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i
Neuroimmunology
ii
What Do I Do Now?
S E R I E S C O -E D ITORS-I N-C HIE F
Lawrence C. Newman, MD
Director of the Headache Division
Professor of Neurology
New York University Langone
New York, New York
Morris Levin, MD
Director of the Headache Center
Professor of Neurology
University of California, San Francisco
San Francisco, California
OT H E R VO L U M E S IN T HE SE RIE S
Headache and Facial Pain
Epilepsy
Neuro-Ophthalmology
Pain
Emergency Neurology
Neuroinfections
Neurogenetics
Neurotology
Pediatric Neurology, Second Edition
Neurocritical Care, Second Edition
Stroke, Second Edition
Peripheral Nerve and Muscle Disease, Second Edition
Cerebrovascular Disease, Second Edition
Movement Disorders, Second Edition
Women’s Neurology
iii
Neuroimmunology
SECOND EDITION
Edited by
Aaron E. Miller, MD
Medical Director
Corinne Goldsmith Dickinson Center for Multiple Sclerosis
Professor and Vice-Chair for Education
Department of Neurology
Icahn School of Medicine at Mount Sinai
New York, NY
Tracy M. DeAngelis, MD
Adjunct Assistant Professor of Neurology
The Mount Sinai Hospital
New York, NY
Michelle Fabian, MD
Assistant Professor of Neurology
New York, NY
Ilana Katz Sand, MD

Assistant Professor of Neurology
Icahn School of Medicine at Mount Sinai
Associate Medical Director
New York, NY
1
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1
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the University’s objective of excellence in research, scholarship, and education
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Press in the UK and certain other countries.
Published in the United States of America by Oxford University Press
198 Madison Avenue, New York, NY 10016, United States of America.
© Oxford University Press 2018
All rights reserved. No part of this publication may be reproduced, stored in
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rights organization. Inquiries concerning reproduction outside the scope of the
above should be sent to the Rights Department, Oxford University Press, at the
address above.
You must not circulate this work in any other form
and you must impose this same condition on any acquirer.
Library of Congress Cataloging-in-Publication Data
Names: Miller, Aaron E., author. | DeAngelis, Tracy M., author. |
Fabian, Michelle, author. | Sand, Ilana Katz, author.
Title: Neuroimmunology / by Aaron E. Miller, Tracy M. DeAngelis,
Michelle Fabian, Ilana Katz Sand. Other titles: What do I do now?
Description: Second edition. | Oxford ; New York : Oxford University Press, [2018] |
Series: What do I do now? | Includes bibliographical references and index.
Identifiers: LCCN 2018009729 | ISBN 9780190693190 (paperback : alk. paper)
Subjects: | MESH: Demyelinating Diseases—diagnosis | Demyelinating
Diseases—therapy | Neurologic Manifestations | Vasculitis, Central
Nervous System | Nervous System—immunology | Case Reports
Classification: LCC QP356.47 | NLM WL 141 | DDC 616.97/8—dc23
LC record available at https://lccn.loc.gov/2018009729
This material is not intended to be, and should not be considered, a substitute for medical or other
professional advice. Treatment for the conditions described in this material is highly dependent on
the individual circumstances. And, while this material is designed to offer accurate information with
respect to the subject matter covered and to be current as of the time it was written, research and
knowledge about medical and health issues is constantly evolving and dose schedules for medications
are being revised continually, with new side effects recognized and accounted for regularly. Readers
must therefore always check the product information and clinical procedures with the most up-to-date
published product information and data sheets provided by the manufacturers and the most recent
codes of conduct and safety regulation. The publisher and the authors make no representations or
warranties to readers, express or implied, as to the accuracy or completeness of this material. Without
limiting the foregoing, the publisher and the authors make no representations or warranties as to the
accuracy or efficacy of the drug dosages mentioned in the material. The authors and the publisher do
not accept, and expressly disclaim, any responsibility for any liability, loss or risk that may be claimed
or incurred as a consequence of the use and/or application of any of the contents of this material.
9 8 7 6 5 4 3 2 1
Printed by Marquis, Canada
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This Book Is Dedicated to
Ellen, whose unwavering support makes everything possible and whose

love makes every day a treasure.
—AEM
To the memory of Dr. Izabella Rozenfeld, dear “Bella,” whose knowledge

and unbridled passion for neurology guide me still.
—TMD
To my mentors, who have given me the priceless gift of their knowledge

and time; and to my patients who have trusted me to share the journey
of illness with them, and who are so much more than a case in a book.
—MTF
To my dad, my first and forever mentor, whom I can always count on for
my “what do I do now?” questions.
—IKS
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vi
Contents
Preface ix
Acknowledgments xi
1 A Case of Monocular Blurred Vision 1

2 A Case of Multifocal Neurological Symptoms 9
3 Irritability in a Man with Multiple Sclerosis 15
4 A Case of Myelitis with a Positive Anticardiolipin Antibody 23
5 A Case of Stiffness in the Legs and Gradual Difficulty

Walking 29
6 Family Matters 35
7 Recurrent Ulcers and a Brainstem Lesion 39
8 Ataxia and Orthostasis 45
9 Blurry Vision, Hearing Loss, and Constant Headache 49
10 The Snowball Effect 55
11 A SREATable Encephalopathy 61
12 A Case of Cognitive Impairment and Ataxia 65
13 A Case of Fever and a Wrist Drop 69
14 Double Vision and Droopy Eyelids 75
15 A Case of Personality Change and Seizure 83
16 Drowsiness and Double Vision 89

17 The One-Sided Encephalitis 93
18 Teratoma: “It’s Driving Me Crazy” 97
19 Gad-Awful Spasms 103
20 On the Right Tract 109
21 A Headache Gone Viral 113
22 To CIDP or Not to CIDP 117
23 Extinguishing a “Burning Fire” 121

vi
24 Confusion, Muscle Cramps, and Weight Loss  127
25 The Unforgettable Encephalitis  133
26 The Peppered Brainstem  139
27 A Case of a Fall After a Trip  143
28 A Case of Relapsing Visual Loss  149
29 Checks and Balances  153
30 A Case of Intractable Vomiting  157
31 A Case of Cognitive Change in HIV  163
32 A Case of Progressive Myelopathy  167
33 A Case of Cranial Neuropathies and Leptomeningeal

Enhancement  173
34 A Case of Diabetes Insipidus and Enhancing Brain

Lesions  177
35 A Case of Optic Neuritis and Leg Weakness  183
36 A Man with Multiple Sclerosis and Continuing Disease Activity

on Disease-Modifying Therapy  189
37 A Case of Syncope and Impaired Micturition  195
38 A Case of Longitudinally Extensive Transverse Myelitis  201
39 A Perplexing Pattern of Weakness  205
40 Progressive Numbness and Tingling  209
Index 215
viii Contents
ix
Preface
In the six years since the publication of the first edition of Neuroimmunology
in the What Do I Do Now? series, novel immunological disorders of the
nervous system have been discovered, and understanding of this fascinating
class of diseases has burgeoned. New therapies based on large clinical trials
for well-known disorders such as MS have proliferated, whereas treatment
for less common disorders remains anecdotal, albeit based on increasing
experience of experts.
In this second expanded edition of Neuroimmunology, our goal remains
to provide a useful framework for clinicians to use when approaching
challenging immune-mediated diseases of both the central and periph-
eral nervous systems. Each chapter begins with a very brief case presenta-
tion, including just enough information to challenge your thinking. The
subsequent discussions focus on localization, differential diagnosis, and
treatment specific to the case and disorder itself. We have presented a range
of conditions, including both those frequently encountered such as mul-
tiple sclerosis and those much more rarely seen, such as several unique au-
toimmune encephalopathies. In MS, the availability of new therapies has
created a variety of scenarios, only a few of which could be presented in this
small volume. Our recommendations for diagnostic testing and therapy
rest, whenever possible, on available current evidence, as reflected in the
updated key references for this edition. Key clinical points are highlighted
in the conclusion of each chapter. In select chapters, tables and figures are
provided to illustrate cardinal teaching points such as diagnostic criteria.
We trust this volume will serve as an accessible and practical tool for
neurologists and other clinicians, both those in practice and those still in
training. We hope it will be an important and useful resource for both
clinicians and their patients in helping to facilitate better recognition and
management of an ever-increasing number of neurological disorders.
Aaron E. Miller, MD
Michelle Fabian, MD
Ilana Katz Sand, MD
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xi
Acknowledgments
Many of the cases described in this book have involved challenging

presentations of neuroimmunological disorders requiring the expertise and
support of a multidisciplinary clinical care team at Mount Sinai Hospital
or North Shore University Hospital. These patients have been the subject
of extensive discussion among our colleagues at the Corinne Goldsmith
Dickinson Center for Multiple Sclerosis at Mount Sinai or at Neurological
Associates of Long Island. These consummate professionals have all shared
their wisdom and experience, in addition to their passionate provision of
excellent, compassionate patient care.
In addition, we acknowledge the invaluable collaboration with our
colleagues in the fields of neuroradiology, neuro-ophthalmology, rheu-
matology, internal medicine, and neuro-critical care, among others. We
would also like to recognize the residents and fellows at the front lines of
managing such difficult cases for their diligence, commitment, and dedica-
tion that inspire us daily. We especially thank Drs. Bradley Delman, Amit
Aggarwal, and Lara Marcuse for sharing their expertise and providing some
of the images, and Drs. David Podwall, Denis Ostrovsky, Michael Han,
and Vincent DeOrchis for their respective case contributions and neuro-
muscular knowledge.
Finally, we extend our sincerest gratitude to the team at Oxford University
Press, Tiffany Lu and Craig Panner, for their help, support, and persistence
in shepherding this volume to completion.
Aaron E. Miller, MD
Michelle Fabian, MD
Ilana Katz Sand, MD
xi
xi
Neuroimmunology
xvi
1
1 A Case of Monocular
Blurred Vision
A 26-year-old white woman consults you one month

