MS, MG, MD Flashcards by Setha Treadwell

Weakness

Considered disorders of nerve conduction

Autoimmune, Lymphocytes?

Common to what two disorders?

Multiple Sclerosis and Myasthenia Gravis

How well did you know this?

Not at all

Perfectly

Autoimmune disease which causes inflammatory demylnation of CNS

Reduces nerurons ability to function

Multiple Sclerosis

How well did you know this?

Not at all

Perfectly

Found primarily in young adults, usually under age of 55 at onset (typically mid-20’s to 30)-if older onset, may be more severe

Women>men (may be more severe in men)

Epidemiology of which condition?

Multiple sclerosis

How well did you know this?

Not at all

Perfectly

CIS

RRMS

primary progessive

secondary progressive

progressive relapsing

Different forms of which condition?

How well did you know this?

Not at all

Perfectly

Likely autoimmine- higher risk with other autoimmune diseases

High risk: Northern Europe, Southern Canada, Northern US

Low risk: Asian, African, American Indian

How well did you know this?

Not at all

Perfectly

Patients of Western European lineage (genetics) who live in temperate zones (environmental)
If patients move from one “zone” to another before age 15, he/she appears to adopt that zone’s risk
Less risk closer to equator—is sunlight or Vitamin D protective?
HLA-DR2 ?, HLA-DRB1 association
Exposure to viral infections—EBV? Varicella?
Genetic predisposition? Increased risk if (+) FHX
Exposure to vaccines?
Smoking? Alcohol?
Month of birth? May>November

Risk factors for which condition?

How well did you know this?

Not at all

Perfectly

Inflammation –> demyelination –> axonal degeneration

Still an area of research

Pathogenesis of what condition?

How well did you know this?

Not at all

Perfectly

Shows response to treatment with immunomodulating rx

Disruption of BBB= rx that blocks T cell movement into CSF improve MS sx

How well did you know this?

Not at all

Perfectly

Signs/Sx:

Weakness, fatigue, numbness, tingling, unsteadiness in a limb, spastic paraparesis, retobulbar neuritis/optic neuritis (blurred or dimmed vision, blind spots (central vision), pain w. eye movement, HA, sudden color blindness, imparied night vision, impaired contrast sensitivity, diplopia), disequilibrium/vertigo, pain, sphincter disturbance (urinary urgency or hesitancy)

How well did you know this?

Not at all

Perfectly

Relapse/remission

Onset between 15-50

Optic neuritis

Lhermitte’s sign

Internuclear opthalmoplegia

Fatigue

Uhtoff’s phenomenon

These are suggestive or not suggestive of MS?

SUGGESTIVE

How well did you know this?

Not at all

Perfectly

Steady progression

Onset before age 10 or after 50

Cortical deficits-aphasia, apraxia, alexia, neglect

Rigidity, sustained dystonia

Convulsions

Early dementia

Deficity developing in minutes

Suggestive/Not suggestive of MS?

NOT suggestive

How well did you know this?

Not at all

Perfectly

TIA/CVA

B12 deficiency

HIV

Lyme Neuroborreliosis

Neurosyohilis

Acute disseminated encephalomyelitis

Acute hemorrhagic leukoencephalitis

Acute/subacute transverse myelitis

DDX with which condition?

How well did you know this?

Not at all

Perfectly

Certain criteria must be met (McDonald)

Must show two or more different areas in central areas of white matter affected to different times

Only one area may be clinically affected—but a “probable” diagnosis can be made in patients with multi-focal disease on imaging but with only one clinical attack or with a history of at least two clinical attacks but signs of only one lesion

Dx for which condition?

How well did you know this?

Not at all

Perfectly

Imaging test of choice to diagnosis clinically suspected MS?

MRI

How well did you know this?

Not at all

Perfectly

Lesion is the cerebral or spinal plaque - descrete region of demyelination with initially preserved axon

Found in the periventricular, juxtacortical, infratentorial and/or spinal cord

MRI results of which condition?

