The history of research and discoveries in the equilibrium system

It was as early as in the 2nd century AD that the Greek doctor, the philosopher and the anatomist Claudius Galenus (c.130 AD - c.210 AD) during his osteological research into skull bones paid attention to the construction of the inner ear. Its winding passage were for the scientist similar to the castle on Crete called “Labyrinthos”, built by the famous legendary Daedalus for King Minos. Galenus decided that the inner ear deserves the name “Labyrinth”. He also revealed that the auditory nerve links the outer ear with the brain and that the outer ear gathers sounds. Galenus pioneered the surgery of the mastoid process and observed that the larynx is a vocal apparatus. At the end of the 18th century after extensive research done by the anatomists of the Renaissance and their successors, many features and hallmarks of the inner ear had been described but no one supposed that it plays yet another role except for the hearing function. Discovering that the membranaceous sac and the canals play another role was reserved for explorers in the 19th century. It was until 19th century that science was completely devoid of knowledge about functioning of the semi-circular canals of the inner ear. The first to begin experimental research in this field was the famous French physiologist Jean Pierre Flourens (1794-1867). His studies were published in 1825. Flourens thought that would be possible to obtain an insight into the functioning of the semi-circular canal by destroying it. Experiments which were performed on pigeons, rabbits and other animals produced quite remarkable and constant disturbances which had not been known earlier. For example, if the horizontal semi-circular canal was destroyed in a pigeon, then the bird went on turning horizontally in a circle. When the vertical semi-circular canal was destroyed, the pigeons rotated doing somersaults. Flourens described these phenomena exceptionally well yet he did not provide any explanation. The researcher did not have the least idea that animals suffered from vertigo. Having removed the cerebellum Flourens found that this operation causes disequilibrium and incoordination (dissynergia) in animals. Destruction of the brainstem (medulla oblongata) causes death. These experiments led Flourens to conclude that the cerebellum regulates and integrates movements and that the brainstem controls essential bodily functions, such as circulation, respiration and the general stability of the body. At the same time a great physiologist in Prague, Johannes Evangelist Purkinje (1787-1869) investigated vertigo in people. He carried out his experiments on himself and on mentally ill people. When the ill became stimulated, they were treated by rotating in a cage until nausea and vomiting appeared. After that the ill became quiet and again were kept in discipline. Similar treatment techniques for mentally ill patients were used by Joseph Mason Cox (1763-1818). He presented the new treatment techniques in his book “Practical observations on Insanity”. Purkinje discovered the involuntary eye movement (nystagmus) during vertigo. This observation was very essential. The researcher also proved the influence of vertigo on the position of the head. He was convinced that the brain was directly irritated during the rotation. Purkinje knew Flourens's publications, he also carried out experiments on animals, and yet he did neither realize that animals in Flourens's experiments suffered from vertigo nor that the place where the feeling of vertigo is caused must be the sensory organ. Here we can see how easily it is to go past the truth. For the next 40 years no scientist was in a position to solve this mystery. It was not until 1861 that the French scientist Prosper Meniere (1799-1862) made a significant step forward describing a disease which was characterized with systemic vertigo, bradyacousia ear buzzing (tinnitus) and a progressing hearing loss. The study appeared in “Gazette medicale de Paris” in 1861. All the time Meniere acted completely differently than his predecessors. Being an otologist he used his purely clinical attitude to observe the coincidence of the occurrence of vertigo, bluntness of hearing and ear buzzing (tinnitus). in patients in whom he had never found any changes in their middle ears. The position of the organ of hearing in the cochlea was well known at that time. It is known that damaging the cochlea or its