Symposium on the Role of the Vestibular Organs in Space Exploration (1970)

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Experimental and Clinical Experiences and Comments on Ultrasonic Treatment of Meniere's Disease ARNE SJOBERG University of Uppsala SUMMARY To date, we have almost 300 patients with Meniere's disease who have undergone ultrasonic treatment and have observed about 200 additional patients who were not so treated. These patients comprise a select series of severely disabled persons in whom no form of medical therapy had been effective. The majority had been referred to us from different parts of our country. The mean dura- tion of the disease was 8 years, but a number of patients had been afflicted for up to 20 years. The patients are carefully examined before, during, and after irradiation. The tests include nystagmography after caloric stimulation with water at 30° and 44° C, ice water, and audiometry. A clinical followup investigation of 228 consecutive patients revealed the following: Freedom from or considerable improvement in vertigo was found in 89 percent; tinnitus had diminished or disappeared in 48 percent: hearing was improved or unchanged in 64 percent; and caloric reaction was clearly reduced in 58 percent. Of the last 200 surgical patients, we have only one with transitory facial paralysis, or a 0.5-percent incidence. INTRODUCTION Meniere's disease is closely linked to sea- sickness, motion sickness, and space sickness — in other words, vestibular sickness —with their special causes and problems. The disease was named in 1861 for the French otologist and teacher of deaf mutes, Prosper Meniere. Today it is the most common of the vestibular-related vertigo conditions. It is estimated that more than 60 percent of all patients with vertigo are afflicted with Meniere's disease, and this prob- ably explains the great interest in this disease all over the world. Meniere's disease is to be regarded today as a classical, well-characterized, and fairly common condition which mainly affects men and women between 20 and 60 years of age almost equally, with some possible predominance in men. The diagnosis is easy to establish from the case history. The symptoms are of both vestibular and cochlear origin and are manifested as a triad: (1) unilateral tinnitus, (2) increasing unilateral deafness, and (3) sudden severe dramatic attacks of dizziness of the vestibular type. True vestibular vertigo is characterized by disturbance in equilibrium, with a subjective sensation of rotatory motion, and, at the same time, a feeling that the surrounding room is moving. Objectively, this rotatory vertigo is observed in the form of an extremely brisk, often third-degree nystagmus which may beat in one particular direction, initially toward the affected side, and then change its direction near the end of the attack toward the unaffected side. But the vertigo and nystagmus are often of the positional type, in which case the direction of the nystagmus varies. It is certainly no exaggeration to state that one of the greatest scourges of mankind is vertigo in the acute phase of Meniere's disease. A pertinent observation has been made that people learn to tolerate pain of different degrees, but that there are very few who can tolerate the particular disorientation which accompanies vestibular vertigo, with the negative explosion 271

272 THE ROLE OF THE VESTIBULAR ORGANS IN SPACE EXPLORATION in the form of nausea, vomiting, and dizziness. In the most severe forms of the disease, the patient may be so severely disabled that he will seek any possible means of being free from his suffering. To many, the dream of becoming free of their attacks seems almost unattainable, since over the course of several years they have probably tested the entire therapeutic arsenal with little relief. As with motion sickness, there is a classical picture of the disease. It should be remembered in this connection once again that in motion sick- ness there is no macroscopical nystagmus nor any sensation of rotatory vertigo. At the Uppsala clinic we have treated ultra- sonically almost 300 patients and have observed in all about 500 Meniere's patients. It should be noted that this is a select series of severely disabled patients, in whom no form of medication had had an effect. Some of the patients were from Uppsala, but the majority had been referred to us from different parts of our country. The results of our neuro-otological work, to be presented here, are the outcome of excellent teamwork. The members of the group are As- sociate Professors Jan Stahle and Biirje Drettner, and the physicist Sven Johnson who designed and constructed our apparatus (refs. 1 to 5). CHARACTERISTICS OF PATIENT GROUP Nystagmographic analyses were made of the caloric response in 300 of the total group (ref. 6). In the majority of patients the disease was unilateral (258, or 86 percent), but in 42 (14 per- cent) both sides were affected. The elapsed time between the onset of the disease in one ear and its development in the other varied between 1 and 20 years. In 84 percent the caloric re- sponse was pathological; in 59 percent it was reduced, and in 11 percent it was increased. Directional preponderance was noted in 52 percent. Most commonly (41 percent) the disease started with both vertigo and impairment of hearing. In 37 percent the first symptom was an attack of vertigo, and in 22 percent the hearing was im- paired first. The configuration of the audiogram was analyzed in 124 patients. After weeks, or sometimes years, of fluctuating hearing, with varying remissions in the course of the disease, hearing impairment often gradually progressed toward an irreversible final stage, when the tone audiogram registered a "flat loss." In 60 per- cent the audiogram curves were of the horizontal type, the majority being severe (ref. 7). Rising curves were seen in 17 percent and falling curves in 12 percent. In 7 percent the curves were trough shaped, and 4 percent were unclassi- fiable. Bekesy audiography showed a reduced limen difference, so-called recruitment, espe- cially in the higher frequencies. Whispering and conversation distances were obviously greatly decreased. Speech audiometry revealed a pro- nounced loss of discrimination, and the spoken words became difficult to understand. TOPICAL DIAGNOSIS With regard to the topical diagnosis in ver- tiginous diseases like Meniere's, it is clear that first and foremost a decision must be made, on the basis of the case history and clinical symp- toms, as to whether the lesion is central or peripheral or in between the two. Vertigo of Central Genesis Vertigo caused by central lesions develops gradually, often very slowly, and persists for a duration of months or years. In these cases the vertigo can be of a rotatory or tactile type, with a tendency to lateropulsion. It is often experi- enced as "positional vertigo"; i.e., it can be more severe when the head is in a particular position. At the same time, nystagmus of the so-called positional type can often be observed. A varied picture of symptoms is obvious in centrally dependent vertigo and is characterized mainly by vestibulo-ocular disturbances with vertigo and nystagmus, but usually, in addition, by ves- tibulospinal disorders, wherein the proprioceptive disturbances are manifested as changes in equi- librium and alterations in tonus. It is well known that these symptoms are seen in diseases of the brainstem, the cerebellum, and the cerebellopontine angle. To this category we can also assign acoustic tumors which lie, so to speak, on the borderline between the central and peripheral portions of the vestibular nerve.

