Postreading

SELF-ASSESSMENT
AND CME

Self-Assessment
and CME Test—Preferred
Responses
By Douglas J. Gelb, MD, PhD, FAAN; D. Joanne Lynn, MD, FAAN

PERIPHERAL NERVE AND MOTOR NEURON DISORDERS

Following are the preferred responses to the questions in the Postreading
Self-Assessment and CME Test in this Continuum issue. The preferred
response is followed by an explanation and a reference with which you
may seek more specific information. You are encouraged to review the
responses and explanations carefully to evaluate your general
understanding of the article topic. The comments and references included
with each question are intended to encourage independent study.

US PARTICIPANTS: Upon completion of the Postreading Self-Assessment and

CME Test and issue evaluation online at continpub.com/CME, participants
may earn up to 20 AMA PRA Category 1 Credits™ toward SA-CME. US
participants have up to 3 years from the date of publication online to earn
SA-CME credits.

CANADIAN PARTICIPANTS: This

program is an Accredited Self-Assessment
Program (Section 3) as defined by the Maintenance of Certification
Program of the Royal College of Physicians and Surgeons of Canada and
approved by the University of Calgary Office of Continuing Medical
Education and Professional Development. Canadian participants should
visit MAINPORT (www.mainport.org) to record learning and outcomes.
Canadian participants can claim a maximum of 20 hours per issue (credits
are automatically calculated).

ARTICLE 1: A STRUCTURED APPROACH TO THE DIAGNOSIS OF PERIPHERAL

NERVOUS SYSTEM DISORDERS

1 The preferred response is D (saphenous). The saphenous nerve has no motor

component, so a focal lesion of the saphenous nerve results in a pure sensory
syndrome. Lesions of mixed nerves can also cause pure or predominantly
sensory syndromes, especially in the early stages, in situations in which
preferential involvement of sensory fascicles exists. For more information, refer

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POSTREADING TEST—PREFERRED RESPONSES

to page 1137 of the Continuum article “A Structured Approach to the Diagnosis of

Peripheral Nervous System Disorders.”

2 The preferred response is B (brachioradialis). Patients with monomelic

amyotrophy (Hirayama disease) primarily have involvement of muscles
innervated by the C7, C8, and T1 roots, resulting in progressive painless
weakness in the hand and forearm, with sparing of the brachioradialis muscle,
which derives its innervation from the C5 and C6 roots. For more information,
refer to page 1150 of the Continuum article “A Structured Approach to the
Diagnosis of Peripheral Nervous System Disorders.”

3 The preferred response is C (posterior interosseous). Most mononeuropathies

will be associated with both sensory and motor manifestations. The most
common mononeuropathies to cause a pure motor syndrome are those involving
nerves without sensory components, such as the posterior interosseous,
anterior interosseous, or suprascapular nerves. Occasionally, entrapment or
other pathologic processes involving a mixed nerve will result in a pure motor
presentation because of preferential sparing of fascicles serving sensation. For
more information, refer to page 1136 of the Continuum article, “A Structured
Approach to the Diagnosis of Peripheral Nervous System Disorders.”

4 The preferred response is E (vasculitic neuropathy). Mononeuritis multiplex

generally presents with significant initial asymmetry affecting multiple individual
nerves in both distal and proximal distributions. Vasculitis and other systemic
inflammatory disorders, lymphoma, diabetes, and viral infection are common
causes of multiple mononeuropathies. Acute inflammatory demyelinating
polyradiculoneuropathy (AIDP) and chronic inflammatory demyelinating
polyradiculoneuropathy (CIDP) most often present as symmetric distal and
proximal distributions. Charcot-Marie-Tooth disease would be expected to
present in a distal symmetric pattern and brachial amyotrophic diplegia in a
proximal symmetric pattern. For more information, refer to page 1139 of the
Continuum article, “A Structured Approach to the Diagnosis of Peripheral
Nervous System Disorders.”

