Neuromuscular Junction Disease Flashcards
List four neuromuscular junction disorders.
Myasthenia Gravis
Lambert Eaton Syndrome
Botulism
Tetanus
Myasthenia Gravis:
- Age of onset; how does this differ bw men and women?
- How does it present (3)?
- At what time of day are the symptoms worse?
- Bimodal distribution F (teens-30s), M (50-70)
- Presentation: generalized, bulbar (face), ocular
- Sx worse at the end of the day (fatiguable weakness; dinural variation)
Describe the pathophysiology of MG:
What are 3 possible etiologies?
1) Direct blocking of skeletal muscle AchR
2) IgG AutoAb crosslinking–> Faster internalization and degradation of AchR
3) Complement mediated lysis of muscle end plate–> decreased invaginations, SA, room for receptors
3 ways complement mediated lysis damages the NMJ motor end plate?
- Less invaginations
- Less surface area
- Less room for receptors
In AchR AutoAb (+) MG, what percent of patients have thyme hyperplasia?
What percent have a thyme tumor?
What is the most effective treatment under these circumstances?
- 50% have thymic hyperplasia
- 10-15% have thymic tumor
**One should always consider thymectomy when treating MG; especially with paraneoplastic syndrome thymoma
What should you expect to find on reflexes and sensory exam for MG?
Normal findings
Pt with MG: sustained up gaze (30-60s) will elicit what effect?
What is the most effected muscle in EOM palsy for these patients?
^ Ptosis and medial rectus weakness
MR is usually most severely involved muscle in EOM palsy
Pt with MG: Sustained abduction of arms (120s) will elicit what effect? (2)
Patient can no longer hold arms up, OR weakness becomes apparent with subsequent manual testing
May ^ dysarthria or SOB
Pt with MG: Sustained elevation of leg while laying supine (90s) will elicit what effect? (2)
Patient can no longer hold leg up, OR weakness becomes apparent with subsequent manual testing
May ^ dysarthria or SOB
Pt with MG: Repeated rising from chair without use of arms (up to 20x) will elicit what effect? (2)
Fatigues after several attempts
Early/mild weakness–> exaggerated lean-forward and buttocks-first maneuver
Pt with MG: Counting aloud (1-50) will elicit what effects?
Enhances dysarthria (nasal, lingual, labial)
What is the gold standard form of immunologic testing done to dx MG?
In what percent of patients is this found? For what form of MG is it useless?
Describe the specificity?
AchR binding Ab test
Found in 80-85% patients, useless for isolated ocular MG
Very low false positive rate;
good specificity
Which Ab is typically seen in patients with generalized MG?
What is the function of the protein it attacks?
How frequently is it isolated in AchR binding Ab negative patients?
“Anti-Muscle Specific Tyrosine Kinase”
Attacks protein responsible for clustering AchR’s
Seen in 40% of AchR binding Ab negative patients
What was the first Ab discovered in MG?
With what type of MG is this Ab heavily associated?
When do we test for this?
Anti-striated muscle Ab
75-80% patients with thymoma asstd MG have this
Test for this in very young (ID thymoma) or very old (ID isolated abnormality) patients
How effective is repetitive nerve stimulation in dx of MG?
What should be done if RNS is normal w/ high suspicion for MG?
- RNS has very low sensitivity
- Important to do SFEMG of at least one symptomatic muscle if RNS is normal
Describe the changes in EPP observed in repeated stimulation of MG patients?
Decreased EPP–> Decreased safety factor for NM transmission–> Repeated stimulation–> Amplitude falls below threshold for activation–> Transmission failure
List 4 advantages and 4 disadvantages to the Edrophonium Test at bedside?
Advantages:
- Rapid onset (30s)
- Short duration (5-10 min)
- Assess ptosis/ weakness improvement
- Sensitive (generalized MG)
Disadvantages:
- Physician blinding
- ADRs: bradycardia, HypoTN
- Not reliable anti-MuSK MG
- Not Specific
What is the DOC for symptomatic treatment of MG?
How does it help?
How quickly does it work and how long does it last?
What are the ADRs?
Pyridostigmine (Mestinon): AchEi
Onset: 30-45 min
Loss of Effect: 3-6 hrs
ADRs: SLUDEBBB
List two short term immune-direct therapies of MG (Emergent Treatment)
1) Plasma exchange (PLEX)
2) IVIG
Describe how PLEX is used to treat MG
How does it work?
How long does it take to work?
How often is it done?
- Decreases # circulating Abs
- Takes days to work
- 3-6 treatments every other day if multi drug resistant; otherwise commonly used as emergent treatment
Describe how IVIG is used to treat MG:
How does it work?
How long does it take to work?
How often is it done?
- Neutralizes/ Downregulates Immune sx. w comparable efficacy to PLEX
- Takes days to work and lasts 4-6 weeks
- 2g/kg given over 2-5 days for emergencies and refractory MG
List three immune direct long term therapies for MG in preferred order:
1) Corticosteroids
2) Chemo agents
- Azathioprine (#1)
- Mycophenolate
* *These take a while to work
3) Thymectomy
What is the singular absolute indication of thymectomy?
THYMOMA
Removal thought to be helpful in patients younger than 50
With what disease is Lambert Eaton Myasthenic Syndrome commonly associated? Does it typically appear before or after the disease?
What are some strong indicators that this disease may be present?
Why is it so frequently undiagnosed?
Small Cell lung cancer
**May precede dx by 9 mos!!!
Look for 50+ yoa and hx of smoking = strong indicators of SCLC
Commonly underdx’ed due to cachectic nature of SCLC patients/ chemo patients
LEMS not associated with SCLS most commonly occurs in which population?
Young females with other autoimmune comorbidities (sjogrens, SLE)
Describe the pathophysiology of LEMS:
IgG against presynaptic VGCC–> Cross link multiple VGCCs–> Decrease Ca influx into–> Decreased Ach released at terminus
Describe the hallmarks of LEMS clinical presentation: (5)
- Proximal limb weakness +/- tenderness; **SPARES face (typically), **IMPROVE W EXERCISE
- Dry eyes + mouth
- Metallic taste
- Worse on CaC blockers
- Prolonged paralysis w paralytics given before intubation
Describe the weakness associated with LEMS:
- Proximal
- BETTER with exercise
- MINIMAL BULBAR/ facial involvement (less than 25%)
Describe the reflex and sensory exam findings associated with LEMS:
- Reduced DTRs
- Normal Sensory exam
What ate the two diagnostic methods used to confirm LEMS?
- Serum testing (VGCC Ab)
- EMG w repetitive stimulation at 3 Hz then 30-50Hz–> will see increase in amplitude
Describe the treatments available too LEMS:
Similar to MG, but not as effective
LEMS: Weakness Bulbar sx? DTR? ANS? RNStimulation? Malignancy? AutoAbs?
- Proximal without diurnal flux
- Rarely bulbar
- Diminished DTRs
- ANS sx present
- Incremental ^ w 30Hz
- SCLC
- VGCC
MG: Weakness Bulbar sx? DTR? ANS? RNStimulation? Malignancy? AutoAbs?
- Proximal, dinural
- Bulbar involvement common
- DTRs present
- No ANS sx
- Decremental RNS @ all Hz
- Thymoma
- AchR, MuSK, Anti-striated Mc
