New developments in the diagnosis of benign paroxysmal positional vertigo

The possible role of loose otoconia within the short arm of the semicircular canals (on the utricular side of the cupula)

In 1992, Epley published his observations and suggested a reposition procedure ⁹ for the most frequent variation of BPPV, the posterior canalithiasis. Until then there existed several hypotheses as to the exact mechanisms of positional nystagmus, but the success of this maneuver helped to develop a universally accepted theory. A few years later, based on anatomic considerations, Buckingham published his hypothesis on the fate of the otoconial debris during and after repositioning ¹⁰ and Oas followed with similar observations. ¹¹ Buki et al. applied these principles to explain sitting up vertigo and positional vertigo without provoking nystagmus by short arm canalithiasis and/or posterior cupulolithiasis. ¹² By now other authors also use this theoretical framework in discussions concerning subjective/atypical BPPV.^4,13–16 Some of these authors suggested the “augmented half Dix–Hallpike maneuver” which is performed with the head turned 45◦ toward the side to be tested and slowly raised until it is flexed at 30 degrees after maintaining the conventional Dix-Hallpike position for a while.^4,14 This procedure is regarded optimal because it shifts the otoconia from the lowermost dependent position onto the tip of the cupula and aligns the affected cupula perpendicular to gravity, thereby allowing a maximal deflection by the gravitational force. As was suggested by Epley, ¹⁷ this position is reportedly best suited to bring the affected cupula to be maximally deflected by the gravitational force. Harmat et al. ¹⁸ evaluated patients with BPPV that manifested as sitting-up vertigo. They used the definition of “type 2 BPPV” coined by Büki et al. for typical complaints of BPPV, no nystagmus in Dix-Hallpike positions but short vertigo spell while sitting up from one side, but not from the other. ¹² In their outpatient ambulance out of all patients presenting with positional dizziness/vertigo, one-third met the criteria for type 2 BPPV; the remainder had a typical posterior or horizontal SCC involvement. The symptoms from type 2 BPPV were of longer duration and responded favorably to physical therapy (repetitive sit-ups). Upon repeat testing, 19 patients treated for posterior canalithiasis developed a weak persistent positional downbeat nystagmus in the Dix–Hallpike position, which the authors proposed as an evidence that the otoconia entered the short arm of the ipsilateral posterior SCC after having traveled through the utricle and attached themselves to the posterior cupula (posterior cupulolithiasis). In Dix–Hallpike position, in the case of a more inferiorly attached ampulla, the cupula may be pulled toward the utriculus by the weight of the otoconial debris, causing a slight, prolonged downbeat nystagmus (see also Figure 5(b)). ¹⁹ OPEN IN VIEWER

According to that study, type 2 BPPV appeared to be a treatable form of vertigo, more common than previously thought. In cases of posterior and horizontal canal canalithiasis, the otoconia that are repositioned into the utricle may subsequently cause canalithiasis in the short arm of the posterior canal, which can be diagnosed with the augmented half Dix-Hallpike maneuver. This observation supports the hypotheses proposed in previous studies. ²⁰

Short arm canalithiasis of the horizontal SCC could cause a unilateral horizontal apogeotropic nystagmus probably only during supine head roll to the affected side. In this position, the otolithic debris would fall out of the utricle and rest onto the lowermost horizontal SCC cupula. ⁴ (Fig. 2).

The possible coexistence of canalithiasis and cupulolithiasis

Canalithiasis evokes usually a crescendo–decrescendo nystagmus with a short duration (mostly no longer than 30 s), in contrast to cupulolithiasis that goes with a longer, more persistent, and less intense nystagmus. ²¹ The examiner may suspect coexistence of canalithiasis and cupulolithiasis when the position of the debris is such that there is a spontaneous inversion of positional nystagmus without a positional change. In such cases, the initial nystagmus may be driven by canalith-induced endolymph flow, whereas subsequent cupular deflection may predominate, often leading to a reversal in nystagmus direction. ²² There are more data on this phenomenon concerning the horizontal SCC.^22–25 However, alternative mechanisms, such as short-term central adaptation and endolymphatic reflux, have also been proposed to explain this phenomenon ²³ . When the canalithiasis causes a nystagmus in the same direction as in the cupulolithiasis (such as in concomitant short arm and long arm canalithiasis of the posterior canal), it may be difficult to discern the two by the temporal dynamics of nystagmus alone.^14,26 According to the pathophysiology and the location of otoconial debris, the posterior canal BPPV can be classified into four distinct types: (a) canalithiasis in the long arm, (b) canalithiasis in the short arm, (c) cupulolithiasis in the long arm, and (d) cupulolithiasis in the short arm. In clinical practice, various patterns of posterior canal BPPV may emerge as a result of different combinations of these subtypes. ²⁶ This classification carries important implications for accurate diagnosis and tailored therapeutic strategies. The observation of ipsicanal conversion from cupulolithiasis to canalithiasis within the same canal and on the same side, in conjunction with application of the Dix–Hallpike, reversed Dix–Hallpike (in which the head is bent forward 90° from the upright position after being turned 45° toward the tested side), half Dix–Hallpike, inversed Half Dix–Hallpike (in which the head is rotated 180° away from the half Dix–Hallpike maneuver), and augmented half Dix–Hallpike maneuvers, can provide diagnostic clues for coexistence of canalithiasis and cupulolithiasis. ²⁶ These cases may pose a difficulty for differential diagnosis because lesions of the vestibulocerebellum may also cause a direction-changing positional nystagmus.^27–29 In general, it can be stated that, unless there is a typical upbeat-geotropic nystagmus in the Dix–Hallpike position which can be eliminated by Epley maneuver, it is not possible to differentiate between BPPV and central positional nystagmus only based on latency, horizontal direction of nystagmus, fatigability, and the crescendo–decrescendo pattern of nystagmus. ³⁰ Central origin has to be assumed for purely upbeat, downbeat, and pure torsional nystagmus. In particular, positional downbeat nystagmus should alert the examiner to a possible central pathology although it may also be caused by posterior cupulolithiasis (Figure 5(b)).^18,19,31 A weak spontaneous nystagmus may also be confused with a positional one if it is missed during examination in sitting posture because the spontaneous nystagmus may be amplified in Dix–Hallpike or lateral supine position. From a practical point of view, it is recommended to search for a central cause of positional vertigo (including brain MRI), especially if either the pattern of nystagmus does not fit one of the typical BPPV types and the treatments for BPPV is ineffective. ³²

