Transcutaneous vagus nerve stimulation (t-VNS): A novel effective treatment for temper outbursts in adults with Prader-Willi Syndrome indicated by results from a non-blind study


Autoři: Katherine E. Manning aff001;  Jessica A. Beresford-Webb aff001;  Lucie C. S. Aman aff001;  Howard A. Ring aff001;  Peter C. Watson aff004;  Stephen W. Porges aff005;  Chris Oliver aff006;  Sally R. Jennings aff001;  Anthony J. Holland aff001
Působiště autorů: Department of Psychiatry, University of Cambridge, Cambridge, Cambridgeshire, United Kingdom aff001;  School of Health and Social Care, University of Essex, Colchester, Essex, United Kingdom aff002;  Essex Partnership University NHS Foundation Trust, Wickford, Essex, United Kingdom aff003;  MRC Cognition and Brain Sciences Unit, University of Cambridge, Cambridge, Cambridgeshire, United Kingdom aff004;  Department of Psychiatry, University of North Carolina, Chapel Hill, North Carolina, United States of America aff005;  School of Psychology, University of Birmingham, Birmingham, West Midlands, United Kingdom aff006
Vyšlo v časopise: PLoS ONE 14(12)
Kategorie: Research Article
doi: 10.1371/journal.pone.0223750

Souhrn

Temper outbursts are a severe problem for people with Prader-Willi Syndrome (PWS). Previous reports indicate that vagus nerve stimulation (VNS) may reduce maladaptive behaviour in neurodevelopmental disorders, including PWS. We systematically investigated the effectiveness of transcutaneous VNS (t-VNS) in PWS. Using a non-blind single case repeat measures modified ABA design, with participants as their own controls, t-VNS was evaluated in five individuals with PWS [three males; age 22–41 (M = 26.8)]. After a baseline phase, participants received four-hours of t-VNS daily for 12 months, followed by one month of daily t-VNS for two-hours. The primary outcome measure was the mean number of behavioural outbursts per day. Secondary outcomes included findings from behavioural questionnaires and both qualitative and goal attainment interviews. Four of the five participants who completed the study exhibited a statistically significant reduction in number and severity of temper outbursts after approximately nine months of daily four-hour t-VNS. Subsequent two-hour daily t-VNS was associated with increased outbursts for all participants, two reaching significance. Questionnaire and interview data supported these findings, the latter indicating potential mechanisms of action. No serious safety issues were reported. t-VNS is an effective, novel and safe intervention for chronic temper outbursts in PWS. We propose these changes are mediated through vagal projections and their effects both centrally and on the functioning of the parasympathetic nervous system. These findings challenge our present biopsychosocial understanding of such behaviours suggesting that there is a single major mechanism that is modifiable using t-VNS. This intervention is potentially generalizable across other clinical groups. Future research should address the lack of a sham condition in this study along with the prevalence of high drop out rates, and the potential effects of different stimulation intensities, frequencies and pulse widths.

Klíčová slova:

Aggression – Behavior – Behavioral disorders – Clinical genetics – Emotions – Epilepsy – Prader-Willi syndrome – Quality of life


Zdroje

1. Whittington J E., Holland A, J., Webb T., Butler J., Clarke D. & Boer H. Population prevalence and estimated birth incidence and mortality rate for people with Prader-Willi syndrome in one UK Health Region. J. Med. Genet. 38, 792–798 (2001). doi: 10.1136/jmg.38.11.792 11732491

2. Holland A. J., Whittington J, E., Butler J., Webb T., Boer H. & Clarke D. Behavioural phenotypes associated with specific genetic disorders: evidence from a population-based study of people with Prader-Willi syndrome. Psychol. Med. 33, 141–153 (2003). doi: 10.1017/s0033291702006736 12537045

3. Woodcock K., Oliver C. & Humphreys G. Associations between repetitive questioning, resistance to change, temper outbursts and anxiety in Prader-Willi and Fragile-X syndromes. J. Intellect. Disabil. Res. 53, 265–278 (2009). doi: 10.1111/j.1365-2788.2008.01122.x 18771510

4. Mazaheri M. M., Rae-Seebach R. D., Preston H. E., Schmidt M., Kountz-Edwards S., Field N. et al. The impact of Prader-Willi syndrome on the family’s quality of life and caregiving, and the unaffected siblings’ psychosocial adjustment. J. Intellect. Disabil. Res. 57, 861–873 (2013). doi: 10.1111/j.1365-2788.2012.01634.x 23057501

5. Bittel D. C. & Butler M. G. Prader–Willi syndrome: clinical genetics, cytogenetics and molecular biology. Expert Rev Mol Med. 7, 1–20 (2005).

