Upright positioning-related reverse nystagmus in posterior canal benign paroxysmal positional vertigo and its effect on prognosis

1 Introduction

Benign paroxysmal positional vertigo (BPPV) is the most common peripheral cause of vertigo [2, 22]. In 1952, Margaret Ruth Dix and Charles Skinner Hallpike defined the classical nystagmus pattern seen in posterior canal BPPV, and the maneuver used for diagnosis [6]. Cupulolithiasis and canalolithiasis theories, which aimed to explain the pathophysiology of the disorder, were developed later in the following decades [7, 20]. Although most of the features and patho-mechanisms of BPPV are well-defined today, there are clinical findings which have not yet been sufficiently understood, and thus we are still far from understanding this common disorder in all its aspects.

Clinical signs and characteristics of BPPV are directly related not only with the mechanism of otolithic displacement, but also with the semicircular canal, to where the otoliths are displaced. The posterior semicircular canal is involved in most BPPV cases [2, 22]. The Dix-Hallpike test, also known as the Nylen-Barany test, is the most commonly-used diagnostic tool for posterior semicircular canal BPPV [2, 22]. Nystagmus that occurs during this provocative maneuver has some characteristic properties such as latency, duration and fatigue. Another important feature of typical posterior canal BPPV nystagmus is that its direction, as a whole, is reversed (remains geotropic), as the patient is re-seated from the provoking head hanging position [6]. This feature is known as reverse nystagmus. As defined by Dix and Hallpike, and depicted in clinical guidelines, reverse nystagmus often, but not always, appears in patients with posterior canal BPPV [2, 22]. However, to the best of our knowledge, the incidence of reverse nystagmus in the Dix-Hallpike test and its relationship with prognosis has not been fully determined.

Benign paroxysmal positional vertigo of the posterior canal is mostly a self-limiting disorder with a good prognosis. Nevertheless, it can significantly disturb the quality of life and result in social withdrawal, fear of falling, and even in immobility in some patients. Canalith repositioning maneuvers (CRM) are used effectively for the treatment of BPPV and a single CRM is enough in most patients [2]. In some patients, however, repetitive CRMs are required to provide an adequate level of treatment. Recurrences may also develop in some patients. Therefore, the availability of a practical tool to predict the prognosis of the disease, or success of the CRM, is important for both patients and clinicians.

The aim of this study was to determine the incidence of upright positioning-related reverse nystagmus in the Dix-Hallpike test, and to assess the relationship between the presence of reverse nystagmus and prognosis of posterior canal BPPV.

2 Material and methods

Approval for this study was granted by Baskent University Institutional Review Board (Project No: KA19/60) and it was supported by Baskent University Research Fund.

A retrospective review was made of the clinical and diagnostic information of all patients who under went video-nystagmography (VNG) in the Neurotology Research Clinic. Data were retrieved from the Hospital Information Management System, and patients diagnosed with BPPV were identified. The video-nystagmography recordings of the BPPV patients were then reviewed by a single researcher (SJ). The videos recorded during testing (Dix-Hallpike maneuver with provoking head hanging and upright positions for the left and right sides) were viewed and analyzed to be able to assess the patient’s response and to detect torsional nystagmus. Patients who met the diagnostic criteria of the Committee for the Classification of Vestibular Disorders of the Bárány Society [22] for posterior canal BPPV were noted. The video recordings of the patients determined to have posterior canal BPPV were then independently examined by another neurotologist (EH) who was blinded to the findings of the first researcher. The records of patients diagnosed with typical posterior canal BPPV by both researchers were used for detailed analysis. Data including age, gender, affected side, duration of nystagmus in the provoking head hanging position, presence of reverse nystagmus on upright position, number of CRM(s) required for treatment, canal conversion on control testing and recurrence(s) were noted.

Patients who did not fully meet the diagnostic criteria for posterior canal BPPV, patients with lateral canal, anterior canal or multi-canal involvement, and those with incomplete or inadequate video records, including those who had been rehabilitated with a CRM and did not have follow-up video records, and those with poor quality video records due to a short recording duration, artifacts or blinking, were excluded from the study group. All patients included in the study had a clean VNG record of at least 10 seconds in the upright position during the Dix-Hallpike maneuver.

All patients were treated with CRM (Epley maneuver). Patients were reassessed and a follow-up Dix-Hallpike test was performed 2–4 days after the initial CRM. For patients witha positive Dix-Hallpike at follow-up visits, the CRM was repeated at 2–4 day intervals, until recovery was observed. In patients that were detected to have lateral canal involvement at their follow-up visits, appropriate canalith repositioning procedure other than the Epley’s was performed.

