Thalamocortical network: a core structure for integrative multimodal vestibular functions.

PURPOSE OF REVIEW: To apply the concept of nonreflexive sensorimotor and cognitive vestibular functions and disturbances to the current view of separate right and left thalamocortical systems. RECENT FINDINGS: The neuronal modules for sensorimotor and cognitive functions are organized in so-called provincial hubs with intracommunity connections that interact task-dependently via connector hubs. Thalamic subnuclei may serve not only as provincial hubs but also in higher order nuclei as connector hubs. Thus, in addition to its function as a cortical relay station of sensory input, the human thalamus can be seen as an integrative hub for brain networks of higher multisensory vestibular function. Imaging studies on the functional connectivity have revealed a dominance of the right side in right-handers at the upper brainstem and thalamus. A connectivity-based parcellation study has confirmed the asymmetrical organization (i.e., cortical dominance) of the parieto-insular vestibular cortex, an area surrounded by other vestibular cortical areas with symmetrical (nondominant) organization. Notably, imaging techniques have shown that there are no crossings of the vestibular pathways in between the thalamic nuclei complexes. Central vestibular syndromes caused by lesions within the thalamocortical network rarely manifest with rotational vertigo. This can be explained and mathematically simulated by the specific coding of unilateral vestibular dysfunction within different cell systems, the angular velocity cell system (rotational vertigo in lower brainstem lesions) in contrast to the head direction cell system (directional disorientation and swaying vertigo in thalamocortical lesions). SUMMARY: The structural and functional separation of the two thalamic nuclei complexes allowed a lateralization of the right and left hemispheric functions to develop. Furthermore, it made possible the simultaneous performance of sensorimotor and cognitive tasks, which require different spatial reference systems in opposite hemispheres, for example, egocentric manipulation of objects (handedness) and allocentric orientation of the self in the environment by the multisensory vestibular system.

Dizziness and vertigo syndromes viewed with a historical eye.

Seasickness, fear of heights, and adverse effects of alcohol were the major areas where descriptions of vertigo and dizziness were found in Roman, Greek, and Chinese texts from about 730 BC-600 AD. A few detailed accounts were suggestive of specific vestibular disorders such as Menière's attacks (Huangdi Neijing, the Yellow Thearch's Classic of Internal Medicine) or vestibular migraine (Aretaeus of Cappadocia). Further, the etymological and metaphorical meanings of the terms and their symptoms provide fascinating historical insights, e.g. Vespasian's feelings of dizzy exultations when becoming Emperor (69 AD) after Nero's suicide or the figurative meaning of German "Schwindel" (vertigo) derived from English "swindle" to express "financial fraud" in the Eighteenth century. The growth of knowledge of the vestibular system and its functions began primarily in the Nineteenth century. Erasmus Darwin, however, was ahead of his times. His work Zoonomia, or The Laws of Organic Life in 1794 described new dizziness syndromes and concepts of sensorimotor control including the mechanism of fear of heights as well as made early observations on positional alcohol vertigo. The latter is beautifully illustrated by the German poet and cartoonist Wilhelm Busch (1832-1908) who also documented the alleviating effect of the "morning after drink". The mechanism underlying positional alcohol vertigo, i.e., the differential gravities of alcohol and endolymph, was discovered later in the Nineteenth century. The first textbook on neurology (Lehrbuch der Nervenkrankheiten des Menschen, 1840) by Moritz Romberg contained general descriptions of signs and symptoms of various conditions having the key symptom of vertigo, but no definition of vestibular disorders. Our current knowledge of vestibular function and disorders dates back to the seminal work of a group of Nineteenth century scientists, e.g., Jan Evangelista Purkinje, Ernst Mach, Josef Breuer, Hermann Helmholtz, and Alexander Crum-Brown.

A Historical View of Motion Sickness-A Plague at Sea and on Land, Also with Military Impact.

