MS Flashcards

Question

Gait issues in MS

Answer 1

Dalfampridine (ampyra) Inhibitor of voltage-dependent K channels to improve conduction along demyelinated axons Improves vision, strength, ambulation, endurance _Contraindicated in patients with seizures or GFR\<50 (seizures at toxic levels)_ Dalfampridine is FDA approved as an oral medication to improve walking in patients with multiple sclerosis. Dalfampridine is a symptomatic therapy, and can be used in combination with disease- modifying agents. It is an extended-release form of 4- aminopyridine (previously known as fampridine). Dalfampridine is a broad-spectrum inhibitor of voltage-sensitive potassium channels. In laboratory studies, dalfampridine has been found to improve impulse conduction in demyelinated nerve fibers and to increase synaptic transmitter release at nerve endings. Dalfampridine is administered as a 10-mg timed-release pill every 12 hours. In two phase III trials in patients with multiple sclerosis randomized to dalfampridine versus placebo, a significantly greater percentage of patients were “responders” on dalfampridine than on placebo. A responder was defined as a patient who showed faster walking speed while on therapy than while not on therapy. About one-third patients responded to dalfampridine in these studies. The increased response rate in the dalfampridine group was observed across all four major types of multiple sclerosis (relapsing-remitting, secondary progressive, progressive relapsing, and primary progressive).

Answer 2

From aberrant discharges from demyelinated nerves, treat with carbamazepine

Answer 3

Decreased risk of relapse during pregnancy, but INCREASED risk in the postpartum period Breastfeeding is protective Steroids are OK (2nd and 3rd trimester) Glatiramer acetate is the safest (or at least best-studied) in pregnancy Teriflunomide is CATEGORY X--\> wash out with cholestyramine!!!

Answer 4

Decreased risk of relapse during pregnancy, but INCREASED risk in the postpartum period Breastfeeding is protective Steroids are OK (2nd and 3rd trimester) Glatiramer acetate is the safest (or at least best-studied) in pregnancy Teriflunomide is CATEGORY X--\> wash out with cholestyramine!!!

Answer 5

The classic clinical course of MS is the relapsing-remitting MS (RRMS) course which accounts for about 85% of patients Most patients with RRMS will develop secondary progressive MS (SPMS) 25-40% of patients transition to SPMS within 15 years of disease onset in adults _Primary progressive MS(PPMS) accounts for 10-15% of MS patients_ Ocrelizumab is the only DMT approved to treat PPMS

Answer 6

The classic clinical course of MS is the relapsing-remitting MS (RRMS) course which accounts for about 85% of patients Most patients with RRMS will develop secondary progressive MS (SPMS) 25-40% of patients transition to SPMS within 15 years of disease onset in adults Primary progressive MS(PPMS) accounts for 10-15% of MS patients Ocrelizumab is the only DMT approved to treat PPMS

Answer 7

Clinically Isolated Syndrome (CIS): an initial CNS event with a presumed demyelinating cause, can be multifocal, may or may not have MRI findings -\> essentially an initial event, not meeting criteria for CDMS _Conversion rate to CDMS is about 43% at 5 years, 59% at 10 years and 63% at 20 years_ If MRI shows evidence of another lesion, 56-88% of MS. If MRI is negative, 22% chance of MS Start DMT to delay CDMS if high risk features No indication for DMT if isolated, otherwise normal MRI Positive OCBs in the CSF and spinal cord lesions are associated with increased risk of conversion to CDMS

Answer 8

MRI consistent with MS but no clinical symptoms. Associated with 30% risk of MS Spinal cord lesion significantly increases risk of developing MS Do not necessarily need to start DMT at time of RIS Serial imaging surveillance is recommended

Answer 9

Most common cause of neurologic disability in young adults after trauma Approximately 2.8 million people have MS worldwide Onset often between 15-45 years of age _Female:Male = 3:1_ Life expectancy is reduced by 7-14 years (narrowing in recent estimates)

Answer 10

Clinical symptoms of MS are variable and result from involvement of sensory, motor, visual, and brainstem pathways Most common disease course of MS is Relapsing Remitting MS (RRMS) During disease course clinical episodes occur called “relapses” _Relapses are defined as episodes that last \>24 hours and occur in absence of fever, infection, or clinical features of encephalopathy_ _Symptoms of a clinical attack typically have acute to subacute onset and reach peak severity within days to weeks, with recovery 2-4 weeks afterwards_

Answer 11

_First neurologic episode in about 25% of patients_ _About 70% of MS patients have optic neuritis during the course of the disease_ Triad of: _Pain with extra-ocular eye movements_ _Dyschromatopsia (deficiency of color vision)_ _Partial or total visual loss in one eye with a central scotoma_ If patient presents with optic neuritis, further evaluate with MRI!

