MS, MG, MD lecture Flashcards
Which cells wrap around axons, insulating them
*Form myelin in the PNS
Schwann cells
What cells myelinated the CNS?
Oligodendrocytes
Form spider-like network in CNS
- *Facilitate nutrient extraction from blood supply (capillaries)
- *Disposal of cellular waste products
Astrocytes
Exclusive to CNS
Circulate nervous system helping with immunity by DESTROYING BACTERIA OR DEAD CELLS
Microglial cells
Line areas of the nervous system that have cerebrospinal fluid, and help circulate the fluid
Ependymal cells
Action potentials travel down axon to terminal bulb, where vesicles filled with Ach are released into synaptic cleft via _____ mediated mechanism
Calcium
After Ach binds to its receptor, ligand gates Na channels are activated. This allows Na to enter into the….
post synaptic membrane
When enough positive ions enter the post synaptic membrane, an excitatory AP causes Ca to be released from the SR, which causes….
Muscle contraction
What does Acetylcholinesterase (AchE) do?
Hydrolizes (inactivates) Ach
Neutrophils
Basophils
Eosinophils
..examples of?
Granulocytes
Antigen presenting cells with epitope (antigen fragment) interacts with…
Helper T cells
Autoimmune (?) disease which causes inflammatory demyelination of CNS
*demyelination of axons reduces neurons ability to function
Multiple Sclerosis (MS)
Is there a specific auto-antibody found in MS?
NO
What is the age of diagnosis in MS?
Usually young adult (under 55 at onset)
- Age of onset usually mid 20s-30
- women more common than men
- likely autoimmune, so risk of other autoimmine dz.
- MC in Northern Europe, Southern Canada, Northern US
MS
Less common in areas closer to equator
HLA-DR2? HLA-DRBI association
MS
In MS….
Inflammation –> demyelination –> ?
Axonal degradation
Weakness Fatigue Numbness, tingling Unsteadiness in a limb Spastic paraparesis Disequilibrium/vertigo Pain Sphincter disturbances (urinary urge/hesitancy) Optic neuritis
MS!
Blurred or diminished vision Blind spots, esp with central vision Pain with eye movements HA Sudden color blindness Impaired night vision Impaired contrast sensitivity Diplopia
Retrobular neuritis/optic neuritis (in MS)
- Relapses and remission
- Onset age 15-50
- Optic neuritis
- Fatigue
- Lhermitte’s sign
- Internuclear ophthalmoplegia
- Uhthoff’s phenomenon
Suggestive features for MS
What is Lhermitte’s sign?
Electrical shock extending down the spine, triggered by flexing the head forward
Internuclear ophthalmoplegia is impairment of _________ eye movement
horizontal
Uhthoff’s phenomenon is the worsening of neurologic symptoms when…
body gets overheated! (i.e. warm weather, exercise, fever, etc)
*generally the optic neuritis and visual symptoms, but can be anything
Can nystagmus be seen in MS pts?
YES
For diagnosis of MS…
Must show ____ or more different areas in central areas of white matter affected at different times
TWO
What if…..
Pt has multi focal disease on imaging but only 1 clinical attack or if pt has a history of at least 2 clinical attacks but signs of only 1 lesion
a probable MS diagnosis can be made
Diagnostic of choice for clinically suspected MS?
MRI
Lesion is cerebral or spinal plaque
*region of demyelination and initially a preserved axon
MS
- Periventricular
- Juxtacortical
- Infratentorial
- Spinal cord
Locations of MS lesions
Increased Gadolinium enhancement may be indicative of….
an acute MS lesion
What labs should be done in a potential MS pt?
LUMBAR PUNCTURE!
also want to get things like B12 and lyme to rule out other causes of neuro symptoms
- Mild lymphocytosis
- IgG in CSF
- Most likely normal opening pressure
- Possible albumin in CSF (indicates disruption of BBB)
- **Oligoclonal bands
Possible findings of lumbar puncture in MS patient
Oligoclonal bands in HIGHLY SUGGESTIVE of….