6. Cassidy S. B., Forsythe M., Heeger S., Nicholls R. D., Schork N., Benn P. et al. Comparison of phenotype between patients with Prader-Willi syndrome due to deletion 15q and uniparental disomy 15. Am. J. Med. Genet. 68, 433–440 (1997). 9021017

7. Woodcock K. A., Oliver C. & Humphreys G. Task-switching deficits and repetitive behaviour in genetic neurodevelopmental disorders: Data from children with Prader—Willi syndrome chromosome 15 q11—q13 deletion and boys with Fragile X syndrome. Cogn. Neuropsychol. 26, 172–194 (2009). doi: 10.1080/02643290802685921 19221920

8. Woodcock K. A., Oliver C. & Humphreys G. W. The relationship between specific cognitive impairment and behaviour in Prader-Willi syndrome. J. Intellect. Disabil. Res. 55, 152–171 (2011). doi: 10.1111/j.1365-2788.2010.01368.x 21199046

9. Woodcock K. A., Humphreys G. W., Oliver C. & Hansen P. C. Neural correlates of task switching in paternal 15q11-q13 deletion Prader-Willi syndrome. Brain Res. 1363, 128–142 (2010). doi: 10.1016/j.brainres.2010.09.093 20920489

10. Manning K. E., McAllister C. J., Ring H. A., Finer N., Kelly C. L., Sylvester K. P. et al. Novel insights into maladaptive behaviours in Prader-Willi syndrome: Serendipitous findings from an open trial of vagus nerve stimulation. J. Intellect. Disabil. Res. 60, 149–155 (2016). doi: 10.1111/jir.12203 26018613

11. Galli R., Bonanni E., Pizzanelli C., Maestri M., Lutzemberger L., Giorgi F. S. et al. Daytime vigilance and quality of life in epileptic patients treated with vagus nerve stimulation. Epilepsy Behav. 4, 185–191 (2003). doi: 10.1016/s1525-5050(03)00003-9 12697145

12. Kossoff E. H. & Pyzik P. L. Improvement in alertness and behavior in children treated with combination topiramate and vagus nerve stimulation. Epilepsy Behav. 5, 256–259 (2004). doi: 10.1016/j.yebeh.2003.12.008 15123029

13. Warwick T. C., Griffith J., Reyes B., Legesse B. & Evans M. Effects of vagus nerve stimulation in a patient with temporal lobe epilepsy and Asperger syndrome: Case report and review of the literature. Epilepsy Behav. 10, 344–347 (2007). doi: 10.1016/j.yebeh.2007.01.001 17300990

14. Hull M. M., Madhavan D. & Zaroff C. M. Autistic spectrum disorder, epilepsy, and vagus nerve stimulation. Child’s Nerv. Syst. 31, 1377–1385 (2015).

15. Murphy J. V., Wheless J. W. & Schmoll C. M. Left vagal nerve stimulation in six patients with hypothalamic hamartomas. Pediatr. Neurol. 23, 167–168 (2000). doi: 10.1016/s0887-8994(00)00170-3 11020644

16. Ellrich J. Transcutaneous vagus nerve stimulation. Eur. Neurol. Rev. 6, 254–256 (2011).

17. Rojahn J., Matson J. L., Lott., Esbensen A. J. & Smalls Y. The Behavior Problems Inventory: an instrument for the assessment of self-injury, sterotyped behavior, and aggression/destruction in individuals with developmental disabilities. J Autism Dev Disord. 31, 577–88 (2001). doi: 10.1023/a:1013299028321 11814269

18. Aman M. G., Singh N. N., Stewart A. W. & Field C. J. The aberrant behavior checklist: A behavior rating scale for the assessment of treatment effects. Am. J. Ment. Defic. 89, 485–491 (1985). 3993694

19. Cummins R. A. & Lau A. D. L. Personal wellbeing index—Intellectual Disability. 3rd Edition. Victoria, Australia: School of Psychology, Deakin University (2005).

