DIMETHYL SULFOXIDE THERAPY IN SUBJECTIVE

TINNITUS OF UNKNOWN ORIGIN

Aristides ZSliliga Caro
Otorhinolaryngology Service
Manuel A rriaran Children's Hospital
Santiago, Chile

In this paper a therapeutic model is presented to confront the troublesome

symptom of unspecific etiology defined as subjective (nonvibratory) tinnit~s.'-~ The
tinnitus symptom has a relatively high incidence in adult ear, nose, and throat
(ENT) patients (50-60%); the incidence is higher when it is accompanied by an
associated pathology such as presbyacusis or otosclerosis.'*a-5 If we discard vibra-
tory-type noises, we can estimate that between 20 and 30% of the ENT consulta-
tions are for nonvibratory tinnitus, which if it is of the continuous, intense type,
severely affects the conduct and well-being of the patient. A practical problem is
facing this patient, as up till now a diversity of therapeutic models have been
proposed for this refractory ~ y m p t o m . ~ . ~ It
. ' . should
~ . ~ be mentioned that generally
only transitory modifications are attained.1.3
Since we do not know the cause and primary localization of nonvibratory tin-
nitus, we face a situation in which we have to take a therapeutic decision that lacks
an exact physiopathological basis. In this paper the works of different authors have
been u ~ e d , ~ - ~which
.~-l~ permit us to infer that if there is a common denominator in
the different pathological factors capable of triggering tinnitus, this would be a me-
tabolic dysfunction caused by alteration of the microcirculation, modified by
vascular spasms and/or a tendency toward a diminished blood flow, due to in-
travascular aggregation of erythrocyte^.^.^.^-^^^^.^^
In elderly patients, cochlear vascular alterations with repercussions on the
normal nutrition of the nervous cell are considered to be a result of the alterations of
the conjunctive-vascular t i ~ ~ ~ e . ~ * ~ * ~ ~ - ~ ~
With this background information, the primary pharmacological and biological
properties of dimethyl sulfoxide (especially its ability to penetrate skin and
membranes) make it of great interest in tinnitus therapy as a vehicle and potentiator
of anti-inflammatory and vasodilatory drugs.

METHOD

Fifteen adult patients with an age range of 32-69 years, who consulted for tin-
nitus of a determined character, intensity, and frequency were submitted to a func-
tional clinical study, in order to establish a diagnosis that would eliminate, both
clinically and by anamnesis, any definite, precise cause of their symptoms. For this a
clinical file was arranged for the patients' clinical identification, laboratory data, and
evolution. Investigation of the anamnesis covered all possibilities of causual relation,
with special emphasis on professional risks, associated pathology, use of drugs and
allergic antecedents, and so on.
The study took careful note of antecedents related to cervical column pathology,
temporal-maxillar articulation, nasopharyngeal infections, and hematological and
cardiovascular alterations. Also psychotic, psychiatric, and physical trauma ante-
cedents were carefully investigated. Exploration of the cervical region was done as a
468
 ZAiiiga: Therapy in Subjective Tinnitus 469

routine. With this screening, two patients were discarded from this study for clear
psychotic antecedents (the noises were voices), as were three patients with histories
of acoustic trauma and aneurysm of the internal carotid. In the ENT examination,
emphasis was put on the otoscopic and nasopharyngeal examinations along with ex-
ploration of the cavum. Routine radiographic examination of the paranasal cavities
and insufflation tests of the Eustachian tubes were included. The Costa test
(Valsalva)” was utilized to investigate the tone, intensity, and character modifica-
tions of the tinnitus. Caloric tests were done; also vestibular response was looked for
in relation to change of position. If the patient said he had the spontaneous sensation
of vertigo, he was asked to describe it objectively with a doll (the Tello test).Is This
sensation of vertigo was considered real only if corporal rotation was demonstrated.
If the patient was unable to describe rotation or displacement with the doll, the
sensation was considered to be only dizziness.
Apart from examination of tonal and discrimination response, the audiometry
also included noise exploration. For the latter a routine examination was applied,
using a stethoscope; the test was a modification of pulse synchronism done by
pressing on the superficial temporal artery or other great neck vessels and testing
for the presence of muscular spasms, and so on. By means of the modified
Josephson test,I6 an attempt was made to localize the homologous frequency, as
well as to establish the intensity of the tinnitus by gauging its masking effect on pure
and “white” tones.
Also included in these tests were the measurement of the tympanic membrane
temperature, by means of an electronic thermometer (after a previous physical and
mental rest for a minimum of 30 min). The measurements were made at the same
hour and in the same environmental conditions of thermic neutrality at intervals
during the month in which the patients under study were treated. The treatment
consisted of the local application of approximately 2 ml spray solution in the
external auditive canal of the affected ear every 4 days during 1 month. The spray so-
lution contained the following drugs: y-ketophenylbutazone, moroxydine HCl,
hydrocortisone, lidocaine HCl, n-propylcarbinol, and dimethyl sulfoxide (DMSO)
as a vehicle and potentiator of the other At the same time the patients
were treated parenterally with a daily intramuscular injection ( 5 ml) for 30 days.
The injections contained buphenine chlorhydrate, y-aminobutyric acid, y-amino-j3-
hydroxybutyric acid, 1-acetylglutamine, lidocaine chlorhydrate, and DMSO (0.5
ml), plus water (q.s. 5 ml).
TABLE1 is a summary of the significant clinical and laboratory data obtained on
the patients before treatment was initiated.