The possible mechanism of “pseudo-spontaneous” nystagmus in BPPV and the theory of “canalith jam”

We speak of pseudo-spontaneous nystagmus when spontaneous nystagmus, usually horizontal, is observed in sitting position, and is not explained by a sustained asymmetry of the vestibular discharge in the afferent vestibular pathways, but is in fact provoked by a gravity-dependent cupular deflection. It is dependent on head position, usually because of debris moving in the horizontal SCC or being attached to the horizontal SCC cupula, or by light cupula.

Nystagmus also can be caused by debris jamming a semicircular canal. This kind of spontaneous nystagmus persists independent of head position, usually caused by bigger otolithic particles obstructing and jamming the horizontal canal. Especially the latter can be misdiagnosed as genuine spontaneous nystagmus.

The persistent geotropic direction-changing positional nystagmus and light cupula

Epley’s discovery of a simple otoconial repositioning maneuver ⁹ suddenly illuminated the possible mechanism of canalithiasis for the researchers because it was so effective and its effectiveness could be used as a proof for the hypothesis. Even before that, there already had been efforts to widen the horizon of positional vertigo syndromes; in 1985 McClure ⁴¹ and in 1989 Pagnini et al. described the involvement of the horizontal SCC. ⁴² The most conspicuous constellation was the horizontal long-arm canalithiasis diagnosed by crescendo–decrescendo type of geotropic nystagmus in both supine lateral positions (left and right); the evoked nystagmus was more intense when the pathological ear is lowermost. ⁴³ With time, the resolution of the observations increased and patterns emerged with otoconia hypothetically located at different positions inside the horizontal SCC. First, the diagnosis of horizontal canal cupulolithiasis was born with an apogeotropic nystagmus that is more intense when the affected ear is uppermost. ⁴⁴

Then, a less frequent variant was described with a persistent bilateral geotropic direction-changing positional nystagmus in the supine lateral head positions in the absence of central neurologic signs. ⁴⁵ Later other authors also verified these initial findings. ⁴⁶ To study the hypothesis that this phenomenon could be caused by a light cupula of the horizontal SCC, this group adopted the model of positional alcohol nystagmus (PAN). Soon after ingestion (PAN1), alcohol reaches the cupular matrix even before it saturates the endolymph. Therefore, the density gradient between the cupula and endolymph transforms the SCCs into gravity-sensitive receptors. This is because alcohol has a lower density than the endolymph (“buoyancy hypothesis” ⁴⁷ ). To simulate the light cupula phenomenon using PAN1, the authors required patients with a unilateral deafferentation of the vestibular organ ⁴⁸ because alcohol would influence both sides. Vestibular dysfunctions were commonly found in caloric and utricular function tests and 40% of the patients suffered from migraine. ⁴⁹ Based on the findings of model experiments and clinical observations, the authors concluded that the cause of this persistent geotropic nystagmus is most probably due to a light cupula phenomenon involving the horizontal SCC, perhaps caused by a reversible metabolic disturbance.