MS
A series of distinct bands found in the immunoglobulin of the CSF
Oligoclonal bands
**highly suggestive of MS
A test in which a pt sits before a screen which displays alternative checkerboard patterns
*used to ID impaired transmission along optic nerve pathways
Visual evoked response (VER)
*positive in 85% of MS pts
- Visual Evoked Response
- Brainstem Auditory Evoked Response
- Somatosensory Evoked Potentials
- CSF with oligoclonal banding
- IgG index of CSF
- CSF albumin
- Brain MRI
Tests that can be done (and may be positive) in MS patients
Albumin in CSF indicates a disruption of…
the Blood Brain Barrier
- Relapsing Remitting
- Secondary Progressive
- Primary Progressive
- Progressively Relapsing
4 types of MS
An initial episode then months or years before new symptoms emerge or previous symptoms return
Relapsing-remitting MS (RRMS)
This cycle can lead to incomplete remissions and progressive disability with:
- weakness
- spasticity
- ataxia of limbs
- impaired vision
- urinary incontinence
Relapsing-remitting MS (RRMS)
Acute exacerbation of symptoms lasting days to weeks (lasting a minimum of 24 hrs)
Relapse
Relapse triggers?
Infection
Trauma
Pregnancy
Which type of MS…
Starts out as relapsing remitting (RRMS) but then beings to progress without relapse. disease beings to progress more steadily
Secondary progressive MS (SPMS)
Which type of MS…
Symptoms progress from the beginning without relapse/attacks.
Primary progressive MS (PPMS)
Which type of MS….
Steady decline from the onset with additional superimposed attacks/relapses
Progressive relapsing MS (PRMS)
Is there a cure for MS?
NO
tx is aimed at improving quality of life
What do you treat acute MS attacks with?
Glucocorticoids (ie Methylprednisone IV for 3-7 days)
Disease modifying therapy is aimed at…
Reducing relapses
Slowing progression of disease
Cytokine that modulates immune responsiveness
Interferon-B
Interferons and Glatiramer are MS treatments given through….
injection
GLATIRAMER* is a mixture of amino acids antigenically similar to…
Myelin protein
Fingolimod is the first oral agent approved for MS and works by down regulating receptors and T cell sequestration in….
lymphoid tissue
Teriflunomide inhibits mitochondrial enzymes involved in DNA replication.
Teriflunomide also decreases T and B cell proliferation and response to ____________
Auto antigens
Natalizumab decreases migration of immune cells into CSF, causing fewer….
fewer LESIONS ON MRI and fewer RELAPSES!
True or false…
Mitoxantrone is cytotoxic?
TRUE
What type of vaccines should be avoided in MS patients?
Live attenuated
Rare, autoimmune disease
MC disease of neuromuscular transmission
Myasthenia Gravis
In myasthenia gravis, there are antibodies found against which type of Ach receptors at the neuromuscular junction?
Nicotonic receptors
Some antibodies impair ability of Ach to bind to receptors
Some antibodies destroy Ach-receptors
Myasthenia gravis
Proteins that mediate clustering of Ach-Receptor during neuromuscular junction formation and are associated with Ach-Receptor maintenance
MuSK (muscarinic tyrosine kinase)
Antibodies are present against MuSK (muscarinic tyrosine kinase)
Myasthenia Gravis
Antibodies against:
- Nicotonic receptors at neuromuscular jxn
- Muscarinic tyrosine kinase (MuSK)
Myasthenia Gravis
2 possible manifestations of myasthenia gravis?
- ocular..limited to lids and EOM
2. generalized
What percent of those with ocular myasthenia gravis will progress to generalized within 2 years?
50%
Seen in both men and women
**Occurs at all ages (infant to elders)
Women, more likely to occur during child bearing years
Men, more likely to occur in 6th or 7th decade
Myasthenia gravis
True or false…
Pregnancy and menstrual periods can exacerbate signs and symptoms of myasthenia gravis?
TRUE
Genetic predisposition (HLA-DR3) is commonly found in myasthenia gravis patients with…
other autoimmune disorders
Can there be placental transmission of maternal antibodies of myasthenia gravis?
YES.
