Double-blind randomized N-of-1 trial of transcranial alternating current stimulation for mal de débarquement syndrome

Abstract

Background Mal de Débarquement Syndrome (MdDS) is a medically refractory neurotological disorder characterized by persistent oscillating vertigo that follows a period of entrainment to oscillating motion such as experienced during sea or air travel. Fronto-occipital hypersynchrony may correlate with MdDS symptom severity. Materials and methods Individuals with treatment refractory MdDS lasting at least 6 months received single administrations of three fronto-occipital transcranial alternating current stimulation (tACS) protocols in an “n-of-1” double-blind randomized design: alpha frequency anti-phase, alpha-frequency in-phase, and gamma frequency control. Baseline assessments were made on Day 1. The treatment protocol that led to the most acute reduction in symptoms during a test session on Day 2 was administered for 10–12 stacked sessions given on Days 3 through 5 (20-minutes at 2-4mA). Pre to post symptom changes were assessed on Day 1 and Day 5. Participants who could clearly choose a preferred protocol on Day 2 did better on Day 5 than those who could not make a short-term determination on Day 2 and either chose a protocol based on minimized side effects or were randomized to one of the three protocols. In addition, weekly symptom assessments were made for four baseline and seven post stimulation points for the Dizziness Handicap Inventory (DHI), MdDS Balance Rating Scale (MBRS), and Hospital Anxiety and Depression Scale (HADS). Results Of 24 participants, 13 chose anti-phase, 7 chose in-phase, and 4 chose control stimulation. Compared to baseline, 10/24 completers noted ≥ 25% reduction, 5/24 ≥50% reduction, and 2/24 ≥75% reduction in oscillating vertigo intensity from Day 1 to Day 5. Stimulating at a frequency slightly higher than the individual alpha frequency (IAF) was better than stimulating at exactly the IAF, and slightly better than stimulating with a strategy of standardized stimulation at 10Hz. A one-way repeated measures ANOVA of weekly DHI, MBRS, and HADS measurements showed significant reductions immediately after treatment with improvement increasing through post-treatment week 6. Conclusion Fronto-occipital tACS may be effective in reducing the oscillating vertigo of MdDS and serve as a portable neuromodulation alternative for longer-term treatment. Stimulation frequency relative to the IAF may be important in determining the optimum treatment protocol [ClinicalTrials.gov study NCT02540616. https://clinicaltrials.gov/ct2/show/NCT02540616].

Treatment Options in Mal de Débarquement Syndrome: A Scoping Review

“…In 2022, this group later sought to determine whether the functional connectivity changes appreciated with rTMS were also found when entraining (coupling of independent oscillatory systems by phase alignment (53)) fronto-occipital networks using tACS, and to also further assess treatment efficacy. Acute improvements were not found to be as remarkable as TMS but comparable at 6 weeks after treatment (39,50).…”

“…Recently, transcranial alternating current stimulation (tACS) has been investigated, which uses low current levels at a frequency that synchronizes or desynchronizes with cortical rhythms (48)(49)(50)(51)(52). Cha et al in 2021 ( 51) developed a home-based protocol for tACS for those who either had not responded to the on-site protocol or who had relapsed after treatment.…”

Frequency-Dependent Reduction of Cybersickness in Virtual Reality by Transcranial Oscillatory Stimulation of the Vestibular Cortex

“…Typically, tACS is used because it is thought to entrain local oscillations in a frequency-specific manner [44], as recently shown in the vestibular domain where tACS at 1 Hz or 2 Hz induced motion sickness and postural sway in healthy subjects [16]. Here, prompted by the observation that 10 Hz-tACS reduced chronic symptoms in a patient with no peripheral vestibular function [16] and that improved persistent oscillatory vertigo following prolonged sea or air travel, even when not precisely targeted at the vestibular cortex [17], we reasoned that this kind of stimulation might be useful in reducing CS via at least two non-mutually exclusive mechanisms: first, that 10 Hz-tACS could reduce local slow wave activity that sustains symptoms [14] via phase interference [46], a common biophysical mechanism [47] useful, for example, in reducing pathological oscillatory brain activity that drives tremor [48]; second, as temporal-parietal alpha (i.e. 10 Hz) suppression appears to be a hallmark of the physiological activation of the multisensory vestibular cortex [18], the entrainment induced by 10 Hz-tACS on residual endogenous alpha oscillations (i.e.…”

“…NiBS techniques are increasingly being used as therapeutic procedures as an alternative or complementary to traditional pharmacological therapies for many neurological and psychiatric disorders, capitalising on the long lasting, predictable and safe [34,40] after-effects of the stimulation interventions [41]. Among these, only a handful of previous pilot studies have used NiBS techniques to reduce vestibular symptoms of motion sickness or kinetosis: repetitive transcranial magnetic stimulation (rTMS) of the prefrontal cortex in cases of mal de debarquement syndrome [17,42] and anodal transcranial direct current stimulation (tDCS) of the right temporoparietal junction applied before a VR rollercoaster game [43]: in this study, anodal tDCS improved the oculomotor but not the nausea sub-score of the Simulator Sickness Questionnaire after the VR experience, but no data are reported on online changes in nausea or other physiological assessment parameters, nor it is known whether online tDCS could have improved CS (or not).…”

“…We therefore reasoned that a similar approach could be used in healthy subjects to reduce CS during a standardised VR experience such as a rollercoaster ride. Mechanistically, a higher stimulation frequency might disrupt symptoms' oscillatory processing at 1 or 2 Hz by phase interference [17], thereby reducing them. Alternatively, but not exclusively, entrainment of local oscillatory alpha activity, the suppression of which is a neurophysiological signature of vestibular activation [18], could disrupt the functioning of the vestibular regions and thereby also reducing symptoms.…”