Video-nystagmography recordings were obtained using Visual Eyes 4 Channel test battery (Micromedical Technologies, IL, USA) and the data were analyzed using Spectrum 9 balance software (Micromedical Technologies, IL, USA). According to the testing protocol used in our clinic, and as recommended by the manufacturer, the software was calibrated before the testing of each patient. As that testing equipment was first used in our clinic in October 2016, the database consisted of the records of patients who had been tested between October 2016 and March 2019.

Data obtained in the study were analyzed statistically using SPSS Statistics v.22.0 software (IBM Corp., Armonk, NY, USA). The Mann-Whitney U test, and the Chi-square test or Fisher’s Exact test were used to compare non-parametric continuous, and dichotomous data, respectively. All p-values were two-sided. Based on the differences between groups in this study (α= 0.05, effect size = 0.5, total sample size = 321 and the ratio of group sample sizes = 5.68), statistical power was computed as 0.876 (G*Power software, v. 3.1.9.2, Heinrich-Heine-Universität Düsseldorf, Germany).

3 Results

The records of 5651 patients who under went VNG between October 2016 and March 2019 were screened from the Hospital Information Management System, from which 883 patients were identified as diagnosed with BPPV. A total of 562 patients were excluded for various reasons (Fig. 1). Data obtained from detailed analysis of the video recordings of 321 patients were used.

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Fig.1

Flowchart for patient selection and exclusion criteria. VNG: Video-nystagmography, BPPV: Benign paroxysmal positional vertigo. *See Reference #22.

The total 321 patients comprised 240 females and 81 males (female to male ratio 3 : 1) with a mean age of 63.9±15.2 years (range, 13–92 years). Reverse nystagmus on upright positioning was seen in 273 (85%) patients (Fig. 2). The demographic and clinical characteristics of the patients with and without reverse nystagmus are shown in Table 1.

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Fig.2

Example video-nystagmography graphs of the patients with (A) and without (B) reverse nystagmus. LH: Left horizontal, LV: Left vertical.

A difference was seen between the patients with and without reverse nystagmus in respect of the number of CRMs required for treatment. The number of CRMs was 1.32±0.68 in patients with reverse nystagmus and 1.81±0.98 in patients without reverse nystagmus (p < 0.001) (Table 1, Fig. 3). In the patients with reverse nystagmus, 78% (n = 213), 14.2% (n = 39), 6.6% (n = 18), 0.4% (n = 1), and 0.8% (n = 2) of the patients received 1, 2, 3, 4, and 5 CRMs, respectively. In the patient group without reverse nystagmus, 48% (n = 23), 33.3% (n = 16), 8.3% (n = 4), and 10.4% (n = 5) of the patients required 1, 2, 3, and 4 CRMs for treatment, respectively (Fig. 3).

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Fig.3

Percentage distribution of the number of canalith repositioning maneuvers required for treatment of the patients with and without reverse nystagmus. RN: Reverse nystagmus, CRM: Canalith repositioning maneuver.

Recurrent posterior canal BPPV was detected in 8.4% (27/321) of the patients within a period of mean 16.45±8.44 months (range, 3–31 months). The recurrence rate was calculated as 8.4% (23/273) in patients with reverse nystagmus and 8.3% (4/48) in patients without reverse nystagmus (p = 0.623) (Table 1). The presence of reverse nystagmus was not determined to have a statistically significant effect on recurrence. Based on the results of disease-free survival analysis using Kaplan-Meier procedure, the estimated mean time until first recurrence was 863.13±36.69 days for patients without reverse nystagmus, and 876.33±15.20 days for patients with reverse nystagmus. It was found that there is no statistically significant difference between two groups in terms of survival time (Breslow χ²= 0.011, p = 0.917 > 0.05). The disease-free survival probabilities for both groups until 6 months, 1 year and 2 years are presented in Table 2. The disease-free survival probabilities of patients with reverse nystagmus are slightly greater than those of patients without reverse nystagmus.

The mean duration of nystagmus on the provoking head hanging position was 17.82±9.23 seconds in patients with reverse nystagmus and 21.77±12.66 seconds in patients without reverse nystagmus (p > 0.05). Canal conversion was seen in 3.7% of all patients (12/321). There was no statistically significant difference in terms of the canal conversion rate between the patients with (4%) and without (2.1%) reverse nystagmus (p > 0.05) (Table 1).

Benign paroxysmal positional vertigo (BPPV) is the most frequent vestibular disorder with a lifetime cumulative incidence of 10% in the general population [22, 23]. Posterior semicircular canal involvement is held responsible in most cases [22]. Posterior canal BPPV is usually self-limiting and can recover spontaneously in some patients [2, 22]. However, it may cause significant morbidity, impairing social, physical and mental capacity for daily activities and increasing the risk of falls, especially in elderly patients [2, 15]. Therapeutic CRMs are highly effective in the treatment of posterior canal BPPV [2]. However, the number of CRMs required for the treatment of BPPV varies among patients. In most patients, a single CRM is adequate for treatment, but in cases that are refractory to treatment, however, multiple CRM sessions are required to achieve a disease-free state [2, 19]. Therefore, it is important to have a practical tool that is able to predict the number of CRM sessions required for treatment and to reflect the prognosis.

