Journal of Neural Transmission

, Volume 121, Issue 10, pp 1303–1312 | Cite as

Quadruple deep brain stimulation in Huntington’s disease, targeting pallidum and subthalamic nucleus: case report and review of the literature

  • D. GruberEmail author
  • A. A. Kuhn
  • T. Schoenecker
  • U. A. Kopp
  • A. Kivi
  • J. Huebl
  • E. Lobsien
  • B. Mueller
  • G.-H. Schneider
  • A. Kupsch
Neurology and Preclinical Neurological Studies - Original Article


Deep brain stimulation (DBS) represents an established treatment option in a growing number of movement disorders. Recent case reports suggest beneficial effect of globus pallidus internus (GPi)-DBS in selected patients suffering from Huntington’s disease with marked disabling chorea. We present a 41-year-old man with genetically confirmed HD following quadruple GPi- and subthalamic nucleus (STN)-DBS. Motor function was assessed by Abnormal Involuntary Movement Scale (AIMS) and by Unified Huntington Disease Rating Scale (UHDRS) presurgery and postsurgery for up to 4 years. Furthermore, cognitive, neuropsychiatric state and quality of life (QoL) including life satisfaction (QLS) were annually evaluated. Chorea assessed by AIMS and UHDRS subscores improved by 52 and 55 %, 45 and 60 %, 35 and 45 % and 55–66 % at 1–4 years, respectively, compared to presurgical state following GPi–STN-DBS. During these time periods bradykinesia did not increase following separate STN- and combined GPi–STN-DBS compared to presurgical state. Mood, QoL and QLS were ameliorated. However, dysexecutive symptoms increased at 4 years postsurgery. The present case report suggests that bilateral GPi- and STN-DBS may represent a new treatment avenue in selected HD patients. Clinically, GPi-DBS attenuated chorea and was associated with a larger effect–adverse effect window compared to STN-DBS. However, GPi-DBS-induced bradykinesia may emerge as one main limitation of GPi-DBS in HD. Thus, quadruple GPi–STN-DBS may be indicated, if separate GPi-DBS does not result in sufficient control of motor symptoms. Future controlled studies need to confirm if the present anecdotal observation of additive beneficial effects of GPi- and STN-DBS in a HD patient with severe generalized chorea and relatively intact cognitive and affective functions indeed represents a new therapeutic option.


Huntington disease Deep brain stimulation Globus pallidus Subthalamic nucleus Chorea 



This research received no specific grant from any funding agency in the public, commercial or not-for-profit sectors except for partial support of AKu’s research by DFG KFO 247 DBS Berlin, KU 810-1. We thank Dr. Klaus Kopitzki, University of Magdeburg, for help calculating the MRI-based stereotactic coordinates.

Conflict of interest

DG, AKi, GHS, BM received speaker’s honoraria from Medtronic. AAK received honoraries from Medtronic, St. Jude Medical, Boston Scientific, Novartis, Bayer AG and support for travel to conferences by Ipsen Pharma. JH received speaker’s honoraria from Merz Pharmaceuticals. AKu received honoraria for speaking from Allergan, Boehringer Ingelheim, Ipsen Pharma, Lundbeck, Medtronic, Merck, Merz Pharmaceuticals, Orion, St. Jude, UCB and grant support from German Research Council & German Ministry of Education and Research. TS, EL, UAK reported no conflict of interest.

Supplementary material

702_2014_1201_MOESM1_ESM.docx (134 kb)
Supplementary material 1 (DOCX 133 kb)

Part I: Presurgical clip with the patient (HD) in resting and sitting position; gait and postural stability are separately assessed. Part II-IV: One–3 years postsurgery following GPi–STN-DBS in resting and sitting position; gait and postural stability are separately assessed. Note that bradykinesia increased in comparison to preoperative state. Part V: 4 years postsurgery a) GPi–STN-DBS OFF in resting, sitting and lying position, HD patient is unable to stand; b) GPi–STN-DBS ON in resting and sitting position; gait and postural stability are separately assessed. Note that bradykinesia increased in comparison to preoperative state. (M4V 16915 kb)


