Given a sufficiently provocative stimulus, almost everyone can be made motion sick, with approximately one-third experiencing significant symptoms on long bus trips, on ships, or in light aircraft.1–4 Current countermeasures are either behavioral or pharmacologic. Behavioral measures include habituation/desensitization treatment protocols5 as well as positioning the head in alignment with the direction of the gravito-inertial force and maintaining a stable horizontal reference frame.5 Pharmacologic measures include antimuscarinics, H1 antihistamines, and sympathomimetics, which all detrimentally impact upon cognitive function, rendering them inappropriate for occupational use.5 All current therapies are only partially effective

Arshad, Q.

Bronstein, A.M.

Casani, A.P.

Cerchiai, N.

Goga, U.

Golding, J.F.

Gresty, M.A.

Nigmatullina, Y.

Roberts, R.E.

WestminsterResearch

WestminsterResearchhttp://www.westminster.ac.uk/westminsterresearch Electrocortical therapy for motion sicknessArshad, Q., Cerchiai, N., Goga, U., Nigmatullina, Y., Roberts, R.E., Casani, A.P., Golding, J.F., Gresty, M.A. and Bronstein, A.M. This is the final version of an article published in Neurology vol. 85 (14), pp. 1257-1259 in 2015.It is available from the publisher at:https://dx.doi.org/10.1212/WNL.0000000000001989© 2015 American Academy of NeurologyThis is an open access article distributed under the terms of the Creative Commons Attribution License 4.0 (CC BY), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. The WestminsterResearch online digital archive at the University of Westminster aims to make the research output of the University available to a wider audience. Copyright and Moral Rights remain with the authors and/or copyright owners.Whilst further distribution of specific materials from within this archive is forbidden, you may freely distribute the URL of WestminsterResearch: ((http://westminsterresearch.wmin.ac.uk/).In case of abuse or copyright appearing without permission e-mail repository@westminster.ac.ukClinical/ScientificNotesQadeer Arshad, PhD*Niccolo Cerchiai, MD*Usman Goga, BScYuliya Nigmatullina, PhDR. Ed Roberts, PhDAugusto P. Casani, MDJohn F. Golding, PhDMichael A. Gresty, PhDAdolfo M. Bronstein,MD, PhDELECTROCORTICAL THERAPY FOR MOTIONSICKNESSGiven a sufficiently provocative stimulus, almosteveryone can be made motion sick, with approxi-mately one-third experiencing significant symptomson long bus trips, on ships, or in light aircraft.1–4Current countermeasures are either behavioral orpharmacologic. Behavioral measures include habitua-tion/desensitization treatment protocols5 as well aspositioning the head in alignment with the directionof the gravito-inertial force and maintaining a stablehorizontal reference frame.5 Pharmacologic measuresinclude antimuscarinics, H1 antihistamines, andsympathomimetics, which all detrimentally impactupon cognitive function, rendering them inappropri-ate for occupational use.5 All current therapies areonly partially effective.Since a functioning vestibular system is critical tothe development of motion sickness,1 we proposedthat suppressing vestibular activity could increasetolerance to nauseogenic motion stimuli. We previ-ously showed that application of transcranial directcurrent stimulation (tDCS), specifically unipolarcathodal stimulation over the left parietal cortex,results in suppression of the vestibular system.6Herein, we assessed whether such suppression of ves-tibular activity using tDCS in normal controls mayalleviate motion sickness.Classification of evidence. This study providesClass II evidence that in normal volunteers undergo-ing off-axis rotation, left parietal cortex cathodalstimulation increases the time to the developmentof moderate nausea.Methods. We implemented a well-established modelof inducing motion sickness termed off-vertical axisrotation (OVAR). Subjects were seated in a motorizedchair (NKI; Pittsburgh, PA) with the torso restrainedby a 5-point seatbelt with the head, legs, and feetadditionally secured with cushioned clamps. The chairwas rotated rightwards in the dark, accelerating andtilting gradually over 30 seconds