The most commonly used diagnostic tests for posterior canal BPPV include the Dix-Hallpike maneuver, and the side-lying test. In both tests, the plane of the semicircular canal of interest is first aligned vertically to the horizontal plane and then the head is quickly rotated in the plane of the semicircular canal towards gravity. If the patient has no back or neck problems preventing testing, the Dix-Hallpike maneuver is used in our clinic. A characteristic finding of the Dix-Hallpike maneuver in posterior semicircular canal BPPV is torsional, up beating nystagmus associated with vertigo, when the patient is brought from upright to provoking head hanging position. Positional nystagmus is thought to be provoked by a hydraulic plunger effect. According to that theory, an otoconial clot settling in the semicircular canal is thought to act as a plunger on the endolymph and cupula, when the head position is rapidly changed from upright to provoking head hanging [3]. After the patient is returned to the upright sitting position, nystagmus is again commonly observed, and the direction of the nystagmus may be reversed [2]. Dix and Hallpike noticed this phenomenon in 1952 and reported that reverse nystagmus and recurrence of the vertigo in a milder form could be seen when the patient sits up [6]. There are current, well-defined, clinical practice guidelines comprising diagnostic criteria and instructions for the management of patients with BPPV [2, 22]. The incidence of reverse nystagmus and its association with prognosis of posterior canal BPPV, however, is not clear. The results of the current study showed that upright positioning-related reverse nystagmus occurred in 85% of the patients with posterior canal BPPV.

Reverse nystagmus is not always seen in patients with posterior canal BPPV. One of the possible explanations for that finding is that dispersion of single particles from the otolithic clot makes the plunger effect less effective [3], similar to the mechanism described for fatiguability, which is another characteristic feature of BPPV nystagmus. Repetition of the Dix-Hallpike test can be considered to be not always required to induce dispersal of the particles in endolymph. In some patients, simply bringing the patient to the provoking head hanging position may be sufficient for the otolithic debris to disperse in the endolymph. When the patient is brought to the sitting position thereafter, dispersed particles may not trigger endolymphatic flow and cupular deflection efficiently.

The absence of reverse nystagmus in some patients might also be related to the test technique. As previously defined for the Dix-Hallpike test, the provocative maneuver should be fast enough to cause adequate endolymph flow and cupula deflection [3]. The same should also be held true for when the patient is positioned sitting up. In other words, reverse nystagmus might not be seen if the patient is brought to the sitting position slowly. For reasons that are inherent to the nature of the Dix-Hallpike test, it is hard to standardize the speed of positioning during testing. This also constitutes one of the limitations of the current study. For many years, including the time period selected for this study, all vestibular tests in our clinic have been applied by the same two experienced technicians. Since this was a retrospective study, tester bias was out of the question. Furthermore, the room camera records were reviewed of the patients without reverse nystagmus, which showed a view of the technician and the patient during the test. Although no systematic technical errors were determined, it is not possible to know whether the patients without reverse nystagmus were positioned slowly or not.

The prognostic value of the positioning nystagmus on the second stage of the Epley maneuver (when the patient rolls laterally onto the opposite side with the head turned 45° downward) has been reported before [17, 18]. According to this, the direction of the nystagmus during the second stage of the particle repositioning maneuver appears to be important in predicting the efficacy, with reversal or absence of nystagmus denoting a poor response [17, 18]. It has also been suggested that the character of the nystagmus in the final position of the CRM is related to the therapeutic outcome [10]. The presence of orthotropic nystagmus in the second position of the Semont maneuver has been claimed to be a sign of a good prognosis [21]. Sudden vertigo that appears when the patient is returning to the final sitting position of the Semont maneuver has been considered a negative prognostic factor [1]. Coexistence or history of sudden sensorineural hearing loss, canal paresis, Meniere’s disease or head trauma have also been associated with poor prognosis in BPPV [5, 24]. In the current study, the absence of reverse nystagmus in the second stage of the Dix-Hallpike test, i.e. when the patient is positioned in an upright sitting position, was found to be an indicator of poor prognosis. This may be of additional value since it can be detected easily during the diagnostic maneuver and predict the outcome of the therapeutic maneuver.

In conclusion, the results of this study demonstrated that reverse nystagmus appeared in 85% of the patients with posterior canal BPPV as the patient is re-seated from the provoking head hanging position in the second stage of the Dix-Hallpike test. In patients without upright positioning-related reverse nystagmus, repeated canalith repositioning (Epley) maneuvers may be required to achieve successful treatment.