destruction causes vertigo and dullness of hearing. At that time it was considered that vertigo could be caused only by diseases of the cerebellum. Meniere observed this kind of patients for many years and did not notice any symptoms of brain illness in them. The cause of this disease was not known then. Meniere reached then a conclusion that the phenomenon of vertigo was a symptom of a disease located in the apparatus of the semi-circular canal. Thanks to these observations he achieved success at that time, which Flourens and Purkinje did not manage to explain. He claimed that animals whose semi-circular canals were operated on by Flourens had to suffer because of vertigo. This was a great achievement of the man who could not enjoy his discovery, because he died in the same year. Meniere did not express his opinion in relation to the importance of semi-circular canals in everyday life. The first scientist who created his own theory on it was the German physiologist Friedrich Goltz (1834-1902). He claimed that if the destruction of the apparatus of the semi-circular canal causes the intensification of vertigo and disequilibrium, then supporting the equilibrium is a natural activity of this system. In 1870 the researcher introduced his hydrostatic hypothesis, explaining the role and the activity of semi-circular canals as the organ of balance. Goltz claimed that the canals are stimulated by the weight of the fluid which they contain. The exerted pressure is variable depending on the position of the head. This theory turned out false, but three years later, in 1873, three scientists working independently: Ernst Mach (1838-1916), a Viennese physicist; Robert Breuer (1842-1925), a practitioner in Vienna and the Scotch chemist Crum Brown (1838-1922), introduced the hydrodynamic theory which maintains that head movement causes the flow of endolymph in the canals and that the canals are stimulated by movements of the fluid or changes of pressure. The three scientists achieved the same results in different ways. Breuer started from repeating the Flourens's experiments in pigeons, improving his technique, and reached straight to the conclusion that endolymph movement in semi-circular canals initiates the Flourens's phenomena. Moreover, he was the first to subject animals to rotation and proved by this that the phenomenon which Flourens produced through destruction of semi-circular canals can be obtained as well by rotating the animals when symptoms will be only temporary and with no harm to them. He also proved that if semi-circular canals are damaged on both sides then rotation does not cause these symptoms any longer. With his experiments he made a serious step towards stabilizing the function of the semi-circular canal. Finally he found that the semi-circular canal is a sensory organ for receiving rotary movements and that vertigo caused by rotation is a result of too strong stimulation of the sensory organ. The further development of otoneurology was contributed by the Hungarian physiologist and the bacteriologist Endre Högyes (1847-1906). In his research he set himself a task to determine the position of the center administering the mechanism of formation of nystagmus. He managed to show that in rabbits this center administering the mechanism of formation of nystagmus is located in the part of the brain between the entry of the vestibulocochlear nerve to medulla oblongata and corpora quadrigemina, and removing of other parts of the brain does not have any bigger influence on the course of this reflex. Högyes also provided an excellent description of symptoms after unilateral and bilateral destruction of the semi-circular canals. He proved particularly that these symptoms appeared most violently immediately after the destruction and then they disappear gradually, and that the violent symptoms caused by the destruction on one side can be reduced to a minimum by the destruction of the other side. He practically proved that the activity of one labyrinth affects the second labyrinth and they balance out. Among the clinicians from that era important, Jansen, the otologist from Berlin, made important observations. He was the first to discover the significant meaning of nystagmus as a symptom of the disease of the semi-circular canal. He showed that injuries of the horizontal canal often occur during the suppuration of the middle ear. He was the first to operationally remove a suppurating semi-circular canal in humans.

