Neuromuscular Disorders Flashcards
Onset of myasthenia gravis (decade):
F: 2nd - 3rd
M: 5th - 6th
What is affected in Myasthenia gravis?
Antibodies to the acetylcholine receptors (B and T cells are both involved)
When are the MG symptoms better?
With rest and with cold
When are MG symptoms worse?
In the summer and as the day progresses
Most common areas of weakness with MG:
- Eyelid/eyes
- Bulbar (swallowing)
- Respiratory
- Extremities (proximal > distal)
What is a distinctive feature of MG?
They maintain good pupil responses
What is generalized MG? What percent become generalized in the first year?
When it spreads anywhere other than the eyes - 75% has generalized in the first year
How can you bring ptosis out?
Sustained upwards gaze - one eye will have more than the other
What is the curtain sign in MG?
If you open the eye with more ptosis really wide, the other one will go down
Do you have intact sensation with MG?
Yes - only motor is lost
What is a myasthenia crisis? (15-20%)
Respiratory failure - very serious (need mechanical ventilation)
What is the Tensilon test?
Diagnoses MG - give a short-acting cholinesterase inhibitor *Need atropine available
What is CMAP?
Compound muscle action potential - will decrease over time in MG patients
Testing for MG (2):
AChR serum testing - if negative, run a Anti-MUSK
What two things are scanned for with a CT in a patient with MG?
- Thymoma (10%)
- Thymic lymphofollicular hyperplasia
Two tests for formal diagnosis of MG:
- EMG and Nerve conduction study
* Increased jitter in MG
Treatment for MG (3):
- Cholinesterase inhibitor: Pyridostigmine
- Corticosteroids: Prednisone
- Chemotherapeutic (3)
What treatment is the first immune therapy choice for MG?
Corticosteroids - Remission in 50%
What are the three chemotherapeutic medications for MG?
- Azathioprine - Takes 1 year
- Cyclosporine - MUST be on BC
- Eculizumab - 3rd line, last resort
What drug that is chemotherapeutic has a risk for meningitis infection with MG?
Ecluizumab
Treatment of Myasthenia crisis - rapid treatment (2):
IV Ig - HA is most common adverse reaction
Plasmapheresis - Remove antibodies and immune complexes
Option for MG patients if medications do not work at all:
Thymectomy - rec. If they have a thymoma (most helpful 1-2 years after symptoms)
What do you want to discontinue if someone is having a myasthenia crisis?
Anticholinesterase meds (will increase secretions)
What do you not want to treat someone with if they are having a myasthenia crisis?
Steroids - Can prolong the crisis
What is transitory neonatal MG?
baby receives antibodies from mom (1st four days - resolve sin 1 week)
Congenital arthrogryposis
Getting stuck in certain positions
Lambert-Eaton Myasthenia Syndrome physiology:
Antibodies at the P/Q calcium gated channels - decrease NT released
LEMS is _____ or ____
Autoimmune or paraneoplastic
If someone has LEMS what type of cancer do 50% of patients have?
Small cell carcinoma of the lung
What are the two oral symptoms of LEMS?
Metallic taste and dry mouth
What are the four autonomic symptoms with LEMS?
- Orthostasis
- Constipation
- Impotence
- Decreased sweating
You can have pain with what neuromuscular disorder?
LEMS
Repetitive Nerve Stimulation for LEMS:
Initially low and then doubles with marked facilitation
If you have a patient with LEMS, you must always evaluate for:
MALIGNANCY - if not found, check again in 2-4 years
Three treatments for LEMS:
- Remove the tumor if there is one
- 2,3-DAP: Blocks volatage gated K+ channels = prolonged action potential
- Guanidine hydrochloride: Inhibits Ca2+ reuptake
What two drugs do not work for LEMS?
- Cholinesterase drugs
- Immunosuppressives
DTRs are ____ in LEMS
Absent or decreased
DTRs are ___ in MG
Normal
Botulism binds:
Irreversibly - ACh not released
What two things will you find on PE with someone that has botulism poisoning?