TABLE1
CLINICALAND LABORATORYEXAMINATIONS
OF FIFTEEN
TINNITUS
PATIENTS WITH NONVIBRATORY

Number of Patients
Examination
Normal Altered
Otoscopy 15 0
Audiometry:
Tonality 9 6 highs
Discrimination 13 2
Positional vertigo 10 5
Radiography of paranasal sinuses II 4
Tympanic temperature 4 I1
470 Annals New York Academy of Sciences

AUo'OGRAM CXTREhE VALUES

Nt MMEER OF PATIEMS X @Up
GROUP
AGE MERAGE RANGE

8 47.7(32-66)

4 61,7(56-701

FIGURE
1. Typical audiograms, with the extreme values found.

The otoscopic examination did not reveal significant alterations. The audio-
metric tone was found to be altered in six patients, with a drop of between 30 and 60
d b in the high frequencies, by osteophonic as well as by aerial conduction. This drop
is shown in FIGUREI , which shows typical audiograms with the extreme values
found. The discrimination was found to be slightly altered in two patients.
In 3 cases tinnitus was localized approximately between 3,000 and 4,000 Hz,with
an intensity of between 15 and 30 db. In 12 cases it was masked with "white" noise of
between 10 and 12db.

D ~UNDERNOURLHCD
0MA:ACUTE nTlTlS

374- -I

2. The range and average of tympanic temperatures, as a function of age.

FIGURE
 Zliiiiga: T h e r a p y in Subjective Tinnitus 47 1

The Costa test did not modify the tone, intensity, o r character of the tinnitus in
this series of patients. The Eustachian tube insufflation tests gave normal results. In
five patients a sensation of paroxysmal vertigo was confirmed with changes in
position, accompanied by latent, transitory mystagmus of short duration. The
search for reflected acousma gave negative results, except in four patients with in-
volvement of the maxillar sinuses. These had clouded radiological images, but were
without clinical discomfort.
The tympanic temperature measurement is worthy of attention, as this was
found to be altered in 12 cases. In general the ear temperature in the presence of tin-
nitus was lower than it is without it. This temperature tended to approach that of the
armpit, which was used as a reference point. The author estimates that the relative
value measured is more significant than the absolute value measured. (FIGURE2
shows the mean tympanic temperature as a function of age, under various condi-
tions.) In this series of patients with tinnitus the ear temperature gave an average of
36.8 0.4"C.The average normal temperature detected in 10 adult patients without
clinical ENT and/or other systemic alterations was 38.1 f 0.7"C. The results of
cardiovascular and hematologic studies of the tinnitus patients (ECG, tests for eye
fundus, cholesterol, and glycernia) were not significant and gave no reason to
suspect other complications.

RESULTS

TABLE 2 is a summary of the principal clinical symptoms found before the initia-
tion of treatment with DMSO combined with anti-inflammatory and vasodilatory
agents, and their modification after one month of treatment. Six months was the
shortest time of evolution of the tinnitus symptom among the patients before
treatment was begun. None of the patients had become adapted to the noise. A t the
end of a month's treatment, nine of the fifteen patients were completely relieved of
the subjective discomfort. In two patients it was diminished. Four continued with
tinnitus, but of a changed character and intensity; the symptom was more easily

TABLE2
PRINCIPAL SYMPTOMS AND PROGRESS OF PATIENTSW I T H SUBJECTIVE
TINNITUS OF UNKNOWN ORIGINAFTER ONE MONTH'STREATMENT WITH
D M S O INTEGRATED WITH ANTI-INFLAMMATORY A N D VASODILATORY AGENTS*
Lower Only
omplete Intensity Occasional

