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Why do benign paroxysmal positional vertigo episodes recover

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Article  in  Journal of Vestibular Research · July 1998

DOI: 10.1016/S0957-4271(97)00080-3 · Source: PubMed

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 Journal of Vestibular Research, Vol. 8, No. 4, pp. 325–329, 1998
Copyright © 1998 Elsevier Science Inc.
Printed in the USA. All rights reserved
0957-4271/98 $19.00 1 .00
PII S0957-4271(97)00080-3

Original Contribution

WHY DO BENIGN PAROXYSMAL POSITIONAL VERTIGO

EPISODES RECOVER SPONTANEOUSLY?

Gianpiero Zucca,* Stefano Valli,† Paolo Valli,* Paola Perin,* and Eugenio Mira†
*Institute of General Physiology, University of Pavia; and †Department of Otolaryngology,
IRCCS Policlinico S. Matteo, Pavia, Italy
Reprint address: Prof. Paolo Valli, Institute of General Physiology, University of Pavia, Via Forlanini, 6,
127100 Pavia, Italy. Tel: 139-382-507608; Fax: 139-382-507527; E-mail: paovalli@ipv36.unipv.it

h Abstract — It is well known that most episodes
of benign paroxysmal positional vertigo (BPPV),
even in untreated, recover spontaneously in 2 to 6
weeks. In the present study, we put forward the
hypothesis that this is mainly due to the fact that
endolymph, owing to its low calcium content (20
mM) is able to dissolve otoconia. To support this,
the fate of frog saccular otoconia immersed in nor-
mal endolymph (Ca21 content 20 mM) and in
Ca21-rich endolymphatic fluids (up to 500 mM)
was studied by observing the crystals at regular
intervals for 3 weeks. The results demonstrated
that normal endolymph can dissolve otoconia very
rapidly (in about 20 hours). When the endolym-
phatic Ca21 content was increased (50 to 200 mM)
otoconia dissolution time was slowed down (about
100 to 130 hours, respectively) and completely
stopped when the endolymphatic Ca21 content
was of 500 mM. The present results therefore
suggest that the major process involved in the
spontaneous recovery of BPPV episodes is the ca-
pability of the endolymph to dissolve dislodged
otoconia. © 1998 Elsevier Science Inc.
h Keywords — BPPV; otoconia; cupulolithiasis;
canalolithiasis.
Introduction
Benign paroxysmal positional vertigo (BPPV),
first described by Adler (1) and Barany (2), and
then so named by Dix and Hallpike (3), is one
of the most common causes of vertigo.
Received 19 December 1996; accepted 26 May 1997.
325
Although the pathophysiologic mechanisms
of BPPV are still a matter of debate (4), it is
generally accepted that this labyrinthine disor-
der is, with few exceptions (central vestibular
dysfunction), mainly due to dislodged otoconia
either settling on the cupula (cupulolithiasis) (5)
or, congealed with other debris, forming clots
free-floating inside a semicircular canal, usually
the posterior one (canalolithiasis) (6,7).
From clinical experience, it is also known
that BPPV is a transient (benign) phenomenon
that, as a rule, recovers spontaneously in about
2 to 6 weeks. Sometimes, however, positional
vertigo episodes are recurrent or persistent (8–
10). A reliable case-record on a large series of
patients is still lacking in the literature.
The processes underlying the remission of
BPPV episodes have never been investigated in
detail, and only a few contradictory hypotheses
have been put forward (4,11).
In the present study, we suggest that the
spontaneous remission of BPPV episodes is
chiefly due to the fact that endolymph, owing to
its low content of ionized calcium (20 mM) (12–
14), is able, by itself, to dissolve dislodged oto-
conia, thus producing a progressive attenuation,
up to disappearance, of BPPV symptoms.
To verify this hypothesis, the fate of otoco-
nia immersed in artificial endolymph with nor-
mal Ca21 content (20 mM) and in solutions with
higher Ca21 content (up to 500 mM) has been
investigated.
326
Methods
Otoconia were removed from the sacculus of
the frog (Rana esculenta L.) and placed, in
small groups, in Petri dishes (capacity 5 ml)
filled either with normal artificial endolymph
(Ca21 20 mM) or with endolymphatic solutions
with an increased Ca21 content (50, 200, 500
mM). The different media were obtained by add-
ing to a common endolymphatic solution (com-
position: NaCl 18 mM; KCl 100 mM; NaHCO3
1.2 mM; NaH2PO4 0.17 mM; CaCl2 1 mM; pH
7.3) suitable amounts of ethylenediaminetet-
raacetic acid (EDTA) (0.98 mM for Ca21 20
mM; 0.95 mM for 50 mM; 0.80 mM for 200
mM; 0.50 mM for 500 mM). In the same experi-
ments, frog otoconia were placed either in hu-
man artificial endolymph (composition: NaCl
16 mM, KCl 150 mM; NaHCO3 1.2 mM;
NaH2PO4 0.17 mM; CaCl2 from 20 mM to 500
mM; pH 7.3) or in human artificial perilymph
(composition: NaCl 160 mM; KCl 5 mM;
NaHCO3 1.2 mM; NaH2PO4 0.17 mM; CaCl2
from 20 mM to 400 mM; pH 7.3) or in plain wa-
Figure 1. SEM image of the otoconia removed from frog sacculus.
G. Zucca et al
ter with the same Ca21 content (CaCl2 from 20
mM to 500 mM). Plain water pH was adjusted to
7.3 by adding Na OH.
The results demonstrated that the EDTA-
Ca21 buffer system adopted in the present study
was very efficient in maintaining Ca21 concen-
tration constant in the different solutions. In
fact, Ca21 levels, measured by means of Ca21-
sensitive microelectrodes, did not change after
the addition of otoconia to the various media.
Ca21-sensitive microelectrodes were made ac-
cording to a procedure already described (15).
As ion exchange resin, the calcium ionophore
I - Cocktail A (Fluka) was employed.
Criteria for the Evaluation of Otoconia
Dissolution Rate
Frog otoconia (Figure 1) constitute a fairly
heterogeneous population of crystals, mainly
cylindrically shaped (length 1 to 20 mm; diame-
ter 0.5 to 4 mm), that, according to Pote and Ross
(16), have a mineral structure mimicking calcite.
Spontaneous Recovery of BPPV Episodes 327