Seasickness and its triggers, symptoms, and preventive measures were well known in antiquity. This chapter is based on an analysis of descriptions of motion sickness, in particular seasickness, in ancient Greek, Roman, and Chinese literature. A systematic search was made from the Greek period beginning with Homer in 800 BC to the late Roman period and ending with Aetios Amidenos in 600 AD, as well as in the Chinese medical classics dating from around 300 AD. Major aspects are the following: body movements caused by waves were identified in all cultures as the critical stimuli. The ancient Greeks and Romans knew that other illnesses and the mental state could precipitate seasickness and that experienced sailors were highly resistant to it (habituation). The Chinese observed that children were particularly susceptible to motion sickness; they first described the type of motion sickness induced by traveling in carts (cart-sickness) or being transported on a litter or in a sedan chair (litter-sickness). The western classics recommended therapeutic measures like fasting or specific diets, pleasant fragrancies, medicinal plants like white hellebore (containing various alkaloids), or a mixture of wine and wormwood. The East knew more unusual measures, such as drinking the urine of young boys, swallowing white sand-syrup, collecting water drops from a bamboo stick, or hiding earth from the kitchen hearth under the hair. The Greek view of the pathophysiology of seasickness was based on the humoral theory of Empedokles and Aristoteles and differed from the Chinese medicine of correspondences, which attributed malfunctions to certain body substances and the life force Qi. Many sources emphasized the impact of seasickness on military actions and famous naval battles such as the Battle of the Red Cliff, which marked the end of the Han dynasty in China, or the defeat of the Spanish Armada by the English in 1588. A peculiar form of motion sickness is associated with Napoleon's camel corps during the Egyptian campaign of 1798/1799, a sickness induced by riding on a camel. Thus, motion sickness in antiquity was known as a physiological response to unadapted body motions during passive transportation as well as a plague at sea.

Descriptions of vestibular migraine and Menière's disease in Greek and Chinese antiquity.

Background Vestibular migraine and Menière's disease are two types of episodic vertigo syndromes that were already observed in Greek and Chinese antiquity. Descriptions first appeared in the work of the classical Greek physician Aretaeus of Cappadocia, who lived in the 2nd century AD, and in Huangdi Neijing, a seminal medical source in the Chinese Medical Classics, written between the 2nd century BC and the 2nd century AD. Aim The aim of this paper is to search in Aretaeus' book De causis et signis acutorum et chronicorum morborum and in Huangdi Neijing for descriptions of vertigo co-occurring with headache or ear symptoms that resemble current classifications of vestibular migraine or Menière's disease. Results Aretaeus describes a syndrome combining headache, vertigo, visual disturbance, oculomotor phenomena, and nausea that resembles the symptoms of vestibular migraine. In the Chinese book Huangdi Neijing the Yellow Thearch mentions the co-occurrence of episodic dizziness and a ringing noise of the ears that recalls an attack of Menière's disease. Conclusions The descriptions of these two conditions in Greek and Chinese antiquity are similar to the vertigo syndromes currently classified as vestibular migraine and Menière's disease. In clinical practice it may be difficult to clearly differentiate between them, and they may also co-occur.

Motion sickness in ancient China: Seasickness and cart-sickness.

OBJECTIVE: To find and analyze descriptions of motion sickness in Chinese historical sources. METHODS: Databases and dictionaries were searched for various terms for seasickness and travel sickness, which were then entered into databases of full texts allowing selection of relevant passages from about the third to the 19th century ad. RESULTS: Already in 300 ad the Chinese differentiated cart-sickness, particularly experienced by persons from the arid north of China, from a ship-illness experienced by persons from the south, where rivers were important for transportation and travel. In the Middle Ages, a third form of motion sickness was called litter-influence experienced by persons transported in a bed suspended between 2 long poles. The ancient Chinese recognized the particular susceptibility of children to motion sickness. Therapeutic recommendations include drinking the urine of young boys, swallowing white sand-syrup, collecting water drops from a bamboo stick, or hiding some earth from the middle of the kitchen hearth under the hair. CONCLUSIONS: The Chinese medical classics distinguished several forms of travel sickness, all of which had their own written characters. The pathophysiologic mechanism was explained by the medicine of correspondences, which was based on malfunctions within the body, its invasion by external pathogens like wind, or the deficit or surfeit of certain bodily substances such as the life force Qi. The concept of motion as the trigger of sickness initially appeared in a chapter on warding off the influence of demons and corpses, e.g., ancient magic and beliefs.