after she was diagnosed with right optic neuritis by
an ophthalmologist. She reports that initially she
“could not see much out of the right eye.” She denied
pain on eye movement, but she did experience
supraorbital headache. She was treated with three
days of intravenous methylprednisolone, followed
by oral taper of prednisone over the next two weeks.
Her vision markedly improved, though she does not
feel it is quite back to normal. Her past medical and
neurological history is negative.
The patient’s neurological examination is normal
except that she notes that a bright red stimulus
appears less intense with the right eye than with
the left, and she has a right afferent pupillary
defect (APD).
What do you do now?
1
2
MULTIPLE SCLEROSIS
This patient presents with optic neuritis, which may be a monophasic

illness, but is very commonly the initial manifestation of multiple sclerosis
(MS). Most cases of optic neuritis occur in the retrobulbar portion of the
nerve so that, acutely, the fundus appears normal. Eventually some degree
of optic atrophy may become evident as pallor of the optic disk. An APD
is demonstrated by the “swinging flashlight” test. When the flashlight is in-
itially shone in the affected right eye, both direct and consensual pupillary
constriction occur.
The light is then shone in the left eye, and both pupils remain constricted.
However, when the flashlight swings back to the right eye, the pupils both
dilate because the intensity of the light stimulus is now perceived as less in
the eye that had the optic neuritis. This sign often persists even in an eye
with normal visual acuity after recovery from optic neuritis, indicating re-
sidual damage to the optic nerve.
A definite diagnosis of MS depends on the demonstration of clinical
symptoms and signs that indicate a disease process that involves the central
nervous system (CNS; brain, spinal cord, and optic nerves), is disseminated
in space (meaning involvement of two or more non-contiguous areas of
the CNS) and time (meaning two or more episodes separated by at least a
month), and the absence of a better clinical explanation. It usually presents
in young to middle-aged adults, but neither young children nor older adults
are completely spared. This patient has had no prior clinical events, but
modern diagnostic criteria allow evidence for dissemination in space or
time (or both) to be obtained with magnetic resonance imaging (MRI).
At this point, therefore, you should order a brain MRI with and without
contrast administration. You should also order dedicated fat-saturated or-
bital imaging to evaluate the optic nerve, mainly to exclude an alternative
diagnosis. In this patient, the brain MRI showed multiple T2 hyperintense
lesions. In addition, she had many gadolinium-enhancing (GdE) lesions
(Figure 1.1). Today, the most widely used criteria for making the diagnosis
of MS are known as the “McDonald criteria,” with the most recent revision
in 2017. Although these criteria allow for the traditional clinical diagnosis,
their use often enables an earlier diagnosis to be made by allowing MRI
findings to satisfy criteria for either dissemination in space or time, or both.
2 WHAT DO I DO NOW? Neuroimmunology

3
FIGURE 1.1 This patient met criteria for definite MS by the 2017 revision of the McDonald
criteria because, at the time of his presentation with a clinically isolated syndrome, his MRI
showed both T2 hyperintense lesions (FLAIR sequence, right) and a gadolinium-enhancing lesion
in the right frontal lobe (left).
The current criteria require the presence of both symptoms suggestive of in-
volvement of the CNS and objective signs on the neurological examination.
Dissemination in space (DIS) could be satisfied by the presence on MRI of
at least one lesion in at least two of the following locations:
• Periventricular
• Juxtacortical or cortical
• Infratentorial
• Spinal cord
Dissemination in time (DIT) can be satisfied by the appearance of any new

lesion on a subsequent MRI performed after a previous MRI. Alternatively,
if both GdE and other non-enhancing lesions appear on the initial MRI,
the criteria for DIT are met.
Cerebrospinal fluid (CSF) studies are also extremely helpful in confirming
the diagnosis of MS. Routine studies on the CSF are usually normal, or may
show a mild mononuclear pleocytosis (under 50 cells) or a mildly elevated
protein. In most cases (as many as 90% in some published series, but prob-
ably closer to 60–70% in early cases in routine clinical practice), the CSF
shows evidence of abnormal immunoglobulin production, demonstrated
by either the presence of oligoclonal bands or elevation of the IgG index of
IgG synthesis rate. While these abnormal CSF findings (oligoclonal bands
1 A Case of Monocular Blurred Vision 3

4
are more specific) are not entirely pathognomonic of MS, they usually help
to eliminate alternative diagnoses. In a major change with the 2017 revision
of the McDonald criteria, the presence of two or more oligoclonal bands
in the CSF of a patient who presents with a typical clinically isolated syn-
drome substitutes for DIT, even when criteria for DIT are not met on the
MRI. Therefore, a patient who presents with an initial event typical of MS,
meets MRI criteria for DIS, and has oligoclonal bands in the CSF may be
diagnosed with definite MS. In all cases, however, it is imperative that there
be no better clinical explanation for the patient’s symptoms (Table 1.1).
Optic neuritis is also a major manifestation of neuromyelitis optica
spectrum disorder (NMOSD), a condition discussed in Chapter 30. The
availability of serological testing for anti-aquaporin4 antibody has greatly
facilitated the diagnosis of this condition and has a sensitivity of more than
70%, with high specificity. Although this patient’s brain MRI is much
more typical of MS than of NMOSD, some experts now routinely order
aquaporin4 antibody testing in anyone presenting with optic neuritis.
TABLE 1.1 2017 Revised McDonald Criteria for Determination

of Dissemination in Space and Time
Attacks Lesions Additional Requirements
2 or more 2 or more None
2 or more 1 DIS:
❑ Further attack or
❑ MRI* (≥1 T2 lesions in ≥2 of 4 areas1)
1 2 DIT:
❑ Further attack or
❑ MR (presence of GdE and non-GdE lesions) or
CSF-OCB
1 1 DIS and DIT
0 1 ❑ >1 year of progression and

❑ 2 of 3 of:
◦ T2 hyperintense lesions in brain—1 of
3 areas2
◦ T2 hyperintense lesions in spinal
cord—≥2 areas
◦ CSF-OCB

5
After the MRI has been completed, you should inform this patient that
she has a diagnosis of definite relapsing-remitting MS (RRMS). MS is cur-
rently described, according to its temporal profile, as RRMS, secondary
progressive (SPMS), or primary progressive (PPMS). Approximately
80–85% of patients begin with RRMS, in which they have episodes of
neurological symptoms, typically lasting days to weeks, followed by re-
covery or improvement before the development of another attack (also
called exacerbation or relapse). Conventionally, an attack is considered
new when it occurs at least 30 days after the onset of symptoms in the
previous exacerbation. Most of the remaining 15–20% of patients have
PPMS, in which symptoms and signs— most often those of spastic
paraparesis—progress gradually without any acute exacerbations. Many
patients—often estimated at about 50% or even more—who begin with
RRMS eventually change to a course that is gradually worsening. Such
a course is then labeled SPMS. This insidiously progressive course may
or may not be accompanied by superimposed exacerbations. Recently, an
international committee has recommended that any type of MS be fur-
ther characterized by the presence or absence of activity (by either clinical
or imaging evidence), always placed within a temporal context (e.g., one
year). Progressive forms of MS may plateau, so these phenotypes should be
further modified by the description “with or without progression,” again
within a temporal framework.
When informing the patient of the diagnosis of MS, you should do so
in the most hopeful terms possible, a position currently justified by the
availability of a variety of medications to treat RRMS and the promise
of additional drugs in the near future. You should always inform the pa-
tient in person, rather than in a telephone conversation or message. You
should tell the patient specifically that he or she has MS and avoid the use
of euphemisms, such as “demyelinating disease.” The diagnosis should be
accompanied by an explanation of the condition in terms that the patient
can readily understand.
After giving the patient the diagnosis of MS, you should recommend
initiation of treatment with a disease-modifying agent. However, generally,
you should defer the discussion of the specific therapeutic options to a sub-
sequent meeting with the patient. Receiving the diagnosis of MS, even if it
was not totally unexpected, is an emotionally upsetting experience, and it

6
will be difficult for the patient to focus on the details of the therapy discus-
sion at that time.
A wide variety of disease-modifying agents is currently available. The
oldest medications, including several interferon beta preparations and
glatiramer acetate, are administered by injection (mainly subcutaneous).
These agents are modestly effective, but extremely safe. Newer medications
are generally more effective but convey additional risks, including those of
serious infection. Oral agents include fingolimod, teriflunomide, and di-
methyl fumarate. Probably the most efficacious disease-modifying agents
are monoclonal antibodies that are administered by intravenous infusion.
These include natalizumab, administered every four weeks; ocrelizumab,
given every six months; and alemtuzumab (which, in the United States,
is recommended only for patients failing or not tolerating multiple other
agents), administered for five days initially and then for three days a
year later. Detailed discussion of the disease-modifying agents’ respective
advantages and disadvantages is beyond the scope of this chapter, but is
available in the suggested readings.
KEY POINTS TO REMEMBER
• Multiple sclerosis is an inflammatory demyelinating disease of

the CNS that usually affects young to middle-aged adults and
women much more often than men.
• The key to diagnosis is the demonstration of DIS and DIT, for
which the MRI is extremely helpful.
• CSF analysis is very helpful in MS, with most patients showing
at least two oligoclonal bands (OCB). In the 2017 McDonald
criteria, the presence of OCB may substitute for DIT.
• The disease phenotype is described as RRMS, SPMS, or PPMS.
• Acute attacks are usually treated with high-dose corticosteroids.
• Many disease-modifying agents are available to treat relapsing
forms of MS, differing in route of administration, efficacy,
tolerability, and risks.

