Parkinson disease and related disorders part - part 1 ppsx

In 1987, he was appointed Professor and Chairman of Neurology at the University of Kansas Medical Center, where he remained until 1999, when he moved to the University of Miami and becam

William C Koller, MD, PhD 1945–2005

William C Koller died unexpectedly on October 3, 2005, in Chapel Hill, North Carolina, while this volume, which he was co-editing, was in preparation Bill was born in Milwau-kee on July 12, 1945, where he graduated with a BS degree from Marquette University in

1968 He went on to Northwestern University in Chicago, where he received a Masters degree in pharmacology in 1971, a PhD in pharmacology in 1974, and an MD in 1976 After completing his internship and residency at Rush Presbyterian St Luke’s Medical Center in Chicago, he held positions at the Rush Medical College, University of Illinois, Chicago VA, Hines VA, and Loyola University In 1987, he was appointed Professor and Chairman of Neurology at the University of Kansas Medical Center, where he remained until 1999, when he moved to the University of Miami and became the National Research Director for the National Parkinson Foundation He subsequently moved on to direct the Movement Disorders clinical program at the Mount Sinai Medical Center in New York, and then to the University of North Carolina, where he laid the foundation for yet another superb clinical and academic program

Bill was a world-renowned neurologist who specialized in Parkinson’s disease, essential tremor and related disorders He published more than 270 peer-reviewed manuscripts, over 160 review papers and numerous books His research interests included the epidemiology and experimental therapeutics of parkinsonism and essential tremor, and his work contributed enormously to the current treatment of these disorders His collaborations were worldwide and many current experts in movement disorders worked with him at one time or another He was

a Fellow of the American Academy of Neurology, Treasurer of the Movement Disorder Society (1999–2000), Executive Board Member of the Parkinson Study Group (1996–1999), President of WE MOVE (2001–2002),

a founding member of the Tremor Research Group and founder of the International Tremor Foundation

Dr Koller will be especially remembered for his humor, warmth and the youthful vigor and enthusiasm that he brought to his work He was the consummate physician, befriending many of his patients who were encouraged to call him on his cell phone at any time Whether lecturing in South America, fishing on the boat he shared with several colleagues, traveling with one of his sons to an international meeting or seeing patients in the clinic, Bill’s smile and the sparkle in his eye endeared him to all who knew him The movement disorders community has lost

a valued colleague, mentor and friend He is survived by his wife and three sons

Kelly Lyons Matthew B Stern

Photo courtesy of Professor Lindsey and

the European Parkinson’s Disease Association.

TheHandbook of Clinical Neurology was started by Pierre Vinken and George Bruyn in the 1960s and continued under their stewardship until the second series concluded in 2002 This is the fifth volume in the new (third) ser-ies, for which we have assumed editorial responsibility The series covers advances in clinical neurology and the neurosciences and includes a number of new topics In order to provide insight to physiological and pathogenic mechanisms and a basis for new therapeutic strategies for neurological disorders, we have specifically ensured that the neurobiological aspects of the nervous system in health and disease are covered During the last quar-ter-century, dramatic advances in the clinical and basic neurosciences have occurred, and those findings related

to the subject matter of individual volumes are emphasized in them The series will be available electronically

on Elsevier’s Science Direct site, as well as in print form It is our hope that this will make it more accessible

to readers and also facilitate searches for specific information

The present volume deals with Parkinson’s disease and related disorders This group of disorders constitutes one of the most common of neurodegenerative disorders and is assuming even greater importance with the aging

of the population in developed countries The volume has been edited by Professor William Koller (USA) and Professor Eldad Melamed (Israel) It is with particular sadness that we must record the sudden and untimely death

of Professor Koller while the volume was coming to fruition An experienced clinician, neuroscientist, author and editor, he was a friend of many of the contributors to this volume, as well as of the series editors, and we shall greatly miss him It is our hope that he would have been proud of this volume, which he did so much to craft

