Epidemiology
This is the most common disorder of neuromuscular junction
What is Myasthenia Gravis
These are the symptoms most commonly seen on initial presentation
What is ocular weakness, binocular diplopia, pstosis
This testing should be considered in patients that are double seronegative and onset of MG occurred in childhood or early adulthood
What is genetic testing for congenital MG
This is commonly the initial treatment for symptomatic MG.
What is Pyridostigmine providing rapid but transient improvement, with muscarinic side effects manageable by dose adjustment. Does not fix MG.
A 24-year-old woman presented to the emergency department following 5 weeks of increasing symptoms of hypernasal flaccid dysarthria, head drop, and dysphagia, which worsened late in the day. A neurologic consultation was requested, and her examination revealed no ptosis and full extraocular movements. She had upper and lower bifacial weakness with weak eye closure and difficulty holding air in inflated cheeks. Attempted smiling elicited a snarling expression. Jaw closure was mildly weak, and shewas unable to protrude her tongue fully into either cheek. Neck flexion and extension, shoulder abduction, and elbow extension were moderately weak. Acetylcholine receptor antibody testing was negative, and chest CT without contrast showed no thymoma. Pyridostigmine bromide 30 mg 3 times a day caused profuse muscle fasciculations. Repetitive nerve stimulation performed at 3 Hz demonstrated a 24% amplitude decrement recorded from the trapezius. Muscle-specific kinase (MuSK) antibodies were positive. Aside from from steroids what immunosupprsion agent can be used in this case.
Rituximab elicited improvement
In patients with MuSK MG, rituximab is often remarkably effective, with symptom improvement within 3 to 8 weeks and durable remissions potentially lasting several years
In Western countries MG affects what age groups in Men and Women
What is younger women, and older men
These are the most frequently affected arm muscles
What is deltoids, triceps brachii, wrist extensors, finger extensors
Axial or limb muscles are weak in about 15% to 20% of patients.22 This weakness is commonly asymmetric, but not unilateral. Neck flexion weakness (typically asymptomatic) is more common than neck extension weakness, which produces a dropped head, if severe.
Some patients initially negative for AChR binding antibodies may seroconvert, usually within this timeframe following MG onset
What is 6-12 months
Excessive dosing of cholinesterase inhibitors for severe MG may elicit this response
What is cholinergic crisis
DUMBBELSS
Depolarization blockade, increased weakness, excessive secretions, and aspiration risk
A 52-year-old man with migraine refractory to triptan medications received botulinum neurotoxin injections in his forehead and periocular muscles. Five days later, he developed asymmetric, fatigable eyelid ptosis without diurnal variability. Examination revealed mild left and moderate right eyelid ptosis with a curtain sign, and bilateral eye closure weakness. Extraocular movements were full and conjugate, and pupillary light responses were normal. Neurologic examination, including jaw closure and lower facial and tongue protrusion strength, was otherwise normal. A diagnosis of ocular myasthenia gravis was considered. Acetylcholine receptor (AChR)-binding, AChR-modulating, and muscle-specific kinase (MuSK) antibody radioimmunoassays were negative. Electrodiagnostic testing was performed for possible seronegative myasthenia gravis, including repetitive nerve stimulation and single-fiber EMG. Routine nerve conduction studies, EMG, and trapezius repetitive nerve stimulation testing were normal. Single-fiber EMG revealed markedly increased jitter and blocking in the frontalis muscle compatible with a primary neuromuscular transmission disorder. The disparity between mild clinical findings and marked electrophysiologic abnormalities prompted the electromyographer to inquire about this therapy.
What is botox
This percentage of patient's devlop generalized weakness within 2 years
What is 85%
bulbar, neck, and limb muscle weakness
These three signs are commonly seen with myasthenic ptosis
What is the Cogan lid twitch, curtain sign, frontalis sign
In this Ab mechanism IgG4 antibodies inhibit MuSK activation, impair AChR clustering, and disrupt acetylcholinesterase anchoring, leading to cholinergic hypersensitivity
What is MuSK antibody pathogenicity
LRP4 antibodies, found in 2% of MG cases, may activate complement or inhibit MuSK but have low specificity, requiring correlation with electrodiagnostics and phenotype for diagnosis
This medicine used to treat MG can be associated with acute exacerbations in up to 15% within 10 days of starting therapy or following a large dose increase
What is corticosteroids
Called called corticosteroid related exacerbation. Can last up to 1 week. For patients at higher risk for corticosteroid related exacerbation (ie, the elderly or those with moderate-to-severe bulbar or neck weakness), IV immunoglobulin (IVIg) or plasma exchange may be used to improve strength before starting prednisone.