  1. Adam OR, Jankovic J (2008) Symptomatic treatment of Huntington disease. Neurotherapeutics 5(2):181–197. doi: 10.1016/j.nurt.2008.01.008 PubMedCrossRefGoogle Scholar
  2. Armstrong MJ, Miyasaki JM (2012) Evidence-based guideline: pharmacologic treatment of chorea in Huntington disease: report of the guideline development subcommittee of the American Academy of Neurology. Neurology 79(6):597–603. doi: 10.1212/WNL.0b013e318263c443 PubMedCrossRefPubMedCentralGoogle Scholar
  3. 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(1):130–132. doi: 10.3171/JNS/2008/109/7/0130 PubMedCrossRefGoogle Scholar
  4. Bonelli RM, Niederwieser G, Diez J, Gruber A, Koltringer P (2002) Pramipexole ameliorates neurologic and psychiatric symptoms in a Westphal variant of Huntington’s disease. Clin Neuropharmacol 25(1):58–60PubMedCrossRefGoogle Scholar
  5. Brierley J, Larcher V (2009) Compassionate and innovative treatments in children: a proposal for an ethical framework. Arch Dis Child 94(9):651–654. doi: 10.1136/adc.2008.155317 PubMedCrossRefGoogle Scholar
  6. Cislaghi G, Capiluppi E, Saleh C, Romano L, Servello D, Mariani C, Porta M (2013) Bilateral globus pallidus stimulation in Westphal variant of Huntington disease. Neuromodulation. doi: 10.1111/ner.12098 PubMedGoogle Scholar
  7. DeLong MR, Wichmann T (2007) Circuits and circuit disorders of the basal ganglia. Arch Neurol 64(1):20–24. doi: 10.1001/archneur.64.1.20 PubMedCrossRefGoogle Scholar
  8. Edwards TC, Zrinzo L, Limousin P, Foltynie T (2011) Deep brain stimulation in the treatment of chorea. Mov Disord 27(3):357–363. doi: 10.1002/mds.23967 PubMedCrossRefGoogle Scholar
  9. 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(9):1289–1292. doi: 10.1002/mds.22116 PubMedCrossRefGoogle Scholar
  10. Follett KA, Weaver FM, Stern M, Hur K, Harris CL, Luo P, Marks WJ Jr, Rothlind J, Sagher O, Moy C, Pahwa R, Burchiel K, Hogarth P, Lai EC, Duda JE, Holloway K, Samii A, Horn S, Bronstein JM, Stoner G, Starr PA, Simpson R, Baltuch G, De Salles A, Huang GD, Reda DJ (2010) Pallidal versus subthalamic deep-brain stimulation for Parkinson’s disease. N Engl J Med 362(22):2077–2091. doi: 10.1056/NEJMoa0907083 PubMedCrossRefGoogle Scholar
  11. Gallay MN, Jeanmonod D, Liu J, Morel A (2008) Human pallidothalamic and cerebellothalamic tracts: anatomical basis for functional stereotactic neurosurgery. Brain Struct Funct 212(6):443–463. doi: 10.1007/s00429-007-0170-0 PubMedCrossRefPubMedCentralGoogle Scholar
  12. Halbig TD, Gruber D, Kopp UA, Schneider GH, Trottenberg T, Kupsch A (2005) Pallidal stimulation in dystonia: effects on cognition, mood, and quality of life. J Neurol Neurosurg Psychiatry 76(12):1713–1716PubMedCrossRefPubMedCentralGoogle Scholar
  13. 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(2):E383. doi: 10.1227/01.NEU.0000195068.19801.18 discussion E383PubMedCrossRefGoogle Scholar
  14. Herzog J, Pinsker M, Wasner M, Steigerwald F, Wailke S, Deuschl G, Volkmann J (2007) Stimulation of subthalamic fibre tracts reduces dyskinesias in STN-DBS. Mov Disord 22(5):679–684. doi: 10.1002/mds.21387 PubMedCrossRefGoogle Scholar
  15. Ho AK, Sahakian BJ, Brown RG, Barker RA, Hodges JR, Ane 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(12):1702–1706PubMedCrossRefGoogle Scholar
  16. Huebl J, Schoenecker T, Siegert S, Brucke C, Schneider GH, Kupsch A, Yarrow K, Kuhn AA (2011) Modulation of subthalamic alpha activity to emotional stimuli correlates with depressive symptoms in Parkinson’s disease1. Mov Disord 26(3):477–483. doi: 10.1002/mds.23515 PubMedCrossRefGoogle Scholar