Answer 12

Named for the eye with the adduction deficit

Answer 13

Sensory symptoms are the first clinical manifestation in up to 43% of patients Sensory symptoms may include: numbness, pins and needle sensation, tightness, “MS hug” Motor symptoms are initial symptoms in 30-40% of patients with MS Motor symptoms may include: paresis, spasticity, pyramidal signs (+Babinski, hyperreflexia), bowel/bladder dysfunction

Answer 14

Cortical or juxtacortical (≥1 lesion) Periventricular (≥1 lesion, unless the patient is over the age of 50 in which case it is advised to seek a higher number of lesions) Infratentorial (≥1 lesion) Spinal cord (≥1 lesion)

Answer 15

Both symptomatic and asymptomatic lesions can count towards t his

Answer 16

Ring opens where lesion touches grey matter _Enhancement is classic for demyelinating lesions, more commonly seen in tumefactive MS_ _Can also feature cystic changes_

Answer 17

Active lesions - relative axonal preservation and infiltration by macrophages Acute active lesions - macrophages containing all stages of myelin degradation products; ill-defined margins Chronic active lesions - macrophages at the edge of the plaque Smoldering lesions - inactive center and rim of activated macrophages and microglia Inactive Lesions - substantial axonal loss and completely demyelinated

Answer 18

Presentation: Optic neuritis, paraparesis secondary to transverse myelitis, area postrema syndrome Diagnostic criteria _1 core clinical feature: ON, TM≥3 segments, area postrema syndrome (unexplained hiccups + N/V), acute brainstem syndrome, symptomatic narcolepsy, or cerebral syndrome PLUS AQP4-IgG (against astrocytic foot processes at BBB)_ _2 clinical features with corresponding MR lesions separated in space. Must have 1: ON, TM, APS (dorsal medullary lesion)._ _Treatment:_ Acute: Steroids, PLEX, IVIG Chronic: 1) Rituximab, 2) Azathioprine + 6 month steroid taper. NOTE: MS therapies worsen NMO. NEW THERAPIES: _(1) Eculizumab (Complement 5) and (2) Tocilizumab (IL-6)_ _Worse than MS, less likely to have OCBs, higher WBCs._

Answer 19

Presentation: _Often follows vaccine/viral illness in kids_ Diagnostic Criteria _One multifocal CNS inflammatory event of WM + deep gray (BG) structures._ _Encephalopathy not explained by fever, seizures or infections._ _Brain MRI is abnormal in acute phase (3 months)_ No new MR findings ≥3 months after onset. _Severe variant: acute hemorrhagic leukoencephalitis (Hurst disease)_ Treatment: Steroids Typically monophasic, but multi-phasic form exists i.e. 2 attacks separated by 3 months Prognosis: Complete recovery

Answer 20

_Triad of encephalopathy, hearing loss, vision loss (retinal branch occlusion)_ _MRI with corpus callosum lesions, but can be scattered throughout WM as well as leptomeningeal enhancement or deep GM (BG and thalamus) lesions_ Thought to be from _an autoimmune process against endothelial cells, not demyelination_ Treatment: Acute: Steroids, IVIG Chronic: _Azathioprine, mycophenolate, cyclophosphamide_

Answer 21

Characterized by: _Migraine headaches_ _Recurrent Strokes_ _Progressive focal neurologic deficits_ _Cognitive deficits_ _Psychiatric disturbances_ MRI with lesions in anterior temporal lobes and external capsule _Caused by mutation in NOTCH 3 gene, chromosome 19_ Treatment: Aspirin for stroke prevention, standard migraine therapies (NO triptans), Acetazolamide (Diamox)

