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Understanding the human pedunculopontine nucleus in Parkinson’s disease

  • Neurology and Preclinical Neurological Studies - Original Article
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Abstract

This paper presents the Brisbane experience of pedunculopontine nucleus (PPN) deep brain stimulation (DBS) in Parkinson’s disease (PD). Clinical outcomes along with studies of the mechanisms and neurophysiology of PPN in PD patients with severe freezing of gait (FoG) and postural imbalance (PI) are summarised and presented. Our results indicate that PPN DBS improves FoG and falls in the relatively uncommon group of PD patients who respond well to medication other than for continuing on time FoG and falls. Our studies indicate that bilateral DBS is more beneficial than unilateral DBS, and that the more caudal region of the PPN seems preferable for stimulation. There is evidence that rapid-release programs for initiation and correction of gait and posture are modulated by the PPN, possibly to some extent independently of the cerebral cortex. These functions were found to be impaired in PD patients with severe FoG/PI, but to some extent corrected by bilateral PPN DBS.

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References

  • Acar F, Acar G, Bir LS, Gedik B, Oguzhanoglu A (2011) Deep brain stimulation of the pedunculopontine nucleus in a patient with freezing of gait. Stereotact Funct Neurosurg 89(4):214–219

    Article  PubMed  Google Scholar 

  • Almeida QJ, Lebold CA (2010) Freezing of gait in Parkinson’s disease: a perceptual cause for a motor impairment? J Neurol Neurosurg Psychiatry 81(5):513–518

    Article  CAS  PubMed  Google Scholar 

  • Chee R, Murphy A, Danoudis M, Georgiou-Karistianis N, Iansek R (2009) Gait freezing in Parkinson’s disease and the stride length sequence effect interaction. Brain. 132(Pt 8):2151–2160

    Article  PubMed  Google Scholar 

  • Deuschl G, Schade-Brittinger C, Krack P, Volkmann J, Schafer H, Botzel K et al (2006) A randomized trial of deep-brain stimulation for Parkinson’s disease. N Engl J Med 355(9):896–908

    Article  CAS  PubMed  Google Scholar 

  • Espay AJ, Fasano A, van Nuenen BF, Payne MM, Snijders AH, Bloem BR (2012) “On” state freezing of gait in Parkinson disease: a paradoxical levodopa-induced complication. Neurology. 78(7):454–457

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Ferraye MU, Debu B, Fraix V, Goetz L, Ardouin C, Yelnik J et al (2010) Effects of pedunculopontine nucleus area stimulation on gait disorders in Parkinson’s disease. Brain 133(Pt 1):205–214

    Article  CAS  PubMed  Google Scholar 

  • Fytagoridis A, Sandvik U, Astrom M, Bergenheim T, Blomstedt P (2012) Long term follow-up of deep brain stimulation of the caudal zona incerta for essential tremor. J Neurol Neurosurg Psychiatry 83(3):258–262

    Article  PubMed  Google Scholar 

  • Garcia-Rill E (1991) The pedunculopontine nucleus. Prog Neurobiol 36(5):363–389

    Article  CAS  PubMed  Google Scholar 

  • Garcia-Rill E, Skinner RD, Fitzgerald JA (1983) Activity in the mesencephalic locomotor region during locomotion. Exp Neurol 82(3):609–622

    Article  CAS  PubMed  Google Scholar 

  • Hely MA, Reid WG, Adena MA, Halliday GM, Morris JG (2008) The Sydney multicenter study of Parkinson’s disease: the inevitability of dementia at 20 years. Mov Disord 23(6):837–844

    Article  PubMed  Google Scholar 

  • Jenkinson N, Nandi D, Miall RC, Stein JF, Aziz TZ (2004) Pedunculopontine nucleus stimulation improves akinesia in a Parkinsonian monkey. NeuroReport 15(17):2621–2624

    Article  PubMed  Google Scholar 

  • Jenkinson N, Nandi D, Muthusamy K, Ray NJ, Gregory R, Stein JF et al (2009) Anatomy, physiology, and pathophysiology of the pedunculopontine nucleus. Mov Disord 24(3):319–328

    Article  PubMed  Google Scholar 

  • Khan S, Mooney L, Plaha P, Javed S, White P, Whone AL et al (2011) Outcomes from stimulation of the caudal zona incerta and pedunculopontine nucleus in patients with Parkinson’s disease. Br J Neurosurg 25:273–280

    Article  PubMed  Google Scholar 

  • Macht M, Kaussner Y, Moller JC, Stiasny-Kolster K, Eggert KM, Kruger HP et al (2007) Predictors of freezing in Parkinson’s disease: a survey of 6,620 patients. Mov Disord 22(7):953–956