7
Further Reading
Bermel RA, Fox RJ. MRI in multiple sclerosis. Continuum: Lifelong Learn Neurol.
2010;16(5):37–57.
Cree BAC. Diagnosis and differential diagnosis of multiple sclerosis.
Continuum: Lifelong Learn Neurol. 2010;16(5):19–36.
Graber JJ, McGraw CA, Kimbrough D, Dhib-Jalbut S. Overlapping and distinct
mechanisms of action of multiple sclerosis therapies. Clin Neurol Neurosurg.
2010;112(7):583–591.
Polman CH, Reingold SC, Banwell B, et al. Diagnostic criteria for multiple
sclerosis: 2010 revisions to the “McDonald criteria.” Ann Neurol.
2011;69(2):292–302.

8
9
2 A Case of Multifocal
Neurological Symptoms
A 25-year-old man presents with two days of double

vision, unsteady gait, and mild confusion. He denies
headache, fever, recent infection, or travel, but
reports receiving a flu vaccination two weeks prior.
On examination, he is oriented to self and place but
does not know the date, and his mentation is slow.
There is a left internuclear ophthalmoplegia and a left
adduction palsy. Strength is full, but he has diffuse
hyperreflexia and a right extensor plantar response.
Vibration and joint position sense involving his right
foot are impaired. Gait is moderately dystaxic.
MRI demonstrates multiple T2 hyperintense white
matter lesions and a lesion in the left rostral midbrain.
The majority demonstrate gadolinium enhancement,
some with a distinct open-ring pattern. There are two
enhancing spinal cord lesions. CSF analysis shows
26 WBC (lymphocytes), protein 55, negative HSV-2
PCR, Lyme serology, VDRL, and normal cytology.
Oligoclonal bands are absent.
What do you do now?
9
10
ACUTE DISSEMINATED ENCEPHALOMYELITIS
This patient presents with a post-vaccinal neurological syndrome with mul-

tifocal symptomatology and deficits with supratentorial and infratentorial
involvement, as well as encephalopathy. MR imaging demonstrates mul-
tiple T2/FLAIR hyperintense white matter abnormalities involving both
the brain and spinal cord, the majority of which demonstrate gadolinium
enhancement, including an open-ring enhancement pattern radiograph-
ically characteristic of demyelination (Figure 2.1). This presentation is
(A) (B)
(C) (D)
FIGURE 2.1 MRI from a patient with acute disseminated encephalomyelitis showing contrast
enhancement in nearly all lesions (lower panels). The upper panels show the lesions hyperintense
on T2-weighted imaging. Reprinted with permission from Bermel RA, Fox RJ. MRI in multiple
sclerosis. Continuum: Lifelong Learning in Neurology. 2010;16(5):46.

1
highly suspicious for acute disseminated encephalomyelitis (ADEM), an

immune- mediated demyelinating disorder characterized by multifocal
CNS involvement and encephalopathy. Children are preferentially affected.
Various vaccines and systemic infections have been linked to ADEM, in-
cluding influenza, varicella zoster, herpes simplex, measles, mumps, rubella,
Borrelia burgdorfei, mycoplasma, and Epstein-Barr virus. Of note, however,
ADEM, more often than not, develops in the absence of any antecedent
infection. In addition to multifocal CNS involvement and encephalopathy,
2013 diagnostic criteria require MRI lesions typical for demyelination as
well as the lack of new symptoms/signs more than three months after onset.
The onset of ADEM is generally rapid, and peak neurological dysfunc-
tion manifests within several days. Clinical symptoms are multifocal and
varied, including encephalopathy, cerebral hemispheric deficits such as
hemiparesis and hemisensory loss, brain stem dysfunction, and myelop-
athy, as well as seizures. The degree of encephalopathy can range from mild
lethargy and confusion to frank coma. Rarely, a hyperacute, severe var-
iant of ADEM occurs, referred to as acute hemorrhagic leukoencephalitis
(AHLE), which pathologically involves petechial hemorrhage and venular
necrosis. In cases of AHLE, CSF analysis generally demonstrates increased
opening pressure, elevated protein, and a pleocytosis of both red and white
blood cells. As such, the differential diagnosis here would include hemor-
rhagic, necrotizing infectious processes such as herpes simplex meningo-
encephalitis, brain abscesses, and neoplasms such as metastatic melanoma.
Peripheral nervous system involvement has been described, in the form of
acute polyradiculoneuropathies, more commonly in adult rather than pe-
diatric presentations.
ADEM can be difficult to distinguish from a severe, fulminant first ep-
isode of multiple sclerosis (MS), but differentiating these two entities has
critical long-term therapeutic implications. ADEM is typically a self-limited
monophasic illness and does not require the chronic immunomodulatory
or immunosuppressive therapies of MS. Factors suggested as supportive
of ADEM include the presence of encephalopathy, seizures, radiographic
presence of poorly marginated, large, sometimes tumefactive-sized lesions,
deep gray matter and cortical lesions, and a predominance of gadolinium-
enhancing lesions. Both incomplete and complete ring-shaped patterns of

12
enhancement have been described. Meningeal enhancement is considered

unusual. On the other hand, periventricular lesions that radiate perpen-
dicularly from the ventricles (Dawson’s fingers) are more suggestive of
MS. Lesions on MRI in ADEM typically completely or at least partially
resolve. Persistent lesions that do not improve on serial scans are more
consistent with MS. The absence of CSF oligoclonal bands (OCBs), com-
monly identified in MS patients, is considered to favor ADEM, but the
utility of OCB positivity remains unknown, as 58% and 29% of adult
and pediatric ADEM cases, respectively, have OCBs. In cases with signif-
icant clinical and paraclinical overlap, the decision about whether to ini-
tiate immunomodulatory therapy can be difficult, and most patients are
followed with close clinical and radiographic surveillance to ascertain new
evidence of disease activity over the subsequent months. In addition to
clinical presentatons that resemble aggressive MS, cases with similarity to
neuromyelitis optica spectrum disorder (NMOSD), including features of
bilateral optic neuropathy and longitudinally extensive spinal cord lesions,
have also been described. As discussed later, these patients may be positive
for antibodies either to myelin oligodendrocyte glycoprotein (MOG) or
anti-aquaporin 4 (AQP4). In addition to demyelinating disease, other can-
didate differential diagnoses for ADEM include cerebral vasculitis, multiple
infarcts, chronic meningitides, neoplastic processes, and granulomatous
disease. Brain biopsy is sometimes required to differentiate these alternative
entities from ADEM.
ADEM is most often monophasic; however, a small subset of patients
will go on to develop recurrent disease. The term “recurrent ADEM” was
replaced in the 2013 criteria revision with “multiphasic ADEM,” referring
to a second ADEM episode. A third episode instead indicates a recurrent,
relapsing disorder. These patients may go on to be diagnosed with NMOSD
or MS. In addition, there is growing interest in the role of antibodies to
MOG. This entity is still being defined; it remains to be seen whether it will
be classified separately or under the umbrella of NMOSD. As compared to
patients with positive AQP4 antibodies, patients with MOG-related dis
ease tend to have better recovery, and some cases seem to be monophasic,
though the majority are relapsing. A patient with typical ADEM who then
develops optic neuritis, or an additional episode of ADEM along with optic
neuritis, should raise a high degree of suspicion for MOG-related disease.

13
Treatment of ADEM generally involves high- dose intravenous

methylprednisolone, sometimes followed by oral steroid tapering doses, as
well as immunotherapies such as plasma exchange or intravenous immu-
noglobulin in corticosteroid-refractory cases. Close respiratory monitoring
in an intensive care unit is often recommended because of the possibility
of respiratory compromise secondary to brain stem involvement and severe
encephalopathy. The prognosis with therapy is generally favorable, but re-
covery time can vary from weeks to months, and persistent cognitive dys-
function is possible.
KEY POINT S TO REMEMBER
• ADEM, an immune-mediated, inflammatory, demyelinating

disorder of the central nervous system, is characterized by
multifocal neurological symptoms and encephalopathy.
• ADEM most often occurs in children but may also affect
adolescents and adults.
• There is a wide variability in the severity of ADEM
presentations, but in the majority of cases, it is a self-limited
illness with a favorable prognosis.
• ADEM can be difficult to distinguish from a fulminant, initial
episode of MS, necessitating ongoing close clinical and
radiographic surveillance for new disease activity suggestive of
the latter.
• Antibodies to myelin oligodendrocyte glycoprotein may be
seen in some patients, particularly those with concomitant
optic neuritis and those with a relapsing course.
Further Reading
Hennes EM. Prognostic relevance of MOG antibodies in children with an acquired
demyelinating syndrome. Neurology. 2017;89(9):900–908.
Krupp LB. International Pediatric Multiple Sclerosis Study Group criteria for pediatric
multiple sclerosis and immune-mediated central nervous system demyelinating
disorders: revisions to the 2007 definitions. Mult Scler. 2013;19(10):1261–1267.
Pohl D. Acute disseminated encephalomyelitis: Updates on an inflammatory CNS
syndrome. Neurology. 2016;87(9 Suppl 2):S38–S45.

