V.1. An autopsy is performed of an 81-year-old woman with a 30-year
history of multiple sclerosis (MS). Which of the following charac-
teristics would most likely be seen in the brain autopsy of this
patient?
a. Creutzfeldt-Peters cells
b. Perivascular complement deposition
c. Extensive cortical demyelination
d. Epidural hematoma
e. Highly inflamed, active white-matter demyelinating lesions
V.1. Answer c.
The patient had a long history of MS, and her brain autopsy
most likely will show the pathologic characteristics of chronic
MS. Cortical demyelination is a typical characteristic of MS
that lasts a long time and becomes more extensive at the
chronic stage. Creutzfeldt-Peters cells are atypical reactive
astrocytes with abundant cytoplasm and fragmented nuclear
inclusions that usually are seen in the active demyelinating
lesions of MS and myelin oligodendrocyte glycoprotein anti-
body-associated disorder and, occasionally, in tumors.
Perivascular complement deposition is seen in the neuromy-
elitis optica pathologic evaluation and is not a characteristic
of MS. Epidural hematoma might be present because of
trauma; however, the clinical manifestation did not indicate
this occurrence. Highly inflamed, active white-matter demy-
elinating lesions are a characteristic of the acute stage of MS
and usually are accompanied with prominent corresponding
central nervous system manifestation. These lesions are
unlikely to be present in this patient with chronic MS.
V.2. A 13-year-old boy had the first episode of cervicothoracic longi-
tudinally extensive transverse myelitis 14 months ago. He was
treated with corticosteroid therapy, with variable benefit. After a
relapse, he received plasma exchange. He now presents with
altered mental status and dysarthria, and magnetic resonance
imaging shows lesions in both the frontal lobe and the pons. The
frontal lobe lesion was biopsied, and the pathologic report cited
“confluent and focal perivascular myelin loss involving both cor-
tex and subcortical white matter” and “consistent with demye-
linating disease.” Which of the following tests is best to confirm
the diagnosis for this patient?
a. Serum anti–aquaporin 4 (AQP4) antibody test
b. Cerebrospinal fluid (CSF) anti-AQP4 antibody test
c. Serum anti–myelin oligodendrocyte glycoprotein (MOG) antibody
test
d. CSF anti-MOG antibody test
e. Serum and CSF oligoclonal bands
V.2. Answer c.
The longitudinally extensive transverse myelitis cortical
lesions with both confluent and perivascular demyelination
patterns present in a pediatric patient with relapsing episodes
is most suggestive of myelin oligodendrocyte glycoprotein
antibody disorder (MOGAD). Cortical demyelinating lesions
have not been seen in AQP4–immunoglobulin G neuromyeli-
tis optica spectrum disorder, and thus the anti-AQP4 antibody
test is not the first choice for the diagnosis. Anti-MOG anti-
body is present in the serum of a patient with MOGAD, but it
is rare in CSF. Oligoclonal bands are not specific for MOGAD.
V.3. A 22-year-old woman was admitted to the hospital for a 2-week
history of irritability. Two days before admission, the patient
was noted to be forgetful and appeared disoriented. Magnetic
resonance imaging showed extensive cerebral edema. The
patient died 5 days later. Brain autopsy showed massive cerebral
edema and multiple demyelinating lesions characterized by cir-
cumferential rings of myelin loss alternating with rings of myelin
preservation. What is the most likely diagnosis for this patient?
a. Prototypic multiple sclerosis (MS)
b. Marburg variant MS
c. Aquaporin 4–immunoglobulin G neuromyelitis optica spectrum
disorder (NMOSD)
d. Myelin oligodendrocyte glycoprotein antibody disorder (MOGAD)
e. Baló concentric sclerosis
V.3. Answer e.