*myasthenia gravis may be transient in neonates
up to 75% of myasthenia gravis patients have ________ abnormalities
THYMIC
Organ in upper anterior portion of chest cavity, just behind sternum
*main function is to provide area for T lymphocyte maturation
Thymus
- Ptosis (uni or bilateral)
- Diplopia
- Bulbar muscle weakness (chewing, swallowing, speech)
- expressionless face
- neck muscles (head drop)
Myasthenia gravis
*commonly associated with facial symptoms!
Can myasthenia gravis progress to respiratory muscles and limb weakness?
YES
Weakness may be focal or generalized
Weakness may fluctuate throughout day (may be worse at night or after exercise)
Myasthenia gravis
Can remit and relapse
*Symptoms usually progress to become more frequent, may peak years after disease onset
Myasthenia gravis
Fluctuate of symptoms in myasthenia gravis is helpful to distinguish from…
Myopathy and motor neuron diseases
- Fatigability of muscles
- NORMAL sensation and reflexes!!!
- May have frank ptosis, slack jaw
- Positive Simpson Test
- Positive Cogan Lid Twitch Sign
Myasthenia gravis physical exam
Test where you…
look down, then up quickly
lid will lag
Simpson test
*positive in Myasthenia Gravis patients
Test where you…
have prolonged downward gaze
look up, and upper eyelid twitches
Cogan Lid Twitch sign
*positive in Myasthenia Gravis patients
The Tensilon test (endrophonium) can confirm a diagnosis of…
Myasthenia gravis
Short acting AchE inhibitor
*works by inhibiting the enzyme that breaks down Ach
Tensilon test
What are 2 contraindications of the Tensilon test when trying to diagnose Myasthenia Gravis
Cardiac disease
Asthma
Increase in salivation
Abdominal cramping
Symptomatic bradycardia
Bronchospams
Potential side effects of Tensilon test
What must you keep bedside during a Tensilon test incase the pt develops symptomatic bradycardia or bronchospasm?
Atropine
Must be administered incrementally!
2 mg every 1 minute, with a max of 10 mg
Tensilon test (for diagnosing Myasthenia Gravis)
In a patient with Myasthenia Gravis, what will the Tensilon test do?
Will improve muscle weakness
ie..if the pt has severe ptosis, it will improve during the test
Neuromuscular transmission is improved at ______ temps
cooler
The ice pack test can help diagnose…
Myasthenia Gravis
The Ice pack test is not helpful in muscles that cannot be cooled, such as….
EOM (extra ocular)
Eyelid muscles can easily be cooled! During the icepack test you place an icepack on them for…
2 minutes
Can ptosis improve immediately after removal of ice pack?
YES
What is the sensitivity of the ice pack test? Can there be false positives?
80% sensitivity
Yes, there can be false positives
Which three antibodies can be seen (but not always) in myasthenia gravis?
Antibodies against:
nAchR
MuSK
anti striated muscle
Which antibody is present in 80-90% of generalized MG
- 3 types: binding, blocking, modulating
- highly specific, almost no false positives
Antibody against nAchR
Which antibody is seen in circulation of 3-7% of MG patients?
Antibody against MuSK
Do levels of circulating antibodies correlate with severity of dz?
NO
Which antibody is seen in 30% of MG patients, and 80% of MG patients who have thymoma
Antibody against striated muscle
Can patients with MG be seronegative (without antibodies against nACHR or MuSK)?
Yes!
these pts have similar response to treatment and similar findings on electrophysiologic testing
True or false…
Most MG patients have thymic abnormalities , especially those with AchR-antibodies
TRUE
Hyperplasia of thymus or thymoma
Thymic abnormalities that can be seen in MG
nAchR-antibodies
MuSK antibodies
Anti-striated muscle antibodies
3 types of antibodies that can be seen in MG
- repetitive nerve stimulation studies
2. single fiber EMG
2 types of electrophysiologic testing in MG
3 things used in diagnosing myasthenia gravis
- labs (Abs against nAchR, MuSK, anti striated muscle)
- thymus imaging
- electrophysiologic testing
What is the use of Penicillamine and what is the importance with myasthenia gravis?
