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Does pallidal neuromodulation influence cognitive decline in Huntington’s disease?

Journal of Neurology volume 268, pages 613–622 (2021)Cite this article

Abstract

Objective

Huntington’s disease (HD) is an autosomal dominant neurodegenerative disorder associated with motor, psychiatric and cognitive deterioration over time. To date, Continuous Electrical Neuromodulation (CEN) of the globus pallidus internus (GPi) has been reported to improve chorea but little is known about cognitive progression in these patients. We propose to examine CEN impact on expected cognitive decline throughout long-term neuropsychological assessment of a cohort of HD patients.

Method

13 consecutive HD patients underwent GPi neuromodulation between January 2008 and February 2019. Over a 5-year follow-up period, they received systematic pre- and post-operative assessment according to the existing protocol in our unit. The main outcome measure was the total score obtained on the Mattis Dementia Rating Scale (MDRS) as an indicator of global cognitive function.

Results

Chorea decreased in all patients postoperatively with a mean improvement of 56% despite disease progression over time, according to previous studies. Moreover we found that the global cognitive profile of HD patients treated with CEN was stable during the first 3 years of treatment.

Conclusion

We report an unexpected positive influence of GPi continuous electrical neuromodulation on the progression of global cognitive functioning in operated HD patients. This is the most important group of patients treated with this method to our knowledge whatever the sample size remains small. This result provides promising evidence of GPi-CEN efficacy not only in reducing chorea, but also in delaying cognitive decline in HD patients operated at an early stage of the disease.

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References

  1. Hebb MO, Garcia R, Gaudet P, Mendez IM (2006) Bilateral stimulation of the globus pallidus internus to treat choreathetosis in Huntington's disease: technical case report. Neurosurgery 58:E383 (discussion E383)

    PubMed  Google Scholar 

  2. Moro E, Lang AE, Strafella AP, Poon YY, Arango PM, Dagher A, Hutchison WD, Lozano AM (2004) Bilateral globus pallidus stimulation for Huntington's disease. Ann Neurol 56:290–294

    PubMed  Google Scholar 

  3. Spielberger S, Hotter A, Wolf E, Eisner W, Müller J, Poewe W, Seppi K (2012) Deep brain stimulation in Huntington's disease: A 4-year follow-up case report. Mov Disord 27:806–807 (author reply 807-808)

    PubMed  Google Scholar 

  4. Velez-Lago FM, Thompson A, Oyama G, Hardwick A, Sporrer JM, Zeilman P, Foote KD, Bowers D, Ward HE, Sanchez-Ramos J, Okun MS (2013) Differential and better response to deep brain stimulation of chorea compared to dystonia in Huntington's disease. Stereotact Funct Neurosurg 91:129–133

    PubMed  Google Scholar 

  5. Chiken S, Nambu A (2016) Mechanism of deep brain stimulation: inhibition, excitation, or disruption? Neuroscientist 22:313–322

    PubMed  Google Scholar 

  6. Biolsi B, Cif L, Fertit HE, Robles SG, Coubes P (2008) Long-term follow-up of Huntington disease treated by bilateral deep brain stimulation of the internal globus pallidus. J Neurosurg 109:130–132

    PubMed  Google Scholar 

  7. Snowden J, Craufurd D, Griffiths H, Thompson J, Neary D (2001) Longitudinal evaluation of cognitive disorder in Huntington's disease. J Int Neuropsychol Soc 7:33–44

    CAS  PubMed  Google Scholar 

  8. Stout JC, Jones R, Labuschagne I, O'Regan AM, Say MJ, Dumas EM, Queller S, Justo D, Santos RD, Coleman A, Hart EP, Dürr A, Leavitt BR, Roos RA, Langbehn DR, Tabrizi SJ, Frost C (2012) Evaluation of longitudinal 12 and 24 month cognitive outcomes in premanifest and early Huntington's disease. J Neurol Neurosurg Psychiatry 83:687–694

    PubMed  PubMed Central  Google Scholar 

  9. Tabrizi SJ, Scahill RI, Owen G, Durr A, Leavitt BR, Roos RA, Borowsky B, Landwehrmeyer B, Frost C, Johnson H, Craufurd D, Reilmann R, Stout JC, Langbehn DR (2013) Predictors of phenotypic progression and disease onset in premanifest and early-stage Huntington's disease in the TRACK-HD study: analysis of 36-month observational data. Lancet Neurol 12:637–649

    PubMed  Google Scholar 

  10. Ho AK, Sahakian BJ, Brown RG, Barker RA, Hodges JR, Ané MN, Snowden J, Thompson J, Esmonde T, Gentry R, Moore JW, Bodner T (2003) Profile of cognitive progression in early Huntington's disease. Neurology 61:1702–1706

