Our first decade of experience in deep brain stimulation of the brainstem: elucidating the mechanism of action of stimulation of the ventrolateral pontine tegmentum
- 361 Downloads
The region of the pedunculopontine tegmental nucleus (PPTg) has been proposed as a novel target for deep brain stimulation (DBS) to treat levodopa resistant symptoms in motor disorders. Recently, the anatomical organization of the brainstem has been revised and four new distinct structures have been represented in the ventrolateral pontine tegmentum area in which the PPTg was previously identified. Given this anatomical reassessment, and considering the increasing of our experience, in this paper we revisit the value of DBS applied to that area. The reappraisal of clinical outcomes in the light of this revisitation may also help to understand the consequences of DBS applied to structures located in the ventrolateral pontine tegmentum, apart from the PPTg. The implantation of 39 leads in 32 patients suffering from Parkinson’s disease (PD, 27 patients) and progressive supranuclear palsy (PSP, four patients) allowed us to reach two major conclusions. The first is that the results of the advancement of our technique in brainstem DBS matches the revision of brainstem anatomy. The second is that anatomical and functional aspects of our findings may help to explain how DBS acts when applied in the brainstem and to identify the differences when it is applied either in the brainstem or in the subthalamic nucleus. Finally, in this paper we discuss how the loss of neurons in brainstem nuclei occurring in both PD and PSP, the results of intraoperative recording of somatosensory evoked potentials, and the improvement of postural control during DBS point toward the potential role of ascending sensory pathways and/or other structures in mediating the effects of DBS applied in the ventrolateral pontine tegmentum region.
KeywordsDeep brain stimulation Ventrolateral pontine tegmentum Pedunculopontine tegmental nucleus Parkinson’s disease Atypical parkinsonisms Somatosensory evoked potentials
The authors wish to thank Prof. Edgar Garcia-Rill for his critical reading of the manuscript and suggestions. We are also grateful to Prof Francesco Masedu and Dr. Annamaria Capozzo, University of L’Aquila, for evaluating data and carrying out statistics concerning correlations between SEPs and anatomical landmarks, and Prof. Paolo Arena, DIEEI, University of Catania, for evaluating the electrical fields generated by DBS.
Compliance with ethical standards
Conflict of interest
The authors declare no conflicts of interest.
Ethical standard statement
All the procedures described in the present paper have been conducted according to ethical standards, approved by local ethical committees and patients gave their informed consent to participate to the described studies.
- Ferraye MU, Debu B, Fraix V, Goetz L, Ardouin C, Yelnik J, Henry-Lagrange C, Seigneuret E, Piallat B, Krack P, Le Bas JF, Benabid AL, Chabardes S, Pollak P (2010) Effects of pedunculopontine nucleus area stimulation on gait disorders in Parkinson’s disease. Brain 133:205–214CrossRefPubMedGoogle Scholar
- Garcia-Rill E (2015) Waking and the reticular activating system in health and disease. Elsevier-Academic Press, AmsterdamGoogle Scholar
- Khan S, Javed S, Mooney L, White P, Plaha P, Whone A, Gill SS (2012) Clinical outcomes from bilateral versus unilateral stimulation of the pedunculopontine nucleus with and without concomitant caudal zona incerta region stimulation in Parkinson’s disease. Br J Neurosurg 26:722–725CrossRefPubMedGoogle Scholar
- Krauthamer GM, Grunwerg BS, Krein H (1995) Putative cholinergic neurons of the pedunculopontine tegmental nucleus projecting to the superior colliculus consist of sensory responsive and unresponsive populations which are functionally distinct from other mesopontine neurons. Neuroscience 69:507–517CrossRefPubMedGoogle Scholar
- Mazzone P, Stanzione P, Lozano A, Sposato S, Scarnati E, Stefani A (2005a) Brain stimulation and movement disorders: Where are we going? In: Meglio M (ed) Proceedings of the 14th meeting of the World Society for Stereotactic and Functional Neurosurgery (WSSFN) Monduzzi, Bologna, ItalyGoogle Scholar
- Mazzone P, Sposato S, Insola A, Scarnati E (2013) The clinical effects of deep brain stimulation of the pedunculopontine tegmental nucleus in movement disorders may not be related to the anatomical target, leads location, and setup of electrical stimulation. Neurosurgery 73:894–906CrossRefPubMedGoogle Scholar
- Olszewski J, Baxter D (1954) Cytoarchitecture of the human brainstem. Lippincott, PhiladelphiaGoogle Scholar
- Paxinos G, Huang XF (1995) Atlas of the human brainstem. Academic Press, San DiegoGoogle Scholar
- Pierantozzi M, Palmieri MG, Galati S, Stanzione P, Peppe A, Tropepi D, Brusa L, Pisani A, Moschella V, Marciani MG, Mazzone P, Stefani A (2008) Pedunculopontine nucleus deep brain stimulation changes spinal cord excitability in Parkinson’s disease patients. J Neural Transm 115:731–735CrossRefPubMedGoogle Scholar
- Schaltenbrand G, Wahren W (1977) Atlas for stereotaxy of the human brain. Thieme, New YorkGoogle Scholar
- Schrader C, Seehaus F, Capelle HH, Windhagen A, Windhagen H, Krauss JK (2013) Effects of pedunculopontine area and pallidal DBS on gait ignition in Parkinson’s disease. Brain StimulGoogle Scholar
- Takakusaki K, Habaguchi T, Ohtinata-Sugimoto J, Saitoh K, Sakamoto T (2003) Basal ganglia efferents to the brainstem centers controlling postural muscle tone and locomotion: a new concept for understanding motor disorders in basal ganglia dysfunction. Neuroscience 119:293–308CrossRefPubMedGoogle Scholar
- Talairach J, David M, Tornoux P, Korredor H, Kvasina T (1957) Atlas d’anatomie stereotaxique des noyaux gris centraux. Masson, ParisGoogle Scholar
- Tjernstrom F, Bjorklund M, Malmstrom EM (2014) Romberg ratio in quiet stance posturography-test to retest reliability. Gait PostureGoogle Scholar
- Welter ML, Demain A, Ewenczyk C, Czernecki V, Lau B, El HA, Belaid H, Yelnik J, Francois C, Bardinet E, Karachi C, Grabli D (2015) PPNa-DBS for gait and balance disorders in Parkinson’s disease: a double-blind, randomised study. J NeurolGoogle Scholar