Noisy vestibular stimulation improves dynamic walking stability in bilateral vestibulopathy.

OBJECTIVE: To examine the effects of imperceptible levels of white noise galvanic vestibular stimulation (nGVS) on dynamic walking stability in patients with bilateral vestibulopathy (BVP). METHODS: Walking performance of 13 patients with confirmed BVP (mean age 50.1 ± 5.5 years) at slow, preferred, and fast speeds was examined during walking with zero-amplitude nGVS (sham trial) and nonzero-amplitude nGVS set to 80% of the individual cutaneous threshold for GVS (nGVS trial). Eight standard gait measures were analyzed: stride time, stride length, base of support, double support time percentage as well as the bilateral phase coordination index, and the coefficient of variation (CV) of stride time, stride length, and base of support. RESULTS: Compared to the sham trial, nGVS improved stride time CV by 26.0% ± 8.4% (p < 0.041), stride length CV by 26.0% ± 7.7% (p < 0.029), base of support CV by 27.8% ± 2.9% (p < 0.037), and phase coordination index by 8.4% ± 8.8% (p < 0.013). The nGVS effects on walking performance were correlated with subjective ratings of walking balance (ρ = 0.79, p < 0.001). Effect of nGVS on walking stability was most pronounced during slow walking. CONCLUSIONS: In patients with BVP, nGVS is effective in improving impaired gait performance, predominantly during slower walking speeds. It primarily targets the variability and bilateral coordination characteristics of the walking pattern, which are linked to dynamic walking stability. nGVS might present an effective treatment option to immediately improve walking performance and reduce the incidence of falls in patients with BVP. CLASSIFICATION OF EVIDENCE: This study provides Class IV evidence that in patients with BVP, an imperceptible level of nGVS improves dynamic walking stability.

What the ancient Greeks and Romans knew (and did not know) about seasickness.

OBJECTIVE: To find and analyze descriptions in ancient Greek and Roman literature that reveal what was known at the time about seasickness. METHODS: A systematic search was made in the original literature beginning in the Greek period with Homer in ca 800 bc and extending up to Aetios Amidenos in the late Roman period in ca 600 ad. RESULTS: Rough seas and unpleasant odors were recognized as the major triggers; susceptibility was greater in persons not adapted to sea travel, of a labile mental state, or with anxiety; nausea, emesis, vertigo, anorexia, faintness, apathy, headache, and impending doom were frequently reported symptoms. Preventive and therapeutic measures included habituation to sea travel, looking at stationary contrasts on the coast, fasting or certain diets, inhaling pleasant fragrances, medicinal plants, and ingesting a mixture of wine and wormwood. CONCLUSION: The triggers, symptoms, and preventive measures of seasickness were well-known in antiquity. The implications for transport of troops and military actions were repeatedly described, e.g., by Livius and Caesar. At that time, the pathophysiologic mechanism was explained by the humoral theory of Empedokles and Aristoteles. Seneca Minor localized the bodily symptoms in various organs such as stomach, gullet, and esophagus, and also attributed them to an imbalance of bile. Recommended medication included ingestion of the plant white hellebore, a violent gastrointestinal poison. This remedy contains various alkaloids but not scopolamine, which today is the most effective anti-motion-sickness drug.

N-acetyl-L-leucine accelerates vestibular compensation after unilateral labyrinthectomy by action in the cerebellum and thalamus.

