The Deep Brain Stimulation of the Pedunculopontine Tegmental Nucleus

Objective. The aim of the present study was to describe the surgical and clinical outcomes of the implantation and stimulation of the pedunculopontine tegmental nucleus in humans. Materials and Methods. Fourteen patients affected by movement disorders (12 Parkinson's disease and 2 progressive supranuclear palsy) underwent surgery for bilateral or monolateral implantation of stimulating electrodes in the pedunculopontine tegmental nucleus. The correct placement of electrodes was established and verified by combining angio‐CT scans with magnetic resonance imaging. Intraoperative and postoperative evaluations were made to assess the clinical effectiveness of stimulation according to different Unified Parkinson's Disease Rating Scale items and neurophysiologic parameters. Results. No major complications occurred following the insertion of electrodes into the pedunculopontine tegmental nucleus. Neuroimaging showed that the electrode contacts were always correctly placed below the ponto‐mesencephalic line. Stimulation of the pedunculopontine tegmental nucleus improved gait, posture, and speech, and modulated reflexes integrated at spinal or pontine levels. Conclusions. The surgical targeting of the pedunculopontine tegmental nucleus requires a careful adaptation of the traditional stereotactic approaches owing to the high variability of brainstem anatomy from one patient to another. The insertion of the leads in the pedunculopontine tegmental nucleus as well as their activation did not appear to induce serious adverse effects. The correct positioning of stimulating electrodes in pontine structures such as the pedunculopontine nucleus may be ascertained not only through neuroimaging techniques but also through clinical neurophysiology. The evolution of the surgical planning that we have developed emphasizes the limited value of single‐unit recordings to identify the pedunculopontine tegmental nucleus and highlights the opportunities offered by functional evaluations of neurophysiologic parameters. As far as the clinical efficacy is concerned, our data suggest a promising outcome for simultaneous implantations of different basal ganglia nuclei in Parkinsonian and in progressive supranuclear palsy patients as well.

[1]  J. Rothwell,et al.  The startle reflex, voluntary movement, and the reticulospinal tract. , 2006, Supplements to Clinical neurophysiology.

[2]  E. Garcia-Rill,et al.  Arousal mechanisms related to posture and locomotion: 1. Descending modulation. , 2004, Progress in brain research.

[3]  B. W. Peterson,et al.  Reticulospinal connections with limb and axial motoneurons , 1979, Experimental Brain Research.

[4]  P. Stanzione,et al.  Peripeduncular and pedunculopontine nuclei: a dispute on a clinically relevant target. , 2007, Neuroreport.

[5]  E. Garcia-Rill The pedunculopontine nucleus , 1991, Progress in Neurobiology.

[6]  A. Benabid,et al.  Bilateral subthalamic nucleus stimulation for severe Parkinson's disease , 1995, Movement disorders : official journal of the Movement Disorder Society.

[7]  Trevor Drew,et al.  Locomotor role of the corticoreticular-reticulospinal-spinal interneuronal system. , 2004, Progress in brain research.

[8]  F. Afshar,et al.  A three-dimensional reconstruction of the human brain stem. , 1982, Journal of neurosurgery.

[9]  A M Graybiel,et al.  The afferent and efferent connections of the feline nucleus tegmenti pedunculopontinus, pars compacta , 1983, The Journal of comparative neurology.

[10]  S. Salamat,et al.  Atlas of the Human Brainstem , 1997 .

[11]  R. Miall,et al.  Pedunculopontine nucleus stimulation improves akinesia in a Parkinsonian monkey , 2004, Neuroreport.

[12]  P. Stanzione,et al.  Implantation of human pedunculopontine nucleus: a safe and clinically relevant target in Parkinson's disease , 2005, Neuroreport.

[13]  J Kohyama,et al.  Medullary reticulospinal tract mediating a generalized motor inhibition in cats: iii. functional organization of spinal interneurons in the lower lumbar segments , 2003, Neuroscience.

[14]  J. Stein,et al.  Pedunculopontine nucleus: a new target for deep brain stimulation for akinesia. , 2005, Neuroreport.

[15]  The pedunculopontine nucleus and related structures. Functional organization. , 1997, Advances in neurology.

[16]  P. Winn,et al.  Experimental studies of pedunculopontine functions: are they motor, sensory or integrative? , 2008, Parkinsonism & related disorders.