As series editors, we reviewed all of the chapters in the volume and made suggestions for improvement, but we were delighted that the volume editors had produced such a scholarly and comprehensive account of the parkin-sonian disorders, which should appeal to clinicians and neuroscientists alike When the Handbook series was initiated in the 1960s, understanding of these disorders was poor, any genetic basis of them was speculative, sev-eral of the syndromes described here had not even been recognized, the prognosis was bleak and the therapeutic options were almost unchanged since the late Victorian era Advances in understanding of the biochemical back-ground of parkinsonism during the 1960s and early 1970s led to dramatic pharmacological advances in the man-agement of Parkinson’s disease and profoundly altered the approach to other degenerative disorders of the nervous system The pace of advances in the field has continued, and the exciting new insights being gained have man-dated a need for a thorough but critical appraisal of recent developments so that future investigative approaches and therapeutic strategies are based on a solid foundation, the limits of our knowledge are clearly defined and

an account is provided for practitioners of the clinical features and management of the various neurological dis-orders that present with parkinsonism

It has been a source of great satisfaction to us that two such eminent colleagues as the late William Koller and Professor Eldad Melamed agreed to serve as volume editors and have produced such an important compendium, and we thank them and the contributing authors for all their efforts We also thank the editorial staff of the pub-lisher, Elsevier B.V., and especially Ms Lynn Watt and Mr Michael Parkinson in Edinburgh for overseeing all stages in the preparation of this volume

Michael J Aminoff Franc¸ois Boller Dick F Swaab

James Parkinson described Parkinson’s disease in his memorableEssay on the Shaking Palsy in 1817 Since then, and particularly in recent years, there has been tremendous progress in our understanding of this complex and fas-cinating neurological disorder Briefly, we have learned that it is not only manifest by motor symptoms but also that there is a whole range of non-motor features, including autonomic, psychiatric, cognitive and sensory impair-ments We now know how to distinguish better clinically between Parkinson’s disease and the various parkinso-nian syndromes Likewise, it is now well established that in this disorder not only the substantia nigra but many other central as well as peripheral neuronal cell populations are involved Novel diagnostic imaging technologies have become available The nature of the Lewy body, the intracytoplasmic inclusion body that is a characteristic element of Parkinson’s disease pathology, is being unraveled

There are new insights in the etiology and pathogenesis of this illness Experimental models are now available

to understand better modes of neuronal cell death and help develop new therapeutic approaches There has been dramatic progress in discovering the genetic causes of dominant and recessive forms of hereditary Parkinson’s dis-ease with the identification of mutations in several genes There is new knowledge in the intricate circuitry of the basal ganglia and the physiology of the connections in the healthy state and in Parkinson’s disease There is more understanding of the role of dopamine and other neurotransmitters in the control and regulation of movement by the brain

All of the above led to the development of many novel pharmacological treatments to improve the motor as well as non-motor phenomena There is better understanding of the mechanisms responsible for the complications caused by long-term levodopa administration Futuristic approaches using deep brain stimulation with electrodes implanted in anatomically strategic central nervous system sites are now in common use to improve basic symp-toms and the side-effects of levodopa therapy Potentially effective neuroprotective strategies are in development

to modify and slow disease progression Likewise, cell replacement therapy with stem cells offers great promise The best of experts in the field joined in this book and contributed chapters that make up an exciting coverage

of all the exhilarating developments in the many aspects of Parkinson’s disease This volume will certainly expand the current knowledge of its readers and it is also hoped that it will stimulate further research that will eventually lead to finding both the cause and the cure of this common and disabling neurological disorder

William C Koller Eldad Melamed

Dr William Koller died suddenly, unexpectedly and prematurely on October 3, 2005, before this volume went to press His loss is painful to all his friends and colleagues His leadership, wisdom and expertise were the main driving force behind the creation of this very special book It is the belief of all involved that Dr Koller would have been pleased and proud of this volume in its final form We hope it will be a tribute to his memory