ULTRASONIC TREATMENT OF MENIERE'S DISEASE 273 Vertigo From Middle-Position Lesions Cervical Syndrome, Barre-Lieou Syndrome, Cervical Migraine Middle-position lesions show the disease pat- terns such as in the cervical syndrome, the Barre-Lieou syndrome, or cervical migraine. The principal symptoms are brachialgia, head- ache, tinnitus, globus sensation and paresthesia in the face, slight impairment of hearing of the neurogenic type, and vertigo. The symptoms can present considerable difficulties in differ- ential diagnosis. The headache can be uni- lateral or localized to the back of the neck, which occupies a central position in the equilibrium system in that the occipital muscles, via the neck reflexes, are under the continuous influence of impulses from the apparatus of equilibrium. The afferent impulses from the occipital and neck muscles pass via the posterior roots from Cl to C3. If, for any reason, the occipital muscles go into a state of traction, then they are unable to function as effector organs for the neck reflexes, and a disturbance in equilibrium will occur, re- sulting in vertiginous symptoms. The occipital muscles can become tender and painful. Elec- tromyography will reveal that the muscles are in a state of contraction. As far as is possible, we examine otoneuro- logically all patients with brachialgia. J. Sand- strom (ref. 8) analyzed a series of patients from the orthopedic clinic of our hospital and found that vertigo with recordable nystagmus on rota- tion of the head occurred in 18 to 20 percent. Figure 1 shows one of our patients with Barre- Lieou syndrome and recordable nystagmus after turning and bending of the head. Vertigo in the cervical syndrome can be of a transitory rotatory type, but is usually tactile with a sensation of propulsion or lateropulsion. It is significant that the vertigo has a sudden onset and is transitory, taking the form of a sen- sation of general insecurity. The patient takes a step sideways or staggers in some direction for a moment as if he were intoxicated. Vertigo can occur on extreme hyperextension or on rapid and sometimes extreme rotatory or nodding movements of the head. The patient may, for example, be backing his car into the garage or doing some painting work above his head, or I Af "lL,RigMI>»«tIng ny.T. RighIb**ting 0 10 20 30-C - Min 4*"C FIGURE 1. — The Barre-Lieou syndrome with recordable nys- tagmus after turning and bending of the head. perhaps he may be visiting a museum or art exhibition wearing bifocal spectacles and will have to bend and turn his head in time with his different up-and-down eye movements. It has been considered pathogenetically that, on rotatory movements of the head, excitation of sympathetic vasomotor fibers may be induced, so that a spasm is provoked in the vertebral artery. This artery passes into the spinal canal at C6, and the excitation can pass via the verte- bral sympathetic nerve, which is connected be- low with the stellate ganglion. The cause would seem to lie in roentgenolog- ically visible spondylotic lesions in the cervical spinal column, with more or less pronounced arteriosclerotic changes in the vertebral artery. It has also been shown that, on rotation of the head to the one side, the contralateral vertebral artery can be compressed, producing ischemia in the areas of the vestibular nuclei and in

274 THE ROLE OF THE VESTIBULAR ORGANS IN SPACE EXPLORATION the brainstem and labyrinth. Other possible etiological factors are cervical trauma and manipulations of the chiropractic type. With the presence of lesions in the cervical spinal column, rotation of the head can produce brain- stem symptoms with vertigo and syncope, or what is called the "syncopal cervical vertebral symptoms." It would thus seem that the cervical syndrome is the result of a unilateral vertebral occlusion that is not immediately compensated by ade- quate collateral supply on the opposite side from a well-functioning circle of Willis. The vestibu- lar nuclei are very vulnerable, since they are supplied by narrow end arteries. If it is con- sidered that the cervical syndrome may be due to intermittent ischemia in the supply areas of the vertebral and basilar arteries, an attempt should be made to investigate the blood flow in the vertebral artery. With the help of surgeons and clinical physi- ologists, my coworkers J. Stahle and K. Eriksson have developed a method for measuring blood flow in the vertebral artery by means of imped- ance plethysmography. One electrode is placed on the posterior wall of the pharynx at the level of the uvula, via the nose, as a suction cup with continuous suction; a second electrode is placed on the back of the neck on the same level as the internal electrode. The curves show arterial pulsations and their amplitudes express the changes in tissue impedance. The smaller the amplitudes, the greater the tissue resistance (impedance), indicating compression. Rotation to the right gives the lowest values in the left vertebral artery. Ever since Sherrington, Magnus, and de Kleijn made their classical studies, we have known the importance to the reflexes of proprioceptive impulses induced from receptors in occipital muscles and tendons and in joints