Answer 22

MOG=Myelin Oligodendrocyte Glycoprotein MOG is a myelin glycoprotein exclusively expressed in the CNS Antibodies have been found in a select group of patients with an acquired demyelinating syndrome and follow a NON-MS course Classic Phenotypes : (1) ADEM, (2) ON, (3) TM, (4) Cortical Encephalitis Classic MRI findings: (1) Large, ill-defined lesions, (2) extensive anterior optic nerve involvement with optic disc edema, (3) LTM with conus involvement, (4) Cortical involvement CSF Findings: Pleocytosis with WBC\>50, variable protein elevation, and negative OCBs Disease course: Predominately monophasic course, though relapse can occur Acute Treatment: IV steroids, PLEX, IVIG For relapsing disease: (_1) Rituximab, (2) Monthly IVIG, (3) Mycophenolate, (4) Azathioprine_

Answer 23

Cardinal clinical features include: Change in behavior or cognition Seizures Orofacial dyskinesias Autonomic instability Can present with psychiatric symptoms in young More than half of patients are found to have ovarian teratomas, early removal associated with better outcomes _EEG often shows “extreme delta brushes” (Rhythmic delta with superimposed beta)_ Acute Treatment: Steroids, IVIG, plasmapheresis Chronic Therapy: Rituximab

Answer 24

Most patients with this disorder have onset between age 20 and 40, though age of onset ranges from early childhood to late adulthood. Women are affected more than men in a 2.3:1 ratio. It is more common further north and south from the equator, and more common in Caucasians. It occurs in about 1 in 1,000 people.

Answer 25

A “relapse” is defined as an episode of new or worsened neurologic symptoms, lasting more than 24 hours, not due to fever or infection.

Answer 26

Primary progressive multiple sclerosis usually occurs in older patients. These patients have a gradually progressive course from onset and do not have relapses. They may have a lower burden of MRI lesions than do patients with RRMS.

Answer 27

Acute disseminated encephalomyelitis (ADEM) is an acute disorder, more common in childhood, and often occurs soon after an infection or vaccination. Patients with ADEM develop a severe disorder with multifocal demyelination in the brain and spinal cord (see discussion to questions 19 to 21).

Answer 28

A rapidly progressive course with repeated relapses that are refractory to standard treatment.

Answer 29

The prognosis for RRMS is better than most people expect. Various studies have shown a good prognosis over 10 years in a representative population without treatment. _However, neurologic examination shows abnormalities after 10 years of disease in most patients. The diagnosis of benign multiple sclerosis is a retrospective one after 15 to 20 years of disease without measurable disability and cannot be reliably predicted._ _This occurs in approximately 10% to 20% of patients with multiple sclerosis._ Pregnancy does not affect the overall course of multiple sclerosis. _Most patients with RRMS will not progress to wheelchair status withi_n 10 years.

Answer 30

This patient has optic neuritis. The results of a large randomized double-blind treatment trial for acute optic neuritis compared intravenous methylprednisolone with prednisone taper, oral prednisone taper, and placebo. This study showed that recovery was hastened by intravenous methylprednisolone with oral prednisone taper, but visual outcome at 1 year was not significantly affected. Oral steroids were at best no better than placebo, and possibly worse. In the Optic Neuropathy Treatment Trial, patients with visual acuity of 20/50 or better did not measurably benefit from intravenous steroids treatment.

Answer 31

In about 80% of patients with acute optic neuritis, _recovery occurs over 2 to 6 weeks. This may be incomplete. Over a 15-year period after an episode of optic neuritis, multiple sclerosis occurs in about 50% of cases._ Factors that increase the risk of multiple sclerosis developing include the presence of brain MRI lesions consistent with demyelination and abnormal CSF findings. If there are one or more well-defined demyelinating lesions on MRI, the risk of multiple sclerosis goes from about 20% in 5 years to approximately 80% over 5 years.

Answer 32

Intravenous methylprednisolone is usually given as a dose of 1,000 mg daily for 3 to 5 days, with an oral steroid taper, and is the treatment of choice for acute relapses. Other options include other forms of steroids, different dosing or duration of taper, not using a tapering dose, and oral high-dose steroids. The goal of treatment is to reduce the functional deficit and increase the speedy recovery of function.