The pathology report of circumferential rings of myelin loss
alternating with rings of myelin preservation describes one of
the typical characteristics of Baló concentric sclerosis. The
patient’s history showing that her condition worsened quickly
is consistent with this diagnosis. Prototypic MS has a better
short-term prognosis and shows confluent cortical and white-
matter demyelination. Besides the typical prototypic MS
pathologic characteristics, Marburg variant MS also might
show focal necrosis. NMOSD and MOGAD often show spinal
cord involvement and confluent perivascular demyelination.
V.4. Which of the following syndromes is atypical of a clinically iso-
lated syndrome?
a. Optic neuritis
b. Tonic spasms
c. Partial myelitis
d. Internuclear ophthalmoplegia
e. Facial numbness
V.4. Answer b.
The term clinically isolated syndrome refers to an underly-
ing pathology of multiple sclerosis. The presence of tonic
spasms should raise concern for neuromyelitis optica.
Neuromyelitis optica–immunoglobulin G and myelin oligo-
dendrocyte glycoprotein–immunoglobulin G should be
tested in patients with this symptom.
V.5. In a patient with an isolated optic neuritis and without brain
magnetic resonance imaging (MRI) abnormalities, which of the
following is the rate of conversion to multiple sclerosis over the
following 15 years?
a. 10%
b. 25%
c. 50%
d. 75%
e. 100%
V.5. Answer b.
Data from the Optic Neuritis Treatment Trial showed that
patients with a single episode of optic neuritis without MRI
brain abnormalities had a 25% chance of conversion to clin-
ically definite multiple sclerosis over a 15-year period.
V.6. Which of the following characteristics, when present, is least
associated with a risk of disability in patients presenting with
new-onset multiple sclerosis?
a. Male sex
b. African American ethnicity
c. Spinal cord lesions
d. Optic neuritis
e. More than 2 gadolinium-enhancing T1-weighted lesions
V.6. Answer d.
Drug selection for disease-modifying therapy for patients
with newly diagnosed multiple sclerosis is challenging,
partly because of the paucity of head-to-head trials between
disease-modifying therapy agents and partly because of
uncertainty in the efficacy of these medications for long-
term prevention of disability. A strong argument can be
made for use of highly potent medications in patients with a
high risk of disability, however. The presence of poor recov-
ery from the initial attack, male sex, African American ethnicity, brainstem and spinal cord lesions, and a large vol-
ume of T2-weighted lesions or T1 gadolinium enhancing
lesions (or both) at presentation or early in the course of
treatment should prompt consideration of highly active ther-
apy in these patients.
V.7. A 25-year-old woman with the diagnosis of multiple sclerosis
(MS) is taking propranolol for migraine and modafinil for fatigue.
Because of relapsing-remitting MS, a disease-modifying drug is
considered. Which of the following would first need to be
weighed before considering fingolimod?
a. Modafinil would need to be discontinued because of concerns of
liver toxicity
b. Spinal fluid examination for herpes simplex virus (HSV) is manda-
tory before starting fingolimod therapy
c. Propranolol would need to be discontinued because of the risk of
heart block
d. Renal function should be assessed at baseline and at 6 weeks
after starting fingolimod therapy
e. An echocardiogram should be obtained at baseline and at 1 year
because of the risk of cardiomyopathy
V.7. Answer c.
Fingolimod may cause bradycardia and heart block. A base-
line electrocardiogram is recommended. β-Blockers or cal-
cium channel blockers, or both, would increase the risk of
heart block and should be discontinued before use of fingo-
limod. Liver function tests require monitoring but not renal
function. Cardiomyopathy is more a concern for mitoxan-
trone and not for fingolimod. Use of fingolimod also requires
assessment of varicella zoster virus status before use and not
HSV status.
V.8. A patient with active clinical and radiographic multiple sclerosis
(MS) undergoes treatment with intravenous (IV) methylpredniso-
lone but has poor recovery. What alternative therapy could be
considered?
a. Interferon beta
b. An additional 2-week trial of IV methylprednisolone
c. Plasma exchange
d. Mitoxantrone
e. Methotrexate
V.8. Answer c.
