Bernard Cohen's research while affiliated with Icahn School of Medicine at Mount Sinai and other places

The Mal de Debarquement syndrome (MdDS) generally follows sea voyages, but it can occur after turbulent flights or spontaneously. The primary features are objective or perceived continuous rocking, swaying, and/or bobbing at 0.2 Hz after sea voyages or 0.3 Hz after flights. The oscillations can continue for months or years and are immensely disturbing. Associated symptoms appear to be secondary to the incessant sensation of movement. We previously suggested that the illness can be attributed to maladaptation of the velocity storage integrator in the vestibular system, but the actual neural mechanisms driving the MdDS are unknown. Here, based on experiments in subhuman primates, we propose a series of postulates through which the MdDS is generated: (1) The MdDS is produced in the velocity storage integrator by activation of vestibular-only (VO) neurons on either side of the brainstem that are oscillating back and forth at 0.2 or 0.3 Hz. (2) The groups of VO neurons are driven by signals that originate in Purkinje cells in the cerebellar nodulus. (3) Prolonged exposure to roll, either on the sea or in the air, conditions the roll-related neurons in the nodulus. (4) The prolonged exposure causes a shift of the pitch orientation vector from its original position aligned with gravity to a position tilted in roll. (5) Successful treatment involves exposure to a full-field optokinetic stimulus rotating around the spatial vertical countering the direction of the vestibular imbalance. This is done while rolling the head at the frequency of the perceived rocking, swaying, or bobbing. We also note experiments that could be used to verify these postulates, as well as considering potential flaws in the logic. Important unanswered questions: (1) Why does the MdDS predominantly affect women? (2) What aspect of roll causes the prolongation of the tilted orientation vector, and why is it so prolonged in some individuals? (3) What produces the increase in symptoms of some patients when returning home after treatment, and how can this be avoided? We also posit that the same mechanisms underlie the less troublesome and shorter duration Mal de Debarquement.

Semicircular canal afferents sense angular acceleration and output angular velocity with a short time constant of ≈4.5 s. This output is prolonged by a central integrative network, velocity storage that lengthens the time constants of eye velocity. This mechanism utilizes canal, otolith, and visual (optokinetic) information to align the axis of eye velocity toward the spatial vertical when head orientation is off-vertical axis. Previous studies indicated that vestibular-only (VO) and vestibular-pause-saccade (VPS) neurons located in the medial and superior vestibular nucleus could code all aspects of velocity storage. A recently developed technique enabled prolonged recording while animals were rotated and received optokinetic stimulation about a spatial vertical axis while upright, side-down, prone, and supine. Firing rates of 33 VO and 8 VPS neurons were studied in alert cynomolgus monkeys. Majority VO neurons were closely correlated with the horizontal component of velocity storage in head coordinates, regardless of head orientation in space. Approximately, half of all tested neurons (46%) code horizontal component of velocity in head coordinates, while the other half (54%) changed their firing rates as the head was oriented relative to the spatial vertical, coding the horizontal component of eye velocity in spatial coordinates. Some VO neurons only coded the cross-coupled pitch or roll components that move the axis of eye rotation toward the spatial vertical. Sixty-five percent of these VO and VPS neurons were more sensitive to rotation in one direction (predominantly contralateral), providing directional orientation for the subset of VO neurons on either side of the brainstem. This indicates that the three-dimensional velocity storage integrator is composed of directional subsets of neurons that are likely to be the bases for the spatial characteristics of velocity storage. Most VPS neurons ceased firing during drowsiness, but the firing rates of VO neurons were unaffected by states of alertness and declined with the time constant of velocity storage. Thus, the VO neurons are the prime components of the mechanism of coding for velocity storage, whereas the VPS neurons are likely to provide the path from the vestibular to the oculomotor system for the VO neurons.

