Demyelinating and Inflammatory Diseases



Demyelinating and Inflammatory Diseases







Questions



1. A patient with newly diagnosed multiple sclerosis asks what sort of environmental risk factors might have predisposed development of multiple sclerosis. She has lived in northern Michigan her entire life and describes a history of a low-salt “Mediterranean” diet and regular exercise. Which of the following historical factors has been suggested to be a potential environmental risk factor for the development of multiple sclerosis?


A. Excessive exercise

B. Living in a latitude far from the equator

C. Low-sodium diet

D. Strep throat infection during childhood

E. Vitamin C deficiency

View Answer

1. Answer B. (MN-71) Living in a latitude far from the equator. Prevalence studies have shown that living further from the equator in either the southern or northern hemisphere increases your lifetime risk for multiple sclerosis from a population standpoint. The basis for these findings remains uncertain but is thought to be among the earliest life course risk factors for development of multiple sclerosis. Excessive exercise has not been associated with development of multiple sclerosis. Epstein-Barr infection has been associated with multiple sclerosis but not streptococcal infections. Vitamin D deficiency has been regarded as a potential risk factor but not vitamin C deficiency. High-sodium diet has been researched as a potential risk for multiple sclerosis, and low-salt heart-heathy diets are often recommended for patients with multiple sclerosis.



2. A 25-year-old man with history of intravenous drug use is referred to neurology for progressive walking difficulty. Examination reveals bilateral lower extremity weakness, increased tone, and brisk deep tendon reflexes. An MRI of his spinal cord shows areas of T2 hyperintensity at levels T9 and C4. MRI of the brain reveals multifocal T2 hyperintense lesions in the subcortical and periventricular white matter. Of the following, which would be most indicated to order as a part of the differential diagnosis workup for multiple sclerosis in this patient?


A. HIV serology

B. MR spectroscopy of the brain

C. Somatosensory evoked potentials

D. Visual evoked potentials

E. Vitamin D status

View Answer

2. Answer A. (MN-71) HIV serology. The vignette describes a young person whose abnormal MRI demonstrates white matter disease in both subcortical as well as periventricular regions. Moreover, his personal history includes a risk factor for HIV infection, which can cause white matter disease and opportunistic CNS infections. MR spectroscopy could be considered if there is concern for malignancy but would not be the best next test of choice. Evoked potentials will likely be abnormal in this patient given the white matter abnormalities on his imaging but will not differentiate potential causes. Vitamin D status is important for patients with confirmed multiple sclerosis, but deficiency alone would not be the direct cause of the white matter disease.




3. A 55-year-old woman with multiple sclerosis (MS) has been on immunotherapy since her diagnosis at age 35 years, when she had optic neuritis. She reports good compliance with her medication and has not had a relapse for many years. At her routine clinic visit, she admits that over the past 2 years, she has gradually noticed increased difficulty with ambulation; specifically, she starts to notice right foot drop with prolonged exertion. She was able to participate in the 5 kilometer (“5K”) multiple sclerosis walk 2 years ago but was not able to complete the course this year. On her routine screening MRI, one new, nonenhancing T2 lesion is identified compared with prior scan 1 year earlier. What clinical course best describes her current disease status?


A. Relapsing remitting MS, with evidence of active disease

B. Relapsing remitting MS, without evidence of active disease

C. Secondary progressive MS, with evidence of active disease, with disease progression

D. Secondary progressive MS, with evidence of active disease, without disease progression

E. Secondary progressive MS, without evidence of active disease, with disease progression

View Answer

3. Answer C. (MN-71) Multiple sclerosis clinical phenotypes are defined by the occurrence of initial and subsequent symptoms, active/new disease burden on neuroimaging, and overall course of progression (see Figure 10.3.1). This woman had relapsing remitting multiple sclerosis (RRMS) at diagnosis, evidenced by her presentation with optic neuritis (a relapse). Over the last several years, she has had gradual progression of symptoms, indicating that she has transitioned to a progressive phenotype (secondary progressive multiple sclerosis) and is currently experiencing disease progression. The presence of a new T2 lesion on her MRI, however, indicates that she is still having evidence of inflammatory disease activity.