Penicillamine is an immunosuppressant used to treat RA
*it is associated with myasthenic syndrome and can progress to myasthenia gravis
What drug can potentially cause myasthenia gravis (but symptoms usually resolve when DC’d)
Penicillamine
- AchE inhibitors
- Immunomodulation
- Surgery (esp if thymoma)
- IV-Ig
- Plasmapheresis (plasma exchange)
Txs for MG
Respiratory weakness may lead to respiratory failure
can be precipitated by: Surgery Infections Meds Tapering of immunosuppression
Myasthenia Gravis Crisis
worsening generalized weakness may precede crisis
Admit to ICU!! May need to intubate Withdraw AchE inhibitors IV Ig High dose ummunomodulating therapy
Myasthenia Gravis Crisis
What classification of MG…
Any ocular weakness, all other muscle strength normal
Class I
What classification of MG…
MILD weakness affecting muscles other than ocular muscles (may also have ocular muscle weakness)
Class II
What classification of MG….
MODERATE weakness affecting muscles other than ocular muscles
Class III
What classification of MG…
Intubation with or without mechanical ventilation
Class V
What classification of MG
SEVERE weakness affecting muscles other than ocular muscles
Class IV
Inherited disorders causing progressive muscle weakness and atrophy due to genetic defect
*multiple types
Muscular dystrophy
Muscular dystrophies are disorders of the…..
muscles
Nerve sends signal to muscle, muscle is unable to respond in __________
myopathies
Defect gene on X chromosome
Lack of dystrophin (a protein that protects muscles)
Occurs in males
Duchenne Muscular Dystrophy (DMD)
Age of onset: 2-3 yo
Wheelchair by ~age 12
Survival into late teens/20s (usually pass away due to respiratory infections, cardiomyopathy)
Duchenne Muscular Dystrophy (DMD)
Which type of muscular dystrophy DOES make some dystrophin
- Enzymatic muscle breakdown
- Later onset, milder symptoms
- Survival into 40s, cardiomyopathy less common
Becker Muscular Dystrophy (BMD)
Which 2 types of MD…
Occurs in males
Asymptomatic female carriers (or mild dz)
Increase in CK
Starts centrally/trunk, moves to legs first
Tx with corticosteroids will increase strength but will NOT change prognosis
DMD and BMD
Cardiomyopathy
Scoliosis
Fractures
Cognitive impairments
Duchenne Muscular Dystrophy (DMD)
Dx made with:
Weakness on exam Family hx CK, AST, ALT Genetic testing EMG Muscle biopsy
DMD and BMD
Tx:
Steroids Ca/Vit D ACE inhibitor Beta blockers Pacemaker/defib Pulm support Immunizations
DMD and BMD
Caused by number of different inheritance patterns
*Seen in MALES and FEMALES
Weakness usually begins in ARMS in teen years, then progresses to legs and face
Emery-Dreifuss Muscular Dystrophy (EDMD)
- contractors of elbows, ankle, plantar flexors and spine EARLY
- later onset of humeroperoneal weakness
- cardiac abnormalities (arrhythmias, cardiomyopathies)
Classic triad of EDMD
Uncommon but distinctive
Weakness usually being in ARMS in teen years
Dx: CK normal or slightly elevated EMG Genetic testing **Often still ambulatory 20 years after dx***
Emery Dreifuss Muscular Dystrophy (EDMD)
MC form of muscular dystrophy in whites
affects MALES and FEMALES
has 2 genetic subtypes
Myotonic dystrophy
Muscle stiffness
Inability to relax muscle after contraction
Muscle loss and weakness: face, arms, legs
Cardiac complications
Cataracts
Change in intellectual fxn
Excessive daytime somnolence
Myotonic dystrophy
Multiple subtypes
- affects shoulder girdle and or hip girdle
- dz progressive is SLOW
Tx= stretching to prevent contractures
Limb-Girdle Muscular Dystrophy
Females and males
autosomal dominant
Reversal of anterior axillary folds
Scapular winging
Decreased hearing
Myotonic EMG pattern
Fascioscapulohumeral muscular dystrophy (FSHMD)
Ptosis Dysphagia Leg weakness Tongue atrophy Fascial muscle weakness
Oropharyngeal muscular dystrophy
“floppy baby”
seen right at birth
Congenital muscular dystrophy
MS image of choice?
MRI!!