The development of otoneurology was largely contributed by Ernst Julius Richard Ewald (1855-1921). He conducted very narrow research into the apparatus of the semi-circular canal in animals. The scheme of his experiment on the semi-circular canal of the labyrinth of a pigeon is presented in physiology and otoneurology textbooks. He determined undoubted connections between a specific direction of the head and movements of eyes in animals with a specific movement of endolymph in the semi-circular canals. His observations from the experiments carried out on animals and then checked in a person suffering from fistula on a semi-circular canal were summed up in two laws: 1) the direction of the free phase of induced nystagmus is compatible with the direction of the flow of endolymph; 2) in horizontal semi-circular canals the ampulopetal flow of endolymph causes a considerably stronger nystagmus reaction than the ampulofugal flow. Inverse reactions occur when the vertical canals are irritated. The ampullary crests of the semi-circular canals have a constant and automatic bioelectric activity  which Ewald called the labyrinthine tension. This bioelectric activity is transmitted to the whole musculature of the body, maintaining its tonus. When one labyrinth was destructed in a frog Ewald registered a rise in the tension of adductors and flexors in the limb on the other side and the lack of tension of extensors and abductors in the limb on the side of the damaged labyrinth. This scientific information provided by Ewald in 1892, became almost one hundred years later a direct inspiration for me to create my own dynamic test of the pendular marking time test and undertake intensive research in order to explain the mechanisms of formation of vestibulo-cerebellospinal reflexes. ROBERT BARANY'S (1876-1936) PLAYED AN IMPORTANT ROLE IN THE HISTORY OF THE RESEARCH INTO THE PHYSIOLOGY AND THE PATHOLOGY OF THE VESTIBULAR APPARATUS. He dealt mainly with otopathies, especially with the role of the labyrinth and the cerebellum in supporting the equilibrium of the body. In 1914 he received the Nobel Prize in physiology and medicine in recognition of his discoveries. I will present his interesting discoveries and observations based on his lecture which he delivered in August 1916 on the occasion of his receipt of the Nobel prize. The lecture was entitled: “Some new methods for functional testing of the vestibular apparatus and the cerebellum”. Robert Barany claimed that despite the earlier pioneering discoveries it was not possible to understand the observed phenomena because there were no real methods to investigate the activity of the vestibular apparatus such as those which had been used for some time in reference to other sensory organs, also appearing in pairs. Such a system of unilateral research into the activity of the vestibular apparatus had been impossible until then. The method of rotations proposed by Breuer stimulated simultaneously both canals and therefore it was not satisfying for the clinical use, where the unilateral examination was almost always required. The galvanic method discovered by Purkinje and further investigated by Hitzing and others did not give results which would be useful for the clinical use. The method of the caloric stimulation of the vestibular apparatus which was discovered by barany was the first one which brought some light into the darkness. Only after that discovery was it possible to do any methodical research into the activity of the semi-circular canals. During his lecture Barany described in detail the history of his discovery. As a young otologist he worked in Professor Politzer's Clinic in Vienna. Many of his patients required rinsing of ears. After that many of them complained of vertigo. Obviously he watched the patients' eyes and noted the occurrence of nystagmus in a certain direction. He took notes from his observations. When he gathered about twelve cases, he compared those investigations and was amazed that the observations had been the same in every patient. He realized that the same rules had to be included but at that time he did not understand them. One day he was visited by a patient whose ears he had rinsed some time before. The patient said to the doctor - I only got daze when the water was not warm enough. After that information Barany rinsed his ears himself at home using water which was hot warm enough but he had never experienced daze or vertigo. Next time his nurse prepared very hot water for rinsing of the patient's ears. When the doctor rinsed the patient's ear, he shouted “Doctor! This water is too hot and I'm having vertigo again!”