in the cervical spinal column. These problems have received increasing interest in modern neurophysiological investigations with experimental electrical stim- ulation of peripheral branches of the vestibular nerve in the cat. Excellent demonstrations have shown the close relationship between proprio- ceptive cervicothoracic spinal cord impulses and the cerebellar vestibular nerve. Exostosis di- rected posteriolaterally can constrict the inter- vertebral foramina and may compress the spinal roots and produce root symptoms in form of pains and vertigo via spinonuclear vestibular communications. These tonic reflexes in the neck, occipital region, and labyrinth regulate the movements of the head, the trunk, and the four extremities in, for example, all the dynamic positions observed in gymnastic exercises and different sports (ref. 9). The extremities on the "nose-knee" side, to which the head is turned, are extended, while those on the other side are bent. Vertigo of the Peripheral Type Vertiginous symptoms provoked from the peripheral portion of the vestibular apparatus are of a different type. They have a sudden onset and are associated with nystagmus, nausea, vomiting, and typical reaction movements. They can be caused by different forms of otitis with labyrinthitis, or vestibular neuritis of a viral origin, and the condition may be referred to as epidemic vertigo. Further causes of vertigo of the peripheral type are Meniere's disease, paroxysmal positional nystagmus, trauma with petrosal fractures, neoplasms, vascular disorders, hematological diseases with labyrinthine hemor- rhage, and also ototoxic lesions due to antibiotics such as streptomycin and kanamycin. TREATMENT OF MENIERE'S DISEASE Even if the long duration and natural tendency to remission of Meniere's disease must be taken into account, one of the following methods of surgically treating severely disabled patients who have resisted all forms of conservative internal therapy should be considered: (1) Radical surgery with destructive labyrinth- ectomy; (2) Drainage of the endolymphatic sac or the subarachnoid shunt operation; or (3) Ultrasonic therapy, in which the vestibular apparatus is selectively destroyed, and hearing conserved. The possibilities of curing vertigo by ultra- sound in Meniere's disease are well documented, but investigators have published no details

ULTRASOAIC TREATMENT OF MEiNIERE'S DISEASE 275 on the reduction of the caloric reaction after ultrasonic irradiation. We have made very careful comparative studies of the caloric reac- tion before and after irradiation in all our patients, and I will present a clinical followup report. The caloric test has been performed with water at 30° and 44° C, and the reactions have been recorded in all cases by means of electronys- tagmography (ENG). In cases with weak or no response to these stimuli, ice water has been used. It was essential for us from the beginning (1959) to build a new apparatus that allowed for small dimensions at the tip of the transducer, and above all provided a well-concentrated sound beam that could be directed as far from the facial nerve and cochlea as possible. Apparatus and Technique As with other instruments of this type, the apparatus we have constructed (fig. 2) consists of two main parts: (1) The radiofrequency generator, consisting of oscillator with power amplifier and power supply. The oscillator is coupled for 1.25 MHz. (2) The treatment head or the transducer with its cooling system. The new type with Teflon tips is shown in figures 3 and 4. Criticisms have been voiced against ultrasonic treatment of Mpniere's disease, mainly because of the relatively high incidence of facial paralysis that constitutes the only serious complication of this form of treatment. The frequency of facial paralysis varies in different series of patients; in general, the paralysis regresses within a few months. We have had 4 incidents of facial paralysis, one of which occurred among the FIGURE 3. — The transducer with Teflon tip, assembled. FIGURE 2. — The Uppsala ultrasonic apparatus. FIGURE 4. — TVre transducer with Teflon tip, unassembled. last 200 operated patients (or 0.5 percent). In each case, the paralysis regressed spontaneously after 1 to 3 months. In order to avoid as far as possible any damage to the facial nerve, it was considered especially important to reduce the danger of lateral radiation and to provide for efficient cooling of the tip. With the present construction, the only fluid necessary in the surgical cavity is a small coupling drop between the tip of the treatment head and that point of the labyrinth into which the ultrasound is to be transmitted. In principle, the apparatus functions as follows: High-frequency alternating current is conveyed from the oscillator to the transducer through a thin, light, flexible cable. Inside the transducer

