The cardiac autonomic control system response to vestibular stimulation in subjects with BPPV compared with healthy controls

Abstract

BACKGROUND:

Vestibulo-sympathetic reflexes (VSR) demonstrate the autonomic interaction between the vestibular system and the cardiovascular system, however little is known about this interaction in patients with benign paroxysmal positional vertigo (BPPV). Although the main complaint of patients with BPPV is vertigo, additional symptoms such as nausea and sweating raise questions whether patients with BPPV have impaired VSR.

OBJECTIVE:

The aim of this study is to assess the cardiac autonomic control system (CACS) response to vestibular stimulation in subjects with BPPV compared with healthy controls.

METHODS:

This is a case-control study. Heart-rate variability (HRV) parameters were monitored in two groups (30–70 years old)- subjects with BPPV (N = 18) and gender and age-matched healthy controls (N = 18), at rest and during vestibular stimulation.

RESULTS:

No significant differences were found between groups in HRV parameters during rest. Both groups demonstrated an autonomic response to vestibular stimulation, yet no differences were found between groups.

CONCLUSIONS:

Patients with BPPV seem to have an intact cardiac response to vestibular stimulation. Over-activation of the Vestibular Semicircular Canals, as shown in BPPV, doesn’t seem to alter the VSR in the cardiac autonomic control system.

Keywords

Benign paroxysmal positional vertigo (BPPV)vestibulo-sympathetic reflex (VSR)heart rate variability (HRV)autonomic nervous system (ANS)

1 Introduction

Benign paroxysmal positional vertigo (BPPV) is a common vestibular disorder (Hanley et al., 2001; Neuhauser & Lempert, 2009) with a lifetime prevalence of 2.4%. (Von Brevern et al., 2007). The main complaint of patients with BPPV is vertigo. Common additional symptoms include nausea, vomiting, unsteadiness (Bhattacharyya et al., 2017), sweating, stress, and anxiety (Jacob & Furman, 2001; Von Brevern et al., 2015). These symptoms might be associated with an impairment of the vestibulo-sympathetic reflex (VSR), a protective mechanism for blood pressure control during postural changes to maintain brain perfusion levels (Kerman et al., 2000).

In some vestibular disorders, such as acute vestibular neuritis, a temporary decrease in blood vessels’ sympathetic activity during orthostatic challenge has been noted (Yates & Bronstein, 2005; Yates et al., 2014). Another study found a temporary reduction in heart-rate variability (HRV) parameters compared with healthy controls (Jáuregui-Renaud et al., 2003).

The role of the semicircular canals (SCCs) in the vestibular-sympathetic interaction is unclear, especially among patients with BPPV. Only one study included a small sample of subjects with posterior SCC BPPV (N = 4) during a maneuver that had orthostatic changes. They compared them to healthy controls and noted smaller heart-rate responses in people with BPPV (Jáuregui-Renaud et al., 2005).

Physiotherapists treat and rehabilitate patients with BPPV by performing repositioning maneuvers and by educating the patient to ensure balance. Understanding the mechanism beyond these symptoms is essential for assessing and treating these patients. When stimulating the vestibular system during physical examination and treatment, it is also essential for a clinician to be aware of the physiological responses of other body systems.

This study aims to assess the cardiac autonomic control system (CACS) response to vestibular stimulation in subjects with BPPV compared with healthy controls.

2 Materials and methods

2.1 Study design

This is a case-control study.

2.2 Participants

The study was performed between 2019 and 2020 in an outpatient general physiotherapy clinic of Clalit Health Services in Tel Aviv, Israel. 18 patients with BPPV and 18 age and gender-matched healthy controls were recruited for this study.

2.2.1 Inclusion criteria

The study group included patients between 30 and 70 years of age, with a diagnosis of BPPV confirmed by: (1) A primary complaint of a spinning sensation (vertigo) provoked by head motion relative to gravity; (2) Positive Dix-Hallpike or Supine Roll Test confirmed by the presence of nystagmus typical for BPPV (Bhattacharyya et al., 2017).

The age and gender matched control group included healthy participants with no complaints of any type of dizziness.