Later it was also found that during PAN1 the light cupula phenomenon can also be elicited in the vertical canals. ⁵ In this respect, the authors proposed the terminology of “peripheral positional vertigo and dizziness” (PPVD) to embrace the persistent types of positional vertigo and nystagmus. Although these mild, longer lasting variants come with less severe symptoms, however, they make the patients ill enough to see a doctor. They may wait longer until seeking help but are grateful for the effective physical therapy. ¹⁸

Under the heading of controversial and emerging syndromes, the authors of the Bárány Committee Consensus Document ¹ discuss the anterior canalithiasis and posterior cupulolithiasis

As listed in our Table 2, when the debris is on the cupula in the anterior canal ampulla and it falls into the long arm during the Dix–Hallpike positioning, anterior canalithiasis should cause a crescendo–decrescendo torsional downbeat nystagmus with a slight torsional fast phase beating toward the affected ear. The nystagmus may be elicited by the Dix–Hallpike maneuver on either side. The direction of the positional nystagmus during Dix–Hallpike maneuver should be the same either when the debris is attached onto the anterior cupula and remains on it (in this case of anterior cupulolithiasis the nystagmus is more persistent) or when the debris floating out of the utricle falls onto the anterior cupula (short arm anterior canalithiasis): in these latter cases, a crescendo-persistent downbeat nystagmus ensues. Kim et al. discuss this entity in their paper on “less talked of variants of benign paroxysmal positional vertigo” and remark that it is rarely observed. ⁴

When discussing the posterior canal cupulolithiasis among the controversial and emerging entities, the consensus diagnostic criteria by the Barany Society suggest that it should be examined using the half Dix–Hallpike maneuver (performed with the head turned 45^o toward the side to be tested and raised from supine about 30^o). ¹ Several authors indeed found this test useful; in hypothetical posterior cupulolithiasis, this maneuver elicits positional nystagmus, after a brief latency, beating upward and ipsitorsionally (the upper pole of the eyes beating to the affected ear).^4,13 Other authors also suggested that posterior cupulolithiasis causes either downbeat nystagmus or no nystagmus in Dix–Hallpike position, only a short vertigo spell when elevated from the head-hanging position (“sitting-up vertigo”),^{12,13,18,50,51} depending on the anatomical position of the posterior ampulla, which varies. ⁵² In the literature, others had already published evidence of positional downbeat nystagmus in the absence of a central vestibular pathology. ⁵³ Theoretically, spontaneous nystagmus should occur in the sitting position in posterior canal cupulolithiasis because the otoconia would exert a stimulatory ampullofugal gravitational vector on the cupula in this position.^31,50 However, previous studies have described no spontaneous nystagmus in the sitting position in cases of posterior canal cupulolithiasis diagnosed with the half Dix-Hallpike maneuver. ³¹ This absence of spontaneous nystagmus can be explained by set-point adaptation that serves to stabilize vision in the neutral position.^31,50,54 Recent studies reported that nystagmus may not be elicited even in the half Dix–Hallpike position in posterior canal cupulolithiasis, thus suggesting that set-point adaptation may also operate in head positions other than the neutral one. ⁵⁵ The set-point adaptation is indeed powerful enough to cancel out the maximal deflection of the cupula caused by the gravitational force during the half Dix–Hallpike maneuver. ⁵⁵ These findings imply that the half Dix–Hallpike maneuver alone may not be sufficient for diagnosing the cupulolithiasis of posterior canal.^26,55 Thus, for secure diagnosis of posterior canal cupulolithiasis, additional maneuvers that would deflect the cupula in the ampullopetal direction, such as the reversed Dix–Hallpike maneuver and the inversed half Dix–Hallpike maneuver, should be performed. For a more refined diagnosis of cupulolithiasis, it is necessary to assess whether nystagmus disappears at the null point of each semicircular canal cupula. ⁵⁶ The null point is defined as the head position where the cupula affected by cupulolithiasis is aligned with gravity, so in this position the positional nystagmus should cease.

Further studies, however, are required to determine and define the precise null point for each canal. According to Harmat et al. ¹⁸ cases with the symptoms of BPPV but without nystagmus are rather frequent. In this study, one-third of the patients met the criteria for type 2 BPPV; the remainder had typical posterior or horizontal SCC involvement. As discussed earlier under the point 1. Short arm canalithiasis, upon repetition of testing, 19 patients treated for posterior canalithiasis developed a small persistent positional downbeat nystagmus in the Dix–Hallpike position, which was interpreted by the authors as post-repositioning posterior cupulolithiasis (see also Figure 5(b)). The symptoms from type 2 BPPV were longer in duration yet responded favorably to physical therapy. The authors completed three-dimensional reconstructions of the posterior ampulla and cupular plane based on cadaver histological sections and suggested that the type 2 BPPV is caused by either short-arm canalithiasis or cupulolithiasis of the posterior SCC. The most important message of this publication was that although the average duration of symptoms was 2 months in type 2 BPPV, 86% of patients showed improvement of symptoms at the 1-week follow-up visit and 54% reported a complete resolution with home exercises that consisted of 10 Dix–Hallpike positions to the affected side 3 times a day.

In summary, the direction of positional nystagmus in the Dix–Hallpike position in cupulolithiasis of the posterior canal is yet controversial. The most important message is that positional downbeat nystagmus may be of central but also of peripheral origin. If it is elicited in Dix–Hallpike position as a post-repositioning nystagmus after a posterior canalithiasis then it is probably peripheral, because during the maneuver the otoconial debris falls through the utricle and may attach itself to the utricular surface of the posterior cupula. In other cases, a possible central pathology should be excluded. Further studies of post-repositioning nystagmus using video nystagmography also recording torsional components may help to refine the diagnostic criteria of the posterior cupulolithiasis.