a bout of gastrointestinal symptoms, P3 suffered persistent dizziness, accompanied by mild bilateral tinnitus, visual lag and nausea.Over several weeks the nausea and tinnitus eased completely and gave way to a persistent headache and a slight blurring of vision and visual lag Key findings of manual assessment: Full, pain free cervical ROM.VBI testing comprised 10 seconds sustained end of range rotation.No symptoms in left rotation or on return to neutral.No symptoms in right rotation -visual lag on return to neutral.Standing balance -tandem stance, eyes closed (TSEC) was unremarkable.Palpation of the spinous process of C2 demonstrated deviation to the right of the midline.Transverse pressure on the C2 spinous process was asymmetrical with increased resistance to manual pressure from right to left when compared to left to right.

Thank you for your feedback. I can see the confusion in my wording indicating a more direct comparison of VM to WAD which was not the intent.The paragraph was intended to highlight a discordant view that despite clinical and experimental evidence, the upper cervical spine is not considered capable of (or rarely) causes the symptom of vertigo, and subsequently would not contribute to VM as a disorder. I have edited the paragraph to refocus the content on vertigo and upper cervical afferents. I understand there are nosological debates around suitable naming of different disorders. I am comfortable citing the term 'cervical vertigo' as this was the label the authors used in their paper proposing a new disorder, although I acknowledge this is a source of contention.
Fourth paragraph -greater MSK is not supported by a recent SR-Liang et al 2019.(Liang,Galeaet al. 2019)1.This sentence is not needed to make the point from previous paragraph supporting cervical afferents for contributing to the cause of dizziness.Suggest remove the first sentence.

Thank you for highlighting the current lack of evidence establishing greater msk dysfunction in migraine. The opening sentence has been removed.
Paragraph 7 -need to discuss current treatment evidence for VM(Byun, Levy et al. 2021)5 as well as current evidence for manual therapy for usual migraine as well.There have been some trials e.g.(Chaibi, Tuchin et al. 2011, Herranz-Gómez, García-Pascual et al. 2021,  Varangot-Reille, Suso-Martí et al. 2022)6,7,8.Thus the aim of the study is to demonstrate effect of this specific MCT in VM.