20. Oliver C., McClintock K., Hall S., Smith M., Dagnan D. & Stenfert-Kroese B. Assessing the Severity of Challenging Behaviour: Psychometric Properties of the Challenging Behaviour Interview. J. Appl. Res. Intellect. Disabil. 16, 53–61 (2003).

21. Hsieh H-F. & Shannon S, E. Three approaches to Qualitative Content Analysis. Qual. Health Res. 15, 1277–1288 (2005). doi: 10.1177/1049732305276687 16204405

22. Murray B. J., Matheson J. K. & Scammell T. E. Effects of vagus nerve stimulation on respiration during sleep. Neurology 57, 1523–1524 (2001). doi: 10.1212/wnl.57.8.1523 11673612

23. Turner-Stokes L. Goal Attainment Scaling (GAS) in Rehabilitation: A practical guide Clinical Rehabilitation. Clin. Rehabil. 23, 362–270 (2009). doi: 10.1177/0269215508101742 19179355

24. Kiresuk T, J. & Sherman R, E. Goal attainment scaling: A general method for evaluating comprehensive community mental health programs. Community Ment. Health J. 4, 443–453 (1968). doi: 10.1007/BF01530764 24185570

25. Dugard P., File P., & Todman J. Single-case and small-n experimental designs: a practical guide to randomization tests. Second edition. Routledge: Hove (2001)

26. Braun V. & Clarke V. Using thematic analysis in psychology Using thematic analysis in psychology. Qual. Res. Psychol. 3, 77–101 (2008).

27. Dykens E, M., Hodapp R, M., Walsh K. & Nash L, J. Profiles, Correlates, and Trajectories of Intelligence in Prader-Willi Syndrome. J. Am. Acad. Child Adolesc. Psychiatry 31, 1125–1130 (1992). doi: 10.1097/00004583-199211000-00022 1429416

28. Usami K., Kawai K., Sonoo M. & Saito N. Scalp-recorded evoked potentials as a marker for afferent nerve impulse in clinical vagus nerve stimulation. Brain Stimul. 6, 615–623 (2013). doi: 10.1016/j.brs.2012.09.007 23088852

29. Porges S.W. & Furman S. A. The Early Development of the Autonomic Nervous System Provides a Neural Platform for Social Behavior: A Polyvagal Perspective. Infant Child Dev. 20, 106–118 (2011). doi: 10.1002/icd.688 21516219

30. Bar-Haim Y., Lamy D., Pergamin L., Bakermans-Kranenburg M. J. & Van Ijzendoorn M. H. Threat-related attentional bias in anxious and nonanxious individuals: A meta-analytic study. Psychol. Bull. 133, 1–24 (2007). doi: 10.1037/0033-2909.133.1.1 17201568

31. Robinson O. J., Letkiewicz A. M., Overstreet C., Ernst M. & Grillon C. The effect of induced anxiety on cognition: threat of shock enhances aversive processing in healthy individuals. Cogn Affect Bheav Neurosci. 11, 217–227 (2011).

32. Prader-Willi California Foundation. Prader-Willi Syndrome: Overview of Food & Behaviour Management.

33. Van Leusden J. W. R., Sellaro R. & Colzato L. S. Transcutaneous Vagal Nerve Stimulation (tVNS ): a new neuromodulation tool in healthy humans? Front. Psychol. 6, (2015).

34. Ben-Menachem E., Hamberger A., Hedner T., Hammond E. J., Uthman B. M., Slater J. et al. Effects of vagus nerve stimulation on amino acids and other metabolites in the CSF of patients with partial seizures. Epilepsy Res. 20, 221–227 (1995). doi: 10.1016/0920-1211(94)00083-9 7796794

35. Capone F., Assenza G., Di Pino G., Musumeci G., Ranieri F., Florio L. et al. The effect of transcutaneous vagus nerve stimulation on cortical excitability. J. Neural Transm. 122, 679–685 (2015). doi: 10.1007/s00702-014-1299-7 25182412

36. Rice L. J., Lagopoulos J., Brammer M. & Einfeld S. L. Reduced Gamma-Aminobutyric Acid Is Associated With Emotional and Behavioral Problems in Prader–Willi Syndrome. Am J Med Genet B Neuropsychiatr Genet. 171, 1041–1048 (2016). doi: 10.1002/ajmg.b.32472 27338833


Článek vyšel v časopise

PLOS One


2019 Číslo 12