The mal de debarquement syndrome (MdDS) is a movement disorder, occurring predominantly in women, is most often induced by passive transport on water or in the air (classic MdDS), or can occur spontaneously. MdDS likely originates in the vestibular system and is unfamiliar to many physicians. The first successful treatment was devised by Dai et al. (1), and over 330 MdDS patients have now been treated. Here, we report the outcomes of 141 patients (122 females and 19 males) treated 1 year or more ago. We examine the patient’s rocking frequency, body drifting, and nystagmus. The patients are then treated according to these findings for 4–5 days. During treatment, patients’ heads were rolled while watching a rotating full-field visual surround (1). Their symptom severity after the initial treatment and at the follow-up was assessed using a subjective 10-point scale. Objective measures, taken before and at the end of the week of treatment, included static posturography. Significant improvement was a reduction in symptom severity by more than 50%. Objective measures were not possible during the follow-up because of the wide geographic distribution of the patients. The treatment group consisted of 120 classic and 21 spontaneous MdDS patients. The initial rate of significant improvement after a week of treatment was 78% in classic and 48% in spontaneous patients. One year later, significant improvement was maintained in 52% of classic and 48% of spontaneous subjects. There was complete remission of symptoms in 27% (32) of classic and 19% (4) of spontaneous patients. Although about half of them did not achieve a 50% improvement, most reported fewer and milder symptoms than before. The success of the treatment was generally inversely correlated with the duration of the MdDS symptoms and with the patients’ ages. Prolonged travel by air or car on the way home most likely contributed to the symptomatic reversion from the initial successful treatment. Our results indicate that early diagnosis and treatment can significantly improve results, and the prevention of symptomatic reversion will increase the long-term benefit in this disabling disorder.

Vasovagal syncope is a significant medical problem without effective therapy, postulated to be related to a collapse of baroreflex function. While some studies have shown that repeated static tilts can block vasovagal syncope, this was not found in other studies. Using anesthetized, male Long–Evans rats that were highly susceptible to generation of vasovagal responses, we found that repeated activation of the vestibulosympathetic reflex (VSR) with ±2 and ±3 mA, 0.025 Hz sinusoidal galvanic vestibular stimulation (sGVS) caused incremental changes in blood pressure (BP) and heart rate (HR) that blocked further generation of vasovagal responses. Initially, BP and HR fell ≈20–50 mmHg and ≈20–50 beats/min (bpm) into a vasovagal response when stimulated with Sgv\S in susceptible rats. As the rats were continually stimulated, HR initially rose to counteract the fall in BP; then the increase in HR became more substantial and long lasting, effectively opposing the fall in BP. Finally, the vestibular stimuli simply caused an increase in BP, the normal sequence following activation of the VSR. Concurrently, habituation caused disappearance of the low-frequency (0.025 and 0.05 Hz) oscillations in BP and HR that must be present when vasovagal responses are induced. Habituation also produced significant increases in baroreflex sensitivity (p < 0.001). Thus, repeated low-frequency activation of the VSR resulted in a reduction and loss of susceptibility to development of vasovagal responses in rats that were previously highly susceptible. We posit that reactivation of the baroreflex, which is depressed by anesthesia and the disappearance of low-frequency oscillations in BP and HR are likely to be critically involved in producing resistance to the development of vasovagal responses. SGVS has been widely used to activate muscle sympathetic nerve activity in humans and is safe and well tolerated. Potentially, it could be used to produce similar habituation of vasovagal syncope in humans.

The vestibulo-sympathetic reflex (VSR) increases blood pressure (BP) upon arising to maintain blood flow to the brain. The optimal directions of VSR activation and whether there are changes in heart rate (HR) are still not clear. This was studied with manually-driven translations, which had pulses and oscillatory linear accelerations of 0.2-2.5 g along the naso-occipital, interaural, and dorso-ventral axes in Isoflurane-anesthetized male, Long-Evans rats. BP and HR were recorded with intra-aortic sensors and accelerationd with 3-D linear accelerometer. Lineard regressions of changes in BP as a function of accelerations along the upward, downward and forward axes had slopes of ≈3-6 mmHg*g(-1) (p<0.05). Lateral and backward accelerations did not produce consistent changes in BP. Thus, upward, downward, and forward translations were the directions that significantly altered BP. Heart rate (HR) was unaffected by these translations. The VSR sensitivity to oscillatory forward-backward translations was ≈6-10 mmHg*g(-1) at frequencies of ≈0.1 Hz (0.2g) decreasing to zero at frequencies above 2 Hz (1.8g). Upward 70° tilts of an alert rat increased BP by 9 mmHg*g(-1) The similarity in BP induced in alert and anesthetized rats indicates that anesthesia had not reduced the VSR sensitivity, which may be relatively insensitive to levels of alertness. The lack of effect on HR in the anesthetized rat indicates the VSR is likely to cause changes in BP through modification of peripheral vascular resistance, directed towards the cardiovascular system, in contrast to the responses in the alert state, which produce sweating, motion sickness, and alteration in BP and HR.