276 THE ROLE OF THE VESTIBULAR ORGANS IN SPACE EXPLORATION is a concave disk of barium titanate or lead zirconate-titanate, which converts the electric energy into ultrasonic waves. The radius of the curvature of the disk is selected to give a con- centration of energy at the apex of the cone. The beam of the rays is focused in such a way that the focal point lies just inside or at the flat tip of the treatment head (fig. 5). The tip of the treatment head is continuously irrigated with sterile, boiled, and degassed dis- tilled or deionized water, circulated in a closed system by a special pump. The surface of the tip has no direct contact with the fluid. The water is boiled for a period of 1 to 2 hours just prior to time of irradiation. The water conducts the ultrasound from the crystal to the tip of the transducer and also cools the whole treatment unit. The entire transducer, including the cable, can be sterilized by boiling or autoclaving. Before we could undertake the responsibility PA TH OF ULTHASOtft BfAM //V IRADIA HfAD Tj FOCO/i KH.URE 5. — The focused ultrasonic beam. for the radiation involved in ultrasonic therapy, it was necessary to first test our apparatus in animal experiments in order to determine its exact potentialities. We also had to gain experi- ence ourselves in this special and sensitive opera- tion technique and learn its elements of risk. To study the histological and functional effects of ultrasound, irradiation experiments were per- formed on pigeon labyrinths. Degeneration of both the neuroepithelium and the secretory epi- thelium was found in the cochlea, ampullae, sacculus, and utriculus. The perilymphatic space and bony labyrinth were obliterated by callus (refs. 4, 10, and 11). With regard to the functional aspects, it was also demonstrated that ultrasound eliminated labyrinthine function by serious histological damage. By electronystagmographic control of the nystagmus of the pigeon's head during rotation, it was possible to record the functional loss (ref. 11). Due to the use of our new Teflon tips, in most cases it has been possible to shorten the irradia- tion times considerably. The quantity of energy emitted from the various tips used with the treat- ment head has been measured calorimetrically. In general, power levels of up to 3 watts are used regularly, and at times as much as 4 watts may. be employed. This results in peak intensities from 60 to 80 W/cm2 for the 2.6-mm tips. The mean dose lies at about 2000 to 3000 joules. Sometimes we see definite paralytic nystagmus after only 2 to 3 minutes' irradiation. With regard to the irradiation technique, I should like to mention that a good surface for application of the Teflon tip is created by boring a rounded hollow at the junction between the horizontal and the upper vertical semicircular canals (fig. 6) with a diamond drill and under the microscope. To attain maximum effect, the bone of the labyrinthine capsule has to be thinned so that the spongy character of the enchondral bone can be retained (fig. 7). The labyrinthine capsule should be 0.3 to 0.5 mm thick for optimal penetration of the bone by the ultrasound and so that this will not be absorbed or reflected too much during its passage toward the ampullae and vestibule. Care has to be taken not to thin the bone to such an extent that the labyrinthine

ULTRASONIC TREATMENT OF MENIERE'S DISEASE 277 FIGURE 6.—Application of the Teflon tip. capsule cracks, which may cause a complete loss of hearing. On schlieren photographs of the penetra- tion of the ultrasound for power levels around 2 to 3 vratts in bone slices of different thicknesses, we can see how the ultrasound heats the bone; no sound can penetrate. When the bone be- comes thinner, less and less sound is reflected, and finally the ultrasonic beam is able to pene- trate a 0.2-mm bone beautifully. Early in our studies we considered it desirable to construct an apparatus that would make it possible to measure the bone thickness in the labyrinthine capsule to fractions of 1.0 mm. It may perhaps become possible to measure the thickness of other thin tissue layers. We hope to be able to measure the thickness of the foot- plate of the stapes in otosclerosis, the walls of a vessel and artery, for the localization of foreign bodies, etc. Our physicist has constructed a rod-shaped probe (refs. 12 and 13) with a barium titanate crystal in its tip. The handle contains titanium, which has an acoustic impedance close to that of lead zirconate. Titanium absorbs and damps extra oscillations in the barium titanate crystal. The instrument has a working frequency of 4 MHz, but a new system which is under trial has double this frequency and a probe diameter of 3 mm (fig. 8). The bony capsule of the Labyrinth FIGURE T. — The spongy character of the enchondral bone. FIGURE 8. — Ultrasonic probe for measuring bone thickness. An electrical generator produces a short pulse, which is emitted from the crystal of the probe, where echoes are also received on changes in tissue density. The echo is observed as vertical spikes on a cathode-ray tube (oscillograph) and, in the usual way, they can be photographed on this and presented as so-called sonograms. On these, the distance is then measured be- tween the basic pulse and the echo signal, and this gives us an idea of the thickness in milli- meters. Figure 9A shows a piece of aorta from a female, 28 years of age; figure 9B shows a sonogram with the thickness of the wall in milli- meters. In figure 9C is a sonogram from an arteriosclerotic aorta from a 70-year-old man.