    CAS  PubMed  Google Scholar 

  11. Nagel SJ, Machado AG, Gale JT, Lobel DA, Pandya M (2015) Preserving cortico-striatal function: deep brain stimulation in Huntington's disease. Front Syst Neurosci 9:32

    PubMed  PubMed Central  Google Scholar 

  12. Sharma M, Deogaonkar M (2015) Deep brain stimulation in Huntington's disease: assessment of potential targets. J Clin Neurosci 22:812–817

    PubMed  Google Scholar 

  13. Shoulson I, Fahn S (1979) Huntington disease: clinical care and evaluation. Neurology 29:1–3

    CAS  PubMed  Google Scholar 

  14. Coubes P, Vayssiere N, El Fertit H, Hemm S, Cif L, Kienlen J, Bonafe A, Frerebeau P (2002) Deep brain stimulation for dystonia. Surg Tech Stereotact Funct Neurosurg 78:183–191

    Google Scholar 

  15. Huntington Study Group (1996) Unified Huntington's disease rating scale: reliability and consistency. Mov Disord 11:136–142

    Google Scholar 

  16. Bachoud-Levi AC, Maison P, Bartolomeo P, Boisse MF, Dalla Barba G, Ergis AM, Baudic S, Degos JD, Cesaro P, Peschanski M (2001) Retest effects and cognitive decline in longitudinal follow-up of patients with early HD. Neurology 56:1052–1058

    CAS  PubMed  Google Scholar 

  17. Lavoie M, Callahan B, Belleville S, Simard M, Bier N, Gagnon L, Gagnon JF, Blanchet S, Potvin O, Hudon C, Macoir J (2013) Normative data for the Dementia Rating Scale-2 in the French–Quebec population. Clin Neuropsychol 27:1150–1166

    PubMed  Google Scholar 

  18. Wechsler D (2008) Wechsler adult intelligence Scale, 4th edn (WAIS IV). Pearson

  19. Van der Linden M, Coyette F, Pointrenaud J, Kalafat M, Calicis F, Wyns C, Adam S, et les membres du GREMEM (2004) L'épreuve de rappel libre/rappel indice à 16 items (RL/RI16). In: Solal (ed) L'évaluation des troubles de la mémoire. Marseille, pp 25–47

  20. Tombaugh TN (2004) Trail Making Test A and B: normative data stratified by age and education. Arch Clin Neuropsychol 19:203–214

    PubMed  Google Scholar 

  21. Cardebat D, Demonet JF, Viallard G, Faure S, Puel M, Celsis P (1996) Brain functional profiles in formal and semantic fluency tasks: a SPECT study in normals. Brain Lang 52:305–313

    CAS  PubMed  Google Scholar 

  22. Mestre TA, Bachoud-Lévi AC, Marinus J, Stout JC, Paulsen JS, Como P, Duff K, Sampaio C, Goetz CG, Cubo E, Stebbins GT, Martinez-Martin P (2018) Rating scales for cognition in Huntington's disease: critique and recommendations. Mov Disord 33:187–195

    PubMed  Google Scholar 

  23. Peavy GM, Jacobson MW, Goldstein JL, Hamilton JM, Kane A, Gamst AC, Lessig SL, Lee JC, Corey-Bloom J (2010) Cognitive and functional decline in Huntington's disease: dementia criteria revisited. Mov Disord 25:1163–1169

    PubMed  PubMed Central  Google Scholar 

  24. Llebaria G, Pagonabarraga J, Kulisevsky J, Garcia-Sanchez C, Pascual-Sedano B, Gironell A, Martinez-Corral M (2008) Cut-off score of the Mattis Dementia Rating Scale for screening dementia in Parkinson's disease. Mov Disord 23:1546–1550

    PubMed  Google Scholar 

  25. Penney JB Jr, Vonsattel JP, MacDonald ME, Gusella JF, Myers RH (1997) CAG repeat number governs the development rate of pathology in Huntington's disease. Ann Neurol 41:689–692

    PubMed  Google Scholar 

  26. Wojtecki L, Groiss SJ, Hartmann CJ, Elben S, Omlor S, Schnitzler A, Vesper J (2016) Deep brain stimulation in huntington's disease-preliminary evidence on pathophysiology efficacy and safety. Brain Sci 6:38

    PubMed Central  Google Scholar 

  27. Gonzalez V, Cif L, Biolsi B, Garcia-Ptacek S, Seychelles A, Sanrey E, Descours I, Coubes C, de Moura AM, Corlobe A, James S, Roujeau T, Coubes P (2014) Deep brain stimulation for Huntington's disease: long-term results of a prospective open-label study. J Neurosurg 121:114–122