Blood Pressure (BP), comprised of recurrent systoles and diastoles, is controlled by central mechanisms to maintain blood flow. Periodic behavior of BP was modeled to study how peak amplitudes and frequencies of the systoles are modulated by vestibular activation. The model was implemented as a relaxation oscillator, driven by a central signal related to Desired BP. Relaxation oscillations were maintained by a second order system comprising two integrators and a threshold element in the feedback loop. The output signal related to BP was generated as a nonlinear function of the derivative of the first state variable, which is a summation of an input related to Desired BP, feedback from the states, and an input from the vestibular system into one of the feedback loops. This nonlinear function was structured to best simulate the shapes of systoles and diastoles, the relationship between BP and Heart Rate (HR) as well as the amplitude modulations of BP and Pulse Pressure. Increases in threshold in one of the feedback loops produced lower frequencies of HR, but generated large pulse pressures to maintain orthostasis, without generating a VasoVagal Response (VVR). Pulse pressures were considerably smaller in the anesthetized rats than during the simulations, but simulated pulse pressures were lowered by including saturation in the feedback loop. Stochastic changes in threshold maintained the compensatory Baroreflex Sensitivity. Sudden decreases in Desired BP elicited non-compensatory VVRs with smaller pulse pressures, consistent with experimental data. The model suggests that the Vestibular Sympathetic Reflex (VSR) modulates BP and HR of an oscillating system by manipulating parameters of the baroreflex feedback and the signals that maintain the oscillations. It also shows that a VVR is generated when the vestibular input triggers a marked reduction in Desired BP.

Dizziness and vertigo are common complaints that can be troubling or disabling for the patient. Diagnosis begins with obtaining a clear description of the symptoms, their onset, duration, and provoking factors. Vertigo, an illusion of motion, usually has its origin in the vestibular system but the cause may be peripheral (inner ear) or central. Dizziness due to orthostatic hypotension can be diagnosed by taking blood pressures lying and standing. Light-headedness or syncope may be a sign of orthostatic hypotension. Gait imbalance or dysequilibrium may have vestibular, motor, sensory, or multiple causes. Physical examination should be directed at the ears, hearing, vestibular system, and neurologic examination. Ancillary tests including audiometry, VOG, and MRI will usually establish the diagnosis, and effective treatment can then be offered. With the exception of ruling out an acoustic neuroma, MRIs are generally not useful in diagnosis of vestibular disorders. Hearing loss is prevalent in older adults but can occur at any age. Examination of the ears and audiometry will establish the diagnosis, and a proper treatment can usually be given. Hearing aids will benefit the majority of patients with moderate to severe degrees of hearing impairment. Cochlear implants are recommended to patients who can no longer derive benefit from hearing aids. Children with suspected hearing loss should always be referred to an audiologist; no child is too young to test, and early intervention has a profound influence on outcome. Unilateral hearing loss requires exclusion of acoustic neuroma. Sudden hearing loss should be evaluated urgently and treated with steroids. Hearing loss in the elderly may contribute to decreased cognitive function, and should not be ignored. A successful treatment for the mal de débarquement syndrome, which may follow voyages on the sea or occur spontaneously, can relieve the troubling rocking, swaying, or bobbing that is a prominent part of this syndrome.