List of contributors

L Alvarez

Movement Disorders Unit, Centro Internacional

de Restauracio´n Neurolo´gica (CIREN), La Habana,

Cuba

M Baker

European Parkinson’s Disease Association (EPDA),

Sevenoaks, Kent, UK

Y Balash

Movement Disorders Unit, Department of

Neurology, Tel-Aviv Sourasky Medical Center,

Tel-Aviv, Israel

E R Bauminger

Racah Institute of Physics, Hebrew University,

Jerusalem, Israel

M F Beal

Department of Neurology and Neuroscience, Weill

Medical College of Cornell University, New York,

NY, USA

P J Be´dard

Centre de Recherche en Neurosciences, CHUL,

Faculte´ de Me´dicine, Universite´ Laval, Quebec,

Canada

A Berardelli

Department of Neurological Sciences and

Neuromed Institute, Universita` La Sapienza,

Rome, Italy

R Betarbet

Department of Neurology, Emory University, Atlanta,

GA, USA

K P Bhatia

Sobell Department of Motor Neuroscience

and Movement Disorders, Institute of Neurology,

University College London,

London, UK

R Bhidayasiri The Parkinson’s and Movement Disorder Institute, Fountain Valley, CA, USA

R E Breeze Department of Neurosurgery, University of Colorado School of Medicine, Denver, CO, USA

C Brefel-Courbon Department of Clinical Pharmacology, Clinical Investigation Centre and Department of Neurosciences, University Hospital, Toulouse, France

D J Brooks MRC Clinical Sciences Centre and Division of Neuroscience and Mental Health, Imperial College London, Hammersmith Hospital, London, UK

R E Burke Departments of Neurology and Pathology, Columbia University, New York, NY, USA

D J Burn Institute of Ageing and Health, University of Newcastle upon Tyne, Newcastle upon Tyne, UK

M G Cerso´simo Program of Parkinson’s Disease and Other Movement Disorders, Hospital de Clı´nicas, University of Buenos Aires, Buenos Aires, Argentina

A Chade The Parkinson’s Institute, Sunnyvale, CA, USA

K R Chaudhuri Regional Movement Disorders Unit, King’s College Hospital, London, UK

Y Chen Morris K Udall Parkinson’s Disease Research Center

of Excellence, University of Kentucky College of Medicine, Lexington, KY, USA

Contents of Part I

Obituary vi

Foreword vii

Preface ix

List of contributors xi

1 Anatomy and physiology of the basal ganglia:

Thomas Wichmann and Mahlon R DeLong (Atlanta, GA, USA)

Pershia Samadi, Claude Rouillard, Paul J B
edard and Th
erese Di Paolo (Quebec, Canada)

Alfredo Berardelli (Rome, Italy)

Richard B Mailman and Xuemei Huang (Chapel Hill, NC, USA)

Jennifer G Goldman and Christopher G Goetz (Chicago, IL, USA)

Meike Kasten, Annabel Chade and Caroline M Tanner (Sunnyvale, CA, USA)

Jayaraman Rao (New Orleans, LA, USA)

Daniel P Perl (New York, NY, USA)

Yoshikuni Mizuno, Nobutaka Hattori and Hideki Mochizuki (Tokyo, Japan)

David J Brooks (London, UK)

Section 1

Scientific foundation

Chapter 2 Functional neurochemistry of the basal ganglia

PERSHIA SAMADI 1,2 , CLAUDE ROUILLARD 2, PAUL J BE´ DARD 2

AND THE´ RE` SE DI PAOLO 1

*

1

Centre de Recherche en Endocrinologie Mole´culaire et Oncologique, CHUL, Faculte´ de Pharmacie, and

2 Centre de Recherche en Neurosciences, CHUL, Faculte´ de Me´dicine,

Universite´ Laval, Que´bec, Canada

Proper execution of voluntary movements results from

the correct processing of feedback loops involving the

cortex, thalamus and basal ganglia (BG) The BG

include a subset of subcortical structures involved in a

variety of processes including motor behavior and also

motor learning and memory process (Graybiel et al.,

1994; Graybiel, 1998; Packard and Knowlton, 2002)

The BG are located in the basal telencephalon and

consist of interconnected structures.The dorsal division

of the BG is associated with motor and associative

func-tions and consists of the striatum, including the caudate

nucleus and putamen; the globus pallidus or pallidum

which comprises the internal (GPi) and external (GPe)

regions; the subthalamic nucleus (STN); and the

substan-tia nigra divided into two main parts, the pars compacta

(SNc) and pars reticulata (SNr).The ventral division of

the BG is associated with limbic functions and consists

of the ventral striatum and nucleus accumbens, the

ven-tral pallidum and venven-tral tegmental area (Blandini et al.,

2000; Bolam et al., 2000; Parent et al., 2000)

