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://ichgcp.net/clinical-trials-registry/NCT02540616].

Conflict of interest statement

The authors have declared that no competing interests exist.

Figures

Fig 1. CONSORT diagram for recruitment.

Fig 2. Study procedures Day 1 through Day 5.

Baseline clinical and symptom assessments were performed in the morning with fMRI and EEG obtained in the afternoon of Day 1. Day 2 entailed test sessions of each of three protocols (anti-phase, in-phase, control) given in an unlabeled and randomized order. Participants elected their individually most effective protocol. Individually chosen optimal treatments were given on the mornings of Days 3 and 4. Final treatments were given on the morning of Day 5 followed by fMRI and EEG in the afternoon.

Fig 3. Model of tACS montage used in study.

10x10cm sponges housing carbonized rubber electrodes were placed over the frontal pole above the eyebrows and above the inion and held down with neoprene straps and headbands. Care was taken to avoid causing wetness of the headbands.

Fig 4. Total treatment response to tACS.

(A) Absolute change and (B) Percent change in symptoms after 10–12 sessions of the tACS paradigm of the participant’s choice. Scores were calculated based on a 0–100 Visual Analogue Scale in which lower values represent lower symptom severity.

Fig 5. Percentage treatment response by stimulation type.

Percentage change in symptoms after 10–12 sessions of alpha tACS according to type of stimulation used: (A) higher than IAF, (B) IAF, (C) standard 10Hz, (D) standard 40Hz. These figures combine both anti-phase and in-phase stimulation.

Fig 6. Longitudinal tACS effects on DHI, MBRS, and HAD scores.

Linear prediction model of repeated measures ANOVA with 95% confidence intervals presented for four baseline measurements, post TMS week, and six weeks post treatment for the DHI, MBRS, and the HADS Anxiety and Depression components. Pre = pre TMS scores, Pst = post TMS scores.