MS, MG, MD lecture Flashcards
(132 cards)
1
Q
Which cells wrap around axons, insulating them
*Form myelin in the PNS
A
Schwann cells
2
Q
What cells myelinated the CNS?
A
Oligodendrocytes
3
Q
Form spider-like network in CNS
- *Facilitate nutrient extraction from blood supply (capillaries)
- *Disposal of cellular waste products
A
Astrocytes
4
Q
Exclusive to CNS
Circulate nervous system helping with immunity by DESTROYING BACTERIA OR DEAD CELLS
A
Microglial cells
5
Q
Line areas of the nervous system that have cerebrospinal fluid, and help circulate the fluid
A
Ependymal cells
6
Q
Action potentials travel down axon to terminal bulb, where vesicles filled with Ach are released into synaptic cleft via _____ mediated mechanism
A
Calcium
7
Q
After Ach binds to its receptor, ligand gates Na channels are activated. This allows Na to enter into the….
A
post synaptic membrane
8
Q
When enough positive ions enter the post synaptic membrane, an excitatory AP causes Ca to be released from the SR, which causes….
A
Muscle contraction
9
Q
What does Acetylcholinesterase (AchE) do?
A
Hydrolizes (inactivates) Ach
10
Q
Neutrophils
Basophils
Eosinophils
..examples of?
A
Granulocytes
11
Q
Antigen presenting cells with epitope (antigen fragment) interacts with…
A
Helper T cells
12
Q
Autoimmune (?) disease which causes inflammatory demyelination of CNS
*demyelination of axons reduces neurons ability to function
A
Multiple Sclerosis (MS)
13
Q
Is there a specific auto-antibody found in MS?
A
NO
14
Q
What is the age of diagnosis in MS?
A
Usually young adult (under 55 at onset)
15
Q
- 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
A
MS
16
Q
Less common in areas closer to equator
HLA-DR2? HLA-DRBI association
A
MS
17
Q
In MS….
Inflammation –> demyelination –> ?
A
Axonal degradation
18
Q
Weakness Fatigue Numbness, tingling Unsteadiness in a limb Spastic paraparesis Disequilibrium/vertigo Pain Sphincter disturbances (urinary urge/hesitancy) Optic neuritis
A
MS!
19
Q
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
A
Retrobular neuritis/optic neuritis (in MS)
20
Q
- Relapses and remission
- Onset age 15-50
- Optic neuritis
- Fatigue
- Lhermitte’s sign
- Internuclear ophthalmoplegia
- Uhthoff’s phenomenon
A
Suggestive features for MS
21
Q
What is Lhermitte’s sign?
A
Electrical shock extending down the spine, triggered by flexing the head forward
22
Q
Internuclear ophthalmoplegia is impairment of _________ eye movement
A
horizontal
23
Q
Uhthoff’s phenomenon is the worsening of neurologic symptoms when…
A
body gets overheated! (i.e. warm weather, exercise, fever, etc)
*generally the optic neuritis and visual symptoms, but can be anything
24
Q
Can nystagmus be seen in MS pts?
A
YES
25
For diagnosis of MS...
Must show ____ or more different areas in central areas of *white matter* affected at different times
TWO
26
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
27
Diagnostic of choice for clinically suspected MS?
MRI
28
Lesion is cerebral or spinal plaque
*region of demyelination and initially a preserved axon
MS
29
* Periventricular
* Juxtacortical
* Infratentorial
* Spinal cord
Locations of MS lesions
30
Increased Gadolinium enhancement may be indicative of....
an acute MS lesion
31
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
32
* 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
33
Oligoclonal bands in HIGHLY SUGGESTIVE of....
MS
34
A series of distinct bands found in the immunoglobulin of the CSF
Oligoclonal bands
**highly suggestive of MS
35
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
36
- 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
37
Albumin in CSF indicates a disruption of...
the Blood Brain Barrier
38
1. Relapsing Remitting
2. Secondary Progressive
3. Primary Progressive
4. Progressively Relapsing
4 types of MS
39
An initial episode then months or years before new symptoms emerge or previous symptoms return
Relapsing-remitting MS (RRMS)
40
This cycle can lead to incomplete remissions and progressive disability with:
* weakness
* spasticity
* ataxia of limbs
* impaired vision
* urinary incontinence
Relapsing-remitting MS (RRMS)
41
Acute exacerbation of symptoms lasting days to weeks (lasting a minimum of 24 hrs)
Relapse
42
Relapse triggers?
Infection
Trauma
Pregnancy
43
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)
44
Which type of MS...
Symptoms progress from the beginning without relapse/attacks.
