BMB 2 - Multiple Sclerosis Flashcards
What is multiple sclerosis?
A demyelinating autoimmune disorder characterized by dissemination in space and time
What does the term ‘transverse myelitis’ indicate?
Myelin damage (myelitis) that extends horizontally (transversely) across the spinal cord
What are the four clinical subtypes of multiple sclerosis?
Relapsing-remitting
Primary progressive
Secondary progressive
Progressive-relapsing
Describe the progression of relapsing-remitting multiple sclerosis.
Describe the progression of primary progressive multiple sclerosis.
Describe the progression of secondary progressive multiple sclerosis.
Describe the progression of progressive-relapsing multiple sclerosis.
Name some of the major S/Sy of multiple sclerosis.
Fatigue, walking issues, numbness, spasms, pain, depression, SIIN (scanning speech, intention tremor, internuclear ophthalmoplegia, incontinence, nystagmus)
In what ways is normal neuronal action affected in multiple sclerosis?
Oligodendrocyte and axonal damage;
upregulation of NOGO
(NOTE: NOGO is an ‘off-switch’ for myelin production.)
In addition to ≥1 symptom being present, a diagnosis of multiple sclerosis requires what else?
Dissemination over space and time
What does it mean if a patient’s mutiple sclerosis lesions seen on MRI are gadolinium+ (i.e. take up gadolinium)?
The lesion occurred within the past 6 weeks.
A patient with scanning speech and pain and numbness in certain parts of her body presents with an MRI that shows T2 hyperintensities that are >3mm, ovoid, & perpendicular to the lateral ventricles. What does this indicate?
‘Dawson’s fingers’ (a sign of multiple sclerosis)
True/False.
The lesions seen in multiple sclerosis can present in various portions of the CNS and can also be either gadolinium+ or gadolinium-.
True.
What would an inflammatory panel likely show in a patient with multiple sclerosis?
Multiple oligoclonal bands + elevated IgG index
Which form of demyelinating disease typically presents in children as either a post-infection or post-vaccine disorder (typically ~2 weeks later) that shows all gadolinium+ lesions?
Acute disseminated encephalomyelitis
Which form of demyelinating disease typically presents as the classic radiologic findings of multiple sclerosis but with no clinical symptoms?
Radiologically isolated syndrome
What is the most common first symptom of multiple sclerosis?
Optic neuritis
A patient’s first clinical sign of multiple sclerosis (e.g. optic neuritis prior to a diagnosis of MS) is known as what?
Clinically isolated syndrome
True/False.
Multiple sclerosis is evidence of an ongoing condition with dissemination over space and time.
True.
What is the likely etiology of multiple sclerosis development?
Genetic factors + environmental insults (e.g. EBV, low vitamin D, etc.)
How long do the non-progressive stages of multiple sclerosis (e.g. the intial stage of relapsing-remitting before the person stops fully recovering; or the beginning of the secondary progressive form before the progressive phase is reached) typically last?
~10 years
(I.e. relapsing-remitting MS patients often make complete recoveries between attacks for the first 5-10 years; then they stop making full recoveries. The non-progressive stage of secondary progressive MS typically also lasts ~10 years.)
What is a multiple sclerosis ‘relapse?’
An event characterized by focal neurologic symptoms (e.g. double-vision) that escalates over ~3-5 days→plateau→recovery
How is primary progressive multiple sclerosis treated?
Ocrelizumab (anti-CD20)
How is secondary progressive multiple sclerosis treated?
Siponimod (S1P1)
Cladribine (inhibits DNA synthesis)
How is progressive-relapsing multiple sclerosis treated?
Disease-modifying therapies
(e.g. interferon, natalizumab, S1P1 agents, etc.)
The progressive forms of multiple sclerosis are characterized by a slow, insidous increase in symptom severity, usually affecting ______ing and ____________ first.
The progressive forms of multiple sclerosis are characterized by a slow, insidous increase in symptom severity, usually affecting _walk_ing and _balance_ first.
True/False.
Specific immunotherapies for multiple sclerosis (e.g. DMTs) are preventive, but don’t necessarily cause improvement.
True.
Optimal Vitamin ______ levels in pediatric cases of multiple sclerosis are as protective as glatiramer acetate (40% lesion reduction).
Optimal Vitamin D levels in pediatric cases of multiple sclerosis are as protective as glatiramer acetate (40% lesion reduction).
There are several options for treating patients with multiple sclerosis to avoid injury (e.g. ____________), improve conduction (e.g. ____________), and improve energy supply (e.g. ____________).