2.2.2 Exclusion criteria

In either group were: (1) Complaints of pain during the day of the visit (such as headache); (2) Postural hypotension; (3) Familial dysautonomia; (4) Diabetic neuropathy; (5) History of whiplash, traumatic brain injury or head trauma within the last year; (6) Central neurological conditions; (7) Cardiovascular conditions (8) Beta-blockers intake; (9) Anxiety disorders; (10) Known vestibular disorders that are not BPPV; (11) Medical conditions with a suspected subluxation of the atlanto-axial joint; (12) Healthcare staff members qualified for the assessment and treatment of vestibular disorders. All the above were taken from each participant’s medical record except for complaints of pain which were obtained by self-report.

2.3 Tests and Measurements

2.3.1 Clinical Characteristics and Classification

Medical history included demographics, characteristics of symptoms, and questions about performing weekly physical activity.

The Dix-Hallpike Test and Supine Roll Test are the recommended clinical tests used to confirm the diagnosis of BPPV. Both tests were performed according to the instructions detailed in the current Clinical Practice Guidelines for assessing and treating BPPV (Bhattacharyya et al., 2017). The Dix-Hallpike Test has a positive predictive value (PPV) of 83.3% and a negative predictive value (NPV) of 52.2% when performed by general practitioners (GPs) (Hanley & O’Dowd, 2002) and has shown high inter-rater reliability (Kappa = 0.92 (0.87–0.98), 95% confidence intervals) (Burston et al., 2012). If the typical nystagmus for BPPV was observed in at least one of these tests, this confirmed the diagnosis of BPPV (Bhattacharyya et al., 2017). Beyond their diagnostic value, the Dix-Hallpike Test and the Supine Roll Test were chosen as the main vestibular stimulation tests, as both aim to stimulate the posterior, anterior, and horizontal SCCs.

Oculo-motor assessment: Smooth pursuit, saccades, optokinetic reflex, convergence and vestibulo-ocular reflex cancellation (VORc) tests. These tests were performed to screen and exclude possible central causes that may mimic BPPV.

2.3.2 Primary Outcome Measures

HRV parameters assessment is a valid, reliable, feasible and non-invasive method that easily allows measuring cardiac autonomic nervous system (ANS) activity. In this study, HRV parameters were monitored using the POLAR RS800CX heart-rate monitor (Polar Electro OY, Kempele, Finland), found to be reliable for measuring HRV parameters and validated with Electrocardiogram (ECG) (Nunan et al., 2009). The sampling rate was 1000 Hz, and the recorded data was analyzed with the Polar ProTrainer 5 software. In this study we analyzed the following time domain HRV parameters:

Average R-R (RR): the average time in milliseconds between successive normal R-R intervals (Sztajzel, 2004).

Standard deviation of the normal-to-normal intervals (SDNN): a statistical index measured in milliseconds validated to assess the total HRV and cardiac sympathetic nervous system activity and is highly correlated to the low frequency HRV parameter (Sztajzel, 2004).

Root mean square of the successive differences (RMSSD): a statistical index measured in milliseconds validated to assess the cardiac parasympathetic nervous system activity and is highly correlated to the high frequency HRV parameter (Sztajzel, 2004).

The SDNN/RMSSD (ratio) reflects the relationship between the sympathetic and parasympathetic branches (Wang & Huang, 2012).

2.4 Procedure

This study was approved by the ethics review boards of Clalit Health Services and Tel Aviv University (NCT number 03867019). All participants provided informed consent before the study protocol began.

The study was conducted during one visit and with a vestibular physiotherapist. Before the visit, all participants were asked to avoid caffeine consumption and physical activity for at least two hours before the visit (Yeragani et al., 2005). The room temperature was between 23°C and 25°C. Heart-rate recordings using the polar RS800CX were performed throughout the following phases: Initial rest - participants sat for five minutes; Vestibular stimulation and assessment - First right and then left Dix-Hallpike Tests, followed by a right and then left Supine Roll Tests.