14
15
3 Irritability in a Man
with Multiple Sclerosis
A 32-year-old high school history teacher had no

limitations in his activities of daily living, except for
mild gait abnormality as a result of relapsing-remitting
MS that limited his ability to walk long distances. At a
visit 18 months after natalizumab therapy was begun
because four new gadolinium-enhancing lesions
were found on MRI, the patient’s wife reported that
her husband had seemed to be particularly irritable
over the previous few weeks and that she had noticed
he seemed to have some difficulty finding words.
The patient himself reported no new concerns. On
neurological examination, the mental status was
normal except for the presence of mild anomia. Mild
weakness of the right upper extremity was detected,
in addition to the previously noted paresis of the
right leg.
What do you do now?
15
16
PROGRESSIVE MULTIFOCAL LEUKOENCEPHALOPATHY

SYNDROME AND IMMUNE RECONSTITUTION
INFLAMMATORY SYNDROME
This patient has classical relapsing-remitting MS. He was appropriately

initiated on Interferon beta-1a (IFNB-1a) as disease-modifying therapy.
Unfortunately, he had recurrent breakthrough disease with relapses involving
optic neuritis and partial myelitis. Because of this suboptimal response, the
treatment was changed to natalizumab. After 18 months of treatment, the
patient developed relatively subtle symptoms of personality change and
word-finding difficulty, as well as new weakness of the right arm. This event
occurring in a patient on natalizumab should definitely raise concern about
the possibility of progressive multifocal leukoencephalopathy (PML), and
investigations should be initiated immediately.
Could the patient be experiencing new MS activity? This is certainly
possible, but seems relatively unlikely. Personality change due to MS is
uncommon, although it may be misinterpreted as such in the context of
depression, which does occur frequently in the disease. Irritability is some-
times encountered in patients taking interferon, but it is not a feature of
natalizumab therapy. Language disturbance, including true word-finding
difficulty or anomia, is distinctly uncommon in MS. Of course, it is im-
portant to distinguish aphasia from dysarthria, which is common in MS.
A hemiparetic pattern of weakness certainly occurs in MS, but is much
less common than paraparesis. In addition, the temporal profile of the
new symptomatology is not characteristic for MS relapses, in which new
symptoms generally come on over a matter of days.
In contrast, this case scenario is strongly suggestive of PML, an oppor-
tunistic viral infection of the CNS caused by the polyoma virus known as
John Cunningham (JC) virus. PML for many years has been principally
associated with HIV infection (occurring in up to 5% of such patients)
and, to a much lesser extent, in people with hematological malignancies.
PML is now a well-recognized, albeit infrequent, consequence of prolonged
exposure to natalizumab in MS patients. It tends to present in a suba-
cute manner. Although symptoms and signs of PML can mimic those of
MS, personality change, cognitive dysfunction, and language disturbance,
as well as hemiparesis, are common early findings in PML. In contrast,

17
involvement of the optic nerves or spinal cord, frequent sites of involve-

ment in MS, rarely, if ever, occurs.
With natalizumab now in use for more than a decade, much has been learned
about the risk factors for PML. Most important is the presence of antibody to
JC virus by the specific STRATIFY assay, provided by Biogen (the distributor
of the medication). Slightly more than 50% of tested adults have a positive
assay. The risk of PML in antibody-negative MS patients is exceedingly low,
probably <1/10,000. In JC virus antibody-positive patients, the risk of PML
increases with the duration of therapy. The risk of PML, even in antibody-
positive patients, is approximately 1/10,000 in the first year of therapy, but
increases to ~1/800 in the second year, and to approximately 1/250 in subse-
quent years. An additional risk factor is the prior use of immunosuppressant
medications (which do not include corticosteroids). PML is significantly re-
lated to the duration of exposure to natalizumab. With over 180,000 patients
exposed to the drug worldwide, as of February 28, 2018, 763 MS patients with
PML had been identified after a mean exposure of 17.9 months. The overall
risk for PML was 1.00 per 1000 patients (confidence interval [CI] 0.20–2/80).
However, the peak incidence was for those patients in the treatment epoch be-
tween 37 and 48 or between 49 and 60 infusions for whom the incidence rate
was 2.05 (1.75–2.32; 1.71–2.42, respectively). Thus far, the incidence rate does
not appear to be increasing beyond that duration of exposure.
As soon as the suspicion of the possibility of PML arises, further therapy
with natalizumab should be halted. MRI of the brain should be obtained.
The appearance of any new brain lesions on MRI obtained after six months
of natalizumab treatment should raise the question of PML (Figure 3.1).
Although similarity to the appearance of MS lesions on MRI may occur,
several specific features of MRI in PML occur, as reported by Boster et al.
(2009). Large, confluent T2 hyperintense lesions occur commonly in PML,
but rarely in MS (74% vs 2%, p < 0.0001). Deep gray matter lesions were
also more frequent in PML (31% vs 7%, p < 0.001). In addition, crescentic
cerebellar lesions were seen only in PML. Although classically PML has been
associated with the absence of gadolinium enhancement, this is not the case
in natalizumab-associated PML. In one report, gadolinium enhancement
was observed in 43% of 28 cases of PML at the time of diagnosis.
Cerebrospinal fluid should be examined and sent for polymerase chain
reaction (PCR) testing for JC virus DNA. It is important to note that
3 Irritability in a Man with MS 17

18
FIGURE 3.1 MRI FLAIR sequence showing large coalescent lesions in both cerebellar
hemispheres that were proven on biopsy to be PML. The patient had been on natalizumab for
approximately two years.
many commercial laboratories doing JC PCR are not capable of detecting

the low number of copies that are often present in natalizumab-associated
PML. Clifford et al. (2010) reported that 16 of 28 cases had fewer than 500
copies, and sometimes very low copy numbers are present.
When PML is diagnosed or strongly suspected, current recommendations
advise that patients be treated with plasma exchange (PLEX) or
immunoabsorption in order to speed the clearance of the monoclonal an-
tibody and restore immunological function. No specific drug therapy has
been demonstrated to be effective in ameliorating the disease.
After natalizumab is withdrawn, and perhaps accentuated by PLEX or
immunoabsorption therapy, an immune reconstitution inflammatory syn-
drome (IRIS) invariably develops, typically recognizable a few weeks after
cessation of the monoclonal antibody. This happens also in the context
of HIV, but it is typically less severe in that setting. IRIS in natalizumab-
associated PML is usually characterized by neurological worsening, which
is usually transient, but may be severe or even fatal. It is accompanied by
brain swelling, which may be associated with increased intracranial pressure
and headache. During IRIS, the brain MRI often shows enlargement of the

19
lesion(s) with prominent edema and usually with gadolinium enhancement

(Figure 3.2). Treatment with high-dose intravenous methylprednisolone
should be given in the setting of IRIS and appears to be beneficial in re-
ducing brain swelling and neurological deterioration. Some have suggested
that steroids be administered prophylactically at the time of PML diagnosis
in order to lessen the development of IRIS. Of the PML cases reported by
Clifford, only 8 of 28 were fatal, resulting in a survival rate of 71%, albeit
in many instances with severe neurological disability.
Natalizumab is a highly effective therapy for relapsing forms of MS and,
until recently, sometimes had to be utilized in patients breaking through
treatment with other disease-modifying therapies, even if they were JC
antibody-positive. However, the more recent availability of other infusible
monoclonal antibodies, ocrelizumab and alemtuzumab, which have much
lower risk of PML, has significantly reduced the need to use natalizumab in
patients who are JC antibody-positive.
FIGURE 3.2 Gadolinium-enhanced T1 images from the same patient depicted in Figure 3.1,
showing innumerable small enhancing lesions believed to be due to the immune response
inflammatory syndrome (IRIS).

20
KEY POINTS TO REMEMBER
• PML is now a well-recognized, albeit infrequent, consequence of

prolonged exposure to natalizumab in MS patients. Almost all
cases develop in patients who test positive for antibodies to JC
virus on the STRATIFY assay.
• Although symptoms and signs of PML can mimic those of
MS, personality change, cognitive dysfunction, and language
disturbance, as well as hemiparesis, are common early findings
in PML.
• As soon as the suspicion of possible PML arises, further therapy
with natalizumab should be halted. MRI of the brain should
be obtained. The appearance of any new brain lesions on MRI
obtained after six months of natalizumab treatment should raise
the question of PML.
• When PML is diagnosed or strongly suspected, patients should
be treated with plasma exchange (PLEX) or immunoabsorption
in order to speed the clearance of the monoclonal antibody and
restore immunological function.
• After natalizumab is withdrawn, and perhaps accentuated by
PLEX or immunoabsorption therapy, an immune reconstitution
inflammatory syndrome (IRIS) invariably develops, typically
becoming recognizable a few weeks after cessation of the
monoclonal antibody.
Further Reading
Boster A, Hreha S, Berger JR, et al. Progressive multifocal leukoencephalopathy
and relapsing-remitting multiple sclerosis: a comparative study. Arch Neurol.
2009;66(5):593–599.
Brandstadter R, Sand IK. The use of natalizumab in multiple sclerosis. Neuropsych
Disease Treat. 2017;13:1691–1702.
Clifford DB, De Luca A, Simpson DM, Arendt G, Giovannoni G, Nath A. Natalizumab-
associated progressive multifocal leukoencephalopathy in patients with
multiple sclerosis: lessons from 28 cases. Lancet Neurol. 2010;9(4):438–446.
Gorelik L, Lerner M, Bixler S, et al. Anti-JC virus antibodies: implications for PML risk
stratification. Ann Neurol. 2010;68(3):295–303.

21
Warnke C, Menge T, Hartung HP, et al. Natalizumab and progressive multifocal

leukoencephalopathy: what are the causal factors and can it be avoided? Arch
Neurol. 2010;67(8):923–930.
Williamson EML, Berger JR. Diagnosis and treatment of progressive multifocal
leukoencephalopathy associated with multiple sclerosis therapies.
Neurotherapeutics. 2017; epub ahead of print, September 14, 2017.

2
23
4 A Case of Myelitis with a

Positive Anticardiolipin
Antibody
A 30-year-old woman presents with difficulty walking.