278 THE ROLE OF THE VESTIBULAR ORGANS IN SPACE EXPLORATION C w FIGURE 9. — A: Piece of aorta from 28-year-old female. B: Sonograms of pieces of aorta o/A. C: Sonograms from arterioscterotic aorta of 70-year-old man. In figure 10 we see the sonograms from bone slices on the 0.50 sample; the first echo is just hidden by the transmitted pulse. The ultrasound transmitter is applied in the dry surgical cavity, and sound transmission is made possible by the use of a small drop of saline as contact medium, whereby the ultra- r«f. 0 1 234 56 mm 'bone FIGURE 10. — Sonograms from bone slices. sound is visualized as pulsating reflections of light or as narrow standing waves of blood. We can localize exactly the orientation of the beam in the direction of the ampullae and vesti- bule, and can thus avoid an orientation toward the facial nerve and cochlea. RESULTS AND DISCUSSION In ultrasonic treatment it is a combination of thermal, mechanical, and chemical influences which gives the biological effect. In order to avoid damage to the facial nerve and to preserve hearing to the highest possible extent, a study had to be made of the way in which the heat energy was distributed in the bone. We there- fore studied closely the thermal effect on isolated human temporal bones and in man during the process of irradiation. The ultrasonic apparatus constructed in Uppsala has been tested on temporal-bone preparations (refs. 14 and 15) in which have been placed fine thermoelements (of copper constantan 0.2 mm) connected to an automatic temperature recorder (Potentiometer Speedomax). When metal tips were directed toward the blue line on the lateral semicircular canal, the temperature inside this canal rose to 50° C after 5 minutes' irradiation with 4 watts. Metal or Teflon tips applied at the junction between the lateral and anterior vertical semicircular canal produced a greater increase in temperature in the lateral semicircular canal and in the vestibule than in the cochlea (fig. 11). In the facial nerve the temperature increase was of the same magnitude or sometimes somewhat smaller than in the vesti- bule (fig. 11). The supposed critical temperature of 46° C in the facial nerve was not reached until after more than 4 minutes of continuous irradia- tion with 4 watts. By fractioning the irradia- tion when treating patients with Meniere's disease, the risk of producing facial paresis is probably reduced. Our results deviate from those of several other investigators who have consistently shown a larger temperature increase in the facial nerve than in the vestibule. On one patient who underwent labyrinthec- tomy, temperature measurements were made in the vestibule and lateral semicircular canal in connection with ultrasonic irradiation. With

ULTRASONIC TREATMENT OF M^NIERE'S DISEASE 279 Temperatures after 3 minutes ultrasonic treatment with 3 wutts to the enchondral bone in the junction between the horizontal and the superior vertical semicircular canal lp of the uansrtuce FlGURE 11. — W ay in which heat energy is distributed in temporal bone during ultrasonic irradiation. lower ultrasonic power the temperature increase was of the same magnitude as in temporal bone preparations, but with higher power the increase was smaller than in the preparations, probably due to heat losses via the circulating blood. Ultrasonic irradiation of rabbits placed in different body positions showed that nystagmus changed its direction when the rabbit was ro- tated 180°. In each body position the direction of the nystagmus was the same regardless of whether the labyrinth was irradiated with ultra- sound or with pure heat. The probe is thus used Thermal Effects of Ultrasound on Inner Ear - i\ x R.gm-Mtt.ng -bMting l*M-b*ating FIGURE 12,—Nystagmography curves from a rabbit with the head in different positions both during irradiation and on the application of pure heat. also for this latter application, water at 70° C being allowed to circulate in the probe with the ultrasound generator turned off. Figure 12 shows nystagmographic curves from a rabbit with its head in different positions both during irradiation and on the application of pure heat (refs. 14 and 15). Nystagmus direc- tion was the same in each position, whether ultrasound or heat was applied. With the posi- tional change of 180°, it can be seen that nystag- mus altered its direction to that opposite the initial direction. This change to an opposite direction was observed both when the position was changed from prone to supine and from the right to the left lateral. Figure 13 shows nystagmographic curves from a patient in whom the left ear was irradiated while the body was in different positions. In position (I) with the face upward, nystagmus beat to the left. In prone position (II) with the face downward, the beat was to the right. After further irradiation in the supine position (HI), a left-beating nystagmus was again observed. After 10 minutes' irradiation there was contra- lateral nystagmus to the right, of the pseudo- paralytic type (IV). This did not change direction when the patient was turned to the prone position, but renewal of irradiation in- I DQ lO FIGURE l3. — Nystagmography curves from a patient during ultrasonic irradiation.