Figure 2. Time course of the dissolution of otoconia when immersed in a 50 mM Ca21 endolymphatic fluid.

For scanning electron microscopy (SEM), Petri dishes were closed by covers that were re-
otoconia were dried, gold-coated, and observed moved only during the time required for taking
with a Joel JXA-840A scanning electron micro- pictures. Petri dishes, containing otoconia, were
scope. To evaluate the dissolution rate of the always kept at room temperature (about 228C).
different otoconia, when they were immersed in All experiments were performed in accor-
the various endolymphatic solutions, crystals dance with the guidelines of the Declaration of
were subdivided by length in 4 classes of 3, 5, Helsinki.
10, and 15 mm, respectively. This was per-
formed by choosing, under microscopic control
(Zeiss Universal microscope), an area in the Results
Petri dish where the otoconia were well separated
from each other and where the majority of them A representative example of the fate of oto-
fell in the desired length class. (The only diffi- conia immersed in Ca21 50 mM endolymphatic
culty was the individuation of 15 mm otoconia, solution is depicted in Figure 2. It may be seen
which are relatively rare in the otoconial mass,
whereas all the other otoconial classes, that is, 3,
5, and 10 mm, were always well represented). Table 1. Otoconia Dissolution Time (hours) versus
Their Dimensions and Endolymphatic Ca21
Once located, the area was photographed Content (N 5 4)
(Nikon A1 camera) every 3 hours during the
first 2 days and every 8 hours for the following Ca21
18 days. Dissolution time of each otoconial 20 mM 50 mM 200 mM 500 mM
class was determined by observing the time at
which otoconia disappeared. Size
3 mm 5.2 6 1.5 68 6 10 100 6 10.3 .480
To avoid evaporation, which might alter the 5 mm 9.7 6 1.5 78 6 4 108 6 4.6 .480
ion composition of the solutions and therefore 10 mm 14.2 6 2.8 84 6 4.6 118 6 7.6 .480
15 mm 19.5 6 3 98 6 4 128 6 6.5 .480
the efficiency of the Ca21 buffer system, the
328
that this medium is able to dissolve otoconia,
even the largest ones, in about 100 h. Figure 2
also shows that, as expected, dissolution was a
progressive process, affecting at first small oto-
conia (3 to 5 mm; 60 to 70 hours) and then in-
creasingly larger ones. After about 100 h, all of
the otoconia were completely dissolved.
The results of the whole series of experi-
ments (n 5 4) are summarized in Table 1. It
may be noted that otoconia dissolution time was
clearly dependent on Ca21 endolymphatic con-
tent. In fact, dissolution was very rapid (about
20 h for the largest ones) in normal endolymph
(Ca21 content 20 mM), quite slower in Ca21 50,
200 mM solutions (100 to 130 hours, respec-
tively), and completely absent (.480 h irre-
spectively on otoconia dimensions) when the
endolymphatic Ca21 content was of 500 mM.
Similar results were observed when frog oto-
conia were placed either in human endolymph
(n 5 2) or in human perilymph (n 5 1) or in
plain water (n 5 2) with the same Ca21 content
(data not shown).
Discussion
The present results clearly demonstrate that
otoconial dissolution rate is strictly dependent
on the Ca21 concentration of the medium in
which crystals are immersed and not on its elec-
trochemical composition. In fact, under the same
Ca21 level, an artificial human endolymph, an
artificial human perilymph, or plain water had
the same capacity to dissolve otoconia.
Our results have also shown that a medium
with a Ca21 content similar to that of a normal
endolymphatic fluid (20 mM) can rapidly dis-
solve otoconia (about 20 h for the largest ones).
The experimental conditions adopted in the
present study are, in all probability, the most fa-
vorable ones for otoconial dissolution (few,
well separated otoconia immersed in a very
large (5 ml) Ca21-buffered volume). It is in fact
presumable that, in physiological conditions,
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