4. A 34-year-old man is seen in your clinic after an episode of right-sided numbness that resolved over 3 weeks. He denies any prior history of neurological symptoms. Examination is nonfocal with the exception of decreased pinprick over the right arm and leg. MRI of the brain reveals one asymptomatic but enhancing lesion in the right periventricular white matter, as well as multiple nonenhancing T2 hyperintensities in the cerebellum and periventricular white matter perpendicular to the lateral ventricles. Cerebrospinal fluid (CSF) studies show the presence of over five oligoclonal bands (OCBs) unique to CSF. According to the 2017 McDonald criteria, in order to receive a formal diagnosis of MS, this patient would need which of the following?


A. Evidence of both dissemination in space and time

B. Evidence of dissemination in space

C. Evidence of dissemination in time

D. No further evidence required for multiple sclerosis diagnosis

View Answer

4. Answer D. (MN-71) No further evidence required for multiple sclerosis diagnosis. With the information provided by MRIs and CSF, this patient no longer would qualify as having a clinically isolated syndrome and would be diagnosed directly with multiple sclerosis. While this patient has only had one clinical attack, he meets criteria for MS due to the presence of dissemination in space and time on MRI (multiple lesions in specified McDonald multiple sclerosis regions as well as both enhancing and nonenhancing lesions) as well as OCBs in his CSF.



5. A 23-year-old African American man presents to the emergency department with incomplete transverse myelitis. His MRI is shown in Figure 10.5.1. Which of the following would be the most appropriate choice for initial disease-modifying therapy?


A. Glatiramer acetate

B. Interferon beta-1a

C. Natalizumab

D. Ocrelizumab

E. Choice C or D

F. Any of the above







View Answer

5. Answer E. (MN-71) This patient has relapsing remitting multiple sclerosis (RRMS) based on 2017 McDonald criteria. He has numerous risk factors for aggressive disease including sex, race, the presence of spinal lesions, and a heavy disease burden on MRI. A highly effective therapy should be initiated immediately. Glatiramer acetate and interferon beta are less effective medications and take months before full efficacy. They would not be the best choice for this patient. Emerging data suggest that most patients with multiple sclerosis have better long-term outcomes when highly effective treatments are initiated early in disease.



6. A 35-year-old woman with relapsing remitting multiple sclerosis (RRMS) has been treated with fingolimod for 3 years and is very happy with her medication. At her clinic visit, she discloses that she has just learned she is pregnant. You advise her to discontinue fingolimod immediately. She then asks whether she will be able to breastfeed her baby once she restarts her fingolimod after delivery. How do you advise her?


A. Breastfeeding is not safe with any disease-modifying therapy

B. Breastfeeding is safe with all types of disease-modifying therapy, including fingolimod

C. Insufficient data are available to determine whether breastfeeding is safe with fingolimod

D. There may be alternative disease-modifying therapies that have a better safety profile for lactation

E. Choices C and D

View Answer

6. Answer E. (MN-71) There are very limited data regarding the safety of lactation with any of the oral disease-modifying therapies. Because these small molecules are likely secreted into milk and are orally bioavailable, their use is not recommended in breastfeeding. The injectable medications (beta-interferons and glatiramer acetate) are typically considered safe in breastfeeding. While direct data in lactation are limited, large monoclonal antibodies (natalizumab, ocrelizumab) are secreted in very limited quantities and are typically not orally bioavailable. A risk/benefit discussion could be held with the patient regarding their use in lactation.



7. A 23-year-old woman with type 1 diabetes is admitted to the medical floor with intractable nausea and vomiting for the past month. An extensive gastrointestinal workup is unrevealing, and as a last resort, the medical team consults Neurology. Upon taking a detailed history, the consulting PGY2 learns that she had experienced a 2-week bout of hiccups about 3 months previously. She denies any neurologic symptoms including vision loss, weakness, and numbness. Which of the following tests would be most likely to provide a definitive diagnosis?