ARTICLE 2: DIABETES AND METABOLIC DISORDERS AND THE PERIPHERAL

NERVOUS SYSTEM

5 The preferred response is C (length-dependent axonal polyneuropathy). The

most common type of diabetic neuropathy is length-dependent axonal
polyneuropathy, which can predominantly affect small-diameter or
large-diameter axons, or both. This type of neuropathy accounts for
approximately 50% to 75% of cases of diabetic neuropathy. Mononeuropathies are
common, and diabetes causes nerves to be more vulnerable to compression.
Autonomic neuropathies are not uncommon and may have multiple different

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 manifestations. Acute diabetic radiculoplexopathies and treatment-induced
neuropathy are relatively uncommon neurologic manifestations of diabetes. For
more information, refer to page 1162 of the Continuum article “Diabetes and
Metabolic Disorders and the Peripheral Nervous System.”

6 The preferred response is B (hyperglycemia). For type 1 diabetes, the risk of

neuropathy is directly linked to glycemic control. Optimal glycemic control in
type 1 diabetes reduces the relative risk of development of neuropathy by
almost 80%. In contrast, tight glycemic control is much less effective at reducing
the risk of development of neuropathy in type 2 diabetes, and other individual
components of the metabolic syndrome appear to contribute significantly to
the overall risk. For more information, refer to page 1163 of the Continuum article
“Diabetes and Metabolic Disorders and the Peripheral Nervous System.”

7 The preferred response is C (microvasculitis). This case is most consistent with

diabetic lumbosacral radiculoplexus neuropathy or diabetic amyotrophy. This
entity is notable for severe pain starting in one lower limb and frequently
progressing to the other associated with the development of proximal weakness
and relative sparing of sensory functions. It is often associated with weight loss.
The underlying pathophysiology has been shown to be a microvasculitic process
causing ischemic nerve injury. It typically progresses over months and takes 1 to
2 years for incomplete recovery to occur. For more information, refer to
page 1171 of the Continuum article “Diabetes and Metabolic Disorders and the
Peripheral Nervous System.”

8 The preferred response is E (orthostatic hypotension). Diabetic cardiovascular

autonomic neuropathy includes manifestations of increased resting heart rate,
diminished heart rate response to physiologic stress, decreased cardiac output,
and orthostatic hypotension. Related to vagus nerve denervation, diabetic
cardiovascular autonomic neuropathy is associated with increased mortality,
especially when orthostatic hypotension is present. For more information, refer
to page 1173 of the Continuum article “Diabetes and Metabolic Disorders and the
Peripheral Nervous System.”

ARTICLE 3: GUILLAIN-BARRÉ SYNDROME

9 The preferred response is E (severe urinary sphincter dysfunction at onset of

symptoms). Most patients with acute inflammatory demyelinating
polyradiculoneuropathy (AIDP) present with back pain, radicular pain, painful
paresthesia, or other sensory symptoms. Cranial nerve symptoms, including
facial weakness, are common. Orthostatic hypotension and other features of
autonomic dysfunction may also occur in AIDP. Although ascending weakness is
the classic pattern, the weakness may start proximally. Severe sphincter
dysfunction at presentation is unusual and suggests the possibility of spinal

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POSTREADING TEST—PREFERRED RESPONSES

cord, conus medullaris, or cauda equina dysfunction. For more information, refer
to page 1186 of the Continuum article “Guillain-Barré Syndrome.”

10 The preferred response is E (severity of weakness). A functional outcome

model based on age, the presence or absence of preceding diarrhea, and
severity of weakness (quantified using the Medical Research Council [MRC]
sum score) predicts the probability of walking independently at 1, 3, and
6 months. For more information, refer to page 1190 of the Continuum article
“Guillain-Barré Syndrome.”