An acute unilateral vestibular lesion leads to a vestibular tone imbalance with nystagmus, head roll tilt and postural imbalance. These deficits gradually decrease over days to weeks due to central vestibular compensation (VC). This study investigated the effects of i.v. N-acetyl-DL-leucine, N-acetyl-L-leucine and N-acetyl-D-leucine on VC using behavioural testing and serial [18F]-Fluoro-desoxyglucose ([18F]-FDG)-µPET in a rat model of unilateral chemical labyrinthectomy (UL). Vestibular behavioural testing included measurements of nystagmus, head roll tilt and postural imbalance as well as sequential whole-brain [18F]-FDG-µPET was done before and on days 1,3,7 and 15 after UL. A significant reduction of postural imbalance scores was identified on day 7 in the N-acetyl-DL-leucine (p < 0.03) and the N-acetyl-L-leucine groups (p < 0.01), compared to the sham treatment group, but not in the N-acetyl-D-leucine group (comparison for applied dose of 24 mg i.v. per rat, equivalent to 60 mg/kg body weight, in each group). The course of postural compensation in the DL- and L-group was accelerated by about 6 days relative to controls. The effect of N-acetyl-L-leucine on postural compensation depended on the dose: in contrast to 60 mg/kg, doses of 15 mg/kg and 3.75 mg/kg had no significant effect. N-acetyl-L-leucine did not change the compensation of nystagmus or head roll tilt at any dose. Measurements of the regional cerebral glucose metabolism (rCGM) by means of µPET revealed that only N-acetyl-L-leucine but not N-acetyl-D-leucine caused a significant increase of rCGM in the vestibulocerebellum and a decrease in the posterolateral thalamus and subthalamic region on days 3 and 7. A similar pattern was found when comparing the effect of N-acetyl-L-leucine on rCGM in an UL-group and a sham UL-group without vestibular damage. In conclusion, N-acetyl-L-leucine improves compensation of postural symptoms after UL in a dose-dependent and specific manner, most likely by activating the vestibulocerebellum and deactivating the posterolateral thalamus.

The bilateral central vestibular system: its pathways, functions, and disorders.

The bilateral anatomical organization of the vestibular system provides three functional advantages: optimal differentiation of head motion and orientation, sensory substitution of a unilateral peripheral failure, and central compensation of a peripheral or central vestibular tone imbalance. The structure is based on bilaterally ascending and descending pathways and at least four crossings: three in the brain stem and one in the cortex. The resulting sensorimotor functions can be subdivided into three major groups: (1) reflexive control of gaze, head, and body in three spatial planes (yaw, pitch, roll) at the brain stem/cerebellar level; (2) perception of self-motion and control of voluntary movement and balance at the cortical/subcortical level; and (3) higher vestibular cognitive functions (e.g., spatial memory and navigation). The bilateral representation of the vestibular system in multiple multisensory cortical areas and the vestibular dominance of the nondominant hemisphere raise the question of how one global percept of motion and orientation in space is formed.

Pharmacotherapy of vestibular disorders and nystagmus.

Vertigo and dizziness are with a life-time prevalence of ~30% among the most common symptoms and are often associated with nystagmus or other oculomotor disorders. The prerequisite for a successful treatment is a precise diagnosis of the underlying disorder. In this overview, the current pharmacological treatment options for peripheral and central vestibular, cerebellar, and oculomotor disorders including nystagmus are described. There are basically seven groups of drugs that can be used (the "7 As"): antiemetics; anti-inflammatory, anti-Menière's, and antimigraine medications; antidepressants, anticonvulsants, and aminopyridines. In acute vestibular neuritis, recovery of the peripheral vestibular function can be improved by treatment with oral corticosteroids. In Menière's disease, a long-term high-dose treatment with betahistine-dihydrochloride (at least 48 mg three times daily) had a significant effect on the frequency of the attacks; the underlying mode of action is evidently an increase in inner-ear blood flow. The use of aminopyridines is a well-established therapeutic principle in the treatment of downbeat and upbeat nystagmus as well as episodic ataxia type 2 and cerebellar gait disorders. As was shown in animal experiments, these potassium channel blockers increase the activity and excitability and normalize irregular firing of cerebellar Purkinje cells. They evidently augment the inhibitory influence of these cells on vestibular and deep cerebellar nuclei. A few studies showed that baclofen improves periodic alternating nystagmus; gabapentin and memantine improve pendular and infantile nystagmus. However, many other eye-movement disorders such as ocular flutter, opsoclonus, central positioning, and see-saw nystagmus are still difficult to treat. Although substantial progress has been made, further state-of-the-art trials must still be performed on many vestibular and oculomotor disorders, namely Menière's disease, vestibular paroxysmia, vestibular migraine, and many forms of central eye-movement disorders.