[17]  Stanley N Cohen,et al.  Midbrain Ataxia: Possible Role of the Pedunculopontine Nucleus in Human Locomotion , 2003, Cerebrovascular Diseases.

[18]  Kaoru Takakusaki,et al.  Forebrain control of locomotor behaviors , 2008, Brain Research Reviews.

[19]  P. Stanzione,et al.  Bilateral deep brain stimulation of the pedunculopontine and subthalamic nuclei in severe Parkinson's disease. , 2007, Brain : a journal of neurology.

[20]  P. Pahapill,et al.  The pedunculopontine nucleus and Parkinson's disease. , 2000, Brain : a journal of neurology.

[21]  S. Skodda,et al.  Speech rate and rhythm in Parkinson's disease , 2008, Movement disorders : official journal of the Movement Disorder Society.

[22]  E. Garcia-Rill,et al.  Pedunculopontine stimulation induces prolonged activation of pontine reticular neurons , 2001, Neuroscience.

[23]  Jérôme Yelnik,et al.  PPN or PPD, what is the target for deep brain stimulation in Parkinson's disease? , 2007, Brain : a journal of neurology.

[24]  Roongroj Bhidayasiri,et al.  Midbrain ataxia: an introduction to the mesencephalic locomotor region and the pedunculopontine nucleus. , 2005, AJR. American journal of roentgenology.

[25]  C. Saper,et al.  Medullary and spinal efferents of the pedunculopontine tegmental nucleus and adjacent mesopontine tegmentum in the rat , 1988, The Journal of comparative neurology.

[26]  J Kohyama,et al.  Changes in the excitability of hindlimb motoneurons during muscular atonia induced by stimulating the pedunculopontine tegmental nucleus in cats , 2004, Neuroscience.

[27]  K. Saitoh,et al.  Medullary reticulospinal tract mediating the generalized motor inhibition in cats: II. Functional organization within the medullary reticular formation with respect to postsynaptic inhibition of forelimb and hindlimb motoneurons , 2002, Neuroscience.

[28]  J. Dostrovsky,et al.  The Globus Pallidus, Deep Brain Stimulation, and Parkinson's Disease , 2002, The Neuroscientist : a review journal bringing neurobiology, neurology and psychiatry.

[29]  M. Hariz,et al.  The peripeduncular nucleus: a novel target for deep brain stimulation? , 2007, Neuroreport.

[30]  Ludvic Zrinzo,et al.  The pedunculopontine and peripeduncular nuclei: a tale of two structures. , 2007, Brain : a journal of neurology.

[31]  A. Benabid,et al.  Electrical stimulation of the subthalamic nucleus in advanced Parkinson's disease. , 1998, The New England journal of medicine.

[32]  P. Winn How best to consider the structure and function of the pedunculopontine tegmental nucleus: Evidence from animal studies , 2006, Journal of the Neurological Sciences.

[33]  K. Mewes,et al.  The subthalamic nucleus in Parkinson's disease: somatotopic organization and physiological characteristics. , 2001, Brain : a journal of neurology.

[34]  S. Datta,et al.  Excitation of the brain stem pedunculopontine tegmentum cholinergic cells induces wakefulness and REM sleep. , 1997, Journal of neurophysiology.

[35]  Tipu Z. Aziz,et al.  Topography of cortical and subcortical connections of the human pedunculopontine and subthalamic nuclei , 2007, NeuroImage.

[36]  J. Stein,et al.  Pedunculopontine nucleus electric stimulation alleviates akinesia independently of dopaminergic mechanisms , 2006, Neuroreport.

[37]  K. Saitoh,et al.  Basal ganglia efferents to the brainstem centers controlling postural muscle tone and locomotion: a new concept for understanding motor disorders in basal ganglia dysfunction , 2003, Neuroscience.

[38]  M. Aramideh,et al.  Brainstem reflexes: Electrodiagnostic techniques, physiology, normative data, and clinical applications , 2002, Muscle & nerve.

[39]  A. Parent,et al.  Pedunculopontine nucleus in the squirrel monkey: Projections to the basal ganglia as revealed by anterograde tract‐tracing methods , 1994, The Journal of comparative neurology.

[40]  K. Saitoh,et al.  Evidence for a role of basal ganglia in the regulation of rapid eye movement sleep by electrical and chemical stimulation for the pedunculopontine tegmental nucleus and the substantia nigra pars reticulata in decerebrate cats , 2004, Neuroscience.