. The otologist suddenly began to observe the patient's eyes and noticed that nystagmus occurred exactly in different direction than earlier when cold water was applied. The researcher got a flash that the temperature of water had been really responsible for nystagmus. Next he drew a certain conclusion from it. If the temperature of water was really responsible for that phenomenon, then the temperature of water conforming to the body temperature will cause neither nystagmus nor vertigo. He then carried out an experiment which confirmed that conclusion. Considering that if the temperature of water is responsible for this phenomenon, then nystagmus can be caused in healthy people and not only in cases of purulent ears. This he also managed to prove. Barany did not doubt about his earlier investigations that nystagmus is a result of a reflex from the semi-circular canal. Hence another conclusion that if semi-circular canals are destroyed, it will not be possible to cause the reflex. Among the abundant material gathered by the Viennese Otologic Clinic was able to find a case with significant suppuration from the middle ear, where despite continuing to rinse the ear with cold water it was not possible to cause a nystagmus reaction. The otologist diagnosed the destruction of the semi-circular canal and proved it during the operation confirming that the diagnosis had been correct. Barany then focused on studying the clinical values of this method of testing the horizontal canal using the caloric test as an instrument for checking its activity. At that time he recognized the importance of the caloric reaction but he was not able to explain it. He admits that he was pondering over it in vain. One day he already had an idea. He recalled the tank for bathing water and his surprise as a child discovering that water located directly over the fire was quite cool and the water located higher on the top was so hot that he had his finger scalded. The labyrinth reminded him of such a water tank filled with liquid. The temperature of the liquid is obviously 37°C and is equal to the body temperature. Let us suppose what will happen if cold water is sprayed on one side of the water tank. Water on that side of the tank will be cool and obviously therefore it will reach a higher specific gravity than the water surrounding it and it will fall down on the bottom of the tank. If an ear is rinsed with hot water then the movement will be exactly in the opposite direction. The movement of the liquid must change whenever the position of the tank is changed. If the tank with the liquid is rotated by 180°, then it must be changed exactly in the opposite direction. Barany was in a position of proposing a kind of test which is used to confirm this theory. If in two positions of the head differing by 180° one from the other there is a possibility of obtaining nystagmus in opposite directions through rinsing whether warm or cold liquid then this theory must be true. Barany confirmed it in his clinic. Therefore this theory is already stabilized and absolutely in accordance with Mach-Breuer theory, which considers the movement of endolymph contained in the semi-circular canals as the reason of their stimulation. This thermal convection theory was Barany's greatest achievement and is still valid. Further on in the mentioned lecture Barany refers to his research connected with the cerebellum. He mentions the studies performed by Santiago Ramon y Cajal (1852-1934), the Spanish histologist and neuroanatomist, the precursor of neurobiology who in 1906 was received the Nobel Prize together with Camilo Golgi for their research into the structure of the nervous system. Cajal's research showed that every fiber of the vestibular nerve is divided into many branches at the entrance of the brain. One branch leads towards the group of cells which are in a direct connection with the ganglion of cells which are the center of the eye muscles innervation and therefore we can understand why stimulation of the semi-circular canal causes nystagmus. One branch goes to the cerebellum and splits into a series of branches leading to both parts of the cerebellum, i.e. the so-called the cerebellum hemispheres and to the central part of the cerebellum, i. e. the worm. It must be mentioned that Romany Cajal carried out this research on embryos of quite small animals. His methods cannot be applied to bigger animals and especially to people. Analogically, it allows inferring that people must also have connections between the nerve of the semi-circular canal and the cerebellum. Until then we can mention such symptoms as vertigo and nystagmus. Yet we all realize other symptoms, particularly activity on muscles of the trunk causing equilibrium disorders. Barany claims that he cannot provide here all reasons which lead him to conclude that this influence on the muscular apparatus of the whole body comes from semicanals through the brain, but the book by the Dutch anatomist, Louis Balk on the cerebellum in mammals, which appeared in 1906, gave him quite a lot of valuable hints. In this book Balk informs that physiologists' efforts show us that the cerebellum has something to do with the innervation of the muscular apparatus. In vertebrates we discover that the muscular apparatus of the body is varied to a great extent in different classes of animals. For example giraffes have very long and movable necks and the mole has a very short and motionless neck. Therefore Balk claims that the parts of the brain which control muscles of the neck must be developed in a