There are several options for treating patients with multiple sclerosis to avoid injury (e.g. disease-modifying therapies** improve conduction (e.g. **dalfamprodine**) and improve energy supply (e.g. **biotin)
Name some of the methods of multiple sclerosis management.
Disease-modifying therapy
Vitamin D supplementation
Nutrition and exercise
Sleep counseling and therapeutic community
Stress management
Via what mechanisms do interferons treat multiple sclerosis?
Pro- to anti-inflammatory shift (TH1 to TH2)
Fingolimod and siponimod treat multiple sclerosis by interacting with which receptor?
How are these medications administered?
S1P1
per oral
How does natalizumab treat multiple sclerosis?
Anti-alpha4-integrin
preventing T cell migration across the blood-brain barrier
How do ocrelizumab and alemtuzumab treat multiple sclerosis?
B cell depletion (anti-CD20 and anti-CD52, respectively)
What is a contraindication to natalizumab use in patients with multiple sclerosis?
JC virus infection
(may result in progressive multifocal leukencephalopathy)
What are the two major dangers of mitoxantrone usage in treating multiple sclerosis?
Cardiomyopathy (10%!) and therapy-related acute leukemia
A patient presents with blurry vision, color-vision decrease, and pain behind her eyes. Assuming this is a clinically isolated syndrome (aka the first sign of multiple sclerosis), what is the likely initial diagnosis?
Optic neuritis
What are some of the S/Sy associated with optic neuritis?
Blurry vision, color-vision decrease, pain behind the eye
A multiple sclerosis patient presents with blurred vision, weakness, and numbness. Where do you suspect their major lesions are?
The brainstem
A multiple sclerosis patient presents with spasticity, bladder incontinence, weakness, and numbness. Where do you suspect their major lesions are?
The spinal cord
A multiple sclerosis patient presents with tremor, vertigo, and repeated falling. Where do you suspect their major lesions are?
The cerebellum
Patients with multiple sclerosis sometimes feel an ‘electric’ sensation go up or down their spine when their neck is flexed (sometimes requires a striking of the cervical region while the head is bent forward). What is the name of this sign?
Lhermitte’s sign
Name two categories of disorders that have a broad array of overlap with multiple sclerosis; i.e., presenting with optic neuritis, myelitis, and MRI findings.
Neuromyelitis optica spectrum disorder
Myelin oligodendrocyte glycoprotein -associated disorder
A patient with multiple sclerosis -like symptoms presents with anti-AQP4 antibodies in serum. What disorder does this indicate?
Neuromyelitis optica spectrum disorder
Area postrema syndrome is mostly seen in which multiple sclerosis -like disorder?
Neuromyelitis optica spectrum disorder
Why does neuromyelitis optica spectrum disorder sometimes result in area postrema syndrome?
There is a high concentration of aquaporin-4 in the circumventricular organs
(NMOSD is characterized by anti-AQ4 antibodies)
A patient with multiple sclerosis -like symptoms presents with anti-MOG antibodies in serum. What disorder does this indicate?
Myelin oligodendrocyte glycoprotein -associated disorder
What disorder is similar to multiple sclerosis and presents with motor, sensory, bladder, and bowl symptoms and involves > 3 spinal segments?
Longitudinally exstensive transverse myelitis (MS exhibits transverse myelitis but not longitudinally as in NMOSD or MOGAD)
Is bilateral optic neuritis more common in neuromyelitis optica spectrum disorder or myelin oligodendrocyte glycoprotein -associated disorder?
Myelin oligodendrocyte glycoprotein -associated disorder
Multiple sclerosis is an oligodendrocytopathy while neuromyelitis optica spectrum disorder is an ______________pathy.
Multiple sclerosis is an oligodendrocytopathy while neuromyelitis optica spectrum disorder is an astrocytopathy.
- Which of the following is associated with internuclear ophthalmoplegia?
- Which is associated with edema?
- Which is associated with area postrema syndrome?
Neuromyelitis optica spectrum disorder
Myelin oligodendrocyte glycoprotein -associated disorder
- Neuromyelitis optica spectrum disorder
- Neuromyelitis optica spectrum disorder
- Neuromyelitis optica spectrum disorder
Which form of myelin oligodendrocyte glycoprotein -associated disorder is seen in children?
Acute disseminated encephalomyelitis
What CSF findings would indicate neuromyelitis optica spectrum disorder or myelin oligodendrocyte glycoprotein -associated disorder instead of multiple sclerosis?
High WBC concentration
High protein concentration
Low rate of oligoclonal bands