A. Anti-aquaporin-4 antibodies in serum

B. Anti-MOG antibodies in serum

C. Brain MRI

D. CSF analysis with testing for oligoclonal bands

E. Upper and lower endoscopy

View Answer

7. Answer A. (MN-71) This young woman most likely has neuromyelitis optica spectrum disorder (NMOSD), presenting with an area postrema syndrome. Her comorbid type 1 diabetes is a clue to the diagnosis, as NMOSD frequently coexists with other autoimmune diseases. In this patient, a medullary lesion would likely be visible on MRI. However, imaging alone is unlikely to be diagnostic. Aquaporin-4 antibodies are positive in ≥70% of NMOSD cases and have 100% specificity. A positive aquaporin-4 antibody result is therefore diagnostic. MOG antibodies are detected less commonly than aquaporin-4 antibodies, and they are more commonly associated with optic neuritis, transverse myelitis, or acute disseminated encephalomyelitis (ADEM).




8. A 37-year-old woman presents to the emergency department with rapidly developing weakness in her legs starting 4 hours ago. Examination is notable for severe myelopathy (paraplegia/quadriplegia), which rapidly progressed, and she is now unable to walk. This presentation is most suggestive of which of the following?


A. Anterior spinal artery infarct

B. Spinal cord sarcoidosis

C. Transverse myelitis in multiple sclerosis

D. Transverse myelitis of aquaporin-4-IgG seropositive neuromyelitis optica spectrum disorder

View Answer

8. Answer A. (MN-72) The rapid onset of a severe deficit reaching its nadir within 4 hours is suggestive of a spinal cord infarct. Transverse myelitis in multiple sclerosis or aquaporin-4-IgG seropositive neuromyelitis optica spectrum disorder typically reaches nadir of deficit between 4 hours and 21 days while spinal cord sarcoidosis typically has a subacute or chronic presentation.



9. The presence of a longitudinally extensive T2-hyperintense lesion accompanying an acute to subacute myelitis is most likely to be associated with which of the following biomarkers?


A. Antinuclear antibody

B. Aquaporin-4-IgG and myelin oligodendrocyte glycoprotein-IgG

C. HTLV-1

D. Serum angiotensin converting enzyme

View Answer

9. Answer B. (MN-72) The presence of longitudinally extensive transverse myelitis should prompt assessment of aquaporin-4-IgG and myelin oligodendrocyte glycoprotein IgG, which commonly associate with such lesions and are diagnostic of neuromyelitis optica spectrum disorder (NMOSD). Serum angiotensin converting enzyme is nonspecific; CT chest or PET-CT to detect lesions of sarcoidosis is preferred to assist with diagnosis of suspected spinal cord sarcoidosis. Antinuclear antibody is a nonspecific biomarker that can be found in patients with lupus. HTLV-1 is more associated with a chronic insidious myelopathy than a subacute myelopathy.



10. The presence of a cervical spine “pancake-like” transverse band of enhancement on sagittal sequences with sparing of the gray matter on axial sequences accompanying a myelopathy of subacute or insidious onset is most suggestive of which of the following?


A. Intramedullary spinal cord metastasis

B. Spinal cord sarcoidosis

C. Spondylotic compressive myelopathy

D. Transverse myelitis aquaporin-4-IgG seropositive neuromyelitis optica spectrum disorder

View Answer

10. Answer C. (MN-72) White matter lesions on MRI have characteristic patterns that suggest a specific pathophysiology (Table 10.10.1). A “pancake-like” transverse band of enhancement often at the midpoint of a T2-hyperintense lesion and just below the site of maximal stenosis sparing the gray matter on axial sequences is highly suggestive of cervical spondylotic myelopathy. Transverse myelitis accompanying aquaporin-4-IgG seropositive neuromyelitis optica spectrum disorder may have ring-like or patchy enhancement. Spinal cord sarcoidosis is associated with linear dorsal subpial enhancement extending along two or more vertebral segments on sagittal sequences often with accompanying central canal enhancement forming a trident appearance on axial sequences. Intramedullary spinal cord metastases are associated with a rim of enhancement around a less enhancing center with a flame pattern at the top or bottom of this rim.










11. In a patient with transverse myelitis with a severe residual deficit despite treatment with intravenous corticosteroids, which of the following treatments is recommended?