280 THE ROLE OF THE VESTIBULAR ORGANS IN SPACE EXPLORATION creased the intensity of the nystagmus. When the patient was then turned to the supine position with the face upward (V), the contralateral- pseudoparalytic nystagmus persisted, but after a few minutes a beat to the left was noted. The labyrinth was thus only habituated to the ultra- sound, but not paralytically or selectively completely destroyed. Nystagmus of the de- structive type which occurs after a certain period of irradiation does not change its direction, on the other hand, when the patient's position is altered from face up to face down. Our experiences with ultrasonic irradiation have provided valuable neuro-otological infor- mation. Experimental therapy in rabbits and treatment of human beings with the head in different positions have shown that the initial nystagmus caused by ultrasound is probably a caloric reaction provoked by the endolymphatic flow caused by the thermal effect. Experimental temperature studies on ultrasonic irradiation of human temporal bone preparations and in man during labyrinthectomy have shown that the temperature increase in the cochlea is negligible and that the critical temperature in the facial nerve is not reached until after more than 4 minutes of irradiation. Therefore, irradiation is now given intermittently in periods of 3 to 4 minutes. During the treatment, the function of the facial nerve and the nystagmic effect are checked in a mirror through Frenzel glasses. Naturally, we sometimes have studied by nystagmography all phases of the therapeutic effect in detail (figs. 14 and 15). In principle, the aim is to first induce a homo- lateral irritative nystagmus, and as a final effect to produce a definite contralateral nystagmus of the destructive type, as a sign that the vestibular apparatus has been selectively destroyed or paralyzed by, or has been habituated to, the ultrasound. The main problem is to assess the final point (fig. 15) at which the irradiation should be dis- continued. Much experience is required for this, and herein lies one of the greatest difficulties in the technique of this treatment. As a rule, we continue until a reversal to contralateral nystagmus has been recorded two to four times MENIfeRE'S DISEASE RIGHT EAR Nyita CaI 10* I 1 Nyda Approi tun* of irradiat,on Thovndpo'nI FIGURE 14. — Nystagmic effect during all phases of the treatment. NVSTAGMUS DURING ULTRASONIC IRRADIATION OF THE RIGHT EAR Boforo irradiatio Irradiation 3 5 W Irradiation 3 5 W No nytIagmul L«It belIing ny».«gmuS Irradiation 3 b W |/^/\ . ^ I/ * ^\/\rW Right beating L«1i betting nysitgmus Loft boating nyttogmui Irrigation SOT FIGURE IS. — Assessing the final point of the irradiation.

ULTRASONIC TREATMENT OF MENIERE'S DISEASE 281 consecutively during the process of irradiation. In all cases it is not possible, however, to invoke such reversal during irradiation (figs. 14 and 15). We then do a caloric test with injection of sterile physiological saline at 50° C directly into the surgical wound. In spite of the fact that, in this way, the labyrinth may perhaps for the moment seem to show no reaction to caloriza- tion —i.e., it may seem habituated to the thermal effect of the ultrasound —a distinct irritative nystagmus of homolateral direction can never- theless often be seen and can fairly quickly change to a contralateral direction during further irradiation (fig. 15). The patient often vomits at the same time, and the excitability of the vestibular apparatus be- comes increasingly reduced. In cases with an especially prolonged tendency, we then discon- tinue the irradiation. We dare not give more ultrasound in these cases because of the risk of damage both to the facial nerve and to the cochlea. As a rule, we have then simultaneously raised the power output of the transducer tip to 3.0 to 3.5 watts. The total irradiation time varies from 2 to 4 minutes and 15 to 30 minutes. A followup examination was made this year of the 228 patients who have been observed for 6 months, 6 years after their operation. All of them answered a questionnaire, and the majority also underwent complete audiological and otoneurological reexaminations. The vertigo had disappeared in 56 percent and had improved in an additional 33 percent; thus there was improvement in a total of 89 percent. The tin- nitus had diminished or disappeared in 48 percent. Hearing was improved or unchanged in 64 percent, and the hearing results were, on the whole, independent of the length of the observation period. An increased capacity for work was noted in 54 percent. The caloric reaction had decreased in 58 percent (example in fig. 16). A statistically significant relation- ship was found between the duration of the postoperative paralytic nystagmus and the reduction in the caloric excitability noted at the followup examination. With regard to the pathogenesis of the Meniere attacks, it is now probable that it is a temporary rise in pressure that provokes the crisis. Wheth- Meniere's disease, Ieft side (Op 2710.1964) 29. 6.1966 30°C 44°C R Ice-water "^"^^ ^^ Calibration 10° 0 !