Primary progressive MS (PPMS)
45
Which type of MS....
Steady decline from the onset with additional superimposed attacks/relapses
Progressive relapsing MS (PRMS)
46
Is there a cure for MS?
NO
tx is aimed at improving quality of life
47
What do you treat acute MS attacks with?
Glucocorticoids (ie Methylprednisone IV for 3-7 days)
48
Disease modifying therapy is aimed at...
Reducing relapses
| Slowing progression of disease
49
Cytokine that modulates immune responsiveness
Interferon-B
50
Interferons and Glatiramer are MS treatments given through....
injection
51
GLATIRAMER* is a mixture of amino acids antigenically similar to...
Myelin protein
52
Fingolimod is the first oral agent approved for MS and works by down regulating receptors and T cell sequestration in....
lymphoid tissue
53
Teriflunomide inhibits mitochondrial enzymes involved in DNA replication.
Teriflunomide also decreases T and B cell proliferation and response to ____________
Auto antigens
54
Natalizumab decreases migration of immune cells into CSF, causing fewer....
fewer LESIONS ON MRI and fewer RELAPSES!
55
True or false...
Mitoxantrone is cytotoxic?
TRUE
56
What type of vaccines should be avoided in MS patients?
Live attenuated
57
Rare, autoimmune disease
*MC disease of neuromuscular transmission*
Myasthenia Gravis
58
In myasthenia gravis, there are antibodies found against which type of Ach receptors at the neuromuscular junction?
Nicotonic receptors
59
Some antibodies impair ability of Ach to bind to receptors
Some antibodies destroy Ach-receptors
Myasthenia gravis
60
Proteins that mediate clustering of Ach-Receptor during neuromuscular junction formation and are associated with Ach-Receptor maintenance
MuSK (muscarinic tyrosine kinase)
61
Antibodies are present against MuSK (muscarinic tyrosine kinase)
Myasthenia Gravis
62
Antibodies against:
* Nicotonic receptors at neuromuscular jxn
* Muscarinic tyrosine kinase (MuSK)
Myasthenia Gravis
63
2 possible manifestations of myasthenia gravis?
1. ocular..limited to lids and EOM
| 2. generalized
64
What percent of those with ocular myasthenia gravis will progress to generalized within 2 years?
50%
65
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
66
True or false...
Pregnancy and menstrual periods can exacerbate signs and symptoms of myasthenia gravis?
TRUE
67
Genetic predisposition (HLA-DR3) is commonly found in myasthenia gravis patients with...
other autoimmune disorders
68
Can there be placental transmission of maternal antibodies of myasthenia gravis?
YES.
*myasthenia gravis may be transient in neonates
69
up to 75% of myasthenia gravis patients have ________ abnormalities
THYMIC
70
Organ in upper anterior portion of chest cavity, just behind sternum
*main function is to provide area for T lymphocyte maturation
Thymus
71
* Ptosis (uni or bilateral)
* Diplopia
* Bulbar muscle weakness (chewing, swallowing, speech)
* expressionless face
* neck muscles (head drop)
Myasthenia gravis
*commonly associated with facial symptoms!
72
Can myasthenia gravis progress to respiratory muscles and limb weakness?
YES
73
Weakness may be focal or generalized
Weakness may fluctuate throughout day (may be worse at night or after exercise)
Myasthenia gravis
74
Can remit and relapse
*Symptoms usually progress to become more frequent, may peak years after disease onset
Myasthenia gravis
75
Fluctuate of symptoms in myasthenia gravis is helpful to distinguish from...
Myopathy and motor neuron diseases
76
* 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
77
Test where you...
look down, then up quickly
lid will lag
Simpson test
*positive in Myasthenia Gravis patients
78
Test where you...
have prolonged downward gaze
look up, and upper eyelid twitches
Cogan Lid Twitch sign
*positive in Myasthenia Gravis patients
79
The Tensilon test (endrophonium) can confirm a diagnosis of...
Myasthenia gravis
80
Short acting AchE inhibitor
*works by inhibiting the enzyme that breaks down Ach
Tensilon test
81
What are 2 contraindications of the Tensilon test when trying to diagnose Myasthenia Gravis
Cardiac disease
Asthma
82
Increase in salivation
Abdominal cramping
Symptomatic bradycardia
Bronchospams
Potential side effects of Tensilon test
83
What must you keep bedside during a Tensilon test incase the pt develops symptomatic bradycardia or bronchospasm?
Atropine
84
Must be administered incrementally!
2 mg every 1 minute, with a max of 10 mg
Tensilon test (for diagnosing Myasthenia Gravis)
85
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
86
Neuromuscular transmission is improved at ______ temps
cooler
87
The ice pack test can help diagnose...