Tinnitus 15 9 2 4
Dizziness 10 5 2 3
Vertigo 5 5 - -
Insomnia 15 8 7 -
Otalgia 3 2 - 1
Headache II 7 I 2
Hypacusis (sensorial-
neural highs) 6 - 3 -
Discrimination 2 2 - -
*The average temperature of tympanic membrane before treatment was 36.08 f 0.4-C;
after 1 month's treatment it was 37.9 f 0.6"C.
47 2 Annals New York Academy of Sciences

FIGURE3. Variations in the temperature measurements of the tympanic membrane, as

compared with measurements of armpit temperatures.

tolerable, and appeared only occasionally. This latter group of patients categorically
related the reappearance of the symptom to exposure to cold weather in the morn-
ings. A notable improvement was observed in the patients who at the beginning of
the treatment had suffered from dizziness and positional vertigo. The insomnia of
eight patients disappeared, and seven slept better. There was also improvement in
headache and otalgia (the latter was not related to temporal-maxillar articulation).
Very noteworthy was the modification in the sensorial-neural hypacusis of some
of the patients, as expressed subjectively by the patients and confirmed by audio-
metric examination. At present we are trying to investigate the objective significance
of this improvement.
FIGURE3 demonstrates the variations in the temperature measurements of the
tympanic membrane, comparing them with the armpit temperature measurements.
In general a correlation was noted between the presence of tinnitus and the con-
vergence of the armpit and tympanic temperatures. The temperature levels sep-
arated again, a s is normal in a healthy person, when the treatment was effective. As
side effects nine patients complained of tachycardia, anguish, and heavy-headedness
after the intramuscular injection. These discomforts were momentary and did not
reoccur after the first three or four injections. Long-term control has not shown evi-
dence of reappearance of the symptoms after an interval of one year.
The tolerance of the intramuscular injections was excellent; no allergic altera-
tions o r cutaneous reactions were noted in any of the patients. The odor was some-
times objected to by the people with whom the patients live. (This can be minimized
by daily consumption of approximately 1 liter of milk.)

DISCUSSION
The common factor that explains the presence of the nonvibratory tinnitus
symptom in our patients is probably malnutrition of the nervous cell, either at the
level of Corti's organ or at a more central level. The vascular and nervous
 ZdGiga: T h e r a p y in Subjective Tinnitus 473

pathology, both cochlear and CNS, as studied by different permits

extrapolation of the possible mechanism of action of the DMSO solution mixed with
anti-inflammatory and vasodilatory substances, given the previously enumerated
pharmacological properties of this drug. Along with this, the author notes the
significant alteration and later modification of the tympanic membrane temperature
that was correlated with the disappearance of the tinnitus symptom and the other
signs and symptoms that accompany it, The author believes that the elevation of the
tympanic temperature after the initiation of treatment could correspond to a better
blood flow through the CNS, and in particular through the auditive system. This
would induce the normalization of the peripheric transductor of the central
temperature, the transductor being localized in the region of the tympanum. The
fact that in control examinations after a year's interval, those patients who com-
plained of occasional reappearance of the tinnitus symptoms directly related this
reappearance t o exposure to cold weather, seems to confirm our hypothesis. I t
should be underlined that from the clinical point of view, the differential diagnosis of
tinnitus must be the principal motive of a clinical and functional study, keeping in
mind that one must first eliminate from among the many and complicated
pathological factors that may provoke this symptom the presence of Mtnitre's syn-
drome, hysterical components, neurinoma of the acoustic nerve, nasopharyngeal
cancer, arterial aneurisms, Costen's syndrome, jugular glomus tumors, syphilis,
and so on.

In fifteen patients affected by essential nonvibratory tinnitus, local applications

in the external auditive canal of 2 ml medicated DMSO spray were made. The spray
solution contained DMSO integrated with anti-inflammatory and vasodilatory
substances. This application was repeated every four days for a month. A t the same
time each patient was administered a daily intramuscular injection of a preparation
that contained DMSO and a vasodilatory component. The therapeutic effect was
evaluated through the subjective modification of the symptom and functional tests
of the auditory system. Of the fifteen patients treated, the tinnitus symptom com-
pletely disappeared in nine, and did not return during a one-year observation period.
The patients' symptoms diminished in two cases, and in four cases the permanent
tinnitus became occasional, triggered principally by environmental cold. I t is im-
portant to note that among the concomitant signs, the five patients with vertigo
noted improvement. Hypacusis diminished in three of the six patients affected. In-
somnia disappeared in eight and diminished in seven cases.
The rise in the average tympanic membrane temperature from 36.8"C before to
37.9"Cafter treatment was noteworthy. This could indicate an improvement of the
blood flow in the inner ear.

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