One day earlier she noted a sensation of tightness
under her breasts and mild numbness and discomfort
in the legs, which then worsened. She has been
unable to urinate for several hours. She has no prior
medical history and takes only an oral contraceptive.
She has never been pregnant.
Examination is significant for 4/5 strength in the
legs and impaired sensation with a T4 level. Brain
MRI shows nonspecific white matter abnormalities.
Spinal cord MRI shows a longitudinally extensive
T2 hyperintensity from T2 down to the conus, which
enhances with gadolinium.
She is admitted to the hospital and started
on corticosteroids. Blood tests reveal a positive
antinuclear antibody as well as positive anticardiolipin
antibody and positive anti-aquaporin 4 antibody.
The staff rheumatologist tells the patient she has
antiphospholipid syndrome (APS) and that she should
begin treatment with anticoagulation.
What do you do now?
23
24
ANTIPHOSPHOLIPID ANTIBODY SYNDROME
From a neurologist’s point of view, the vexing question sometimes arises as

to whether a patient has demyelinating disease such as neuromyelitis optica
or multiple sclerosis, or manifestations of APS. Of course, it is also possible
for the patient to have more than one issue, but a decision about which
entity is responsible for the current problem is essential to the proper se-
lection of treatment. In this patient, the physician should begin by consid-
ering whether the longitudinally extensive spinal cord lesion is more likely
to be due to APS, given the positive anticardiolipin antibody, or due to
neuromyelitis optica spectrum disorder (NMOSD), given the positive anti-
aquaporin 4 antibody. Longitudinally extensive spinal cord lesions have
been reported in patients with positive antiphospholipid antibodies; how-
ever, the causal relationship is a source of controversy. Anti-aquaporin 4 an-
tibody by cell binding assay is highly specific for the diagnosis of NMOSD,
and in the setting of a longitudinally extensive myelitis, this patient meets
formal NMOSD criteria. In addition, it is very common for patients with
NMOSD to be positive for multiple autoantibodies. In some cases, patients
with NMOSD will show clinical manifestations of additional autoimmune
diseases requiring further management, and in others they will have positive
autoantibodies alone.
The patient should therefore be treated for an NMOSD exacerbation
with steroids and, potentially, plasma exchange. However, the questions
regarding the clinical significance of the positive anticardiolipin antibody
and whether or not the patient should be placed on anticoagulation remain.
The current diagnosis of APS, which can be a primary disorder or occur
secondarily in patients with lupus, is based on the revised Sapporo criteria,
which require clinical evidence of either vascular thrombosis or pregnancy
morbidity (Table 4.1). The former is characterized by one or more clinical
episodes, in any organ, of arterial, venous, or small-vessel thrombosis. To
satisfy the criterion of pregnancy morbidity, a woman should experience
(a) one or more unexplained deaths of a morphologically normal fetus at
>10 weeks’ gestation; (b) one or more premature births of a morphologically
normal baby before the 34th week of gestation because of eclampsia, severe
preeclampsia, or placental insufficiency; or (c) three or more unexplained
consecutive spontaneous abortions before the 10th week of gestation. One

25
TABLE 4.1 Classification Criteria of Antiphospholipid Antibody Syndrome

Clinical Criteria
Vascular thrombosis
I. One or more clinical episodes of arterial, venous, or small vessel

thrombosis in any tissue or organ. Thrombosis must be confirmed via
imaging, Doppler studies, or histopathology, with the exception of
superficial venous thrombosis.
Pregnancy morbidity
I. One or more unexplained deaths of a morphologically normal fetus at

or beyond the 10th week of gestation, with normal fetal morphology
documented by ultrasound or examination.
Or
II. One or more premature births of a morphologically normal neonate
at or before the 34th week of gestation because of preeclampsia or
severe placental insufficiency.
Or
III. Three or more unexplained consecutive spontaneous abortions before
the 10th week of gestation with maternal anatomical or hormonal
abnormalities and exclusion of maternal and paternal chromosomal
causes.
Laboratory criteria
I. Anticardiolipin antibody of immunoglobulin (Ig) G and/or IgM isotype

and measured by a standardized enzyme-linked immunoabsorbent
assay or anti–b2-glycoprotein 1 of IgG and/or IgM isotype in blood,
present in medium or high titer, on two or more occasions 12 weeks
or more apart.
II. Lupus anticoagulant present in plasma on two or more occasions
12 weeks or more apart and detected according to the guidelines
of the International Society of Thrombosis and Hemostasis, in the
following steps:
A. Demonstration of a prolonged phospholipid-dependent
coagulation screening test (e.g., activated partial thromboplastin
time, Kaolin clotting time, dilute Russell’s viper venom time, dilute
prothrombin time, Textarin time)
B. Failure to correct the prolonged screening test by mixing with
normal platelet-poor plasma
C. Shortening or correction of the prolonged screening test by the
addition of excess phospholipid
D. Exclusion of other coagulopathies as appropriate (e.g., factor VIII
inhibitor, heparin)
Data from Miyakis S, Lockshin MD, Atsumi T, et al. International consensus statement on an
update of the classification criteria for definite antiphospholipid syndrome. J Thromb Haemost.
2006;4(2):295–306.
26
or more of the following laboratory criteria regarding antiphospholipid

antibodies (aPL) must be satisfied:
1. Lupus anticoagulant present in plasma on at least two occasions a

minimum of 12 weeks apart
2. Anticardiolipin antibody (IgG and/or IgM) in plasma or serum in
medium or high titer (>1:40) or >99th percentile on at least two
occasions a minimum of 12 weeks apart
3. Anti-β2 glycoprotein I antibody (IgG and/or IgM) in titer >99th
percentile on at least two occasions a minimum of 12 weeks apart.
Definite diagnosis of APS requires the presence of at least one clinical

criterion and at least one laboratory criterion. One should avoid making
a definitive diagnosis if the time between the clinical manifestation and
the demonstration antiphospholipid antibody titer is less than 12 weeks or
more than five years (Table 4.1).
In addition to thromboembolism, common systemic manifestations
of APS include livedo reticularis and thrombocytopenia, which is typi-
cally mild and does not result in bleeding complications. Neurological
manifestations of APS are predominantly ischemic. These may be prima-
rily arterial thromboses, but cardioembolic events may also occur, as APS
not infrequently affects the heart, particularly with valvular involvement.
In addition, venous thromboses may involve the cerebral veins or venous
sinuses. The former may result in venous infarction, and the latter may, at
times, result in raised intracranial pressure. Of course, the occurrence of
venous thrombosis in the leg veins may be associated with paradoxical ce-
rebral embolization through a patent foramen ovale or other abnormality
leading to right-to-left shunting. In young patients who present with stroke
or transient ischemic attack of unclear etiology, APS should be a primary
consideration. In this case, anticoagulation is typically warranted, though in
certain cases an antiplatelet agent may be used. In addition, close attention
to the management of other vascular risk factors such as hypertension, hy-
perlipidemia, and smoking is important.
APS has also been associated with several non-ischemic neurological phe-
nomena, most of which are thought to be related to direct neuronal injury
by aPL. Cognitive dysfunction is relatively common and has been shown to
be associated with the presence of white matter lesions on MRI and livedo

27
reticularis. T2 hyperintensities on MRI may be difficult to distinguish

from those seen in multiple sclerosis. In these cases, the location/distribu-
tion, shape, size, presence or absence of diffusion restriction, and pattern
of gadolinium enhancement must be carefully considered. In cases that do
not look distinctively like MS, additional data must be sought. Imaging the
spinal cord, particularly the cervical region, can be very helpful. Vascular dis
ease seldom involves the cervical spinal cord, whereas MS commonly does.
Examination of the CSF may also be helpful. Although oligoclonal bands
and elevated IgG index occasionally occur in APS, these findings are much
more likely in patients with MS. Less common but reported neurological
symptoms associated with aPL include chorea, transverse myelopathy, mi-
graine, seizures, sensorineural hearing loss, and neuropsychiatric symptoms.
In this patient, the diagnosis of APS was not justified, because only one
set of serological observations had been obtained and the patient had not
had a clear clinical event to meet APS criteria, given that the spinal cord
lesion was better explained by NMOSD than APS.
Based on a randomized clinical trial, the prophylactic treatment of
asymptomatic patients with anticardiolipin antibodies or lupus anticoag-
ulant with antiplatelet or anticoagulant agents does not appear warranted.
Therefore, this patient should not be started on either of these agents at this
time. Of course, it is always prudent to vigorously address additional cardi-
ovascular risk factors.
KEY POINT S TO REMEMBER
• Antiphospholipid syndrome (APS) is an autoimmune disorder

characterized by thromboembolic events and/or pregnancy
morbidity in the setting of persistent antiphospholipid
antibodies (aPL).
• APS may occur as a primary disorder or in the setting of
underlying lupus.
• Common manifestations of APS include deep vein
thrombosis and/or pulmonary embolism, livedo reticularis,
thrombocytopenia, fetal loss, and stroke/transient ischemic
attack.
4 Myelitis and Anticardiolipin Antibody 27

28
• Neurological manifestations associated with APS other than

stroke include cognitive dysfunction, chorea, transverse
myelopathy, and seizure.
• Patients with stroke/transient ischemic attack and persistently
positive aPL should be treated with long-term anticoagulation
therapy.
Further Reading
Espinosa G. Current treatment of antiphospholipid syndrome: lights and shadows.
Nat Rev Rheumatol. 2015;11(10):586–596.
Graf J. Central nervous system manifestations of antiphospholipid syndrome.
Rheum Dis Clin North Am. 2017;43(4):547–560.
Yelnik C, Kozora E, Appenzeller S. Non-stroke central neurologic manifestations in
antiphospholipid syndrome. Curr Rheumatol Rep. 2016;18(2):111.

