Audiotympanometric Findings Myasthenia Gravis
in
Wilfred T. Morioka, MD; Palmer A. Neff, MA; Thomas E. Boisseranc; Paul W. Hartman, PhD; Robert W. Cantrell, MD
\s=b\ Myasthenia gravis can be a difficult diagnostic and therapeutic problem. Our study on six patients consisted of puretone audiograms, tympanometry, and acoustic reflex tests. Positive findings in the myasthenia gravis patients prior to medication included hyperacusis and increase in the intensity of sound required to elicit an acoustic reflex. Following medication, the hyperacusis lessened and the intensity of sound required to elicit the
acoustic reflex decreased. During follow-up of two of the patients we encountered cholinergic (overdosage) crisis in one patient and myasthenic (underdosage) crisis in the other patient. Muscle weakness can be a common factor in both conditions. The acoustic reflex test can differentiate between the two types of crises. We believe audiotympanometric tests can aid in diagnosis and treatment of myasthenia gravis patients.
(Arch Otolaryngol 102:211-213, 1976)
Accepted for publication Nov 11, 1975. From the Department of Otolaryngology and the Clinical Investigation Center, Naval Regional Medical Center, San Diego, Calif.
Read before the Committee for Research in Otolaryngology of the American Academy of Ophthalmology and Otolaryngology, Dallas, Oct 5, 1974. The opinions or assertions contained herein are those of the authors and are not to be construed as official or reflecting the views of the Department of the Navy. Reprint requests to the Department of Otolaryngology, Naval Regional Medical Center, San Diego, CA 92134 (Dr Morioka).
is a disease in and evaluation difficult. This pre-
gravis Myastheniadiagnosis which
of treatment
are
liminary report presents audiotympanometric findings in six patients with myasthenia gravis seen in the Department of Otolaryngology, Naval Regional Medical Center, San Diego, Calif. Positive
findings in the myasthenia gravis patients prior to medication include hyperacusis in the 1,000- to 4,000-hertz range and a high intensity of sound required to elicit the acoustic
reflex. Within 20 to 90 minutes after medication, there is a decrease of the hyperacusis and a noticeable improvement in the acoustic reflex levels. The cause of myasthenia gravis is unknown; however, several explanations are given1.2 as follows: 1. The abnormal presence of a competitive neuromuscular blocking agent synthesized by the body. 2. Decreased production of acetylcholine at the myoneural junction. 3. Nerve terminals of subnormal area, an apparent misalignment of the nerve terminals with the muscle motor end-plates, a lack or decreased number of muscle motor end-plates, or a combination of these conditions. 4. Decreased sensitivity of the motor
end-plates to acetylcholine.
5. A connection between myas-
thenia gravis and an autoimmune process similar to hypersecretion of thymin, which causes myasthenic symptoms in experimental animals. The distribution of muscle weakness usually involves, in ordered sequence, the extraocular, bulbar, neck, limb girdles, distal parts of the limbs, and trunk muscles.3 Myasthenia gravis involves all cranial nerves.
Otolaryngologists are usually consulted when patients have dysphagia, dysphonia, and respiratory problems of aspiration or inability to handle airway secretions, leading to the necessity for tracheostomy for airway
management.4.5 We demonstrate that
emphasis should be placed on audiotympanometric studies for assistance in diagnosis and evaluation of treatment of myasthenia gravis. more
PROCEDURE Six normal
myasthenic patients and three subjects were evaluated by routine
pure-tone audiometry, tympanometry, and
of the acoustic reflex. The tests done in a sequential manner, that is, a base line battery of tests followed by postmedication tests at 20- or 30-minute intervals. Tests were necessarily conducted on the patients receiving different types and amounts of medications. Patients were
recording were
receiving pyridostigmine bromide, neostigmine bromide, or corticosteroids. The three control subjects received 60 mg of
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Table 1.—Test Results of
5
< 20
«
^^
^
Peak Positive Positive
1/M/22 2/M/24 3/M/55 4/M/35 5/F/45 6/M/62
""
--SH
Increased SPL for Acoustic Reflex No test* No test* Positive Positive Positive
Audiogram
Patient/Sex/Age, yr
Oh
Myasthenia Gravis Patients
Negative! Positive Positive
Negative}:
Negatlvef
40-
No sequential premedicatlon and postmedication test for acoustic reflex changes given. t Patients had moderate sensorineural loss. J Patient had Eaton-Lambert syndrome. *
60-
was
P ra
80-
Table
2.—Representative Acoustic Reflexes*
100-
Results 250 Air Conduction
1,000 2,000 4,000 Frequency in Hz
500
°^>-"i9r" —X-Left x—x
-
8,000
Subject
^"^--C-Right
Conduction >- -ILeft Premedication Post Medication
Normal
~-Representative pure-tone audiogram, left ear of patient 2. Premedication and postmedication air conduction
Patient 5— optimal medication Patient 4—
audiogram.