- DTRs are absent
- Pupils unreactive
GI symptom onset with botulism:
3-4 hours
Those with botulism will have these three symptoms:
- Descending paralysis
- Autonomic (constipation, postural hypotension, urinary retention)
- Ocularbulbar problems
Treatment for botulism:
Intensive supportive care
***Trivalent botulism antitoxin may work but only on the nerves where the toxin has not bound yet
When 5-10% of people die with botulism poisoning, what are the two causes of death?
- Respiratory failure
- Pulmonary/systemic infections
Genetics for Duchenne Muscular dystrophy:
Mutation in the DMD (dystrophin) - located on the X chromosome (recessive)
If the female mom for DMD has symptoms, what two systems are affected?
cardiac or cognitive involvement
Job of dystrophin protein:
Strengthen the muscle fibers and provide tensile strength, cell/cell communication.
15% of DMD patients have which type of mutation?
Point mutation/substitution
DMD milestone plans: Walking, wheel chair and death
Walking: 14 - 16 months
Wheel chair: 10 - 15 (current tx).
Death: 20’s - 30’s
Three PE findings of DMD:
- Calf hypertrophy (fat)
- Proximal weakness
- DTRs diminished then gone
What is the Gower’s Maneuver?
In DMD - Weak and need to push themselves up
What neuromuscular disorder has the walling Trendelenburg gait?
DMD
What three labs do you order for DMD?
- CK (10-50x higher than normal)
- Aldose
- Gene test
If you see high AST/ALT in a young male with weakness…think:
DMD - AST/ALT are also in muscles (breakdown)
Medications for DMD (they also all get supportive care):
Corticosteroids (Emflaza/Prenisone)
What four things are you monitoring if a patient with DMD is on corticosteroids?
- Hyperglycemia
- HTN (have them on low Na diet)
- Osteoporosis (annual bone scans)
- PUD (have on PPIs)
Someone with DMD can have common complications in what three systems?
- Pulmonary (yearly PFTs)
- Cardiac (ACE/BB)
- Ortho (scoliosis, clinical evals/xray annually)
Becker Muscular dystrophy is like DMD but:
More mild (later onset) - live longer/walk longer
In terms of cardiac problems, people with Becker’s compared to DMD have:
Less cardiomyopathy but MORE CONDUCTION PROBLEMS
Myotonic Dystrophy - Most common in:
Adults
DMD is most common in:
Kids
Myotonic dystrophy genetics:
Autosomal dominant, trinucleotide expansion disorder *Anticipation
Five symptoms of Myotonic dystophy:
- Myopathic face (tent)
- Frontal balding
- Ptosis
- Distal over proximal weakness
- Cardiac problems - risk for SCD
You must do a ___ to look for ___ in someone with Myotonic Dystrophy
EKG; conduction abnormalities
CK will be __ in people with Myotonic Dystrophy
Mild/normal
Two drug for the treatment of Myotonic Dystrophy:
Mexilitine, phenytoin
Congenital Myotonic Dystrophy
Babies born with 3,000-4,000 repeats that have super severe disease - need respiratory support; high rate of death
Spinal Muscular Atrophy types and genetics:
Type 1, Type 2 (rarer)
Chromosome 5
Autosomal-recessive *2nd most common
What is SMA?
Progressive weakening of the lower motor neurons
SMA type 1 is ___
Most severe (die in 7 months)
SMA type 2 and 3 are ___
Better. Type 2 lives to 20’s and type 3 can live normally.
SMA types and sitting/standing patterns:
1: Never sit - severe
2. Sit but don’t stand - Respiratory problems
3. Stand but not long term
SMA type 1 mental status:
Intact
Gene for SMA (2):
SMN1: Whole length protein
SMN2: Makes truncated protein
Loss of the SMN1 gene results in:
Destruction of the anterior horn and peripheral nerves just like ALS
Future genetic treatment - Exon skipping for SMA:
Nusinersen and Zolgensma