completely different manner. He investigated the cerebellum in both species and noticed an extremely and strikingly different construction of a certain part in the giraffe in which there was almost completely no mole. These observations led Balk to infer that this special part of the cerebellum had been connected with the innervation of muscles of the neck. He found in a similar manner that the muscular apparatus for upper and lower limbs was represented in side parts of the cerebellum and the trunk in the central part. The research into the influence of the semi-circular canal on the muscles of the trunk is very simple. The patient is asked to stand up or to walk and then disequilibrium or deviating from the right line is visible when the semi-circular canal is stimulated by for example cold water. The influence of stimulation on upper limbs is also very simple to demonstrate. The patient is asked to reach out his/her arms straight forward and keep them still with his/her closed eyes. If the right ear is then rinsed with cold water, the right arm will slowly deviate,  the patient being unaware of it. This deviation to the right will also concern the left upper limb as well as lower limbs. This experiment is the most certain way to demonstrate the direct influence on the muscular mechanism. Normally in order to study these reflexes, the pointing test was used, which in the Polish literature is well known as the past-pointing test). The patient is asked to reach out his/her upper limbs forward, then use his/her forefinger to touch the researcher's forefinger, lower his/her upper limbs knee-high with his/her eyes closed and then put them up. In normal conditions this is very simple and can be performed without any difficulties. After stimulating the right ear with cold water a healthy patient will not be in a position to touch the researcher's forefinger, but he will pass it on the patient's right side and on the researcher's left side. The direction of the deviation will always be contrary to appearing nystagmus. For instance, if nystagmus appears to the right, the finger will pass the aim on the left. If nystagmus appears downwards, the deviation of the limbs will be upward. Nystagmus appearing upward will be connected with the limbs falling downwards. The reactions always concern all four limbs and the whole muscular apparatus. The researcher succeeded in proving in this way that the direction of the movement was located in the cerebellum. Barany found cases in which reactions of the limbs did not appear only in one direction (towards the hemisphere which was ill), while reactions of the limbs on the healthy side and all other reactions in the limbs on the ill side were normal. This indicates that nerve cells and nerve fibers associated with the reaction in a certain direction must lie close to one another in the cerebellar hemisphere. Research proves that there are many cases of spontaneous deviations, cases where there was no stimulation in the semi-circular canals. On the basis of the gathered experiments Barany arrived at the final conception of the modes of operation of the cerebellum. He assumed the presence of four centers which are connected with the muscular apparatus, firstly according to the direction - one center to the right and one to the left, one upward and one downward. In normal people, as long as there is no stimulation of the horizontal canals, these four centers are supplied with a certain tension, called tonus, for muscles during the movement of limbs, each pair of these centers acts as two "reins" between which the arm moves. If  these "reins" are properly tense, the arm performs no deviation. One can pull one rein more strongly than the other one. This will follow when one stimulates the mechanism of the semi-circular canal. If nystagmus to the left is caused, this is tantamount with the pulling the reins with the right hand and therefore the right arm deviates to the right. But one can also cause a deviation of the right arm to the right if the left-handed rein is cut; it is already present without any stimulation of the semi-circular canal and will spontaneously pull the right arm to the right. If one tries now to tighten the left-handed rein, it will be obviously impossible from the moment of their previous cutting. The only thing that now can be done is to loose the right-handed reins completely and the arm will indicate properly again. Let us now translate this comparison into the medical language. The disease of a certain center, e.g. the center for the tonus of the right arm to the left, will cause the right arm to deviate to the right without stimulating the mechanism of the semi-circular canal: it is a spontaneous deviation of the right arm to the right in the indication test. If nystagmus to the right is caused and if an attempt to stimulate the center of the tonus is undertaken for the right arm to the left, it will be unsuccessful because this center is ill and does not function properly. The only thing that can be done is to inhibit the tonus center for the right arm right completely, thus obtaining