Aging of human supraspinal locomotor and postural control in fMRI.

Standing, walking, and running are sensorimotor tasks that develop during childhood. Thereafter they function automatically as a result of a supraspinal network that controls spinal pattern generators. The present study used functional magnetic resonance imaging (fMRI) to investigate age-dependent changes in the supraspinal locomotor and postural network of normal subjects during mental imagery of locomotion and stance. Sixty healthy subjects (ages: 24-78 years), who had undergone a complete neurological, neuro-ophthalmological, and sensory examination to rule out disorders of balance and gait, were trained for the conditions lying, standing, walking, and running in order to imagine these conditions on command in 20-second sequences with the eyes closed while lying supine in an magnetic resonance imaging (MRI) scanner. The following blood oxygen level-dependent (BOLD) signal changes during locomotion and stance were found to be independent of age: (1) prominent activations in the supplementary motor areas, the caudate nuclei, visual cortical areas, vermal, and paravermal cerebellum; (2) significant deactivations in the multisensory vestibular cortical areas (posterior insula, parietoinsular vestibular gyrus, superior temporal gyrus), and the anterior cingulate during locomotion. The following differences in brain activation during locomotion and stance were age-dependent: relative increases in the cortical BOLD signals in the multisensory vestibular cortices, motion-sensitive visual cortices (MT/V5), and somatosensory cortices (right postcentral gyrus). In advanced age this multisensory activation was most prominent during standing, less during walking, and least during running. In conclusion, the functional activation of the basic locomotor and postural network, which includes the prefrontal cortex, basal ganglia, brainstem, and cerebellar locomotor centers, is preserved in the elderly. Two major age-dependent aspects of brain activation during locomotion and stance were found: the mechanism of cortical inhibitory reciprocal interaction between sensory systems during locomotion and stance declines in advanced age; and consequently, multisensory cortical control of locomotion and stance increases with age. These findings may indicate a more conscious locomotor and postural strategy in the elderly.

Discovery of a clinical candidate from the structurally unique dioxa-bicyclo[3.2.1]octane class of sodium-dependent glucose cotransporter 2 inhibitors.

Compound 4 (PF-04971729) belongs to a new class of potent and selective sodium-dependent glucose cotransporter 2 inhibitors incorporating a unique dioxa-bicyclo[3.2.1]octane (bridged ketal) ring system. In this paper we present the design, synthesis, preclinical evaluation, and human dose predictions related to 4. This compound demonstrated robust urinary glucose excretion in rats and an excellent preclinical safety profile. It is currently in phase 2 clinical trials and is being evaluated for the treatment of type 2 diabetes.

Integrated center for research and treatment of vertigo, balance and ocular motor disorders.

The German BMBF (German Ministry of Education and Research) has decided to establish an Integrated Center for Research and Treatment (IFB(LMU)) of Vertigo, Balance and Ocular Motor Disorders in Munich in 2010. With funding of 50 euros million over a ten-year period, the long-term continuation of the IFB(LMU) is envisioned.

Institutional profile: integrated center for research and treatment of vertigo, balance and ocular motor disorders.