overdosage Patient 3—
bromide by mouth after their base line tests. Otoadmittance tests for middle ear func¬ tion were done using an otoadmittance meter with the 220- and 660-Hz probe tone. Hearing threshold levels were measured with an audiometer. Acoustic reflexes were induced by a tone pulse from an audiom¬ eter. The 660-Hz probe tone was used on the otoadmittance meter for acoustic reflex measurements, and the change in susceptance indicated on the meter showed the presence of reflexes.
pyridostigmine
RESULTS Prior to medication, four of the myasthenia gravis patients had puretone audiometrie findings that re¬ vealed a threshold improvement, or peak, at the 1,000- to 4,000-Hz range (Figure and Table 1). Within 20 to 90 minutes, there was a noticeable decrease or flattening of the peak, averaging 10 dB (Figure). Subsequent testing, after the effects of the medi¬ cation had lessened, revealed that the peaks were again present. Patients 3 and 6 did not exhibit this peak in their audiograms, presumably because of a high-frequency hearing loss in the same
frequency region.
myasthenia grav¬ patients, two of three normal subjects given pyridostigmine bro¬ In contrast to the
is
mide showed an improvement of 5 dB to 25 dB in the 1,000 to 4,000 Hz range.
underdosage *
with
Time of Test
250 Hz
Premedication Postmedication Premedication Postmedication
At
Premedication Postmedication Premedication Postmedication
A A
90 A A
A A
500 Hz 95 90 A 82 95 110 110 105
(dB) 4 kHz
and from
patients
86 85 A 90 95 A 105 100
Representative acoustic reflex from one ear of a normal subject optimal medication, overdosage, and underdosage.
t A, absent
2 kHz 85 90 A 86 95 103 105 100
1kHz
TOO A 102 100 A
reflex.
The change occurred 30 to 90 minutes after medication. Subsequent audiograms revealed a return to the pre¬ medication pattern. The acoustic reflex level in the myasthenia gravis patients was ele¬ vated prior to medication. That is, it took a greater intensity of sound to elicit the reflex. After medication,
lower intensity levels were required to elicit the reflex (Table 2). In normal subjects, the acoustic reflex levels for both premedication and postmedica¬ tion tests were consistent with normal values established at our facility
(Table 2).