29
5 A Case of Stiffness in the

Legs and Gradual Difficulty
Walking
A 40-year-old woman with a 20-year history of

rheumatoid arthritis was switched to etanercept a
year ago because of the failure of nonsteroidal anti-
inflammatory drugs (NSAIDs) and methotrexate
to control her joint pain and swelling. She has had
substantial improvement in her joint symptoms, but
for the past nine months, she has been experiencing
headache and neck pain. For the past six months,
she has noticed increased stiffness in her legs, not
specifically in the joints. Her walking has become
slower, and she notices she is having increased
difficulty going up stairs, as well as occasionally
tripping over curbs. She has no additional medical
history. She does not smoke, nor drink alcohol, and
she consumes a healthful diet. Her family history is
negative for neurological disease.
What do you do now?
29
30
RHEUMATOID ARTHRITIS
The predominant feature of this woman’s neurological syndrome is a spastic

paraparesis, and this warrants an expedited evaluation. Most critical is MRI
of the spinal cord in both the cervical and thoracic regions, because this
patient’s examination does not provide a clear indication of the potential
level of involvement. This is necessary to determine whether a compressive
myelopathy is present, and the MRI may also show intrinsic lesions of the
spinal cord to suggest an inflammatory/demyelinating process. Depending
on the findings of the spinal cord imaging, additional imaging of the brain
might be warranted if MS is a possibility. The signs of lateral column
(spastic paraparesis) and dorsal column (impaired vibratory sensation)
suggest the possibility of subacute combined degeneration, so vitamin B12
and methylmalonic acid levels should be determined. Though uncommon
in this situation, serological evidence for syphilis should also be sought. In
some circumstances, examination of the CSF might be indicated.
Rheumatoid arthritis is a systemic inflammatory disease that is
characterized principally by a polyarthritis characterized by synovial in-
flammation, which can lead to destruction of cartilage and bone erosion.
Although any synovial joint can be involved, most typical is inflammation
and deformity of the proximal interphalangeal and metacarpophalangeal
joints of the hands, often in a symmetrical pattern.
RA can be associated with a number of neurological complications.
Most pertinent to this case is that of atlantoaxial subluxation, which can
result in compression of the high cervical spinal cord. The rheumatoid in-
flammatory process leads to synovial proliferation, called pannus, which
can damage adjacent ligaments, cartilage, and bones. If this involves the
atlantoaxial joint, atlantoaxial subluxation may occur, which may result in
compressive myelopathy. When mild, the subluxation is often asympto-
matic. Early symptoms include neck pain and occipital headache. As the
compression progresses, symptoms may include painless sensory loss in
the hands and a mild spastic para-or quadriparesis. Although conservative
management is appropriate for patients with no or mild symptoms, the
presence of myelopathy warrants surgical intervention to stabilize the spine.
Other cervical spine abnormalities may also be associated with RA
(Figure 5.1). Because of rheumatoid destruction of the articular facets (lateral

Another random document with
no related content on Scribd:
Massachusetts.
See (in this volume)

MASSACHUSETTS: A. D. 1897.
POET LAUREATE.
To the line of English Poets Laureate (see, in volume 3,

LAUREATE, ENGLISH POETS), there was added on the 1st of
January, 1896, the name of Alfred Austin, succeeding Tennyson,
who died October B, 1892.
POLAND, Russian:
Relaxation of oppressions.

RUSSIA: A. D. 1897.
POLAR EXPLORATION, Arctic and Antarctic:

A chronological record.
Until quite recent years, the antarctic region had had few
explorers. In 1598-9 Dirk Gerritz was carried south by a storm
and found land, probably the South Shetlands, at 64° South
latitude. Capt. Cook made two antarctic voyages, in the second
one reaching latitude 71° 10' South, at longitude 106° 54'
West, sailing entirely around the southern ocean in a high
latitude, and discovering many islands. In a Russian
expedition, 1819-21, Bellinghausen discovered Peter I. Island
and Alexander I. Land. Enderby Land was discovered by John
Biscoe in 1831-2. In 1840-3 the great English expedition under
Captain (afterward Sir) James Ross, in the Erebus and Terror,
discovered and named Victoria Land, and reached latitude 78°
11', February 23, 1842. The continent which Captain Charles
Wilkes claimed to have discovered in 1840 has not been found
by later explorers. In 1874 the Challenger was turned back by
the ice in latitude 66° 43' South.
POLAR EXPLORATION: 1892-1893.
Whaling voyage of the Dundee vessels, the Balæna, Active,

Diana and Polar Star, equipped for geographical observation by
the Royal Geographical Society and others interested, carrying
William S. Bruce, C. W. Donald, and W. G. Burn Murdoch.
Accompanied by the Norwegian sealer Jasen, under Captain
Larsen. South Shetlands and Graham Land visited and valuable
observations made.

Scientific exploration of Labrador by A. P. Low.
Operations still in progress.
Commercial voyage of the Norwegian whaler Antarctic, under

Captain Kristensen, sent by Captain Svend Foyn, fitted out by
H. J. Bull, and carrying the scientist C. E. Borchgrevinck.
The valuable right whale was not found, but large beds of
guano were discovered in Victoria Land, where a landing was
made near Cape Adare.
POLAR EXPLORATION: 1895.
Return of Peary relief expedition with Lieutenant Robert E.

Peary and his companions. In spite of great difficulties
Lieutenant Peary had again crossed the ice-sheet to
Independence Bay, determined the northern limits of Greenland,
charted 1,000 miles of the west coast, discovered eleven
islands and the famous Iron Mountain (three great meteorites),
and obtained much knowledge of the natives. The purely
scientific results of the expedition are of great value. The
relief expedition was organized by Mrs. Peary.

Cruise of Mr. Pearson and Lieutenant Feilden in Barents Sea.
Return of Martin Ekroll from Spitzbergen after a winter's

study of the ice conditions there. Convinced that his plan of
reaching the pole by a sledge journey had little chance of
success.
Survey of the lower Yenesei River and Obi Bay by Siberian

hydrographic expedition.
Commercial expedition of Captain Wiggins from England to

Golchika, at the mouth of the Yenesei.
Russian geological expedition to Nova Zembla.
Russian expedition under the geologist Bogdanovich to the Sea

of Okhotsk and Kamchatka.
Two scientific voyages of the Danish cruiser Ingolf

in the seas west and east of Greenland.
Summer expedition of naturalists and college students to the

northern coast of Labrador.
Attempt of Lieutenant Peary to remove the great meteorite

discovered by him at Cape York, Greenland. After dislodging it
he was compelled by the ice to leave it. Small parties from
Cornell University and Massachusetts Institute of Technology
and one under Mr. George Bartlett, left by Peary at different
points to make scientific observations and collections,
returned with him.
Hydrographical survey of the Danish waters of Greenland and

Iceland.
Hansen sent to Siberia to look for traces of Nansen.
{407}
Return of Dr. Nansen from voyage begun in 1893. After skirting

the coast of Siberia almost to the Lena delta, the Fram was
enclosed by the ice and drifted with it north and northwest.
On March 14, 1895, in 84° 4' North latitude, 102° East
longitude, Nansen and Johansen left the Fram and pushed
northward with dogs and sledges across an ice floe till they
reached latitude 86° 13.6', at about 95° West longitude, on
April 8, within 261 statute miles of the pole. With great
difficulty they made their way to Franz Josef Land, where they
wintered, and in June met explorer Jackson. Returning on the
Jackson supply steamer Windward, they reached Vardö August 13.
The Fram drifted to latitude 85° 57' North, 66° East
longitude, then southwestward, reaching Tromsoë August 20,
1896. Nansen demonstrated the existence of a polar sea of
great depth, comparatively warm below the surface, apparently
with few islands; though he did not find the trans-polar
current he sought.
Spitzbergen crossed for the first time, by Sir W. Martin

Conway and party.
Many parties visit the northern coast of Norway and Nova

Zembla to view the total eclipse of the sun, August 8-9.
Expedition sent by Russian Hydrographic Department to find

site for a sealers' refuge in Nova Zembla. Bielusha Bay, on
the southwest coast, chosen.
Expedition sent by Canadian government to investigate Hudson

Bay and Strait as a route to Central Canada. Passage found to
be navigable for at least sixteen weeks each summer.
Seventh Peary expedition to Greenland. Accompanied by parties

for scientific research. Preliminary arrangements made with
the Eskimos for the expedition of 1898, and food-stations
established. Relics of Greeley's expedition found on Cape
Sabine, and the great meteorite at Cape York brought away at
last.