  17. Huys D, Bartsch C, Poppe P, Lenartz D, Huff W, Prutting J, Timmermann L, Klosterkotter J, Maarouf M, Rommel T, Hartmann A, Sturm V, Kuhn J (2013) Management and outcome of pallidal deep brain stimulation in severe Huntington’s disease. Fortschr Neurol Psychiatr 81(4):202–205. doi: 10.1055/s-0033-1335097 PubMedCrossRefGoogle Scholar
  18. 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(3):272–277. doi: 10.1136/jnnp.2009.202903 PubMedCrossRefGoogle Scholar
  19. Krauth A, Blanc R, Poveda A, Jeanmonod D, Morel A, Szekely G (2010) A mean three-dimensional atlas of the human thalamus: generation from multiple histological data. Neuroimage 49(3):2053–2062. doi: 10.1016/j.neuroimage.2009.10.042 PubMedCrossRefGoogle Scholar
  20. Kupsch A, Benecke R, Muller J, Trottenberg T, Schneider GH, Poewe W, Eisner W, Wolters A, Muller JU, Deuschl G, Pinsker MO, Skogseid IM, Roeste GK, Vollmer-Haase J, Brentrup A, Krause M, Tronnier V, Schnitzler A, Voges J, Nikkhah G, Vesper J, Naumann M, Volkmann J (2006) Pallidal deep-brain stimulation in primary generalized or segmental dystonia. N Engl J Med 355(19):1978–1990PubMedCrossRefGoogle Scholar
  21. Ligot N, Krystkowiak P, Simonin C, Goldman S, Peigneux P, Van Naemen J, Monclus M, Lacroix SF, Devos D, Dujardin K, Delmaire C, Bardinet E, Delval A, Delliaux M, Defebvre L, Yelnik J, Blond S, Destee A, De Tiege X (2011) External globus pallidus stimulation modulates brain connectivity in Huntington’s disease. J Cereb Blood Flow Metab 31(1):41–46. doi: 10.1038/jcbfm.2010.186 PubMedCrossRefPubMedCentralGoogle Scholar
  22. Meissner W, Harnack D, Reese R, Paul G, Reum T, Ansorge M, Kusserow H, Winter C, Morgenstern R, Kupsch A (2003) High-frequency stimulation of the subthalamic nucleus enhances striatal dopamine release and metabolism in rats. J Neurochem 85(3):601–609PubMedCrossRefGoogle Scholar
  23. Moreau C, Defebvre L, Destee A, Bleuse S, Clement F, Blatt JL, Krystkowiak P, Devos D (2008) STN-DBS frequency effects on freezing of gait in advanced Parkinson disease. Neurology 71(2):80–84. doi: 10.1212/01.wnl.0000303972.16279.46 PubMedCrossRefGoogle Scholar
  24. 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(2):290–294. doi: 10.1002/ana.20183 PubMedCrossRefGoogle Scholar
  25. Munetz MR, Benjamin S (1988) How to examine patients using the Abnormal Involuntary Movement Scale. Hosp Community Psychiatry 39(11):1172–1177PubMedGoogle Scholar
  26. Odekerken VJ, van Laar T, Staal MJ, Mosch A, Hoffmann CF, Nijssen PC, Beute GN, van Vugt JP, Lenders MW, Contarino MF, Mink MS, Bour LJ, van den Munckhof P, Schmand BA, de Haan RJ, Schuurman PR, de Bie RM (2013) Subthalamic nucleus versus globus pallidus bilateral deep brain stimulation for advanced Parkinson’s disease (NSTAPS study): a randomised controlled trial. Lancet Neurol 12(1):37–44. doi: 10.1016/S1474-4422(12)70264-8 PubMedCrossRefGoogle Scholar
  27. Ostrem JL, Racine CA, Glass GA, Grace JK, Volz MM, Heath SL, Starr PA (2011) Subthalamic nucleus deep brain stimulation in primary cervical dystonia. Neurology 76(10):870–878. doi: 10.1212/WNL.0b013e31820f2e4f PubMedCrossRefGoogle Scholar
  28. Quinn N, Brown R, Craufurd D, Goldman S, Hodges J, Kieburtz K, Lindvall O, MacMillan J, Roos R (1996) Core assessment program for intracerebral transplantation in Huntington’s Disease (CAPIT-HD). Mov Disord 11(2):143–150. doi: 10.1002/mds.870110205 PubMedCrossRefGoogle Scholar
  29. Racette BA, Perlmutter JS (1998) Levodopa responsive parkinsonism in an adult with Huntington’s disease. J Neurol Neurosurg Psychiatry 65(4):577–579PubMedCrossRefPubMedCentralGoogle Scholar
  30. Reuter I, Hu MT, Andrews TC, Brooks DJ, Clough C, Chaudhuri KR (2000) Late onset levodopa responsive Huntington’s disease with minimal chorea masquerading as Parkinson plus syndrome. J Neurol Neurosurg Psychiatry 68(2):238–241PubMedCrossRefPubMedCentralGoogle Scholar