[41]  Antonio Oliviero,et al.  Bilateral Implantation in Globus Pallidus Internus and in Subthalamic Nucleus in Parkinson's Disease , 2005, Neuromodulation : journal of the International Neuromodulation Society.

[42]  E Garcia-Rill,et al.  Locomotor projections from the pedunculopontine nucleus to the medioventral medulla. , 1990, Neuroreport.

[43]  A. Morel,et al.  Single-unit analysis of the pallidum, thalamus and subthalamic nucleus in parkinsonian patients , 2000, Neuroscience.

[44]  Clement Hamani,et al.  Pedunculopontine nucleus microelectrode recordings in movement disorder patients , 2008, Experimental Brain Research.

[45]  M. Hallett,et al.  Practice Parameter: Treatment of Parkinson disease with motor fluctuations and dyskinesia (an evidence-based review): Report of the Quality Standards Subcommittee of the American Academy of Neurology , 2006, Neurology.

[46]  P. Torterolo,et al.  GABAergic mechanisms in the pedunculopontine tegmental nucleus of the cat promote active (REM) sleep , 2002, Brain Research.

[47]  M. Hariz,et al.  Stereotactic localization of the human pedunculopontine nucleus: atlas-based coordinates and validation of a magnetic resonance imaging protocol for direct localization. , 2008, Brain : a journal of neurology.

[48]  Á. Esteban A neurophysiological approach to brainstem reflexes. Blink reflex , 1999, Neurophysiologie Clinique/Clinical Neurophysiology.

[49]  P. Delwaide,et al.  Projections from basal ganglia to tegmentum: a subcortical route for explaining the pathophysiology of Parkinson’s disease signs? , 2000, Journal of Neurology.

[50]  E. Scarnati,et al.  Short-latency excitation of hindlimb motoneurons induced by electrical stimulation of the pontomesencephalic tegmentum in the rat , 1994, Neuroscience Letters.

[51]  A. Stefani,et al.  Bilateral Implantation of Centromedian‐Parafascicularis Complex and GPi: A New Combination of Unconventional Targets for Deep Brain Stimulation in Severe Parkinson Disease , 2006, Neuromodulation : journal of the International Neuromodulation Society.

[52]  G. Schaltenbrand,et al.  Atlas for Stereotaxy of the Human Brain , 1977 .

[53]  J. D. Boyd,et al.  Cytoarchitecture of the Human Brain Stem , 1955 .

[54]  S. Zanini,et al.  Language recovery following subthalamic nucleus stimulation in Parkinson's disease , 2003, Neuroreport.

[55]  E. S. Watkins,et al.  Stereotaxic atlas of the human brainstem and cerebellar nuclei : a variability study , 1978 .

[56]  P. Winn Frontal syndrome as a consequence of lesions in the pedunculopontine tegmental nucleus: A short theoretical review , 1998, Brain Research Bulletin.

[57]  J. Obeso,et al.  Bilateral deep brain stimulation in Parkinson's disease: a multicentre study with 4 years follow-up. , 2005, Brain : a journal of neurology.

[58]  S. Gill,et al.  Bilateral deep brain stimulation of the pedunculopontine nucleus for Parkinson's disease , 2005, Neuroreport.

[59]  C. Saper,et al.  Pedunculopontine tegmental nucleus of the rat: Cytoarchitecture, cytochemistry, and some extrapyramidal connections of the mesopontine tegmentum , 1987, The Journal of comparative neurology.

[60]  S. Gill,et al.  A Magnetic Resonance Imaging–Directed Method for Transventricular Targeting of Midline Structures for Deep Brain Stimulation Using Implantable Guide Tubes , 2010, Neurosurgery.

[61]  J. Stein,et al.  Connectivity of the human pedunculopontine nucleus region and diffusion tensor imaging in surgical targeting. , 2007, Journal of neurosurgery.

[62]  E Garcia-Rill,et al.  Locomotor projections from the pedunculopontine nucleus to the spinal cord. , 1990, Neuroreport.

[63]  J. Paul Bolam,et al.  Pedunculopontine nucleus and basal ganglia: distant relatives or part of the same family? , 2004, Trends in Neurosciences.

[64]  Cytoarchitecture of the Human Brain Stem , 1954, Neurology.

[65]  S. Mori,et al.  Medullary reticulospinal tract mediating the generalized motor inhibition in cats: Parallel inhibitory mechanisms acting on motoneurons and on interneuronal transmission in reflex pathways , 2001, Neuroscience.