to reach a constantrotational velocity of 72 deg/s, frequency of 0.2 Hz,at a tilt of 18 degrees.7 Twenty right-handed subjects(10 M; 10 F not within 3 days of menstruation) wererandomly allocated into 2 age- and sex-matched groups(groups 1 and 2). It was ensured that individuals inboth groups were matched for susceptibility to motionsickness as determined by adult-based motion sicknessquestionnaire scores (MSB scores; see the figure, B foreach individual’s susceptibility score).8The experimental design was specifically chosento test whether tDCS is potentially effective as a pro-phylactic or abortive treatment. Both groups under-went an initial OVAR session during sham tDCSstimulation only. The time taken to self-report (1)onset of symptoms (i.e., stomach awareness); (2)the primary outcome measure, onset of moderatenausea (i.e., total OVAR duration, with no uppertime limit); and (3) subsequent self-recovery were re-corded. Subjects were given a 1-hour rest period in aseparate room, after which all reported full recovery.Critically, despite recovery, at this time point previ-ous research has shown that subjects have highermotion sickness susceptibility,9 thus allowing us totest the efficacy of tDCS during enhanced suscepti-bility. After recovery, unipolar tDCS was applied(1.5 mA with a ramp-up and fade-out time of 10seconds; electrode placement area 25 cm2; for elec-trode placement on the scalp, we parted the hair andelectrodes were held in place with an EEG cap6) with2 possible different polarities in a double-blinddesign.6 For group 1 (cathodal) and group 2 (anodal),stimulation was applied initially for 15 minutesimmediately prior to the second OVAR session over leftparietal cortex and stimulation continued for either afurther 15 minutes during the rotation or until subjectsreported moderate nausea (i.e., whichever came first).No subjects dropped out or complained of any symp-toms associated with either tDCS stimulation or tDCS-mediated vestibular suppression.Results. The figure summarizes the results of theexperiment. Repeated-measures analysis of variancefor cathodal tDCS stimulation with within-subjectsfactors measurement (OVAR duration, first onset ofsymptoms, and time to recovery) and condition(before tDCS, after tDCS) showed a significantmeasurement 3 condition interaction (F 5 9.48,df 5 2, p 5 0.033; figure, A). Post hoc paired ttests (2-tailed) with Bonferroni corrections showedthat following cathodal stimulation, OVAR duration(i.e., time taken for the onset of moderate nausea)Neurology 85 October 6, 2015 1257ª 2015 American Academy of Neurology. Unauthorized reproduction of this article is prohibited.was significantly increased (t 5 2.68, p , 0.05;figure, A). In contrast, for anodal stimulation, themeasurement 3 condition interaction was notsignificant. That is, following left cathodalstimulation, it took subjects in the second OVARsession 207 seconds (range 32–382 seconds) longerto develop moderate nausea, whereas following leftanodal stimulation subjects developed moderatenausea on average 57 seconds sooner (range 22 to2153 seconds). Notably, those subjects lesssusceptible to motion sickness (i.e., lower MSBscores) derived the largest benefit following leftcathodal tDCS stimulation (r 5 0.86, p , 0.001;figure, B). Further, the time taken to recoverfollowing cathodal stimulation was significantlyreduced (t 5 6.0, p , 0.001; figure, A).Discussion. Following cathodal tDCS over the lefthemisphere, we observed both an increased durationin the time taken to develop moderate nausea duringOVAR and a more rapid recovery from symptoms. Asno significant effects were observed during anodalstimulation, this excludes the role of both adaptationand nonspecific effects due to tDCS.10 We provide anovel treatment for motion sickness that is, so far,apparently free of side effects.