Second expedition of Sir Martin Conway for the exploration of
Spitzbergen.
A summer resort established on west coast of Spitzbergen, with

regular steamer service for tourists during July and August.
Cruise of Mr. Arnold Pike and Sir Savile Crossley among the
islands east of Spitzbergen.
Cruise of Mr. Pearson and Lieutenant Feilden in the Laura in

the Kara Sea and along the east coast of Nova Zembla, for the
purpose of studying the natural history of the region.
Expedition of F. W. L. Popham with a fleet of steamers through

Yugor Straits to the Yenesei.
Hydrological and commercial expedition, comprising seven

steamers, under Rear-Admiral Makaroff, sent by the Russian
government to the north Siberian sea.
Balloon voyage of Salamon August Andrée and two companions,

Mr. Strindberg and Mr. Fraenkel, starting from Danes' Island,
north of Spitzbergen, in the hope of being carried to the
pole. Four buoys from the balloon have been found. The first,
found in Norway in June, 1899, and containing a note from
Andrée, was thrown out eight hours after his departure. The
"north pole buoy," to be dropped when the pole was passed, was
found empty on the north side of King Charles Island,
north-east of Spitzbergen, September 11, 1899. A third buoy,
also empty, was found on the west coast of Iceland July 17,
1900. Another, reported from Norway, August 31, 1900,
contained a note showing that the buoy was thrown out at 10 P.
M., July 11, 1897, at an altitude of 250 metres (820 feet),
moving North 45 East, with splendid weather. Many search
expeditions, some equipped at great expense, have returned
unsuccessful. In spite of many rumors nothing definite is
known of the fate of any of the party. One message from Andrée
was brought back by a carrier pigeon. It was dated July 13,
12.30 P. M., in latitude 82° 2', longitude 12° 5' East, and
stated that the balloon was moving eastward.
New islands on the southern coast of Franz Josef Land

discovered by Captain Robertson of the Dundee whaler Balæna.
Return of Jackson-Harmsworth expedition from three years'

exploration of Franz Josef Land and the region north of it.
Franz Josef Land was resolved into a group of islands and
almost entire]y mapped. Small parties journeying northward
over the ice, establishing depots of supplies, the most
northern in latitude 81° 21', discovered and named Victoria
Sea, the most northern open sea in the world.
Anglo-Australasian antarctic conference in London.

Journey of Andrew J. Stone through the Canadian Rockies, down
Mackenzie River and along the arctic coast, in search of rare
mammals and information concerning the native tribes. Mr.
Stone often had only one companion. He traveled rapidly, in
one period of five months covering 3,000 miles of arctic coast
and mountains, between 70° and 72° North latitude and between
117½° and 140° West longitude.
Belgian antarctic expedition under Captain Adrien de Gerlache

to lands south of America. Sailed from Antwerp to explore and
chart coast line, expecting to leave party to winter at Cape
Adare and explore interior. Near Alexander I. Land the Belgica
caught in the ice pack and held for a year, drifting as far
south as latitude 71° 36', in longitude 87° 39' West. Finally
released by the cutting of a canal through the ice. This
dreary winter the first spent by men far enough south to lose
sight of the sun. The continent found to be mountainous,
glaciated, and without land animals except a few insects,
though sea fowl abounded. One flowering grass, and a few
mosses, rock lichens, and fresh-water algæ constitute the
flora. Some 500 miles of coast chartered.
Expedition of Dr. K. J. V. Steenstrup to Greenland to study

the glaciers of Disko island.
Completion by Dr. Thoroddsen of his systematic exploration of

Iceland, begun in 1881.

Spitzbergen circumnavigated and surveyed by Dr. A. G.
Nathorst. Coast mapped and important scientific observations
made.
Pendulum observations made in Spitzbergen by Professor J. H.

Gore, with instruments of the United States Coast and Geodetic
Survey, for the determination of the force of gravity in that
latitude.
Cruise of Prince Albert of Monaco, on coast of Spitzbergen,

for the purpose of making scientific observations.
Some claim to Spitzbergen made by Russia. Never before claimed

by any nation.
German arctic expedition under Theodor Lerner to the islands

east of Spitzbergen, for scientific purposes and to obtain
news of Andrée if possible.
Andrée search expedition under J. Stadling sent to the Lena

delta, the mouth of the Yenesei and the islands of New Siberia
by the Swedish Anthropological and Geographical Society.
{408}

Conference on antarctic exploration held in the rooms of
the Royal Society, London, February 24.
Reconnoitring expedition by Danish party under Lieutenant G.

C. Amdrup, to east coast of Greenland. Coast explored and
mapped from Angmagsalik, 65¾ North latitude, to 67° 22'.
Remains of a small extinct Eskimo settlement found.
Second attempt by Walter Wellman to reach the north pole.

Wintered in Franz Josef Land, establishing an outpost, called
Fort McKinley, in latitude 81° North. In February Mr. Wellman,
with three companions, started northward and seemed likely to
succeed in their undertaking, but a serious accident befalling
Mr. Wellman, and an icequake destroying many dogs and sledges,
a hurried return to headquarters was necessary. Here important
scientific observations were made. The 82d parallel was
reached by the explorer.
German expedition for deep-sea exploration in antarctic

waters, in charge of Professor Carl Chun, on the Valdivia.
Southern ocean found to be of great depth.
British antarctic expedition under Borchgrevinck to Victoria

Land; the funds provided by Sir George Newnes. Latitude 78°
50' South reached, and the present position of the southern
magnetic pole determined.

Carefully planned expedition of Lieutenant Peary, purposing to
advance toward the pole by west coast of Greenland,
establishing food stations and depending upon picked Eskimos
for co-operation with his small party. In the last dash for
the pole, supply sledges to be sent back as emptied, and the
returning explorer, with two companions only, to be met by a
relief party of Eskimos. The Windward was presented by Mr.
Harmsworth for this expedition. Lieutenant Peary was disabled
for several weeks in 1898-9 by severe frost-bites, causing the
loss of seven toes. The Greeley records were found at Fort
Conger and sent back by the annual supply vessel. Sextant and
record of the Nares expedition found and sent back; presented
by Lieutenant Peary to the Lords of the Admiralty of Great
Britain and placed in the museum of the Royal Naval College at
Greenwich. Vessel sent to Greenland each summer to carry
supplies and bring back letters, carrying also small parties
of explorers, scientists, university students and hunters, to
be left at various points and picked up by the vessel on its
return.

Expedition of Captain Sverdrup to northern Greenland
Lieutenant Peary's especial field.
Having planned a polar expedition similar to Peary's he sailed

up the west coast, but the Fram was frozen in near Cape
Sabine. Sverdrup therefore explored the western part of
Ellesmere Land, then sailed again in an attempt to round the
northern coast of Greenland.
International conference held at Stockholm in June recommended

a program for hydrographical and biological work in the
northern parts of the Atlantic ocean, the North Sea, the
Baltic, and adjoining seas.
Scientific expedition of Edward Bay, a Dane, to Melville Bay,

Greenland.
Swedish expedition under Dr. A. G. Nathorst to search for

Andrée in eastern Greenland. Valuable observations made and
fjord-systems of King Oscar Fjord and Kaiser Franz Josef Fjord
mapped.
Explorations in Iceland by F. W. W. Howell and party.
Hydrographic surveys on the coasts of Iceland and the Färoe

Islands by MM. Holm and Hammer in the Danish guard-ship Diana.
Joint Russian and Swedish expedition to Spitzbergen, for the

measurement of a degree of the meridian. Owing to the
condition of the ice, the northern and southern surveying
parties unable to connect their work.
Explorations in Spitzbergen by the Prince of Monaco, with a

scientific staff.
Successful experimental voyage of the Russian Vice-Admiral

Makaroff in his ice-breaking steamer, the Yermak, north of
Spitzbergen.
Russian government expedition, to cost £5,400, to explore

northern shores of Siberia to mouths of the Obi and Yenesei.
Arctic expedition of the Duke of the Abruzzi. His ship, the

Stella Polare, was left at Crown Prince Rudolf Land during the
winter. The Duke became incapacitated by a fall and by the loss
of two joints from the fingers of his left hand, incurably
frost-bitten; but a small party under Captain Cagni pushed
northward till provisions were exhausted. Nansen's record was
beaten, the Italian party reaching latitude 86° 33', at about
56° East longitude. No land was found north or northwest of
Spitzbergen. Three men were lost from Cagni's party.
Exploration of Ellesmere Land, Greenland, by Dr. Robert Stein,

of the United States Geological Survey, Dr. Leopold Kann of
Cornell, and Samuel Warmbath of Harvard, who took passage in
the Peary supply ship Diana, trusting to chance for conveyance
home. Their totally inadequate outfit was generously augmented
by Peary's friends of the Diana. Dr. Kann returned in 1900,
leaving Dr. Stein.
Seward peninsula, the most westward extension of Alaska,

explored and surveyed by five government expeditions.
Exploration of the interior of northern Labrador by a party

from Harvard University. Soundings along the coast by schooner
Brave.
Second Danish expedition under Lieutenant Amdrup to east

Greenland, completing the work of 1898-9 by mapping the coast
between 67° 20' North and Cape Gladstone, about 70° North, and
making valuable scientific collections.
Swedish expedition, under Gustav Kolthoff, to eastern

Greenland, for study of the arctic fauna.
Swedish scientific expedition of Professor G. Kolthoff to

Spitzbergen and Greenland.
Exploration of Spitzbergen by a Russian expedition under

Knipovich.
Russian expedition to east coast of Nova Zembla by Lieutenant

Borissoff to complete survey of the islands.
Dr. Nansen's expedition under the leadership of Dr. J. Hjort,

for the physical and biological examination of the sea between
Norway, Iceland, Jan Mayen and Spitzbergen.