How well did you know this?

Not at all

Perfectly

Increased Gadolinium enhancement may indicate ______ lesion?

Acute or chronic

Acute

How well did you know this?

Not at all

Perfectly

Is an acute lesion symptomatic/asymptomatic in MS?

Asymptomatic!

How well did you know this?

Not at all

Perfectly

What other lab should be performed for MS?

Lumbar puncture

Also useful to rule out other dx: B12, Lyme, etc

How well did you know this?

Not at all

Perfectly

May have mild lymphocytosis, may have IgG in CSF

Probably normal opening pressure

Albumin in CSF indicates disruption in BBB

Lumbar puncture results in which condition?

How well did you know this?

Not at all

Perfectly

Presense of ________ on lumbar puncture is highly suggestive of MS

oligoclonal bands

How well did you know this?

Not at all

Perfectly

What is the most common form of MS?

Relapsing-remitting MS

How well did you know this?

Not at all

Perfectly

How many forms of MS are recognized?

How well did you know this?

Not at all

Perfectly

Initial episode then months or years before new sx emerge or previous sx return

Can lead to incomplete remissions and progressive disability with weakness, spatsticity, ataxia of limbs, impaired vision, and urinary inconinence

PE: optic atrophy, nystagmus, dysarthria, pyramidal/sensory/cerebellar deficits in one or multiple limbs

What form of MS?

RRMS

How well did you know this?

Not at all

Perfectly

Acute exacerbation of sx lasting says to weeks, at minimum 24 hours

Defintion of what?

Relapse

How well did you know this?

Not at all

Perfectly

Can be previous sx or new sx Relapse triggers/infection/trauma/stress/pregnancy? Frequency of relapse is variable --\> more common in early dx Uhthoff's phenomenon What form of MS?

RRMS

In some patients, clinical course changes to secondary progressive (SPMS). Some studies indicate that most patients will progress to SPMS Primary progressive (PPMS)—less common (~10%), Symptoms are steadily progressive from onset. Progressive relapsing MS (PRMS)—a subset of MS which has some remissions, but steady decline still dominates disease course. Other forms of what dx?

Fully functional in all neurological systems 15 years after disease onset What severity of MS?

Benign

Rapidly progressive course leading to significant disability What severity of MS?

Malignant

No cure Tx aimed at improving quality of life and limiting disability Strong support network- family, therapists, social services Tx for what?

What are acute attacks of MS most commonly treated with?

Glucocorticoids | (methylprednisolone 1g IV x 3-7 days)

Aimed at reducing relapses and slowing progression of MS?

Disease Modifying Therapy

Historically SC or IM (IV for certain patients) Now 3 oral options What type of therapy for MS?

Disease Modifying Therapy

* Interferon-b-- cytokine that modulates immune responsiveness * Betaseron / Extavia(Interferon-b1b) * 250mcg SC administered QOD * Rebif (Interferon-b1a) * 44mcg SC administered 3x/week * Avonex (Interferon-b1a) * 30mcg IM administered weekly * Plegridy (Pegylated Interferon-b1a) * 125mcg SC every other week Tx for which condition?

Injection site reactions Flu-like sx Depression Elevated LFTs Leukopenia/anemia S/E of which type of drugs for MS therapy?

Interferons

What can develop and limit the effectiveness of IFNB treatment in MS?

Neutralizing antibody formation

Mixture of amino acids antigenically similar to myelin protein. Works by competing for T cells - but process not entirely understood Daily 20mg SC admin No routine bloodwork neeed What tx for MS?

Glatiramer (Copaxone | Teva)

Injection site reactions (MC) Transient flushing/anxiety/chest pains S/E of which drug for MS?

Glatiramer (Copaxone)

First oral agent approved for MS Sphingosine 1-phosphate receptor modulator on T-cells Results in down-regulation of receptors and T-cell sequestration in lymphoid tissue Generally well tolerated What drug tx for MS?

