A Primer of Neuroimmunological Disease

211 Pages·2012·3.736 MB·English

by  Andrew R. Pachner (auth.)

A Primer of Neuroimmunological
Disease

Andrew R. Pachner
A Primer
of Neuroimmunological
Disease
Andrew R. Pachner
Department of Neurology and Neuroscience
New Jersey Medical School
University of Medicine and Dentistry of New Jersey
Newark, NJ, USA
ISBN 978-1-4614-2187-0 e-ISBN 978-1-4614-2188-7
DOI 10.1007/978-1-4614-2188-7
Springer New York Dordrecht Heidelberg London
Library of Congress Control Number: 2012930829
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Preface
Neuroimmunologists deal with the nervous system and the immune system,
both of which are giant, complex communication networks. One would think
that we would be excellent communicators ourselves, but we have not com-
municated well with individuals outside our fi eld. This is very unfortunate
because the fi eld of neuroimmunology is more dependent than most on input
from fi elds outside its own. Researchers in basic neuroscience, basic immu-
nology, clinical neurology (to name just a few) have much to contribute and
these contributions would be enhanced if those researchers had a better under-
standing of neuroimmunology. This book is an attempt to provide a basic
understanding of some of the neuroimmunological diseases to individuals
who are not neuroimmunologists.
Who should use this book? I have lofty ambitions for this book in that
I think it can be helpful to a large number of people, such as basic scientists
in both neuroscience and immunology, neurologists, and motivated individu-
als in pharmaceutical companies who are neither PhDs nor MDs. Like Icarus,
who had to navigate a path not too close to the sun nor too close to the sea,
I tried to be basic enough to be understood by neophytes yet having enough
depth so that it would not lose the attention of more-educated readers. Time
will tell whether I succeeded.
Why now? There are many reasons. One reason is that the most common
neuroimmunological disease, multiple sclerosis, covered in fi ve chapters in
this book, is attracting increasing interest from pharmaceutical companies as
a therapeutic target. “Unmet need” is an understatement when it comes to
improving our therapy of this prevalent disabling disease of the young.
Another reason for the need now for this book is that there has been a para-
digm shift in our understanding of the immune response within the nervous
system. Far from being an “immune-privileged” tissue, haughtily excluding
itself from any immune functions, the nervous system is actively involved in
immune responses; it is simply that it participates using its own rules which
are actively being researched but remain to be fully elucidated. A third reason
for the need for this book is that increasingly, diseases thought to have a
“degenerative” etiology, such as stroke or Alzheimer’s, have a component
related to the immune system. This subdivision within neuroimmunology, dis-
cussed briefl y in Chap. 15 , will likely grow substantially in the near future.
How could I possibly cover neurology, immunology, neuroimmunology, and
neuroimmunological disease in a short book? The short answer is that I can’t.
v
vi Preface
However, this is a primer, not a complete textbook. It will help the reader most as
an introduction, and as a guide to what areas to pursue in the literature. It is cus-
tomary for an author to lament about how large his subject is, and how many
corners needed to be cut, and I will certainly adhere to the custom. But I tried to
make the fi eld of neuroimmunology understandable to a wide audience without
being too lengthy.
Have I been too cynical about the state of our knowledge and the effi cacy
of available therapy? One of the physicians in the fi eld who reviewed some of
the chapters thought so. He felt I was “riding roughshod” and being too
“ curmudgeonly” and wished me to “explain the various drugs with great
enthusiasm.” I apologize to him, and to those who wanted this book to be
more upbeat. I did not intend to have any part of the book interpreted in a way
that in any way is negative about the fi eld of neuroimmunology or those prac-
ticing this subspecialty. I have been a neuroimmunologist for 30 years and
love the fi eld and the people who work in it. However, I also adhere to the
tenet, “primum non nocere” (the fi rst rule is to do no harm), and I feel that the
benefi t/risk considerations should be clearly weighted toward benefi t prior to
recommending a therapy. Unfortunately, the trend in the fi eld is to move in
the other direction, toward therapies that are increasingly risky with question-
able benefi t to show for it. It is possible that in a future of evidence-based
medicine and increasing accountability, we will have better tools to measure
benefi t/risk ratios in order to avoid major side effects and to maximize
benefi t.
What’s in the future for neuroimmunology? I see the partnership between
basic neuroscience and neuroimmunology becoming stronger, and advances
in our understanding leading to further major advances in diagnosis and ther-
apy. We will benefi t from advances toward neuroprotective therapies in other
parts of neuroscience to provide clues to ameliorate neurodegeneration in
neuroimmunological diseases. Ultimately, our understanding of MS will
increase and we will identify more and more effective therapies. From my
mouth to God’s ears…
I could not have written this book without a great deal of help. Steve
Kamin, the chairman of our department of neurology at UMDNJ—New
Jersey Medical School, was very supportive and allowed me to take sabbati-
cal time. Susan Goelz, Lew Fredane, David Lagunoff, Norm Kachuk, Steve
Kamin, and Stuart Selonick edited chapters, and aligned my frequently mud-
dled efforts. The staff at Springer were extremely helpful, especially Andy
Kwan and Richard Lansing. My daughter, Anna, helped considerably with
image issues. And of course my long-suffering wife, Barbara, who had to put
up with my periods of both mania and depression, was always there for
emotional support.
Newark, NJ, USA Andrew R. Pachner
Acknowledgments
Acknowledgments for Helpful Discussions and Providing Material
Special thanks to Susan Goelz, Lew Fredane, Norm Kachuk, Steve Kamin,
David Lagunoff, and Stuart Selonick who patiently read through the tortured
prose of early versions and made much-needed recommendations.
Jack Antel
Klaus Bendtzen
Joe Berger
Bruce Cohen
Nicolas Collongues
Kathy Conant
Gary Cutter
Martin Daumer
Peter Dyck
Florian Eichler
Patricia Fitzgerald-Bocarsley
John Foley
Doug Green
Ken Gorson
Wayne Hogrefe
Doug Jeffrey
Dimetrios Karussis
Susumu Kusunoki
Norman Latov
Hans Lassman
Vanda Lennon
Howard Lipton
Bob Lisak
Michael Lockshin
Christina Marra