11 The preferred response is E (GQ1b). This patient has ophthalmoparesis, ataxia,

and areflexia, the classic triad of the Miller Fisher variant of Guillain-Barré
syndrome. More than 80% of patients with Miller Fisher syndrome have
anti-GQ1b antibodies in their serum. For more information, refer to page 1189 of
the Continuum article “Guillain-Barré Syndrome.”

ARTICLE 4: CHRONIC INFLAMMATORY DEMYELINATING

POLYRADICULONEUROPATHY AND ITS VARIANTS

12 The preferred response is D (sural). The presence of the sural sparing pattern
on electrophysiologic studies is a hallmark of chronic inflammatory
demyelinating polyradiculoneuropathy (CIDP) and other acquired primary
demyelinating neuropathies. For more information, refer to page 1208
of the Continuum article “Chronic Inflammatory Demyelinating
Polyradiculoneuropathy and Its Variants.”

13 The preferred response is C (infectious or neoplastic polyradiculitis). Chronic

inflammatory demyelinating polyradiculoneuropathy (CIDP) and most of its
variants are associated with a CSF albuminocytologic dissociation with
elevated protein but normal cell count or a normal profile as in multifocal
CIDP. A significant CSF pleocytosis should raise concern for the possibility
of an infectious or neoplastic cause of symptoms such as human
immunodeficiency virus (HIV), lymphoma, or leptomeningeal carcinomatosis.
For more information, refer to page 1207 of the Continuum article “Chronic
Inflammatory Demyelinating Polyradiculoneuropathy and Its Variants.”

14 The preferred response is E (nodal and paranodal antibodies).

Approximately 10% of patients with chronic inflammatory demyelinating
polyradiculoneuropathy (CIDP) will have autoantibodies directed against
paranodal or nodal antigens. These nodo-paranodopathies should be
suspected if the presentation includes distal-predominant presentation,
sensory ataxia, prominent tremor, and poor response to the usual beneficial
treatments. Some patients with this variant have been observed to respond

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 to rituximab. For more information, refer to page 1217 of the Continuum article
“Chronic Inflammatory Demyelinating Polyradiculoneuropathy and Its Variants.”

15 The preferred response is B (conduction block). Multifocal motor neuropathy

(MMN) generally presents as a painless asymmetric progressive weakness
associated with cramps and fasciculations. These findings are also common in
amyotrophic lateral sclerosis. However, conduction block in multiple nerves is
the hallmark of MMN. For more information, refer to page 1214 of the Continuum
article “Chronic Inflammatory Demyelinating Polyradiculoneuropathy and Its
Variants.”

ARTICLE 5: CHARCOT-MARIE-TOOTH DISEASE AND OTHER HEREDITARY

NEUROPATHIES

16 The preferred response is D (patchy slowing and abnormal temporal

dispersion on nerve conduction studies). Inherited demyelinating neuropathies
usually cause uniform slowing of conduction velocities, although exceptions
exist. In contrast, patchy slowing, partial or total conduction blocks, and
abnormal temporal dispersion are common in acquired demyelinating
neuropathies. Patients with inherited neuropathies often have no affected
family members because of de novo mutations. Areflexia, weakness of ankle
dorsiflexion and plantar flexion, and slow conduction velocities are typical of
both inherited and acquired demyelinating neuropathies. For more information,
refer to page 1229 of the Continuum article “Charcot-Marie-Tooth Disease and
Other Hereditary Neuropathies.”

17 The preferred response is D (peripheral myelin protein 22). The most common
form of Charcot-Marie-Tooth disease (CMT) is type 1A, which accounts for
approximately 70% of all CMT1 cases and more than 50% of all CMT cases.
CMT1A is caused by mutations in the gene for peripheral myelin protein 22. For
more information, refer to page 1230 of the Continuum article “Charcot-Marie-
Tooth Disease and Other Hereditary Neuropathies.”