2.1 Functional basal ganglia circuit

The striatum, the input structure of the BG, receives

two major inputs:

1 a massive excitatory glutamatergic projection from

most areas of the cerebral cortex organized in a

highly topographical manner, and

2 a dopaminergic projection from the SNc (Parent

et al., 1995b, 2000; Smith et al., 1998; Bolam

et al., 2000)

The striatum also receives glutamatergic inputs from

the amygdala, the hippocampus and the centromedian–

parafascicular thalamic complex (Parent et al., 2000; Smith et al., 2004) and serotoninergic afferents from the raphe and caudal linear nuclei (Parent et al., 1995b; Blandini et al., 2000) In addition, the activity

of the BG components in controlling movements is modulated by the pedunculopontine nucleus (PPN) (Delwaide et al., 2000; Parent et al., 2000)

The mammalian striatum has two anatomical com-partments: the striosomes (patches) and the matrix with distinct chemical compositions and connections (Graybiel et al., 2000; Prensa and Parent, 2001; Lev-esque et al., 2004) High densities ofm opioid receptor

binding and low levels of acetylcholinesterase staining define striosomes, while the matrix has high levels of the Ca2þ-binding protein, calbindin (Graybiel and Ragsdale, 1978) Striosomes express a higher density

of gamma-aminobutyric acid (GABA)Areceptor com-pared to the matrix (Waldvogel et al., 1999) The areas

of cortex associated with the limbic system innervate striosomes whereas the neocortical inputs to the matrix originate from the association and sensorimotor cor-tices, which innervate medial and lateral parts of the striatum, respectively (Graybiel et al., 2000) It has been suggested that the balance of activity between the matrix and striosomal compartments has an impor-tant role in the modulation of BG motor functions (Graybiel et al., 2000)

The principal output nuclei of the BG are SNr and GPi (Parent and Hazrati, 1995a, b; Parent et al.,

2000) These nuclei, SNr and GPi, tonically inhibit the ventral anterior and ventral lateral (VA/VL) motor nuclei of the thalamus, thereby reducing excitatory thalamic innervation of cortical motor areas (Alexander

*Correspondence to: Dr The´ re` se Di Paolo, Molecular Endocrinology and Oncology Research Center, Laval University Medical Center (CHUL), 2705 Laurier Boulevard, Que´ bec PQ, G1V 4G2, Canada E-mail: therese.dipaolo@crchul.ulaval.ca, Tel: 418-654-2296; Fax: 418-654-2761

Parkinson’s disease and related disorders, Part I

W.C Koller, E Melamed, Editors

# 2007 Elsevier B.V All rights reserved

Corticostriatal Nerve terminal

Glutamate

Dopamine

Endogenous opioids

Endogenous opioids Opioid receptor

Opioid

receptor

Adenosine

NMDA

receptor

cAMP signaling cascade

Ca 2+

ATP

ATP cAMP

cAMP

-D 2

Gs

+

-+

-Protein kinase activation

CREB-P Fos-P

Motor behavior

IEG Short term responses

LOG Long-term adaptive responses

DARPP-32 phosphorylation PP-1 inhibition

-Corticostriatal Nerve terminal

Protein kinase activation

Synaptic vesicle Synaptic

vesicle

CREB-P Fos-P

Motor behavior

Glutamate Acetylcholine

M2 or M3 mACh receptor

Opioid receptor

Adenosine

NMDA receptor

IEG Short term responses

LOG Long-term adaptive responses

DARPP-32 phosphorylation PP-1 inhibition

cAMP signaling cascade

Ca 2+

ATP

ATP cAMP

cAMP

-D1 Gs

A1

receptor

Gi Ac

striato

-Acetylcholine

M2 or M3

mACh receptor

M1 mACh receptor

-Ca2+

PP-2B

-+

PP-2B

-+

M1 mACh receptor

mOpioid receptor

Gi Ac

Ac