    PubMed  Google Scholar 

  28. Fasano A, Mazzone P, Piano C, Quaranta D, Soleti F, Bentivoglio AR (2008) GPi-DBS in Huntington's disease: results on motor function and cognition in a 72-year-old case. Mov Disord 23:1289–1292

    PubMed  Google Scholar 

  29. Kang GA, Heath S, Rothlind J, Starr PA (2011) Long-term follow-up of pallidal deep brain stimulation in two cases of Huntington's disease. J Neurol Neurosurg Psychiatry 82:272–277

    PubMed  Google Scholar 

  30. Zittel S, Tadic V, Moll CKE, Bäumer T, Fellbrich A, Gulberti A, Rasche D, Brüggemann N, Tronnier V, Münchau A (2018) Prospective evaluation of Globus pallidus internus deep brain stimulation in Huntington's disease. Parkinsonism Relat Disord 51:96–100

    CAS  PubMed  Google Scholar 

  31. Wojtecki L, Groiss SJ, Ferrea S, Elben S, Hartmann CJ, Dunnett SB, Rosser A, Saft C, Südmeyer M, Ohmann C, Schnitzler A, Vesper J (2015) A Prospective Pilot Trial for Pallidal Deep Brain Stimulation in Huntington's Disease. Front Neurol 6:177

    PubMed  PubMed Central  Google Scholar 

  32. Gruber D, Kuhn AA, Schoenecker T, Kopp UA, Kivi A, Huebl J, Lobsien E, Mueller B, Schneider GH, Kupsch A (2014) Quadruple deep brain stimulation in Huntington's disease, targeting pallidum and subthalamic nucleus: case report and review of the literature. J Neural Transm (Vienna, Austria 1996) 121:1303–1312

  33. Loutfi G, Linder J, Hariz G-M, Hariz M, Blomstedt P (2014) Pallidal deep brain stimulation in the treatment of Huntington's chorea. Brain Disord Therapy. https://doi.org/10.4172/2168-975X.1000136

    Article  Google Scholar 

  34. López-Sendón Moreno JL, García-Caldentey J, Regidor I, del Álamo M, García de Yébenes J (2014) A 5-year follow-up of deep brain stimulation in Huntington's disease. Parkinsonism Relat Disord 20:260–261

    PubMed  Google Scholar 

  35. Mason SL, Wijeyekoon R, Swain R, Ho AK, Smith EL, Sahakian B, Barker RA (2010) Cognitive follow up of a small cohort of Huntington's disease patients over a 5 year period. PLoS Curr 2:RRN1174

  36. Salthouse TA, Schroeder DH, Ferrer E (2004) Estimating retest effects in longitudinal assessments of cognitive functioning in adults between 18 and 60 years of age. Dev Psychol 40:813–822

    PubMed  Google Scholar 

  37. Stout JC, Queller S, Baker KN, Cowlishaw S, Sampaio C, Fitzer-Attas C, Borowsky B (2014) HD-CAB: a cognitive assessment battery for clinical trials in Huntington's disease 1,2,3. Mov Disord 29:1281–1288

    PubMed  Google Scholar 

  38. Stout JC, Glikmann-Johnston Y, Andrews SC (2016) Cognitive assessment strategies in Huntington's disease research. J Neurosci Methods 265:19–24

    PubMed  Google Scholar 

  39. Schramm C, Katsahian S, Youssov K, Démonet JF, Krystkowiak P, Supiot F, Verny C, Cleret de Langavant L, Bachoud-Lévi AC (2015) How to Capitalize on the Retest Effect in Future Trials on Huntington's Disease. PLoS ONE 10:e0145842

    PubMed  PubMed Central  Google Scholar 

  40. Beglinger LJ, Adams WH, Fiedorowicz JG, Duff K, Langbehn D, Biglan K, Caviness J, Olson B, Paulsen JS (2015) Practice effects and stability of neuropsychological and UHDRS tests over short retest intervals in Huntington Disease. J Huntington's Dis 4:251–260

    CAS  Google Scholar 

  41. Julayanont P, McFarland NR, Heilman KM (2020) Mild cognitive impairment and dementia in motor manifest Huntington's disease: classification and prevalence. J Neurol Sci 408:116523

    PubMed  Google Scholar 

  42. Chaganti SS, McCusker EA, Loy CT (2017) What do we know about Late Onset Huntington's Disease? J Huntington's Dis 6:95–103

    Google Scholar 

  43. Baake V, Reijntjes R, Dumas EM, Thompson JC, Roos RAC (2017) Cognitive decline in Huntington's disease expansion gene carriers. Cortex 95:51–62

    PubMed  Google Scholar 

  44. Huntington Study G (2006) Tetrabenazine as antichorea therapy in Huntington disease: a randomized controlled trial. Neurology 66:366–372