In 2009 the German BMBF (German Ministry of Education and Research) established an Integrated Center for Research and Treatment (IFB(LMU)) of Vertigo, Balance and Ocular Motor Disorders in Munich. After the 10-year period of funding by the BMBF, it is envisioned that the (IFB(LMU)) will continue over the long term with the joint support of the University Hospital, the Medical Faculty, and the Bavarian State. Vertigo is one of the most common complaints in medicine. Despite its high prevalence, patients with vertigo generally receive either inappropriate or inadequate treatment. This deplorable situation is internationally well known and its causes are multiple: insufficient interdisciplinary cooperation, no standardized diagnostics and therapy, the failure to translate findings of basic science into clinical applications, and the scarcity of clinical multicenter studies. The (IFB(LMU)) will constitute a suitable tool with which these structural, clinical, and scientific deficits can be overcome. It will also make possible the establishment of an international interdisciplinary referral center. Munich has become the site of a unique concentration of leading experts on vertigo, balance and ocular motor disorders, both in the clinical and basic sciences. Academic structures have paved the way for the creation of an interdisciplinary horizontal network that also allows structured, vertical academic career paths via the Bachelor's and Master's degree programs in Neuroscience, a Graduate School of Systemic Neurosciences, and the Munich Center for Neurosciences - Brain and Mind. The (IFB(LMU)) has the following objectives as regards structure and content: to create an independent patient-oriented clinical research center under the auspices of the Medical Faculty but with autonomous administration and budget; to overcome existing clinical and academic barriers separating the traditional specializations; to establish a standardized interdisciplinary longitudinal and transversal network at one site for the management of patients. This should professionalize both the management and the international recruitment of patients (integrated care, telemedicine); to organize the study infrastructure for prospective multicenter clinical studies as well as to free clinical scientists from administrative tasks; to promote translational research with a focus on the innovative topics of molecular, functional and structural imaging, experimental and clinical pharmacotherapy, clinical research of vertigo and balance disorders, mathematical modelling, interaction between biological and technical systems (robotics), and research on functionality and the quality of life; to offer new attractive educational paths and career images for medical doctors, students of the natural sciences, and engineers in clinical research in order to overcome traditional hierarchical structures. This should promote the principles of efficiency and self-reliance; to supplement the existing excellence with up to eight groups of young scientists and up to eight professorships (tenure track). This should also be seen as an incentive that will attract the best young scientists; to incorporate (IFB(LMU)) competence into the existing medical and biological graduate schools. The (IFB(LMU)) is a unique center - worldwide.

Real versus imagined locomotion: a [18F]-FDG PET-fMRI comparison.

The cortical, cerebellar and brainstem BOLD-signal changes have been identified with fMRI in humans during mental imagery of walking. In this study the whole brain activation and deactivation pattern during real locomotion was investigated by [(18)F]-FDG-PET and compared to BOLD-signal changes during imagined locomotion in the same subjects using fMRI. Sixteen healthy subjects were scanned at locomotion and rest with [(18)F]-FDG-PET. In the locomotion paradigm subjects walked at constant velocity for 10 min. Then [(18)F]-FDG was injected intravenously while subjects continued walking for another 10 min. For comparison fMRI was performed in the same subjects during imagined walking. During real and imagined locomotion a basic locomotion network including activations in the frontal cortex, cerebellum, pontomesencephalic tegmentum, parahippocampal, fusiform and occipital gyri, and deactivations in the multisensory vestibular cortices (esp. superior temporal gyrus, inferior parietal lobule) was shown. As a difference, the primary motor and somatosensory cortices were activated during real locomotion as distinct to the supplementary motor cortex and basal ganglia during imagined locomotion. Activations of the brainstem locomotor centers were more prominent in imagined locomotion. In conclusion, basic activation and deactivation patterns of real locomotion correspond to that of imagined locomotion. The differences may be due to distinct patterns of locomotion tested. Contrary to constant velocity real locomotion (10 min) in [(18)F]-FDG-PET, mental imagery of locomotion over repeated 20-s periods includes gait initiation and velocity changes. Real steady-state locomotion seems to use a direct pathway via the primary motor cortex, whereas imagined modulatory locomotion an indirect pathway via a supplementary motor cortex and basal ganglia loop.

Human hippocampal activation during stance and locomotion: fMRI study on healthy, blind, and vestibular-loss subjects.