*Q. Arshad and N. Cerchiai contributed equally to this work.From Imperial College (Q.A., N.C., U.G., Y.N., R.E.R., M.A.G.,A.M.B.), Charing Cross Hospital, London, UK; Otorinolaringoia-tria 1 Universitaria (N.C., A.P.C.), Pisa, Italy; and the Universityof Westminster (J.F.G.), London, UK.Author contributions: Q. Arshad: conceptualized study, acquireddata, and wrote the manuscript. N. Cerchiai: conceptualized studyand acquired data. U. Goga: acquired data and revisedFigure Effects of electrocortical stimulation on motion sickness susceptibility(A) (Left upper panel) Following left cathodal transcranial direct current stimulation (tDCS) stimulation, the susceptibility tomotion sickness was reduced, as reflected by the significant increase in off-vertical axis rotation (OVAR) duration requiredto induce moderate nausea. Also, we observe a significant reduction in the time taken for symptom recovery. In contrast,following left anodal stimulation, we did not observe any significant effects (right upper panel). (B) Adult motion sicknesssusceptibility scores (MSB) showed significant correlation with the change in OVAR duration (post-pre tDCS) for the leftcathodal stimulation only (left lower panel), indicating that less susceptible subjects derived the largest benefit from tDCS.Error bars represent standard errors. *p , 0.05; **p , 0.01.1258 Neurology 85 October 6, 2015ª 2015 American Academy of Neurology. Unauthorized reproduction of this article is prohibited.manuscript. Y. Nigmatullina: data analysis and figure prepa-ration. E. Roberts: data analysis and revised manuscript. A.Casani: revised manuscript. J. Golding: conceptualized study,technical expertise, and revised manuscript. M. Gresty: concep-tualized study, technical expertise, and wrote manuscript. ABronstein: conceptualized study, supervised study, and wrotemanuscript.Study funding: No targeted funding reported.Disclosure: The authors report no disclosures relevant to the manu-script. Go to Neurology.org for full disclosures. The Article ProcessingCharge was paid by Research Councils-UK (RCUK).This is an open access article distributed under the terms of theCreative Commons Attribution License 4.0 (CC BY), which permitsunrestricted use, distribution, and reproduction in any medium, pro-vided the original work is properly cited.Received September 24, 2014. Accepted in final form April 14, 2015.Correspondence to Dr. Bronstein: a.bronstein@imperial.ac.uk© 2015 American Academy of Neurology1. Murdin L, Chamberlain F, Cheema S, et al. Motion sick-ness in migraine and vestibular disorders. J Neurol Neuro-surg Psychiatry 2015;86:585–587.2. Turner M, Griffin MJ. Motion sickness in public roadtransport: the effect of driver, route and vehicle. Ergonom-ics 1999;42:1646–1664.3. Turner M, Griffin MJ, Holland I. Airsickness and aircraftmotion during short-haul flights. Aviat Space EnvironMed 2000;71:1181–1189.4. Lawther A, Griffin MJ. A survey of the occurrence ofmotion sickness amongst passengers at sea. Aviat SpaceEnviron Med 1988;59:399–406.5. Golding JF, Gresty MA. Pathophysiology and treatment ofmotion sickness. Curr Opin Neurol 2015;28:83–88.6. Arshad Q, Nigmatullina Y, Roberts RE, Bhrugubanda V,Asavarut P, Bronstein AM. Left cathodal trans-cranial directcurrent stimulation of the parietal cortex leads to an asym-metrical modulation of the vestibular-ocular reflex. BrainStimul 2014;7:85–91.7. Bijveld M, Bronstein AM, Golding JF, Gresty MA. Nause-ogenicity of off-vertical axis rotation vs. equivalent visualmotion. Aviat Space Environ Med 2008;79:661–665.8. Golding JF. Motion sickness susceptibility questionnairerevised and its relationship to other forms of sickness.Brain Res Bull 1998;47:507–516.9. Golding JF, Stott JR. Objective and subjective time courses ofrecovery from motion sickness assessed by repeated motionchallenges. J Vestib Res 1997;7:421–428.10. Kyriakareli A, Cousins S, Pettorossi VE, Bronstein AM. Effectof transcranial direct current stimulation on vestibular-ocular andvestibulo-perceptual thresholds. Neuroreport 2013;24:808–812.TPP1 DEFICIENCY: RARE CAUSE OF ISOLATEDCHILDHOOD-ONSET PROGRESSIVE ATAXIANeuronal ceroid lipofuscinoses (NCLs) are neurode-generative disorders characterized by lysosomal ceroiddeposition. Historically, NCLs were classified byonset age and electron microscopy abnormalities asinfantile, late infantile, juvenile, and adult.1,2 Molec-ular techniques have broadened diagnostic subgroupswith identification of at least 13 NCL genes (http://www.ucl.ac.uk/ncl/mutation), though categorizationremains difficult due to wide-ranging genetic, allelic,and phenotypic heterogeneity.1,2CLN2 disease (late infantile NCL) is an autosomalrecessive disorder associated with deficiency oftripeptidyl-peptidase-1 (TPP1).1–3 Neurodevelop-mental regression typically begins between 2 and 4years of age with onset of seizures, cognitive decline,ataxia, visual loss, spasticity, and death usually in the2nd decade.1–3 Tissue electron microscopic studiestypically reveal curvilinear profiles.1,2 A recent reportof 6 adult members in 2 families, with symptom onsetin childhood, broadened the phenotype of TPP1 par-tial deficiency to include spinocerebellar ataxia(SCAR7).4,5 All patients were compound heterozy-gotes (c.509-1G.C/c.1397T.G).4,5 We report achild with progressive ataxia and compound hetero-zygous TPP1 mutations (common splice, c.509-1G.C and c.1029G.C, p. Glu343Asp) associatedwith TPP1 enzyme deficiency. This case highlightsthe power of next-generation sequencing (NGS) indiagnosing rare and atypical disease. Increasedawareness of TPP1-deficiency ataxia phenotype iscrucial to identify patients with atypical CLN2 dis-ease. These patients may benefit from TPP1 enzymereplacement therapy currently in trials for classic late-infantile CLN2 disease.Case report. The patient is a 10-year-old AfricanAmerican/Caucasian girl with prenatal gastroschisis.Delivery was by cesarean section at 35 weeks. Devel-opment was normal except for stuttering (age 3). Finemotor difficulties began at age 4. Abnormalities ofgait, balance, coordination, and difficulties with aca-demic performance were noted at age 6. Neurocogni-tive assessment (age 8) identified impaired visualprocessing, visual memory, and attention, and expres-sive/receptive language skills in the below average toaverage range. There has been no frank loss of cogni-tive skills, although symptoms of cerebellar dysfunc-tion have been progressive. The patient continuesto ambulate and run independently with balance dif-ficulties, but can no longer ride a bike.Neurologic examination is notable for scanningspeech. Ophthalmologic examination demonstratesunilateral Mittendorf dot, intermittent bilateralhorizontal gaze-evoked nystagmus, saccadicbreakdown of ocular pursuit, overshoot of horizon-tal saccades, and oculomotor apraxia. Movementabnormalities include bilateral upper extremitydysmetria, slowed fine finger movements, and trun-cal titubation. Gait is wide-based and moderatelyunsteady. The patient is able to stand on one footMarisela E. Dy, MDKatherine B. Sims, MDJennifer Friedman, MDSupplemental dataat Neurology.orgNeurology 85 October 6, 2015 1259ª 2015 American Academy of Neurology. Unauthorized reproduction of this article is prohibited.DOI 10.1212/WNL.00000000000019892015;85;1257-1259 Published Online before print September 4, 2015Neurology Qadeer Arshad, Niccolo Cerchiai, Usman Goga, et al. Electrocortical therapy for motion sicknessThis information is current as of September 4, 2015ServicesUpdated Information & http://www.neurology.org/content/85/14/1257.full.htmlincluding high resolution figures, can be found at:References http://www.neurology.org/content/85/14/1257.full.html##ref-list-1This article cites 10 articles, 1 of which you can access for free at: Subspecialty Collections http://www.neurology.org//cgi/collection/all_neurotologyAll Neurotologyfollowing collection(s): This article, along with others on similar topics, appears in the  Permissions & Licensing http://www.neurology.org/misc/about.xhtml#permissionsits entirety can be found online at:Information about reproducing this article in parts (figures,tables) or in  Reprints http://www.neurology.org/misc/addir.xhtml#reprintsusInformation about ordering reprints can be found online:rights reserved. Print ISSN: 0028-3878. Online ISSN: 1526-632X.1951, it is now a weekly with 48 issues per year. 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Electrocortical therapy for motion sickness

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Electrocortical therapy for motion sickness

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