18 The preferred response is D (hereditary neuropathy with liability to pressure

palsies [HNPP]). In most patients with HNPP, the genetic cause is a deletion in
the gene for peripheral myelin protein 22, the same gene responsible for
Charcot-Marie-Tooth disease type 1A (CMT1A). For more information, refer to
page 1239 of the Continuum article “Charcot-Marie-Tooth Disease and Other
Hereditary Neuropathies.”

19 The preferred response is E (transthyretin amyloidosis). Two small

oligonucleotide-based gene therapies have been approved by the US Food and
Drug Administration (FDA) for transthyretin amyloidosis. One (patisiran) is a small

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POSTREADING TEST—PREFERRED RESPONSES

interfering RNA, and the other (inotersen) is an antisense oligonucleotide. For

more information, refer to page 1243 of the Continuum article “Charcot-Marie-
Tooth Disease and Other Hereditary Neuropathies.”

ARTICLE 6: PERIPHERAL NEUROPATHIES ASSOCIATED WITH VASCULITIS

AND AUTOIMMUNE CONNECTIVE TISSUE DISEASE

20 The preferred response is E (polyarteritis nodosa). Polyarteritis nodosa

is a vasculitis that affects medium blood vessels such as arterioles. Polyarteritis
nodosa is one of the vasculitides that is most frequently associated with
neuropathy. For more information, refer to page 1258 of the Continuum article
“Peripheral Neuropathies Associated With Vasculitis and Autoimmune
Connective Tissue Disease.”

21 The preferred response is A (drug-induced vasculitis). Antineutrophil

cytoplasmic antibody (ANCA) positivity is common in multiple types of
vasculitis, including those associated with infections, inflammatory bowel
disease, and other autoimmune diseases. ANCA specificity to myeloperoxidase
is typically seen in microscopic polyangiitis and eosinophilic granulomatosis
with polyangiitis. Proteinase 3 specificity is typically seen in granulomatosis with
polyangiitis. If positivity for both myeloperoxidase and proteinase 3 is present,
then drug-induced vasculitis should be suspected. For more information, refer
to page 1265 of the Continuum article “Peripheral Neuropathies Associated
With Vasculitis and Autoimmune Connective Tissue Disease.”

22 The preferred response is E (serum positive for hepatitis B virus antigen). The
American College of Rheumatology classification criteria require that patient
presentations fulfill three or more of 10 criteria for the identification of
polyarteritis nodosa vasculitis patients for research purposes. The presence of
hepatitis B virus antigen is one characteristic supportive of a diagnosis of
polyarteritis nodosa. Antineutrophil cytoplasmic antibody antibodies,
glomerulopathy, adult-onset asthma, and cryoglobulinemia are generally not
present in patients with polyarteritis nodosa. For more information, refer to
page 1266 of the Continuum article “Peripheral Neuropathies Associated With
Vasculitis and Autoimmune Connective Tissue Disease.”

23 The preferred response is A (cryoglobulinemic vasculitis). The majority of

patients with cryoglobulinemia present with the classic triad of generalized
weakness, palpable purpura, and diffuse joint pain. Associated neuropathy may
occur in several different forms: distal and symmetric, small fiber predominant,
or multifocal neuropathy. Diagnosis requires careful testing for cryoglobulins,
and treatment must be focused at the underlying causative condition. For more
information, refer to page 1267 of the Continuum article “Peripheral

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 Neuropathies Associated with Vasculitis and Autoimmune Connective Tissue
Disease.”

24 The preferred response is B (eosinophilic granulomatosis with polyangiitis).

This presentation of subacute multifocal neuropathy with adult-onset asthma is
most consistent with eosinophilic granulomatosis with polyangiitis. Eosinophilic
granulomatosis with polyangiitis is accompanied by peripheral blood
eosinophilia and extravascular granulomatosis, which can affect multiple
organs. Patients with neuropathy have a high incidence of myeloperoxidase
antineutrophil cytoplasmic antibody positivity. For more information, refer to
page 1265 of the Continuum article “Peripheral Neuropathies Associated with
Vasculitis and Autoimmune Connective Tissue Disease.”