A. Cyclophosphamide

B. Intravenous immune globulin (IVIg)

C. Plasma exchange

D. Rituximab

View Answer

11. Answer C. (MN-72) Plasma exchange has been shown to benefit patients with transverse myelitis or other central nervous system demyelinating episodes that do not respond to intravenous corticosteroids and would be favored over IVIg, rituximab, or cyclophosphamide.



12. Which of the following characteristics best distinguish MS from NMOSD?


A. CSF pleocytosis with 25 WBC/mm3 at the time of initial event

B. Optic neuritis at presentation

C. Presence of cerebral lesions on MRI scan of the head

D. Presence of oligoclonal bands

View Answer

12. Answer D. (MN-73) No clinical or radiologic features absolutely distinguish multiple sclerosis from neuromyelitis optica spectrum disorder (NMOSD). However, oligoclonal bands are present in over 80% of patients with multiple sclerosis even at initial presentation, whereas they are present in fewer than 20% of patients with NMOSD. Optic neuritis is a common presentation of both conditions. Pleocytosis of greater than 50 WBC/mm3 or five polymorphonuclear cells/mm3, although present in a minority of patients with NMOSD, and almost exclusively during an acute attack, is hardly ever present in MS; however, 25 WBC/mm3 does not distinguish multiple sclerosis from NMOSD under these conditions. Cerebral lesions are extremely common in multiple sclerosis, but are not rare in NMOSD, although uncommon at first presentation; often brain lesions are distinctive from multiple sclerosis and include hypothalamic and diencephalic lesions, longitudinally extensive lesions of the corpus callosum, and tumefactive brain lesions.



13. Which of the following characteristics is more typical of MOG-IgG than AQP4-IgG-associated neuromyelitis optica spectrum disorder (NMOSD)?


A. Longitudinally extensive transverse myelitis

B. Meets international panel diagnostic criteria for NMOSD (2015)

C. Papillitis manifesting as optic nerve swelling on fundoscopy

D. Relapsing course

View Answer

13. Answer C. (MN-73) Optic neuritis associated with MOG-IgG is more frequently bilateral and affects the anterior optic nerves leading to prominent papillitis evident on funduscopic examination. Both AQP4-IgG and MOG-IgG-associated NMOSD may relapse and be associated with longitudinally extensive transverse myelitis. MOG-IgG associated disease less commonly satisfied criteria for diagnosis of NMOSD, and the most common clinical presentations are recurrent optic neuritis and acute disseminated encephalomyelitis.




14. A lesion in which of the following anatomic regions will most likely be associated with a clinical attack of neuromyelitis optica spectrum disorder (NMOSD) consisting of prolonged hiccups?


A. Cervical cord

B. Dorsal medulla

C. Midbrain

D. Thalamus

View Answer

14. Answer B. (MN-73) Area postrema syndrome was included as one of three characteristic clinical events that is required for diagnosis of NMOSD in a seronegative patient. The phenotypic presentation of area postrema syndrome includes intractable nausea, vomiting, or hiccups without other explanation. This phenomenon is associated with isolated lesion in the area postrema located in the dorsal medulla at the floor of the fourth ventricle, although a lesion in the cervical cord may be contiguous with a lesion in the area postrema.



15. Which of the following is the most appropriate step in management of an acute attack of transverse myelitis in neuromyelitis optica spectrum disorder (NMOSD) with poor response to 5-day course of intravenous methylprednisolone?


A. Alemtuzumab

B. Another course of IV methylprednisolone

C. Oral prednisone

D. Plasmapheresis

View Answer

15. Answer D. (MN-73) NMOSD acute attacks are usually treated with intravenous methylprednisolone (IVMP), 1,000 mg daily, for three to seven consecutive days. Plasmapheresis (PLEX), usually administered as five to seven exchanges of approximately 1.5 plasma volumes every other day, is a rescue therapy or possibly an adjunctive treatment that may enhance the recovery from an acute attack of NMOSD. A second course of intravenous methylprednisolone is not likely to be beneficial and oral prednisone even less likely. Alemtuzumab is an anti-CD52 drug that targets a wide variety of immune cells and is used to prevent attacks of MS, but it is not shown to be beneficial in NMOSD, and in fact, several patients have been reported who appeared to worsen following treatment with alemtuzumab.