Answer 33

Multiple sclerosis is more prevalent the further north or south of the equator one lives. The cause for this has not been established. _Moving after the age of 12 does not seem to alter this risk._ However, various epidemiologic studies suggest a link between vitamin D levels and multiple sclerosis, with lower vitamin D levels being correlated with higher risk of multiple sclerosis

Answer 34

Lymphocytes enter the CNS from the periphery. There are focal areas of demyelination (plaques) with glial cell infiltration and inflammatory cell accumulation. Macrophages are present in the core of the plaques. Areas of remyelination can be seen (“shadow plaques”). Oligodendroglial cells are reduced in the plaque core and increased at the periphery. White matter is typically affected in multiple sclerosis; myelin is removed from around axons, and early in lesion formation, axons are also injured and measurably transected.

Answer 35

_White cells can be elevated in the CSF in multiple sclerosis. Usually, there is a predominance of lymphocytes and no more than 50 cells/mm3._ A neutrophilic predominance should suggest an alternative diagnosis - bacterial meningitis\>NMO

Answer 36

Tumefactive multiple sclerosis appears to be a subform of relapsing multiple sclerosis with large, mass-like lesions. _These often have incomplete peripheral enhancement, showing the “open-ring sign,” which is suggestive of this pathology._ Patients may improve with intravenous steroids but, on occasion, may require other immunologic treatment such as plasmapheresis or intravenous immunoglobulin

Answer 37

Histologically, focal areas of demyelination are seen with significant leukocyte infiltration and some areas of frank necrosis and cavitation. There may be nearly complete axon loss within lesions. There are antibodies, neuromyelitis optica immunoglobulin G (NMO-IgG), that bind selectively to the aquaporin-4 water channel. _This is a component of the dystroglycan-protein complex located in astrocytic foot processes at the blood–brain barrier._

Answer 38

Devic’s disease progresses with relapses, but does not tend to progress in between relapses. It can have a monophasic or relapsing course. It is often severe. It can exhibit a spinal form. Relapses are frequently severe and may not recover completely. Treatment is urgent in relapses of Devic’s disease and many of the deficits do not resolve completely. Interferon β does not seem to be effective in Devic’s disease. There are no data on the use of natalizumab in Devic’s disease. _Medicines that have been used anecdotally include steroids, azathioprine, cyclophosphamide, rituximab, and other immunosuppressants_. For acute exacerbations, IV steroids or plasmapheresis can be used.

Answer 39

ADEM is usually a monophasic syndrome often occurring after an infection or vaccination. It is a multifocal demyelinating syndrome with large lesions that can be peripheral and may involve the basal ganglia. CSF may show a pleocytosis, but usually does not show oligoclonal bands. Patients are often febrile and encephalopathic. It may leave residual deficits. First-line treatment for ADEM is intravenous methylprednisolone. All treatment recommendations are anecdotal. Treatment consists of initial intravenous methylprednisolone and if this fails, a trial of plasmapheresis. There is no indication for antibacterial or antiviral agents to treat this condition.

Answer 40

ADEM is usually a monophasic syndrome often occurring after an infection or vaccination. It is a multifocal demyelinating syndrome with large lesions that can be peripheral and may involve the basal ganglia. CSF may show a pleocytosis, but usually does not show oligoclonal bands. Patients are often febrile and encephalopathic. It may leave residual deficits. First-line treatment for ADEM is intravenous methylprednisolone. All treatment recommendations are anecdotal. Treatment consists of initial intravenous methylprednisolone and if this fails, a trial of plasmapheresis. There is no indication for antibacterial or antiviral agents to treat this condition.

Answer 41

_The hemorrhagic leukoencephalopathy of Weston Hurst is a severe immune-mediated encephalopathy with areas of hemorrhage often in the temporal lobes. It may be a subform of ADEM._

Answer 42

_Balo’s concentric sclerosis_ refers to a progressive demyelinating disorder _in which concentric rings of demyelination are seen either pathologically or on MRI._

Answer 43

_There is an approximately 1 in 1,000 risk of developing progressive multifocal leukoencephalopathy (PML) in patients on natalizumab. The risk appears to be higher with prior or additional immunosuppressing medicines and after 2 years of continuous use_. Patients with positive serum JC virus antibodies are at even higher risk.