ARTICLE 7: PERIPHERAL NEUROPATHIES DUE TO VITAMIN AND MINERAL

DEFICIENCIES, TOXINS, AND MEDICATIONS

25 The preferred response is D (vitamin B12 [cobalamin]). Long-term metformin

use has been associated with poor absorption of vitamin B12 (cobalamin). For
more information, refer to page 1281 of the Continuum article “Peripheral
Neuropathies Due to Vitamin and Mineral Deficiencies, Toxins, and
Medications.”

26 The preferred response is C (vitamin B6 [pyridoxine]). Vitamin B6 toxicity

causes direct damage to dorsal root ganglion sensory neurons.
For more information, refer to page 1285 of the Continuum article “Peripheral
Neuropathies Due to Vitamin and Mineral Deficiencies, Toxins, and
Medications.”

27 The preferred response is C (lead). Lead toxicity classically produces a

neuropathy with a motor-predominant upper extremity phenotype. For more
information, refer to page 1290 of the Continuum article “Peripheral
Neuropathies Due to Vitamin and Mineral Deficiencies, Toxins, and
Medications.”

28 The preferred response is E (oxaliplatin). Toxicity from cisplatin, oxaliplatin, or

carboplatin manifests as a sensory ganglionopathy; in addition, oxaliplatin causes
acute cold-induced hyperalgesia, which is probably due to increased neuronal
excitability resulting from oxaliplatin’s effect on voltage-gated sodium
channels. For more information, refer to page 1293 of the Continuum article
“Peripheral Neuropathies Due to Vitamin and Mineral Deficiencies, Toxins, and
Medications.”

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POSTREADING TEST—PREFERRED RESPONSES

29 The preferred response is B (ciguatoxin). Ciguatoxin (ciguatera toxin) is

produced by a dinoflagellate and concentrated as it moves up the food chain
to reef-dwelling fish, such as barracuda, grouper, and snapper. It produces
gastrointestinal symptoms and a neuropathy, which often has the distinctive
feature of temperature inversion, in which cold objects are perceived as very
hot. For more information, refer to page 1296 of the Continuum article
“Peripheral Neuropathies Due to Vitamin and Mineral Deficiencies, Toxins, and
Medications.”

ARTICLE 8: MANAGEMENT OF NEUROPATHIC PAIN IN POLYNEUROPATHY

30 The preferred response is B (diffuse allodynia). Opioid-induced hyperalgesia

should be considered when patients report worsening pain rather than
improvement with opioid treatment and experience diffuse allodynia. The
underlying mechanisms are thought to involve neuroplastic changes and opioid
activation of immune cells with resultant sensitization of opioid receptors. For
more information, refer to page 1310 of the Continuum article “Management of
Neuropathic Pain in Polyneuropathy.”

31 The preferred response is A (α-lipoic acid). α-Lipoic acid is an antioxidant that

has been shown to provide greater symptomatic relief compared to placebo
for patients with painful diabetic neuropathy, although several large clinical
trials have yielded conflicting evidence. α-Lipoic acid is generally well tolerated
and is a good option for use as second-line or adjunctive therapy and for
patients who are averse to conventional pharmacotherapeutics. Anecdotal
reports of improvement in neuropathy symptoms exist for curcumin. For more
information, refer to page 1311 of the Continuum article “Management of
Neuropathic Pain in Polyneuropathy.”

ARTICLE 9: AMYOTROPHIC LATERAL SCLEROSIS AND OTHER MOTOR

NEURON DISEASES

32 The preferred response is A (behavioral variant frontotemporal dementia). Of

the 5% to 15% of patients with amyotrophic lateral sclerosis who have frank
frontotemporal dementia, the majority have the behavioral variant. For more
information, refer to page 1326 of the Continuum article “Amyotrophic Lateral
Sclerosis and Other Motor Neuron Diseases.”