    Article  PubMed  Google Scholar 

  • Mazzone P, Lozano A, Stanzione P, Galati S, Scarnati E, Peppe A et al (2005) Implantation of human pedunculopontine nucleus: a safe and clinically relevant target in Parkinson’s disease. NeuroReport 16(17):1877–1881

    Article  PubMed  Google Scholar 

  • Mazzone P, Sposato S, Insola A, Scarnati E (2011) The deep brain stimulation of the pedunculopontine tegmental nucleus: towards a new stereotactic neurosurgery. J Neural Transm 118(10):1431–1451

    Article  PubMed  Google Scholar 

  • Moro E, Hamani C, Poon YY, Al-Khairallah T, Dostrovsky JO, Hutchison WD et al (2010) Unilateral pedunculopontine stimulation improves falls in Parkinson’s disease. Brain. 133(Pt 1):215–224

    Article  PubMed  Google Scholar 

  • Okuma Y (2006) Freezing of gait in Parkinson’s disease. J Neurol 253(Suppl 7):VII27–VII32

    PubMed  Google Scholar 

  • Ostrem JL, Christine CW, Glass GA, Schrock LE, Starr PA (2010) Pedunculopontine nucleus deep brain stimulation in a patient with primary progressive freezing gait disorder. Stereotact Funct Neurosurg 88(1):51–55

    Article  PubMed  Google Scholar 

  • Plaha P, Gill SS (2005) Bilateral deep brain stimulation of the pedunculopontine nucleus for Parkinson’s disease. NeuroReport 16(17):1883–1887

    Article  PubMed  Google Scholar 

  • Schuepbach WM, Rau J, Knudsen K, Volkmann J, Krack P, Timmermann L et al (2013) Neurostimulation for Parkinson’s disease with early motor complications. N Engl J Med 368(7):610–622

    Article  CAS  PubMed  Google Scholar 

  • Stefani A, Lozano AM, Peppe A, Stanzione P, Galati S, Tropepi D et al (2007) Bilateral deep brain stimulation of the pedunculopontine and subthalamic nuclei in severe Parkinson’s disease. Brain 130(Pt 6):1596–1607

    Article  PubMed  Google Scholar 

  • Tattersall TL, Stratton PG, Coyne TJ, Cook R, Silberstein P, Silburn PA et al (2014) Imagined gait modulates neuronal network dynamics in the human pedunculopontine nucleus. Nat Neurosci 17(3):449–454

    Article  CAS  PubMed  Google Scholar 

  • Thevathasan W, Silburn PA, Brooker H, Coyne TJ, Khan S, Gill SS et al (2010) The impact of low-frequency stimulation of the pedunculopontine nucleus region on reaction time in parkinsonism. J Neurol Neurosurg Psychiatry 81(10):1099–1104

    Article  PubMed  Google Scholar 

  • Thevathasan W, Coyne TJ, Hyam JA, Kerr G, Jenkinson N, Aziz TZ et al (2011a) Pedunculopontine nucleus stimulation improves gait freezing in Parkinson disease. Neurosurgery 69(6):1248–1253

    Article  PubMed  Google Scholar 

  • Thevathasan W, Pogosyan A, Hyam JA, Jenkinson N, Bogdanovic M, Coyne TJ et al (2011b) A block to pre-prepared movement in gait freezing, relieved by pedunculopontine nucleus stimulation. Brain 134(Pt 7):2085–2095

    Article  PubMed  PubMed Central  Google Scholar 

  • Thevathasan W, Cole MH, Graepel CL, Hyam JA, Jenkinson N, Brittain JS et al (2012) A spatiotemporal analysis of gait freezing and the impact of pedunculopontine nucleus stimulation. Brain. 135(Pt 5):1446–1454

    Article  PubMed  PubMed Central  Google Scholar 

  • Wilcox RA, Cole MH, Wong D, Coyne T, Silburn P, Kerr G (2011) Pedunculopontine nucleus deep brain stimulation produces sustained improvement in primary progressive freezing of gait. J Neurol Neurosurg Psychiatry 82(11):1256–1259

    Article  PubMed  Google Scholar 

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Correspondence to Terry J. Coyne.

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Fytagoridis, A., Silburn, P.A., Coyne, T.J. et al. Understanding the human pedunculopontine nucleus in Parkinson’s disease. J Neural Transm 123, 769–774 (2016). https://doi.org/10.1007/s00702-016-1505-x

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  • DOI: https://doi.org/10.1007/s00702-016-1505-x

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