Fingolimod (Gilenya | Novartis)

Elevated LFT's bradycardia (transient) macular edema skin cancers varicella infections S/E of which drug for MS?

Fignolimod

Underlying cardiac conditions including those on rate-controlling medications Diabetics Exclusion criteria for which drug tx of MS?

Fingolimod

2nd oral med for MS Inhibits a mitochondrial enzyme involved in DNA replication Reduces T- and B-cell proliferation and response to autoantigens Well tolerated Which drug tx for MS?

Teriflunomide (Aubagio | Genzyme)

Diarrhea Abnormal LFTs Nausea hair loss birth defects (PG X) increased infections peripheral neuropathy renal failure hyperkalemia HTN S/E of which drug for MS?

Teriflunomide (Aubagio | Genzyme

How long can Teriflunomide (Aubagio | Genzyme) remain in your system?

Up to 2 years!

3rd oral MS medication Once used as a psoriasis medication Formerly called BG-12 Exact mechanism of action is not known Thought to inhibit immune cells and molecules, and may have anti-oxidant properties that could be protective against damage to the brain and spinal cord Generally well tolerated

Dimethyl Fumarate (Tecfidera | Biogen IDEC)

First line treatment for MS?

Glatiramer with or without Interferon B

Autoimmune disease -- Uncommon 10-20: 1,000,000 new cases in US **MC disease of neuromuscular transmission**

Myasthemia Gravis

Ab against nicotinic AchR at NMJ (Ab vs nAchR @ NMJ) nSome Ab impair ability of Ach to bind to AchR, other Ab destroy AchR Also, Ab against MuSK (Muscle-specific receptor tyrosine kinase) MuSK proteins mediate clustering of AchR during NMJ formation and associated with AchR maintenance—research ongoing to explain pathogenetic role of MuSK

Ocular: limited to lids, EOM Generalized Two primary manifestations of what disorder?

About \_\_\_% of those wtih ocular progress to generazlied in 2 years

50%

Common in men and women (slight predisposition for women) Occurs at all ages (women most likely in child bearing years, and later in life, 6-7th decade, in men) Genetic predisposition (HLA DR3), also, commonly found in patients with other auto-immune disorders May be transient in neonates—placental transmission of maternal Ab

Up to \_\_% of patients with MG have thymic abnormalities

75%!

MG: mind to ground (**descending**) Facial sx: ptosis (unilateral/bilateral), diplopia, bulbar muscle weakness (chewing, swallowing, speech), expressionless face, neck muscles (head drop) May progress **DOWN** to respiratory muscles, limb weakness that is focal or generalized and may fluctuate through the day (may be worse at night or after exercise)

Signs/Sx of MG

Weakness may remit and relapse (can last for weeks) Sx usually progress to become more frequent Fluctuations of sx helpful to distinguish from myopathy and motor neuron disease

Signs/Sx of MG

FATIGABILITY of muscles- normal sensation, normal reflexes Frank ptosis on exam, slack jaw Simpson test Cogan lid twitch sign MG crisis: respiratory failure

Short acting AchE inhibitor Administered incrementally May produce increased salvation or abdominal cramping May produce symptomatic bradycardia or bronchospasm—need Atropine at bedside as well May see response at lower dose before onset of S/E - may not see response at all Not really used much anymore Test used to dx MG?

Tensilon test (edrophonium)

Brainstem or motor cranial nerve pathology Kearns-Sayre Syndrome Generalized fatigue Motor neuron disease (ALS) Lambert-Eaton Myasthenic Syndrome (LEMS) Botulism GBS OPMD Diff Dx with what condition?

Neuromuscular transmission improved at cooler temperatures Ice pack test not helpful for testing weak muscles that can’t be cooled (EOM) Eyelid muscles easily cooled (ice pack for two minutes) Ptosis may immediately improve after removal of ice pack About 80% sensitive but may have many false positives Test to dx MG?