proper pointing. This is the main interpretation of the physiology and the pathology of the cerebellum which was professed by Barany. The exact message of the lecture delivered by Barany shows us how much he tried to decipher the mechanisms of the vestibulocerebellar system. Unfortunately, Barany did not succeed in it. His lecture concerning the role of the cerebellum is not completely comprehensible, knowing the true mechanisms of the vestibulocerebellar system, which I discovered almost one hundred years later. Barany's biography shows that he stayed for some time on the Polish ground. During World War I, as a volunteer doctor, he was conscripted for the Eastern front. After short training he started to serve in the Galician fortress of Przemyśl. He went through hell in fights for Przemyśl and in 1915 he was imprisoned by the Russians. At that time, the fourth commander of Tarnów was colonel Piotr  Kozłow, a world-famous traveler, a geographer, researcher and the discoverer of the ancient city of Char Chot, a member of Przywalski's expeditions and an outstanding expert of Tibet. Barany was interested in the history of the East and read the book by Kozłow entitled “Asia”. Kozłow knew Barany's medical publications which were useful in distant expeditions. Having found out about Barany's position, Kozłow took intensive measures to liberate him from captivity. As a result of pressures Barany was bought out from captivity in 1916 by his Swedish friends. Kozłow contributed to the liberation of the Austrian, bribing Czar's clerks. Barany never knew himself about Kozłow's protection but several years later he repaid Kozłow for the book, which became a faithful comrade of misery and more than once saved his life. On hearing the news about Kozłow's problems, Barany appealed to the scientific world, Nobel prize winners and his influential friends for help for the scientist. After the captivity Barany returned to Vienna, was terrified with his friends' reaction to awarding him with the Nobel Prize, despite the fact that the researcher had expressed appropriate recognition for those explorers who went before him. 

 Barany contributed considerably to integrating the research by Goltz, Mach, Breuer and Crum with the clinical research by Prosper Meniere. He summed up their aspirations with a musical allusion: Purkinje and Flourens invented an ingenious introduction, Meniere introduced the first phrase, Goltz addressed a new theme and the theory by Mach, Breuer and Crum Brown inferred a movement with an absolutely strong chord. The second movement is like a fugue where many voices rotates around one another; once harmonically connected, a moment later they are in a conflict (Barany 1913, page 399). In 1917 Barany moved to Upsala, where he spent the rest of his academic life in Sweden. From the history of discoveries in the field of otoneurology one must not forget to mention the observations made by Bechterew (1883), who was the first to describe the phenomenon consisting in the fact that if, having damaged one labyrinth and waited for a suitable time necessary for paralytic nystagmus to retreat, we will destroy the other labyrinth, then nystagmus will appear again directed this time towards the originally damaged labyrinth. Although these observations were described such a long time ago, the theoretical bases explaining this phenomenon have not been revealed yet. One must also mention the observations made by Ruttin (1911), who paid attention to the fact of the slow compensation of the nystagmus reaction in rotation tests in the course of the recession of the symptoms of sharp destruction of the labyrinth. Such compensation of after-rotation reactions, with the permanently damaged labyrinth, confirmed by a caloric test, were named Ruttin's symptom in the literature. In 1906 Abels introduced the term “habituation” to the professional literature. He used this term to explain the phenomenon of slow regression of the symptoms of seasickness. Generally, habituation is used to define a temporary reduction of oculomotor and spinal reactions as well as subjective ones to repeated vestibular stimulation with a similar power and character. Despite numerous clinical and experimental works, the mechanism of the habituation process has not been not explained yet. Is it true that Bechterew's phenomenon, Ruttin's symptom, compensation or vestibular habituation have different mechanisms of formation or do they all have one common mechanism. We will find out about it a little later while discussing the principles of operation of the vestibulocerebellar system which I discovered in the 1990s. The introduction of electronystagmography as an objective method of recording the vestibulo-cerebello-ophthalmic reflex occurring as a result of pathological or deliberate stimulation of labyrinths, made most explorers stop being interested in the research of vestibulo-cerebellospinal reflexes. On the other hand, lack of thorough knowledge on formation of vestibulo-cerebellospinal reflexes did not allow deciphering the principles of operation of the vestibulocerebellar system.