The hippocampal formation, including the parahippocampal gyrus, is known to be involved in different aspects of navigation and spatial orientation. Recently, bilateral parahippocampal activation during mental imagery of walking and running was demonstrated in fMRI. For the current study the question was whether distinct functional regions within the hippocampal formation could be defined from the analysis of brain activity during imagery of stance and locomotion in healthy, blind, and vestibular-loss subjects. Using the same experimental paradigm in all groups (fMRI during mental imagery of stance and locomotion after training of actual performance, regions of interest [ROI] analysis), activations were found in the hippocampal formation, predominantly on the right side, in all subjects. In healthy subjects, standing was associated with anterior hippocampal activation; during locomotion widespread activity was found in the right parahippocampal gyrus. Compared to healthy controls, blind subjects showed less activity in the right dorsal parahippocampal region, whereas vestibular-loss subjects had less activity in the anterior hippocampal formation. The findings show that the hippocampal formation in humans processes visual and vestibular signals in different regions. The data support the assumption that the anterior hippocampus and the entorhinal cortex in the parahippocampal region are input areas for vestibular and somatosensory signals. Posterior parahippocampal and fusiform gyri, which are connected to visual cortical areas, are more important for visually guided locomotion and landmark recognition during navigation. The right-sided dominance reflects the importance of the right hemisphere for spatial orientation.

Medical treatment of vestibular disorders.

BACKGROUND: The lifelong prevalence of rotatory vertigo is 30%. Despite this high figure, patients with vertigo generally receive either inappropriate or inadequate treatment. However, the majority of vestibular disorders have a benign cause, take a favorable natural course, and respond positively to therapy. OBJECTIVE: This review puts special emphasis on the medical rather than the physical, operative, or psychotherapeutic treatments available. METHODS: A selected review of recent reports and studies on the medical treatment of peripheral and central vestibular disorders. RESULTS/CONCLUSIONS: In vestibular neuritis, recovery of the peripheral vestibular function can be improved by oral corticosteroids; in Menière's disease, there is first evidence that high-dose, long-term administration of betahistine reduces attack frequency; carbamazepine or oxcarbamazepine is the treatment of first choice in vestibular paroxysmia, a disorder mainly caused by neurovascular cross-compression; the potassium channel blocker aminopyridine provides a new therapeutic principle for treatment of downbeat nystagmus, upbeat nystagmus, and episodic ataxia type 2.

Current treatment of vestibular, ocular motor disorders and nystagmus.

Vertigo and dizziness are among the most common complaints with a lifetime prevalence of about 30%. The various forms of vestibular disorders can be treated with pharmacological therapy, physical therapy, psychotherapeutic measures or, rarely, surgery. In this review, the current pharmacological treatment options for peripheral and central vestibular, cerebellar and ocular motor disorders will be described. They are as follows for peripheral vestibular disorders. In vestibular neuritis recovery of the peripheral vestibular function can be improved by treatment with oral corticosteroids. In Menière's disease a recent study showed long-term high-dose treatment with betahistine has a significant effect on the frequency of the attacks. The use of aminopyridines introduced a new therapeutic principle in the treatment of downbeat and upbeat nystagmus and episodic ataxia type 2 (EA 2). These potassium channel blockers presumably increase the activity and excitability of cerebellar Purkinje cells, thereby augmenting the inhibitory influence of these cells on vestibular and cerebellar nuclei. A few studies showed that baclofen improves periodic alternating nystagmus, and gabapentin and memantine, pendular nystagmus. However, many other eye movement disorders such as ocular flutter opsoclonus, central positioning, or see-saw nystagmus are still difficult to treat. Although progress has been made in the treatment of vestibular neuritis, downbeat and upbeat nystagmus, as well as EA 2, state-of-the-art trials must still be performed on many vestibular and ocular motor disorders, namely Menière's disease, bilateral vestibular failure, vestibular paroxysmia, vestibular migraine, and many forms of central eye movement disorders.