2.5 Statistical analysis

Differences between groups were assessed by the χ ² test for nominal variables, Mann-Whitney test for ordinal variables and ratio variables not normally distributed, and the Student’s T-Test for independent samples for ratio variables normally distributed. Within each group, differences were assessed with the Wilcoxon test. Statistical analysis was performed with SPSS Statistics version 24 (IBM Corp., Armonk, NY, USA). Statistical significance was assumed if p < 0.05.

3 Results

Table 1 summarizes the demographics and frequency of subjects performing physical activity. Table 2 summarizes the clinical characteristics of subjects in the study group.

Table 1
Demographics and physical activity performance of subjects with BPPV in comparison with healthy controls

Subjects with BPPV (N = 18) Healthy controls (N = 18) p-value

Age (years)¹ 51.8±10.9 51.3±10.0 0.89

Gender (women)² 12 (66.7) 12 (66.7) 1.00

Performing aerobic physical activity (yes)² 8 (44.4) 13 (72.2) 0.09

	Subjects with BPPV (N = 18)	Healthy controls (N = 18)	p-value
Age (years)¹	51.8±10.9	51.3±10.0	0.89
Gender (women)²	12 (66.7)	12 (66.7)	1.00
Performing aerobic physical activity (yes)²	8 (44.4)	13 (72.2)	0.09

¹Ratio scale variables are shown as mean±SD, p-values calculated with Student’s T-test. ²Nominal scale variables are shown as number (%), p-values calculated with χ ² test.

Table 2

Clinical characteristics of subjects in the study group

	Subjects with BPPV (N = 18)
Clinical presentation
Canalithiasis	18 (100)
Cupulolithiasis	0 (0)
Semicircular canal affected
Unilateral pSCC	15 (83.3)
Unilateral hSCC	2 (11.1)
Unilateral aSCC	0 (0)
Unilateral pSCC and hSCC	1 (5.6)
Nausea on the day of assessment
No	11 (61.1)
Yes	7 (38.9)
Vertigo medication intake
No	13 (72.2)
Yes, not on the day of assessment	3 (16.7)
Yes, including the day of assessment	2 (11.1)

pSCC- Posterior Semicircular Canal, hSCC- Horizontal Semicircular Canal, aSCC- Anterior Semicircular Canal. Nominal scale variables are shown as number (%).

Two participants reported oral intake of one type of medication for vertigo on the day of assessment (Cinnarizine or Betahistine). Table 3 summarizes the differences in RR, SDNN, RMSSD and SDNN/RMSSD parameters during initial rest and in response to vestibular stimulation.

Table 3

Heart-rate variability parameters during rest and in response to vestibular stimulation in subjects with BPPV in comparison with healthy controls

	Subjects with BPPV (N = 18)	Healthy controls (N = 18)	p-value³(between groups)
RR (milliseconds)
During rest	841 (586 –1203)	893 (701 –1211)	0.815
Degree of change (Δ)¹	–9 (–125 –126)	–12 (–151 –100)	0.323
p-value (within group)²	0.231	0.149
SDNN (milliseconds)
During rest	44 (15 –86)	41 (19 –127)	0.963
Degree of change (Δ)¹	28 (8 –136)	27 (–51 –111)	0.542
p-value (within group)²	<0.001	0.002
RMSSD (milliseconds)
During rest	24 (5 –134)	27 (9 –80)	0.815
Degree of change (Δ)¹	3 (–51 –36)	3 (–40 –73)	0.791
p-value (within group)²	0.043	0.102
SDNN/RMSSD
During rest	1.6 (0.6–2.9)	1.6 (0.8–2.6)	0.542
Degree of change (Δ)¹	0.7 (–0.6–2.4)	0.7 (–0.1–1.7)	0.650
p-value (within group)²	<0.001	0.002

RR- the average R-R time between successive normal R-R intervals, SDNN- Standard Deviation of the normal-to-normal intervals, RMSSD- Root mean square of the successive differences. Variables in this table are shown as median (minimum - maximum). ¹Degree of change (Δ) represents the difference in values: vestibular stimulation - initial rest. ²p-values calculated with Wilcoxon test; ³p-values calculated with Mann-Whitney test.

No significant differences between groups were found during rest. Vestibular stimulation induced significantly higher SDNN values than SDNN values at rest in both groups, and significantly higher RMSSD values than RMSSD values at rest in the study group. However, no significant differences between groups were found.