16. A 70-year-old man presents with headache and hearing loss, without cognitive dysfunction. Head MRI is normal, but CSF reveals lymphocyte-predominant leukocytosis. Whole-body imaging, blood evaluation of lymphoma, cytology, and flow cytometry of CSF and infectious diseases workup are negative. Which of the following is true?


A. Referral for audiology and otolaryngology should be made and will guide next steps

B. This could have an autoimmune or other inflammatory cause and requires further workup; GFAP-IgG testing, meningeal biopsy, and a trial of corticosteroids should be considered

C. This is infectious meningitis, and a trial of steroids is not warranted

D. This is likely hearing loss due to Susac syndrome; empiric immunotherapy should be started and clinical recovery can be assessed in 3 months

E. This is likely lymphomatous or carcinomatous meningitis, and the workup should be repeated in 3 months to assess for progression

View Answer

16. Answer B. (MN-74) The differential diagnosis is broad and includes infectious, carcinomatous, lymphomatous, autoimmune, and other inflammatory causes. Although Susac syndrome is particularly associated with sensorineural hearing loss, this is a rare condition that typically occurs in younger patients and causes concomitant encephalopathy; other processes should be considered and excluded. Although audiology assessment may be useful to establish hearing baseline and assess disease progression, it is unlikely to yield a working diagnosis.



17. A 60-year-old man presents with cognitive complaints. Which of the following are most suggestive of autoimmune encephalitis?


A. Insidious onset, history of systemic autoimmune disease, cancer history

B. Insidious onset, history of systemic autoimmune disease, hippocampal atrophy on MRI

C. Rapid progression, history of systemic autoimmune disease, cancer history

D. Rapid progression, history of systemic autoimmune disease, hippocampal atrophy on MRI

View Answer

17. Answer C. (MN-74) Autoimmune encephalitis tends to be subacute in onset and progresses over days to weeks. Some patients have a history of autoimmunity affecting other organs. Some patients with autoimmune encephalitis have a paraneoplastic cause (in the context of cancer-triggered autoimmunity). Insidious onset and hippocampal atrophy on MRI can be encountered also in neurodegenerative diseases, such as Alzheimer disease.



18. A 20-year-old woman is being evaluated for possible NMDA receptor encephalitis. Which of the following best represents the typical sequence of symptoms in that illness?


A. Anxiety and behavioral changes, dyskinesia, encephalopathy, coma, slow recovery

B. Anxiety and behavioral changes, encephalopathy, coma, dyskinesia, slow recovery

C. Coma, slow recovery, anxiety and behavioral changes, encephalopathy, dyskinesias

D. Dyskinesias, encephalopathy, coma, anxiety and behavioral changes, slow recovery

E. Encephalopathy, coma, dyskinesia, slow recovery, anxiety and behavioral changes

View Answer

18. Answer B. (MN-74) Patients with NMDA receptor encephalitis typically have some psychiatric symptoms at onset with progression to coma. In the midst of severe coma, dyskinetic movements of the craniocervical segment and limbs may evolve. Although 80% of patients appear to make a good recovery, this recovery may take up to 2 years from onset.




19. A 50-year-old woman presents with headache, blurred vision, and an MRI of head revealing radial periventricular enhancement on brain MRI (T1 post-gadolinium). This finding is typically encountered with:


A. GABAA receptor encephalitis

B. GFAP autoimmunity detected in CSF

C. GFAP autoimmunity detected in serum

D. Hashimoto encephalopathy

E. LGI1 encephalitis

View Answer

19. Answer B. (MN-74) As shown in Panel F of the Figure 10.19.1, radial periventricular enhancement on brain MRI is characteristic of autoimmune GFAP astrocytopathy. GFAP-IgG is nonspecific diagnostically when detected in serum only. GABAA receptor encephalitis and limbic encephalitis are characteristically accompanied by other MRI abnormalities (multifocal or hippocampus restricted, respectively). Hashimoto encephalopathy is diagnosed on the basis of a triad of encephalopathy, thyroid autoantibodies detected in serum, and robust repose to corticosteroids and does not have specific radiological features recognized.