German expedition, under Captain Bade, to explore East
Spitzbergen, King Charles' Land and Franz Josef Land, and to
look for traces of Andrée.
Attempt of a German, Captain Bauendahl, to reach the north

pole, leaving his vessel in the ice north of Spitzbergen and
traveling over the ice with provisions for two years, weighing
ten tons.
{409}
Scientific expedition of Baron E. von Toll to the unexplored

Sannikoff Land, sighted in 1805 from the northern coast
islands of New Siberia. Preceded by a party which established
food depots at various places months before.
Three exploring parties sent to Alaska by the United States

Geological Survey.
Expedition sent by the Duke of the Abruzzi to Franz Josef Land

to search for the three men lost from his party in 1900.
North polar expedition under Mr. Evelyn B. Baldwin of the

United States Weather Bureau; splendidly equipped by Mr.
William Ziegler of New York. Mr. Baldwin, who has had arctic
experience with Lieutenant Peary and Mr. Wellman, will
probably proceed by way of Franz Josef Land.
Several expeditions to co-operate in exploration of the

antarctic region and to reach the south pole if possible. The
British expedition, long striven for by the Royal Geographical
Society and the Royal Society and made possible by L. W.
Longstaff's contribution of £25,000, to be under the command
of Captain Robert Scott and to explore the Victoria (90°-180°
East) and Ross (180°-90° West) quadrants,—in the main the
region south of the Pacific. The Weddell (90° West-0°,
Greenwich) and Enderby (0°-90 East) quadrants assigned to the
finely equipped German expedition, under Drygalski, which will
first explore south of the Indian Ocean. The Swedish expedition
under Dr. Nordenskïold to explore the lands south of America.
A private Scottish expedition under William S. Bruce to
explore the Weddell Sea region south of the Atlantic Ocean. An
Argentine expedition to visit the South Shetlands.
Projected expedition of Captain J. E. Bernier of Quebec, on

Nansen's principle, with a specially built vessel, to sail
through Bering Strait, coast Siberia to longitude 170° or 165°
East, then enter the ice. Sledging parties to push toward the
pole, marking the route with hollow signal poles (of aluminum)
packed with records and provisions, and maintaining
communication with the ship by wireless telegraphy. This is
one of two plans which he lays before the Canadian government.
The other contemplates a movement, with dogs and reindeers,
from Franz Josef Land, coming back to Spitzbergen, taking 12
or 14 men, all scientists.
Projected expedition of Herr Annschütz-Kämpfe, of Munich, to

the north pole, in a submarine boat capable of carrying five
men and remaining under water for fifteen hours at a time.
As this goes to press (April, 1901), a national antarctic

expedition is being fitted out, jointly, by the Royal
Geographical Society and the Royal Society of Great Britain,
assisted by a subsidy of £45,000 from the British government.
A steamer named the "Discovery," built especially for the
expedition, at Dundee, was launched in March, and is being
equipped with remarkable completeness. Special arrangements,
says "The Times," will be made for magnetic work, while
meteorology, geology and biology will be well cared for. "The
staff of navigating officers and of scientific specialists has
been carefully selected, and under Commander Robert Scott. R.
N., who will be in command of the expedition, their work, we
may be sure, will be so well organized that nothing of
importance will be neglected. There will be five navigating
officers, three of them belonging to the Royal Navy and two
others to the Royal Naval Reserve, while the special
scientific staff, including the two medical officers, will be
of equal strength. … Captain Scott is at present investigating
the question of the utility of balloons."
POLISH PARTY, in Austria.

AUSTRIA-HUNGARY: A. D. 1895-1896, and after.
POONA, The Plague at.

PLAGUE.
POPE LEO XIII.

PAPACY.
POPULATION:
Of Europe and countries peopled from Europe.

NINETEENTH CENTURY: EXPANSION.
POPULIST PARTY, The.

UNITED STATES OF AMERICA:
A. D. 1896 (JUNE-NOVEMBER);
and 1900 (MAY-NOVEMBER).
PORT ARTHUR: A. D. 1894.

Capture by Japanese.

CHINA: A. D. 1894-1895.

Trans-Siberian Railway.
Russo-Chinese Treaty.

RUSSIA IN ASIA: A. D. 1891-1900.

Lease to Russia.

CHINA: A. D. 1898 (MARCH-JULY).
----------PORTO RICO: Start--------

Map of Porto Rico.
PORTO RICO:
Area and Population.
In the testimony given, January 13, 1900, before the United

States Senate Committee on Pacific Islands and Porto Rico,
General George W. Davis, Military Governor of Porto Rico, gave
the following information: "The island of Puerto Rico has an area
of about 3,600 square miles, according to the best information
that now exists, but that area has to be verified, and it is
doubted if the area is quite so large. It has a population of
about a million, perhaps—certainly one of the most densely
populated areas of 3,000 or 4,000 square miles on the face of
the earth, approximating the density of population of Belgium,
I think, and considerably greater than that of any of our
thickly settled agricultural regions in the United States. New
England has about 200 to the square mile while Puerto Rico has
nearly 300. The inhabitants are mostly of Spanish
origin—emigrants from Spain during the last 400 years and
their descendants. There is a large representation from the
Canary Islands and the Balearic group in the Mediterranean, a
large number of Corsicans and their descendants, and
consequently they are French subjects, a few Germans, a few
English, and very few Americans before the occupation; a few
Venezuelans, a few from Santo Domingo, and a few Cubans, but
the most of the population is Spanish. Included in that
million are about 300,000 negroes and mulattoes, approximately
a little more than that number.
{410}
About one-third of the entire population is of the negro or
mixed race, what would be called in the United States
'colored' people. Of pure-blood negroes there are about
70,000, the remainder mulattoes, and all speaking Spanish, and
largely the slaves liberated in 1874. The number of slaves
liberated at that time was considerably less than the number

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Neuroimmunology 2nd Edition Aaron E.

S E R I E S C O -​E D ITORS-​I N-​C HIE F

Ilana Katz Sand, MD

This Book Is Dedicated to

Ellen, whose unwavering support makes everything possible and whose

To the memory of Dr. Izabella Rozenfeld, dear “Bella,” whose knowledge

To my mentors, who have given me the priceless gift of their knowledge

1 A Case of Monocular Blurred Vision 1

3 Irritability in a Man with Multiple Sclerosis 15

4 A Case of Myelitis with a Positive Anticardiolipin Antibody 23

5 A Case of Stiffness in the Legs and Gradual Difficulty

7 Recurrent Ulcers and a Brainstem Lesion 39

8 Ataxia and Orthostasis 45

9 Blurry Vision, Hearing Loss, and Constant Headache 49

10 The Snowball Effect 55

12 A Case of Cognitive Impairment and Ataxia 65

13 A Case of Fever and a Wrist Drop 69

14 Double Vision and Droopy Eyelids 75

15 A Case of Personality Change and Seizure 83

16 Drowsiness and Double Vision 89

18 Teratoma: “It’s Driving Me Crazy” 97

19 Gad-Awful Spasms 103

20 On the Right Tract 109

21 A Headache Gone Viral 113

22 To CIDP or Not to CIDP 117

23 Extinguishing a “Burning Fire” 121

24 Confusion, Muscle Cramps, and Weight Loss 127

25 The Unforgettable Encephalitis 133

26 The Peppered Brainstem 139

27 A Case of a Fall After a Trip 143

28 A Case of Relapsing Visual Loss 149

29 Checks and Balances 153

30 A Case of Intractable Vomiting 157

31 A Case of Cognitive Change in HIV 163

32 A Case of Progressive Myelopathy 167

33 A Case of Cranial Neuropathies and Leptomeningeal

34 A Case of Diabetes Insipidus and Enhancing Brain

35 A Case of Optic Neuritis and Leg Weakness 183

36 A Man with Multiple Sclerosis and Continuing Disease Activity

37 A Case of Syncope and Impaired Micturition 195

38 A Case of Longitudinally Extensive Transverse Myelitis 201

39 A Perplexing Pattern of Weakness 205

40 Progressive Numbness and Tingling 209

Many of the cases described in this book have involved challenging

A 26-​year-​old white woman consults you one month

What do you do now?

This patient presents with optic neuritis, which may be a monophasic

2 WHAT DO I DO NOW? Neuroimmunology

Dissemination in time (DIT) can be satisfied by the appearance of any new

1 A Case of Monocular Blurred Vision 3

TABLE 1.1 2017 Revised McDonald Criteria for Determination

Attacks Lesions Additional Requirements

2 or more 2 or more None

1 1 DIS and DIT

0 1 ❑ >1 year of progression and

4 WHAT DO I DO NOW? Neuroimmunology

1 A Case of Monocular Blurred Vision 5

KEY POINTS TO REMEMBER

• Multiple sclerosis is an inflammatory demyelinating disease of

6 WHAT DO I DO NOW? Neuroimmunology

1 A Case of Monocular Blurred Vision 7

A 25-​year-​old man presents with two days of double

What do you do now?

S E R I E S C O -E D ITORS-I N-C HIE F

24 Confusion, Muscle Cramps, and Weight Loss  127

25 The Unforgettable Encephalitis  133

26 The Peppered Brainstem  139

27 A Case of a Fall After a Trip  143

28 A Case of Relapsing Visual Loss  149

29 Checks and Balances  153

30 A Case of Intractable Vomiting  157

31 A Case of Cognitive Change in HIV  163

32 A Case of Progressive Myelopathy  167

35 A Case of Optic Neuritis and Leg Weakness  183

37 A Case of Syncope and Impaired Micturition  195

38 A Case of Longitudinally Extensive Transverse Myelitis  201

39 A Perplexing Pattern of Weakness  205

40 Progressive Numbness and Tingling  209

A 26-year-old white woman consults you one month

1 A Case of Monocular Blurred Vision 3

1 A Case of Monocular Blurred Vision 5

1 A Case of Monocular Blurred Vision 7

A 25-year-old man presents with two days of double

This patient presents with a post-vaccinal neurological syndrome with mul-

Treatment of ADEM generally involves high- dose intravenous

• ADEM, an immune-mediated, inflammatory, demyelinating

A 32-year-old high school history teacher had no

This patient has classical relapsing-remitting MS. He was appropriately

3 Irritability in a Man with MS 17

3 Irritability in a Man with MS 19

• PML is now a well-recognized, albeit infrequent, consequence of

3 Irritability in a Man with MS 21

A 30-year-old woman presents with difficulty walking.

I. One or more clinical episodes of arterial, venous, or small vessel

I. Anticardiolipin antibody of immunoglobulin (Ig) G and/or IgM isotype

A 40-year-old woman with a 20-year history of