  31. Saint-Cyr JA, Trepanier LL, Kumar R, Lozano AM, Lang AE (2000) Neuropsychological consequences of chronic bilateral stimulation of the subthalamic nucleus in Parkinson’s disease. Brain 123(Pt 10):2091–2108PubMedCrossRefGoogle Scholar
  32. Schjerling L, Hjermind LE, Jespersen B, Madsen FF, Brennum J, Jensen SR, Lokkegaard A, Karlsborg M (2013) A randomized double-blind crossover trial comparing subthalamic and pallidal deep brain stimulation for dystonia. J Neurosurg 119(6):1537–1545. doi: 10.3171/2013.8.JNS13844 PubMedCrossRefGoogle Scholar
  33. Schonecker T, Kupsch A, Kuhn AA, Schneider GH, Hoffmann KT (2009) Automated optimization of subcortical cerebral mr imaging-atlas coregistration for improved postoperative electrode localization in deep brain stimulation. AJNR Am J Neuroradiol. doi: 10.3174/ajnr.A1741 PubMedGoogle Scholar
  34. Schuepbach WM, Rau J, Knudsen K, Volkmann J, Krack P, Timmermann L, Halbig TD, Hesekamp H, Navarro SM, Meier N, Falk D, Mehdorn M, Paschen S, Maarouf M, Barbe MT, Fink GR, Kupsch A, Gruber D, Schneider GH, Seigneuret E, Kistner A, Chaynes P, Ory-Magne F, Brefel Courbon C, Vesper J, Schnitzler A, Wojtecki L, Houeto JL, Bataille B, Maltete D, Damier P, Raoul S, Sixel-Doering F, Hellwig D, Gharabaghi A, Kruger R, Pinsker MO, Amtage F, Regis JM, Witjas T, Thobois S, Mertens P, Kloss M, Hartmann A, Oertel WH, Post B, Speelman H, Agid Y, Schade-Brittinger C, Deuschl G (2013) Neurostimulation for Parkinson’s disease with early motor complications. N Engl J Med 368(7):610–622. doi: 10.1056/NEJMoa1205158 PubMedCrossRefGoogle Scholar
  35. Spielberger S, Hotter A, Wolf E, Eisner W, Muller J, Poewe W, Seppi K (2012) Deep brain stimulation in Huntington’s disease: A 4-year follow-up case report. Mov Disord 27(6):806–807. doi: 10.1002/mds.24959 author reply 807-808PubMedCrossRefGoogle Scholar
  36. Volkmann J, Allert N, Voges J, Sturm V, Schnitzler A, Freund HJ (2004) Long-term results of bilateral pallidal stimulation in Parkinson’s disease. Ann Neurol 55(6):871–875. doi: 10.1002/ana.20091 PubMedCrossRefGoogle Scholar
  37. Volkmann J, Daniels C, Witt K (2010) Neuropsychiatric effects of subthalamic neurostimulation in Parkinson disease. Nat Rev Neurol 6(9):487–498. doi: 10.1038/nrneurol.2010.111 PubMedGoogle Scholar
  38. Volkmann J, Wolters A, Kupsch A, Muller J, Kuhn AA, Schneider GH, Poewe W, Hering S, Eisner W, Muller JU, Deuschl G, Pinsker MO, Skogseid IM, Roeste GK, Krause M, Tronnier V, Schnitzler A, Voges J, Nikkhah G, Vesper J, Classen J, Naumann M, Benecke R (2012) Pallidal deep brain stimulation in patients with primary generalised or segmental dystonia: 5-year follow-up of a randomised trial. Lancet Neurol 11(12):1029–1038. doi: 10.1016/S1474-4422(12)70257-0 PubMedCrossRefGoogle Scholar

Copyright information

© Springer-Verlag Wien 2014

Authors and Affiliations

  • D. Gruber
    • 1
    • 2
    Email author
  • A. A. Kuhn
    • 1
  • T. Schoenecker
    • 1
  • U. A. Kopp
    • 1
  • A. Kivi
    • 1
    • 3
  • J. Huebl
    • 1
  • E. Lobsien
    • 1
    • 4
  • B. Mueller
    • 1
    • 3
  • G.-H. Schneider
    • 5
  • A. Kupsch
    • 1
    • 6
  1. 1.Department of NeurologyCharité-University Medicine BerlinBerlinGermany
  2. 2.Movement Disorders ClinicBeelitz-HeilstättenGermany
  3. 3.Department of NeurologyVivantes Klinikum SpandauBerlinGermany
  4. 4.Department of NeurologyHelios Klinikum ErfurtErfurtGermany
  5. 5.Department of NeurosurgeryCharité-University Medicine BerlinBerlinGermany
  6. 6.Department of Neurology and Stereotactic NeurosurgeryOtto-von-Guericke-UniversityMagdeburgGermany

Personalised recommendations