Answer 44

Pregnancy does not change the course of multiple sclerosis appreciably. Like other women contemplating pregnancy, patients should be on prenatal vitamins with folic acid. There are no specific issues in the conduct of pregnancy and patients can have an epidural anesthetic and can have a regular delivery or Cesarean section as needed obstetrically. Steroids can be used during pregnancy though should be limited as much as possible and preferably should not be given in the first trimester. Interferons (category C in pregnancy) should be stopped at least 1 month before conception. Glatiramer acetate is category B in pregnancy, but it is usually stopped before conception. _Women with multiple sclerosis tend to have fewer exacerbations during pregnancy and more in the first 6 months after delivery (see Chapter 16). Breast- feeding may be protective against exacerbations._ _Children of women with multiple sclerosis have a 3% to 5% lifetime chance of developing multiple sclerosis._

Answer 45

There is an approximately _1 in 1,000 risk_ of developing progressive multifocal leukoencephalopathy (PML) in patients on natalizumab. The risk appears to be higher with prior or additional immunosuppressing medicines and after 2 years of continuous use. Patients with positive serum JC virus antibodies are at even higher risk.

Answer 46

There is an approximately 1 in 1,000 risk of developing progressive multifocal leukoencephalopathy (PML) in patients on natalizumab. The risk appears to be higher with prior or additional immunosuppressing medicines and after 2 years of continuous use. Patients with positive serum JC virus antibodies are at even higher risk. Treatment for PML in this population includes stopping natalizumab as soon as there is a suspicion of PML, checking JC virus PCR, and beginning plasmapheresis to clear residual natalizumab more rapidly from the system.

Answer 47

Transverse myelitis is a term used for patients with a subacute onset of myelopathy, which appears to have an immunologic basis. It may occur after a viral illness, Mycoplasma infection, or vaccination, but is often not preceded by an illness. Symptoms include paresthesias and sensory deficit often ascending to a specific level, weakness, back pain, and bowel and bladder dysfunction.

Answer 48

_This is Uhthoff’s phenomenon, in which transient symptoms are elicited by heat or exercise. I_n this patient, it manifests as blurring of vision with exercise due to impaired conduction in an optic nerve that has had demyelinating injury.

Answer 49

Lhermitte’s sign is electrical sensations in the body with neck flexion.

Answer 50

The useless hand of Oppenheim can be seen with a relapse of multiple sclerosis where the hand can be moved but is perceived as useless by the patient.

Answer 51

Pulfrich’s sign refers to a visual phenomenon _where patients have trouble following moving objects visually, and lateral motion in the field of vision is perceived as having a depth component._

Answer 52

LGI1 is a protein associated with the voltage-gated potassium channel. It is one of the ion channel or cell surface protein–associated antibody syndromes recently defined. The seizure activity described is characteristic of this cell surface antibody syndrome, and is known as faciobrachial dystonic seizures. It does not respond to antiepileptic medicines but is very responsive to immune therapy. Patients may develop a limbic encephalitis with behavioral and memory changes. There may be abnormal imaging findings (MRI or PET) in the hippocampal regions especially in the setting of cognitive dysfunction; however, MRI may be unremarkable. CSF may be unrevealing.

Answer 53

Episodes of neurological worsening or new symptoms in MS not due to fever or infection, and lasting \>24 hours

Answer 54

Finger-like extensions of demyelination and inflammation extending rostrally from the corpus callosum in MS

Answer 55

Electrical sensations down the neck, back, or limbs with neck flexion. Often related to demyelinating in cervical sign.

Answer 56

Transient symptoms elicited with heat or exercise

Answer 57

Due to disorder in MLF common in MS. With a right INO, on left gaze, cannot adduct right eye with left eye abduction nystagmus. Can be bilateral.

Answer 58

Form of demyelination with concentric sclerosis, may appear as onion skin lesion son MRI

Answer 59

Also known as NMO, neuromyelitis optic immunoglobulin G to aquaporin-4

Answer 60

Because of sensory deafferentation where the hand feels useless with otherwise normal function

Answer 61

Visual phenomenon where patients have trouble following moving objects visually and lateral movement in the field of vision is perceived as having a depth component