°SPC FIGURE 16. — Results of a followup examination. er the consequence is then a rupture in a weak place in the membranous endolymphatic wall is an open question. Of recent great interest are the experiments of Dohlman and Fernandez on the frog and ape where it was shown that potassium chloride seemed to have the greatest importance for the transport of ions in labyrin- thine stimulations, and which may also have a depolarizing effect on labyrinthine nerve branches. When later we studied our results of irradiation in man, we found complete or, in most cases, partial destruction of vestibular function. This appears to correspond well with the hypothesis that the endolymphatic secretion is reduced on irradiation. Conditions are thus created for a reduction of labyrinthine hydrops. Our own irradiation experiments on animals and those of others have shown histologically and histochemically that the secretory epithe- lium in the cochlea and ampullae is undoubtedly damaged. Hypothetically, it would seem to be justifiable to assume, therefore, that conditions are thereby created for reduction of the endo- labyrinthine pressure in a Meniere hydrops after ultrasonic irradiation. In addition to its thermal effect, ultrasound also has a mechanical action. Hughes and Chou (ref. 16) have shown that this mechanical effect can influence osmotic processes, with an increase

282 THE ROLE OF THE VESTIBULAR ORGANS IN SPACE EXPLORATION in the capillary permeability in cell membranes and an effect on the microcirculation of the blood. The pH can be changed. It is con- sidered that the cavitation can damage or burst cells and break open macromolecules in serum, whereby biochemical changes with altered pro- tein concentrations can occur. Blood is hemo- lyzed, bacteria killed, etc. Hughes and Chou have experimentally shown biochemical changes with an alteration in the electrolyte content in the labyrinthine fluids. Similarly, on ultrasonic irradiation the transport of sodium and potassium ions is altered, and thereby the capacity of the neuroepithelial sys- tem to respond to different stimuli is eliminated or reduced, or at any rate changed. In other words, it would seem that all these biochemical changes after ultrasonic irradiation, which among other things causes damage to the secretory epithelium in the cochlea and ampullae, might theoretically explain not only the favorable effect of such irradiation in Meniere's disease but also the positive results which have been obtained without always producing full destruc- tion of the sensory cells of the vestibular organ. In this connection it is also of interest to re- member the beneficial effect of our diuretics in Meniere's disease. Apart from the fluid loss, there is also an increased excretion of potassium. The intracellular fluid, the endolymph, has a high- potassium and low-sodium concentration. The question can be asked then whether part of the favorable effect of diuretics can also be due to a decrease of the potassium concentration in the endolymph. Can we perhaps dare, in our Meniere patients, for short, critical periods, to avoid administration of extra potassium when treating them with diuretics? It is probably no exaggeration to claim that about 90 percent of our operated cases become free of their vertigo attacks, or considerably im- proved, and the majority return to full working capacity. Our figures correspond well with those of Arslan in Padova. He operated on 1500 patients from 1952 to 1964. and 90 percent of them were freed of vertigo. Arslan estimated that up to now about 3000 patients have been operated on in the world. As I have mentioned, we do have patients with recurrent attacks of vertigo of short or long dura- tion after ultrasonic therapy. Sometimes the patient himself has noted, or in answer to particu- lar questioning has stated, that he is now having symptoms from the untreated ear. On some occasions it has been necessary to reoperate be- cause of recurrence. This is very easily done, and no reaction is ever seen in the surgical wound. No signs of labyrinthine neurosis have been seen. A final but important facet of ultrasonic oto- surgery is its stimulating effect upon present- day neuro-otological concepts. REFERENCES 1. SJOBERG, A.: Clinical Experience From the Treatment of Meniere's Disease. Acta Oto-Laryngol., suppl. 192, 1964, pp. 139-153. 2. SJOBERG, A.; AND STAHLE. J.: Treatment of Meniere's Disease with Ultrasound. Arch. Otolaryngol., vol. 82,1965, pp. 498-502. 3. SJOBERG, A.: STAHLE, J.: DRETTNER, B.; AND JOHNSON, S.: Aktuella behandlingsproblem vid morbus Meniere samt demonstration av ultraljudapparatur. Nord. Med., vol. 74,1965, pp. 1146-1147. 4. SJOBERG, A.; STAHLE, J.; JOHNSON. S.: AND SAHL, R.: Treatment of Meniere's Disease by Ultrasonic Irradiation. Physical, Experimental, and Clinical Studies. Acta Oto-Laryngol., suppl. 178, 1963, pp. 1-86. 5. JOHNSON, S.: An Ultrasonic Unit for the Treatment of Meniere's Disease. Ultrasonics, vol. 5, July 1967, pp. 173-17o. 6. STAHLE, J.; AND BERGMAN, B.: The Caloric Reaction in Meniere's Disease. An Electronystagmographic Study in 300 Patients. Laryngoscope, vol. 77. 1967. pp. 1629-1643. 7. ENANDER, A.; AND STAHLE, J.: Hearing in Meniere's Disease. A Study of Pure Tone Audiograms in 334 Patients. Acta Oto-Laryngol., vol. 64. 1967. pp. 543-556. 8. SANDSTROM, J.: Cervical Syndrome with Vestibular Symptoms. Acta Oto-Laryngol., vol. 54, 1962, pp. 207-226. 9. KUKUDA, T.: Studies on Human Dynamic Postures From the Viewpoint of Postural Reflexes. Acta Oto-Laryngol., suppl. 161, 1961. pp. 1-52. 10. STAHLE, J.: Ultrasonic Irradiation of the Labyrinth. Acta Oto-Laryngol., suppl. 188, 1964, pp. 183-189. 11. STAHLE, J.: Some Effects of Ultrasound on the Inner Ear Acta Oto-Laryngol., suppl. 192, 1964, pp. 192-198.