Table 3.—Impedance Values ¡ Myasthenia Gravis Patient 3
Impedance,
Time After Medication
,-»660 Hz 220 Hz
(min) Right ear 0 +20 +40 +60
710 650 785 750
940 780 780 375
550 575 570 535
640 640 600 672
Left ear
+5 +25 +45 +70
pattern. They changed
Patient 6 did not have a high acoustic reflex level on premedication tests. This patient had the EatonLambert syndrome'" which consists of small cell carcinoma of the bronchus and a characteristic myasthénie syn¬ drome with involvement of shoulder and pelvic girdle muscles. The muscles supplied by cranial nerves are
not establish
values calculated from the tympanograms for myasthenia gravis patients measured at premedi¬ cation and postmedication periods did
patient's tympanogram revealed
spared. Impedance
a
in a random manner, unrelated to time of medication (Table 3). All patients were asked to return to our department when they visited the neurologist or noticed a change in symptoms. Patient 4 returned because he thought the medication made him weaker. An impending overdosage cholinergic crisis was suspected. The neg¬
ative middle ear pressure, and the acoustic reflexes after medication showed that greater intensity of
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sound
was
required to elicit the reflex
(Table 2). The neurologist confirmed our um
findings by injecting edrophoni-
chloride, a rapid-acting cholinergic
drug, which produced no improvement in muscle weakness. The patient's medication dose was appropriately
reduced. Patient 3 reported difficulty clear¬ ing his middle ear. He was tested and the tympanogram revealed that he had a negative middle ear pressure. The acoustic reflex improved after medication but not as successfully as in previous tests (Table 2). An impending myasthénie crisis of under¬ dosage was suspected. Three weeks later, despite an increase in his medi¬ cation dose, he developed a myasthén¬ ie crisis and was admitted to the medical intensive care unit for defini¬ tive care, including a tracheostomy. COMMENT
Pure-tone audiometrie findings in myasthenia gravis patients showed a peak in the threshold hearing curve at 1,000 to 4,000 Hz. A possible explana¬ tion for this unusual peak is that weakened stapedius muscle tonus en-
hances the transmission of sound in this frequency range. It is known that a standard dose of neostigmine bro¬ mide in a normal subject may cause localized weakness or paralysis of muscles.7 This weakness or paralysis may explain the duplication of the finding of improved hearing or peak at 1,000 to 4,000 Hz in normal subjects after administration of pyridostig¬ mine bromide. Borg8 described atten¬ uation of sound transmission on recov¬ ery of the stapedius muscle function in Bell palsy patients. He found greater attenuation at 500 Hz (12 to 15 dB) compared with 1,450 Hz (0 to 6 dB). In our patients, the hyperacusis occurred at 1,000 to 4000 Hz. One must have an intact afferent and efferent system to elicit an acoustic reflex. In myasthenia gravis patients, the middle ear muscle weak¬ ness may affect the acoustic reflex efferent arc. One study describes a linear relationship between im¬ pedance change and electromyogram recording from the stapedius muscle." With our method of measuring acous¬ tic reflex levels, an accurate evalua¬ tion can be made of the medication
effect on the middle ear muscles. Both cholinergic crisis (overdosage) and myasthénie crisis (underdosage) result in muscle weakness. The acous¬ tic reflex proved to be especially valu¬ able in the two patients who had a change in their myasthenia gravis status. The acoustic reflex threshold level revealed the difference between the two crises, since with medication the reflex increased in the cholinergic crisis patient, while in the myasthénie crisis patient, a decrease in the reflex level occurred after medication. This decrease was not as dramatic as when the patient had optimal medication dosage, and it caused us to suspect a possible myasthénie crisis. In both crisis patients, the tympa¬ nogram showed negative pressures. The weakness of the tensor veli pala¬ tini muscle may cause decreased Eustachian tube function and produce subsequent negative middle ear pres¬ sure.
In view of our experience, we believe audiometry and tympanom¬ etry provide a valuable adjunct in the diagnostic work-up as well as followup in myasthenia gravis patients.
References 1. Lott RS: Myasthenia gravis. J Am Pharm Assoc 13:440-450, 1973. 2. Ryan M, Egbert B, Ziegler DK: Myasthenia gravis and immunity. Kan Med Soc J 74:72-77, 1973. 3. Harvard CWH: Progress in myasthenia gravis. Br Med J 3:437-440, 1973. 4. Calcaterra T, Stern F, Herrmann C, et al: The otolaryngologist's role in myasthenia gravis. Trans Am Acad Ophthalmol Otolaryngol 76:308\x=req-\
312, 1972.
5. Stuart WD: The otolaryngologic aspects of myasthenia gravis. Laryngoscope 75:112-121,
1965. 6. McQuillen MP, Johns RS: The nature of the defect in the Eaton-Lambert syndrome. Neurology 17:527-533, 1967. 7. Koelle GB, Anticholinesterase agents, in Goodman LS, Gilman A (eds): The Pharmacological Basis of Therapeutics, ed 4. London,
Macmillan & Co Ltd, 1970. 8. Borg E: A quantitative study of the effect of the acoustic stapedius reflex on sound transmission through the middle ear of man. Acta Otolaryngol 66:461-472, 1968. 9. Borg E: On the change in the acoustic impedance of the ear as a measure of middle ear muscle reflex activity. Acta Otolaryngol 74:163\x=req-\ 171, 1972.
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