Jennifer Michaels
Jana Preiningerova
Harry Prince
Kotil Rammohan
John Richert
David Richman
vii
viii Acknowledgments
Moses Rodriguez
Myrna Rosenfeld
Walter Royal
Subraminam Sriram
Israel Steiner
Carlo Tornatore
Helen Tremlett
Ken Tyler
Angela Vincent
Brian Weinshenker
Hugh Willison
Gil Wolfe
Robert Yu
Special thanks to my wife, Barbara, who patiently tolerated my idiosyncrasies, and to my daughter,
Anna, who assisted me with getting images ready for the book. Thanks also to Richard Lansing,
my editor, who made my fi rst experience as an author of a single-author text a pleasant one.
Contents
1 Immunology for the Non-immunologist ...................................... 1
1 The Beginnings of Immunology ............................................... 1
2 The Components of the Healthy Immune Response ................. 2
2.1 White Blood Cells ............................................................ 4
2.2 Molecules ......................................................................... 8
References ....................................................................................... 13
2 Neurology for the Non-neurologist .............................................. 15
1 Organization of the Nervous System ........................................ 15
1.1 Electrical Nature: Nerve Transmission
and Neurotransmitters ...................................................... 15
1.2 Cells of the Nervous System ............................................ 16
1.3 Structure of the Nervous System: CNS, PNS,
Upper and Lower Motor Neurons .................................... 18
2 The Neurological Evaluation .................................................... 21
2.1 Neurological Examination ............................................... 21
2.2 Imaging of the Nervous System ....................................... 22
2.3 EEG and EMG ................................................................. 23
References ....................................................................................... 24
3 Neuroimmunology for the Non-neuroimmunologist .................. 25
1 The Beginnings of Neuroimmunology: Post-vaccinial
Encephalomyelitis ..................................................................... 25
2 Semple Rabies Vaccine Autoimmune Encephalomyelitis:
Temporal Progression. Interplay Between the Nervous
and Immune Systems ................................................................ 29
2.1 Stage 1. DAY 0: Exposure to the Antigen ....................... 29
2.2 Stage 2. Days 0–7: Lymph Node Drainage
and Processing of Antigen in Peripheral
Lymph Node ..................................................................... 29
2.3 Stage 3. Days 7–10: Recruitment of Myelin-Specifi c
Lymphocytes into the CNS .............................................. 30
2.4 Stage 4. Days 10–20: Maximal Infl ammation
with Involvement of Local CNS Immunity,
Including Cervical Lymph Nodes .................................... 30
2.5 Stage 5. Days 20 and Later: Recovery ............................. 31
ix
x Contents
3 The Tools of the Neuroimmunologist ....................................... 31
4 Aspects of Infl ammation in Neuroimmunology Unique
to the Nervous System .............................................................. 32
5 The Necessity for Great Care in Classifying
a Neuroimmunological Disease as “Autoimmune” .................. 33
6 The Importance of Antibodies .................................................. 34
References ....................................................................................... 35
4 The Prototypic Neuroimmunological CNS Disease:
Multiple Sclerosis, a Precis .......................................................... 37
1 Defi nition .................................................................................. 37
2 Etiopathogenesis ....................................................................... 37
3 Pathology .................................................................................. 38
4 Genetics and Epidemiology ...................................................... 39
5 Clinical Manifestations ............................................................. 39
5.1 Initial Symptoms .............................................................. 39
5.2 The MS Attack ................................................................. 40
6 Natural History and Prognosis .................................................. 42
7 MS Clinical Classifi cations ....................................................... 43
7.1 “Form of MS” .................................................................. 44
7.2 Disability .......................................................................... 45
7.3 Activity............................................................................. 45
7.4 Severity ............................................................................ 46
References ....................................................................................... 46
5 Multiple Sclerosis: Diagnosis ....................................................... 49
1 History and Examination .......................................................... 50
2 Laboratory Findings .................................................................. 51
2.1 Routine Studies: Blood, Urine, Chest X-Ray .................. 51
2.2 CNS Imaging ................................................................... 51
2.3 Cerebrospinal Fluid Analysis ........................................... 54
References ....................................................................................... 55
6 Multiple Sclerosis Mimics ............................................................ 57
1 Cerebrovascular Disease/Stroke................................................ 58
2 Neurological Infections ............................................................. 60
2.1 HIV .................................................................................. 60
2.2 Neurosyphilis ................................................................... 60
2.3 Neurocysticercosis ........................................................... 61
2.4 Lyme Disease ................................................................... 61
2.5 Tropical Spastic Paraparesis ............................................ 61
2.6 Tuberculosis ..................................................................... 61
2.7 Brain Abscess ................................................................... 62
3 NMO ......................................................................................... 62
4 ADEM ....................................................................................... 63
5 Leukodystrophies ...................................................................... 63