Ice pack test

80-90% OF PTS WITH GENERALIZED MG HAVE CIRCULATING AB AGAINST NACHR THREE TYPES: BINDING, BLOCKING, MODULATING—MOST GO WITH BINDING HIGHLY SPECIFIC WITH VIRTUALLY NO FALSE-POSITIVES 3-7% HAVE CIRCULATING AB AGAINST MUSK (MUSCARINIC TYROSINE KINASE) SEROPOSITIVE (ABOUT 50% OF THOSE WITH OCULAR MG, ABOUT 90% WITH GENERALIZED) LEVELS OF CIRCULATING AB DO NOT CORRELATE WITH SEVERITY OF DISEASE SERONEGATIVE—NO AB AGAINST ACHR OR MUSK, BUT SIMILAR RESPONSE TO TREATMENT (DISCUSSED BELOW), SIMILAR FINDINGS ON ELECTROPYSIOLOGIC TESTING Blood test for diagnosis of what disorder?

More commonly performed Easier to do Faily good sensitivity and specificity Checking nerve condiction: speed and amplitude at certain muscle Distinct "U" shaped pattern What test for MG?

Repetitive nerve stimulation studies

More complex specialized procedure Reserved for patients w/ suspected MG that have not been adequately dx'd through other tests Needles directly on nerves Last test used What test for MG?

Single fiber EMG

Acetylcholinesterase inhibitors Immunomodulation Surgery (especially if thymoma) IV-Ig Plasmapheresis (plasma-exchange) Tx options for what disorder?

Inhibits the enzymes that breakdown Ach=more Ach=more muscle stimulation Pyridostigmine Neostigmine What drug tx for MG?

Anticholinesterase inhibitors

Often leads to symptomatic relief and may lead to remission Consider risk factors (age-usually recommended for younfer patients) Can take up to 10 years to lead up to ultimate remission What type of tx for MG?

Thymectomy

Respiratory weakness may lead to respiratory failure Can occur spontaneously during active phase of disease or be precipitated by surgery, infection, medications (memorize list) or tapering of immunosuppresion. Worsening generalized weakness may precede MG Crisis, but variable time course Must monitor VC, up to q2hrs, MIP (NIF) Accessory muscle weakness may mask underlying respiratory distress

MG crisis

Admit to ICU Monitor FVC MIP (NIF) Electively intubate if FVC \<15mL/kg or serial decline approaching 15mL/kg or clinical signs of respiratory distress Withdraw acetylcholinesterase inhibitors Begin IVIg or plasmapheresis Begin high dose immunomodulating therapy Wean off mechanical ventilation as FVC improves Tx for what type of MG?

MG crisis

Useful for acute decline or MG crisis 2/3 of patients will improve with treatment about 7-10 days after starting Monitor for side effects: volume overload, rash, fever and flu-like symptoms, headaches, chest and abdominal pain, anaphylaxis, renal failure, transaminitis, aseptic meningitis What type of tx for MG?

IVIg

useful for acute decline or MG crisis 2/3 of patients will improve in 2-3 days Equally efficacious as IVIg but more adverse effects Reduces AChR titers by 50-70% What type of tx for MG?

Plasma Exhange (PLEX)

Inherited disorders causing progressive muscle weakness and atrophy due to genetic defect Multiple types Some forms can cause cardiac dysfunction and cognitive defects

Muscular Dystrophies

What is the common theme with the different types of MD?

Muscle weakness

Nerve sends the signal to the muscle, but the muscle is unable to respond normally

Myopathies

Defectie gene on X chromosone responsible for producing dystrophin (a protein that protects muscles) Dystrophin deficits --\> enzymatic muscle breakdown What type of MD?

Duchenne Musclar Dystrophy (DMD)

Disease occurs in males Age of onset 2-3 y/o May be wheelchair bound by 12 Survival into late teens/20s What type of MD?

DMD

Sx likely start centrally (trunk) and spread to legs first Will likely see elevations in CK May cause: cardiomyopathy, scoliosis, fractures (from falls), and some cognitive impairment What type of MD?

DMD

Corticosteroids can increase strength, will not change prognosis Tx for what types of MD?