4 Discussion

The main findings of the current study are that both groups demonstrated similar autonomic responses to vestibular stimulation, as no significant differences between groups were found.

Moreover, no differences between groups were found in HRV parameters during rest. One study that evaluated cardiovascular function among subjects with BPPV who were admitted to an emergency department found different repolarization ECG features in comparison with healthy controls (Yıldırım et al., 2020). Another study sought to identify changes in cardiovascular features among patients who suffer from peripheral vertigo in comparison with healthy controls, found no differences in ECG features between groups during static head position (Rosario & Sequeira, 2018). One possible explanation for the conflicting results may be related to different research settings, tests and measurements, e.g. emergency department, tertiary care hospital and outpatient physiotherapy clinic. Furthermore, performing physical activity or consumption of caffeine prior to assessment may affect heart-rate during rest (Yeragani et al., 2005). In the current study, early instructions relating to physical activity and caffeine were given to all subjects, and it is reasonable that patients who were unexpectedly admitted to an emergency department did not receive such instructions.

Both groups in this study demonstrated an autonomic response to vestibular stimulation. The literature concerning the degree of the response is sparse, and due to differences in research methods between this study and other studies, comparison is limited. One study that performed a vestibular stimulus similar to the Dix-Hallpike Test reported that subjects with peripheral vertigo, including subjects with BPPV, demonstrated higher heart-rate immediately and three minutes after stimulation of the affected side. However, the study lacks basic information about the statistical analysis, and subjects with BPPV were included in the same group with other study populations (Rosario & Sequeira, 2018). Another study that included four subjects with BPPV, performed a vestibular stimulus of a whole-body tilt rotation from an upright standing position to a head-down lying position (135° backwards), with the head oriented in the plane of the vertical SCCs. The researchers reported that the healthy controls who remained in the tilted position for two minutes demonstrated lower average pulse-rate, whereas subjects with BPPV demonstrated a smaller change in pulse-rate when the stimulus was performed in the plane of the affected SCC. The authors concluded that the tilt in the plane of the affected SCC can interfere with cardiac response. However, it should be noted that only four cases of BPPV were included, parametric statistical analysis for a very small sample size was done, and the tilt performed may have also elicited a strong stimulus to the otolithic organs, since subjects remained in a head-down tilted position (Jáuregui-Renaud et al., 2005). Due to lack of high-quality evidence in the literature, we can safely conclude from the results of the current study that the cardiac response to vestibular stimulation with the Dix-Hallpike and Supine Roll Tests is similar in patients with BPPV and healthy controls.

4.1 Study Limitations

The main limitation of this study is related to the analysis of the vestibular stimulation sampling interval. Since minimal sampling time was required for reliable HRV parameters, in our analysis we decided to consider both Dix-Hallpike and Supine Roll Tests as one stimulation. However, it is possible that if each of these tests were considered as separate stimulations, the results may have shown a different cardiac autonomic response between groups or between affected to non-affected SCC.

5 Conclusions

Similar cardiac autonomic response to vestibular stimulation was observed in subjects with BPPV and healthy controls. A similar response between these groups implies that patients with BPPV have an intact cardiac response to vestibular stimulation. The findings of this study may indicate that over-activation of the SCCs of the vestibular system, as shown in BPPV, doesn’t seem to alter the VSR in the cardiac autonomic control system. Clinicians should not expect an abnormal cardiac response during the Dix-Hallpike or Supine Roll tests when treating patients with BPPV. If such an abnormal cardiac response occurs, a further medical investigation may be required.

Conflict of interest

The authors have no conflicts of interest to declare.

Funding

This study did not receive any funding or grant in the public, commercial, or non-profit sectors.

Footnotes

Acknowledgments

The authors would like to thank Clalit Health Services and Horowitz Physiotherapy staff members for their assistance.

References

Bhattacharyya,

, Gubbels,

S. P.

, Schwartz,

S. R.

, et al. (2017). Clinical practice guideline: benign paroxysmal positional vertigo (update), Otolaryngology–Head and Neck Surgery, 156(3_suppl), S1–S47.