    Google Scholar 

  45. Tedroff J, Waters S, Barker RA, Roos R, Squitieri F, Group ERS (2015) Antidopaminergic medication is associated with more rapidly progressive Huntington's Disease. J Huntington's Dis 4:131–140

  46. Unti E, Mazzucchi S, Palermo G, Bonuccelli U, Ceravolo R (2017) Antipsychotic drugs in Huntington's disease. Expert Rev Neurother 17:227–237

    CAS  PubMed  Google Scholar 

  47. Hart EP, Marinus J, Burgunder JM, Bentivoglio AR, Craufurd D, Reilmann R, Saft C, Roos RA (2013) Better global and cognitive functioning in choreatic versus hypokinetic-rigid Huntington's disease. Mov Disord 28:1142–1145

    PubMed  Google Scholar 

  48. Jacobs M, Hart EP, van Zwet EW, Bentivoglio AR, Burgunder JM, Craufurd D, Reilmann R, Saft C, Roos RA (2016) Progression of motor subtypes in Huntington's disease: a 6-year follow-up study. J Neurol 263:2080–2085

    CAS  PubMed  PubMed Central  Google Scholar 

  49. Hart EP, Dumas EM, Schoonderbeek A, Wolthuis SC, van Zwet EW, Roos RA (2014) Motor dysfunction influence on executive functioning in manifest and premanifest Huntington's disease. Mov Disord 29:320–326

    PubMed  Google Scholar 

  50. Hart EP, Dumas EM, Giltay EJ, Middelkoop HA, Roos RA (2013) Cognition in Huntington's disease in manifest, premanifest and converting gene carriers over ten years. J Huntington's Dis 2:137–147

    Google Scholar 

  51. Carlozzi NE, Tulsky DS (2013) Identification of health-related quality of life (HRQOL) issues relevant to individuals with Huntington disease. J Health Psychol 18:212–225

    PubMed  Google Scholar 

  52. Ho AK, Gilbert AS, Mason SL, Goodman AO, Barker RA (2009) Health-related quality of life in Huntington's disease: which factors matter most? Mov Disord 24:574–578

    PubMed  Google Scholar 

  53. Delorme C, Rogers A, Lau B, Francisque H, Welter ML, Vidal SF, Yelnik J, Durr A, Grabli D, Karachi C (2016) Deep brain stimulation of the internal pallidum in Huntington's disease patients: clinical outcome and neuronal firing patterns. J Neurol 263:290–298

    PubMed  Google Scholar 

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Funding

This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.

Author information

Affiliations

  1. Unité Pathologies Cérébrales Résistantes, Département de Neurochirurgie, Institut génomique Fonctionnelle, Hôpital Gui de Chauliac, INSERM, CNRS, Univ Montpellier, CHU Montpellier, 80 Avenue Augustin Fliche, 34 295, Montpellier Cedex 5, France

    Emily Sanrey, Victoria Gonzalez, Laura Cif, Fabienne Cyprien, Emilie Chan Seng, Philippe Coubes & Gaetan Poulen

  2. Unité de Recherche Sur Les Mouvements Et Comportements Anormaux, Montpellier, France

    Emily Sanrey, Victoria Gonzalez, Laura Cif, Fabienne Cyprien, Emilie Chan Seng, Philippe Coubes & Gaetan Poulen

  3. Clinical Research and Epidemiology Unit, CHU Montpellier, Univ Montpellier, Montpellier, France

    Valérie Macioce

Authors
  1. Emily Sanrey
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  2. Valérie Macioce
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  3. Victoria Gonzalez
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  4. Laura Cif
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  6. Emilie Chan Seng
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  7. Philippe Coubes
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Corresponding author

Correspondence to Emily Sanrey.

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Conflicts of interest

The authors declare that they have no conflict of interest.

Ethics approval

This study was approved by the local ethic committee (IRB).

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Consent was obtained from the patients and/or legal representative for participating in the study.

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Data will be available upon reasonable request.

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415_2020_10206_MOESM1_ESM.pdf

Additional file1 (PDF 41 kb) ESM_1. Stimulation settings at each time point during the five years follow-up period and at last follow-up. Electrode E1 is in the ventral part of motor GPi; E2 is in the dorsal part, verified on intra-operative stereotactic MRI. E1 is first tested, then E2, then both. Pulse width is adapted in every patient given GPi volume but reference pulse width is 450. Frequency is constantly 130HZ

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Sanrey, E., Macioce, V., Gonzalez, V. et al. Does pallidal neuromodulation influence cognitive decline in Huntington’s disease?. J Neurol 268, 613–622 (2021). https://doi.org/10.1007/s00415-020-10206-w

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  • DOI: https://doi.org/10.1007/s00415-020-10206-w

Keywords

  • Huntington’s disease
  • Cognitive decline
  • Continuous electrical neuromodulation
  • Longitudinal follow-up