ULTRASONIC TREATMENT OF MENIERE S DISEASE 283 12. JOHNSON. S.; SJOBERG, A.: AND STAHLE, J.: Ultral- judssonografi av tunna skikt. Nord. Med., vol. 78, 1967, p. 1590. 13. JOHNSON, S.: SJOBERG, A.; AND STABLE, J.: Studies of the Otic Capsule. I. Reduced Deadtime Ultrasonic Probe for Measurement of Bone Thickness. Acta Oto-Laryngol., vol. 62, Dec. 1966. pp. 532-544. 14. DRETTNER, B.: JOHNSON, S.; SJOBERG. A.; AND STAHLE, J.: Some Thermal Effects of Ultrasound on the Inner BIBLIOGRAPHY BARAC, B.: HAGBARTH, K.-E.; AND STAHLE, J.: EEG in Meniere's Disease. A Study of EEG and Caloric Direc- tional Preponderance Before and After Irradiation of the Labyrinth. Acta Oto-Laryngol., vol. 62, 1966, pp. 333- 340. SJOBERG, A.: Studien iiber den Ausliisungsmechanisms der Seekrankheit. Acta Oto-Laryngol., suppl. 14, 1931, pp. 1-136. DISCUSSION (iraybiel: What was the time course of the postural dis- equilibrium effects; that is to say, what was it before the ultrasound treatment and afterward? Were the patients ataxic afterward? Sjoberg: They had some difficulty in walking for 1 or 2 months, but no more. They became accustomed very easily afterward, but they had a slight feeling of lateropulsion and unsteadiness in darkness during this time. Graybiel: But it did last 1 to 2 months? Sjoberg: Yes. They could work after 2 or 3 months. Tolhurst: Have you explored enough so that you can say something about the time-intensity relationship of exposure to ultrasound? As you increase the wattage, do you have to reduce the time, and do you know the parameters of each? Sjoberg: As a rule we have raised the power output of the transducer to 3.0 to 3.5 watts. The total irradiation time varies between 2 to 3 minutes and 15 to 30 minutes. But the treatment time depends on the quality of the bone, which can be different in every individual. With a hard bone it can be more difficult for the ultrasonic beam to go through the bony capsule at the labyrinth. Lowy: Dr. Sjoberg is to be congratulated on having a presentation equally interesting from a medical as well as a scientific standpoint, if we will be permitted to separate those two aspects. Dr. Sjoberg has presented us with an over- whelmingly voluminous number of cases. He also made the statement that, according to his own experience, Meniere's Ear. Acta Oto-Laryngol., vol. 64, 1967, pp. 464-476. 15. DRETTNER, B.; JOHNSON, S.; SJOBERG, A.; AND STAHLE, J.: Studier over ultraljudets termiska effekt i innerorat. Nord. Med., vol. 78, 1967. p. 1591. 16. HUGHES, D. E.; AND CHOU, J. T.: The Biochemistry of the Inner Ear and the Consequences of Treatment by Ultrasound. Acta Oto-Laryngol., suppl. 192, 1963, pp. 199-206. SJOBERG, A.: YRSEL (1-2). Lakartidningen, vol. 64, 1967. pp. 337-344, 452-460. STAHLE, J.; AND SAHL, R.: Electronystagmography in Men- iere's Disease Before, During and After Ultrasonic Irradia- tion. Acta Oto-Laryngol., suppl. 192, 1964, pp. 154 166. disease is the most frequent vestibular affliction encountered in his practice. It is conceivable that there are very con- siderable regional differences, because I believe that the consensus of American otologists is probably that Meniere's disease is by no means the most frequent affliction and that benign positional vertigo and so forth occur much more frequently. Do you have any comments on this? Sjoberg: With regard to the topical diagnosis in vertigi- nous diseases of the Meniere's type, it is very important to decide whether the lesion is peripheral or central. There- fore, I have just mentioned the Barre-Lieou syndrome, or cervical migraine, which can present considerable difficulties in differential diagnosis. We have not yet treated such cases with ultrasound. Money: I was interested to see that the rate of retention of hearing was 64 percent. Can Dr. Graybiel tell us what the rate of retention of hearing was in the streptomycin series which he studied? Graybiel: Our study was based on four patients of Profes- sor Schuknecht's, and we conducted our tests long after they had been treated with streptomycin sulfate. Three normal and five diseased ears were involved. Serial audio- grams revealed a substantial and permanent improvement in hearing in four ears which came about over periods measured in months or years. Hearing in one ear improved temporarily but reverted to its pretreatment level.