33 The preferred response is A (C9orf72). Hexanucleotide expansions in the

noncoding region of C9orf72 are the most common cause of familial
amyotrophic lateral sclerosis, accounting for 40% of familial cases in a European
amyotrophic lateral sclerosis population. For more information, refer to

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 page 1335 of the Continuum article “Amyotrophic Lateral Sclerosis and Other
Motor Neuron Diseases.”

34 The preferred response is A (androgen receptor). Spinal bulbar muscular

atrophy, an X-linked disorder caused by a trinucleotide repeat expansion in the
androgen receptor gene, typically presents in adulthood. It is characterized by
weakness, fasciculations, prominent facial twitching, and symptoms of
androgen sensitivity, including gynecomastia and reduced fertility. Most
patients also have sensory nerve involvement. For more information, refer to
page 1330 of the Continuum article “Amyotrophic Lateral Sclerosis and Other
Motor Neuron Diseases.”

ARTICLE 10: SPINAL MUSCULAR ATROPHY

35 The preferred response is B (spinal muscular atrophy type 1). Spinal muscular
atrophy (SMA) type 1 is the most common form of SMA and represents
approximately 60% of infants born with a SMA genotype. Infants affected with
SMA type 1 present in the first few months of life with muscle weakness and
delay or absence of early motor milestones. For more information, refer to
page 1352 of the Continuum article, “Spinal Muscular Atrophy.”

36 The preferred response is C (gene replacement of SMN1). Approved

by the US Food and Drug Administration (FDA) in 2019, onasemnogene
abeparvovec-xioi is an adeno-associated virus 9–delivered SMN1 gene
replacement therapy administered as a single IV dose. Clinical trials
demonstrated therapeutic benefits, including attainment of ability to sit
unassisted for at least 5 seconds in 92% of treated infants and improved
survival free of respiratory intervention. For more information, refer to
page 1357 of the Continuum article, “Spinal Muscular Atrophy.”

37 The preferred response is C (intrathecal). Nusinersen is an antisense

oligonucleotide that improves the inclusion of exon 7 during splicing of the SMN2
gene and is dosed intrathecally every 14 days for the first three loading doses,
followed by a dose 1 month later and then every 4 months for life. For more
information, refer to page 1363 of the Continuum article, “Spinal Muscular Atrophy.”

ARTICLE 11: PERIPHERAL NEUROPATHIES ASSOCIATED WITH MONOCLONAL

GAMMOPATHIES

38 The preferred response is A (gangliosides with a disialosyl epitope). This

patient’s clinical presentation, with gradually progressive sensory loss, ataxia,

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POSTREADING TEST—PREFERRED RESPONSES

and ophthalmoparesis, is typical of CANOMAD (chronic ataxic neuropathy,

ophthalmoplegia, IgM paraprotein, cold agglutinins, and disialosyl antibodies)
syndrome. For more information, refer to page 1375 of the Continuum article
“Peripheral Neuropathies Associated With Monoclonal Gammopathies.”

39 The preferred response is E (vascular endothelial growth factor [VEGF]). This

patient has polyneuropathy, organomegaly, monoclonal gammopathy, and skin
changes, four of the features of POEMS (polyneuropathy, organomegaly,
endocrinopathy, monoclonal plasma cell disorder, and skin changes)
syndrome. Most patients with this syndrome have levels of VEGF that are more
than 5 times normal values. For more information, refer to page 1376 of the
Continuum article “Peripheral Neuropathies Associated With Monoclonal
Gammopathies.”

40 The preferred response is B (chemotherapy). Chemotherapy-induced

peripheral neuropathy is the most frequent cause of polyneuropathy in
multiple myeloma. For more information, refer to page 1375 of the Continuum
article “Peripheral Neuropathies Associated with Monoclonal Gammopathies.”

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