Myasthenia Gravis
88
The Ice pack test is not helpful in muscles that cannot be cooled, such as....
EOM (extra ocular)
89
Eyelid muscles can easily be cooled! During the icepack test you place an icepack on them for...
2 minutes
90
Can ptosis improve immediately after removal of ice pack?
YES
91
What is the sensitivity of the ice pack test? Can there be false positives?
80% sensitivity
Yes, there can be false positives
92
Which three antibodies can be seen (but not always) in myasthenia gravis?
Antibodies against:
nAchR
MuSK
anti striated muscle
93
Which antibody is present in 80-90% of generalized MG
* 3 types: binding, blocking, modulating
* highly specific, almost no false positives
Antibody against nAchR
94
Which antibody is seen in circulation of 3-7% of MG patients?
Antibody against MuSK
95
Do levels of circulating antibodies correlate with severity of dz?
NO
96
Which antibody is seen in 30% of MG patients, and 80% of MG patients who have thymoma
Antibody against striated muscle
97
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
98
True or false...
Most MG patients have thymic abnormalities , especially those with AchR-antibodies
TRUE
99
Hyperplasia of thymus or thymoma
Thymic abnormalities that can be seen in MG
100
nAchR-antibodies
MuSK antibodies
Anti-striated muscle antibodies
3 types of antibodies that can be seen in MG
101
1. repetitive nerve stimulation studies
| 2. single fiber EMG
2 types of electrophysiologic testing in MG
102
3 things used in diagnosing myasthenia gravis
1. labs (Abs against nAchR, MuSK, anti striated muscle)
2. thymus imaging
3. electrophysiologic testing
103
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
104
What drug can potentially cause myasthenia gravis (but symptoms usually resolve when DC'd)
Penicillamine
105
* AchE inhibitors
* Immunomodulation
* Surgery (esp if thymoma)
* IV-Ig
* Plasmapheresis (plasma exchange)
Txs for MG
106
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
107
```
Admit to ICU!!
May need to intubate
Withdraw AchE inhibitors
IV Ig
High dose ummunomodulating therapy
```
Myasthenia Gravis Crisis
108
What classification of MG...
Any ocular weakness, all other muscle strength normal
Class I
109
What classification of MG...
MILD weakness affecting muscles other than ocular muscles (may also have ocular muscle weakness)
Class II
110
What classification of MG....
MODERATE weakness affecting muscles other than ocular muscles
Class III
111
What classification of MG...
Intubation with or without mechanical ventilation
Class V
112
What classification of MG
SEVERE weakness affecting muscles other than ocular muscles
Class IV
113
Inherited disorders causing progressive muscle weakness and atrophy due to genetic defect
*multiple types
Muscular dystrophy
114
Muscular dystrophies are disorders of the.....
muscles
115
Nerve sends signal to muscle, muscle is unable to respond in __________
myopathies
116
Defect gene on X chromosome
Lack of dystrophin (a protein that protects muscles)
Occurs in males
Duchenne Muscular Dystrophy (DMD)
117
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)
118
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)
119
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
120
Cardiomyopathy
Scoliosis
Fractures
Cognitive impairments
Duchenne Muscular Dystrophy (DMD)
121
Dx made with:
```
Weakness on exam
Family hx
CK, AST, ALT
Genetic testing
EMG
Muscle biopsy
```
DMD and BMD
122
Tx:
```
Steroids
Ca/Vit D
ACE inhibitor
Beta blockers
Pacemaker/defib
Pulm support
Immunizations
```
DMD and BMD
123
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)
124
1. contractors of elbows, ankle, plantar flexors and spine EARLY
2. later onset of humeroperoneal weakness
3. cardiac abnormalities (arrhythmias, cardiomyopathies)
Classic triad of EDMD
125
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)
126
MC form of muscular dystrophy in whites
affects MALES and FEMALES
has 2 genetic subtypes
Myotonic dystrophy
127
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
128
Multiple subtypes
* affects shoulder girdle and or hip girdle
* dz progressive is SLOW
Tx= stretching to prevent contractures
Limb-Girdle Muscular Dystrophy
129
Females and males
**autosomal dominant**
Reversal of anterior axillary folds
Scapular winging
Decreased hearing
Myotonic EMG pattern
Fascioscapulohumeral muscular dystrophy (FSHMD)
130
```
Ptosis
Dysphagia
Leg weakness
Tongue atrophy
Fascial muscle weakness
```
Oropharyngeal muscular dystrophy
131
"floppy baby"
| seen right at birth
Congenital muscular dystrophy
132
MS image of choice?
MRI!!