DMD Beckers MD

Patients affected make *_some_* dystrophin Defectie gene on X chromosome responsoible for producing dystrophin --\> enzymatic muscle breakdown What type of MD?

Becker Muscular Dystrophy

Disease occurs in males Age of onset is later than DMD Comorbid cardiomyopathies less common but can be more severe than DMD, survival into 40s what type of MD?

Becker MD

Sx milder than that of DMD Likely elevations in CK Sx start centrally (trunk) and spread to legs first What type of MD?

Becker MD

Exam: weakness Family history CK, AST, ALT Genetic testing EMG Muscle biopsy Dx of what types of MD?

DMD and BMD

Steroids Ca++/Vit. D ACEI B-blockers Pacer/Defib Pulm support Immunizations Tx for what types of MD?

DMD and BMD

Muscle weakness that usually begins in arms in teen years then progresses to legs and face Uncommon but distinctive Caused by a number of different inheritance patterns Occurs in males and females What type of MD?

Emery-Dreifuss MD

Contractures of elbows, ankle platar flexors, and spine early Later onset of humeroperoneal weakness Cardiac abnormalities (arrhythmias, cardiomyopathies-can lead to malignant arrhythemias) **Classic Triad** for what type of MD?

Emery-Dreifuss MD

CK normal or slightly elevated EMG Genetic testing Often still ambulatory after 20 years Dx for what type of MD?

Emery-Dreifuss MD

What is the most common inheritance pattern in Emery-Dreifuss MD?

X linked

What is the most common form of MD?

Myotonic dystrophy

Affects males and females Two genetic types: Type 1: Classic adult onset, congenital, child onset, late onset oligosymptomatic Type 2 What type of MD?

Myotonic Dystrophy

Muscle stiffness, inability to relax muscles after contraction Affects different body systems causing muscle loss in weakness - facial muscles, arms, legs Cardiac complications Cataracts Abnormal intellectual functioning Excessive daytime somnolence Signs/Sx of what type of MD?

Myotonic dystrophy

Clinical findings normal to slightly elevated CK Variable EMG patterns Genetic testing Bx Dx for what type of MD?

Myotonic dystrophy

Multiple subtypes (\>20) Characterized by: Age of onset Muscle weakness patterns Cardiac involvement Contractures Bx features Inheritance patterns What type of MD?

Limb-Girdle MD

Affects shoulder girdle and/or hip girdle May see elevations in CK Dx prgression slow and comorbid conditions (cardiac, cognitive) are rare What type of MD?

Limb-girdle MD

Subtypes 1b, 1e, 2g, and 2m are more prone to what involvement?

Cardiac

Treatment focused on stretching to prevent contractures What type of MD?

Limb-girdle MD

Affects males and females May progress slowly Extremely variable age of onset and severity of onset Has 3 different forms: Autosomal dominant, Infant form, and Classical form What type of MD?

Facioscapulohumeral MD (FMD)

Parent with disease has 50% chance of passing disease to offspring What type of FMD?

Autosomal dominant

Sx early in life profound facial weakness (inability to close eyes, etc) Progresses to include shoulders, hip, etc Most wheelchair bound by 9-10 y/o May have seizures, cognitive deficits, hearing loss What type of FMD?

Infant form

Sx between 20-30 y/o Slow progression with milder weakness of facial muscles (pouting appearance) shoulders and arms usualy involved eventually What type of FMD?

Classical form

Try to push up, sit up, reversal of anterior axillary folds, scapular winging, decresed hearing Slightly elevated CK Myotonic EMG pattern Genetic testing Dx of what type of MD?

FMD

Ptosis and dysphagia Present in 4-5th decade Most develop leg weakness eventually Tongue atrophy and facial muscle weakness Dx based on clinical findings and exclusion of other causes Normal to slightly elevated CK Genetic testing What type of MD?

Oculopharyngeal MD

Sx apparent at birth "floppy baby" No treatments available What type of MD?

Congential MD