During an MS relapse, high-dose corticosteroid treatment is
typically prescribed. If a patient has poor functional recov-
ery within 3 months of a relapse, plasma exchange or cyclo-
phosphamide (or both) could be considered. (See Figure
66.2.)
V.9. Which of the following statements is true regarding choice of a
disease-modifying drug (DMD)?
a. DMDs may affect lesion burden on magnetic resonance imaging
(MRI) but not symptomatic relapses
b. DMDs reduce the rate of progression to disability in multiple
sclerosis (MS)
c. Patients should consider the most efficacious DMD without con-
sideration of preference or cost
d. Patients with mild disease should consider mitoxantrone because
they have the most to gain from early suppression of MS
e. DMDs should be considered early on for treatment of patients
with radiographically isolated MS
V.9. Answer a.
DMDs may affect lesion burden on MRI but not symptomatic
relapses. They may not affect the progressive course of the
disease (axonal loss). Cost, patient preferences, and comor-
bidities should be considered when selecting a DMD. (See
Box 66.1 and Figure 66.2.) Patients who have radiographi-
cally isolated MS or good recovery with no spinal cord or
brainstem lesions and have low disease burden may be
observed before consideration of a DMD. In the consideration
of DMD treatment, clinical parameters and radiographic
imaging should guide which tier of medications to select.
V.10. A 38-year-old woman presents with rapid onset of bilateral optic
neuritis that has initial robust improvement with corticosteroids
but has relapsed multiple times while attempting corticosteroid
therapy taper. At onset, fundoscopy showed optic disc edema,
and magnetic resonance imaging (MRI) of the orbits showed
optic nerve sheath enhancement of the anterior portion of the
optic nerves bilaterally. What is the most likely diagnosis?
a. Sarcoidosis
b. Multiple sclerosis
c. Myelin oligodendrocyte glycoprotein antibody disorder (MOGAD)
d. Aquaporin-4–immunoglobulin G seropositive neuromyelitis optica
e. Inflammatory connective tissue disease
V.10. Answer c.
Relapsing corticosteroid-responsive bilateral optic neuritis
with the described MRI findings is a classic characteristic of
MOGAD.
V.11. A 63-year-old woman presents with rapid-onset paraparesis and
lower-extremity sensory loss over 2 days. Magnetic resonance imaging of the spinal cord shows a long lesion over the course of
6 vertebral body segments throughout the thoracic cord, with
patchy gadolinium enhancement throughout. The patient reports
a previous episode of intense hiccups and relentless nausea and
vomiting lasting 2 weeks about 1 year prior, with negative gastro-
intestinal tract evaluation at the time. What is the most likely
underlying diagnosis?
a. Multiple sclerosis
b. Chronic lymphocytic inflammation with pontine perivascular
enhancement responsive to corticosteroids
c. Behçet syndrome
d. Aquaporin-4–immunoglobulin G (AQP4-IgG) seropositive neuro-
myelitis optica spectrum disorder
e. Myelin oligodendrocyte glycoprotein antibody disorder
V.11. Answer d.
Area postrema syndrome with severe nausea, vomiting, and
hiccups is a classic heralding characteristic seen in some
patients with AQP4-IgG seropositive neuromyelitis optica
spectrum disorder. Therefore, despite some of the other
causes listed that can contribute to a long spinal cord lesion,
neuromyelitis optica would strongly be suspected with this
history.
V.12. Which of the following is required before making a diagnosis of
“probable” neurosarcoidosis?
a. Elevation of serum angiotensin-converting enzyme (ACE) level
b. Elevation of cerebrospinal fluid (CSF) ACE level
c. Lymphocytic pleocytosis on CSF analysis
d. Pachymeningeal gadolinium enhancement
e. Systemic tissue diagnosis showing nonnecrotizing granulomas
V.12. Answer e.
Biopsy evidence of sarcoidosis outside of the nervous sys-
tem is required to confirm a diagnosis of “probable” neuro-
sarcoidosis and is recommended in all cases of suspected
neurosarcoidosis when possible.
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