Burston,

, Mossman,

, Weatherall,

(2012). Are there diurnal variations in the results of the Dix–Hallpike manoeuvre? Journal of Clinical Neuroscience, 19(3), 415–417.

Hanley,

, O’Dowd,

(2002). Symptoms of vertigo in general practice: a prospective study of diagnosis, British Journal of General Practice, 52(483), 809–812.

Hanley,

, O’Dowd,

, Considine,

(2001). A systematic review of vertigo in primary care, British Journal of General Practice, 51(469), 666–671.

Jacob,

R. G.

, Furman,

J. M.

(2001). Psychiatric consequences of vestibular dysfunction, Current Opinion in Neurology, 14(1), 41–46.

Jáuregui-Renaud,

, Aw,

S. T.

, Todd,

M. J.

, McGarvie,

L. A.

, Halmagyi,

G. M.

(2005). Benign paroxysmal positional vertigo can interfere with the cardiac response to head-down tilt, Otology & Neurotology, 26(3), 484–488.

Jáuregui-Renaud,

, Hermosillo,

A. G.

, Gómez,

, Márquez,

M. F.

, Cárdenas,

, Bronstein,

A. M.

(2003). Autonomic function interferes in cardiovascular reflexes, Archives of Medical Research, 34(3), 200–204.

Kerman,

I. A.

, McAllen,

R. M.

, Yates,

B. J.

(2000). Patterning of sympathetic nerve activity in response to vestibular stimulation, Brain Research Bulletin, 53(1), 11–16.

Neuhauser,

H. K.

, Lempert,

(2009). Vertigo: Epidemiologic aspects, Seminars in Neurology, 29(5), 473–481.

10.

Nunan,

, Donovan,

G. A. Y.

, Jakovljevic,

, Hodges,

, Sandercock,

, Brodie,

(2009). Validity and reliability of short-term heart-rate variability from the Polar S810, Medicine+ Science in Sports+ Exercise, 41(1), 243.

11.

Rosario,

D. D.

, Sequeira,

(2018). Cardiovascular changes in patients presenting with vertigo, International Journal of Research in Medical Sciences, 6(4), 1368.

12.

Sztajzel,

(2004). Heart rate variability: a noninvasive electrocardiographic method to measure the autonomic nervous system, Swiss Medical Weekly, 134(35-36), 514–522.

13.

Von Brevern

, Bertholon,

, Brandt,

, Fife,

, Imai,

, Nuti,

, Newman-Toker,

(2015). Benign paroxysmal positional vertigo: diagnostic criteria, Journal of Vestibular Research, 25(3-4), 105–117.

14.

Von Brevern

, Radtke,

, Lezius,

, Feldmann,

, Ziese,

, Lempert,

, Neuhauser,

(2007). Epidemiology of benign paroxysmal positional vertigo: a population based study, Journal of Neurology, Neurosurgery & Psychiatry, 78(7), 710–715.

15.

Wang,

H. M.

, Huang,

S. C.

(2012). SDNN/RMSSD as a surrogate for LF/HF: a revised investigation. Modelling and Simulation in Engineering, 2012.

16.

Yates,

B. J.

, Bolton,

P. S.

, Macefield,

V. G.

(2014). Vestibulo-sympathetic responses, Comprehensive Physiology, 4(2), 851–887.

17.

Yates,

B. J.

, Bronstein,

A. M.

(2005). The effects of vestibular system lesions on autonomic regulation: observations, mechanisms, and clinical implications, Journal of Vestibular Research, 15(3), 119–129.

18.

Yeragani,

V. K.

, Krishnan,

, Engels,

H. J.

, Gretebeck,

(2005). Effects of caffeine on linear and nonlinear measures of heart rate variability before and after exercise, Depression and Anxiety, 21(3), 130–134.

19.

Yıldırım,

Ö.T.

, Kaya,

Ş.

, Kaya,

F. B.

(2020). Evaluation of the Tp-e interval and Tp-e/QTc ratio in patients with benign paroxysmal positional vertigo in the emergency department compared with the normal population, Journal of Electrocardiology, 58, 51–55.