A 42-year-old man was diagnosed with moderately severe, bulbar-predominant, nonthymomatous acetylcholine receptor generalized myasthenia gravis (MG) after presenting with 3 months of nasal speech, chewing fatigue, and dysphagia. He subsequently improved with an initial series of plasma exchanges, high-dose prednisone, and mycophenolate mofetil 1000 mg 2 times a day. He approached minimal manifestation status after 6 weeks. Over several months under the supervision of his neurologist, prednisone was gradually tapered from 60 mg to 7.5 mg a day, and he continued mycophenolate mofetil 1000 mg 2 times a day. Further reducing prednisone to 5 mg a day resulted in a return of nasal speech, so he resumed 7.5 mg a day. On this regimen, he reported no MG symptoms but still had eye closure and mild bulbar weakness on examination. He later developed an upper respiratory infection with purulent sinus drainage and 39.7°C (103.5°F) fever. He sought care in an urgent care clinic where azithromycin was prescribed. One day after starting azithromycin, he defervesced, but dysarthria, dysphagia, and chewing fatigue returned, and he presented to an emergency department, where examination revealed severe bulbar and new neck flexion weakness. What is the next best step TWO steps in his treatment plan?
Switch azithromycin to a different Abx Start IVIG or consider PLEX.
Azithromycin is a macrolide antibiotic known to impair neuromuscular transmission
This Ab form of MG is more common in women
What is Muscle-Specific Kinase (MuSK) Ab
This is an example of what two signs
What is curtain sign and frontalis sign
Curtain sign. A, At rest, the right eyelid is more ptotic. B, After the examinermanually relieves the right ptosis, the weakness in the left levator palpebrae is unmasked with increased ptosis of the left eyelid. Note the frontalis muscle contraction in an effort to relieve eyelid ptosis (frontalis sign).
Single fiber EMG is the most sensitive test to support diagnosis of MG. These are the two muscles most commonly tested.
What are the frontalis, or orbicularis oculi muscles
These two medications are commonly used for MG as nonsteroidal immune suppressants
What is Azathioprine and Mycophenolate
Prospective, randomized controlled trials of mycophenolate mofetil did not demonstrate improved MG outcomes over prednisone 20 mg a day in patients with generalized AChR MG treated over 90 days39 or steroid-sparing effect during a 9-month prednisone taper.
A prospective, observational, multicenter study comparing azathioprine and mycophenolatemofetil revealed no difference in clinical outcomes An idiosyncratic reaction involving malaise, fever, nausea, vomiting, abdominal pain, and rash occurs in 10% to 15% of patients within 3 weeks of initiation and requires permanent discontinuation.
A 30yo F presents with inital ocular and bulbar weakness starting 1 year ago that has progressed to generaized weakness, found to have AChR Ab positive generalized MG. On imaging her CT chest she does not have evidence of thymoma. Should she undergo thymectomy?
What is yes
Current treatment guidelines recommend thymectomy for patients 18 to 50 years old early in the course of nonthymomatous, AChR generalized MG. This increases the likelihood of improved MG outcomes, reduced immunotherapy requirements, and reduced hospitalizations for MG exacerbations, particularly when there are inadequate responses or intolerable side effects to immunotherapy.
A multicenter, rater-blinded randomized controlled trial of transsternal thymectomy in early (less than 5 years) AChR generalized MG without thymoma demonstrated improved clinical outcomes in patients treated with thymectomy and prednisone over those treated with prednisone alone. Improvementwas observed at 1 year, sustained at 3 years, and persistent after 5 years.
In the early 1900s MG had this mortality rate related to respiratory failure
What is 70%
In the 1930s, cholinesterase inhibitor treatment reduced mortality to approximately
30%. Currently, 75% of patients achieve minimal manifestations of disease or
remission within 2 years using conventional therapies. 10-15% pt are still refractory to tx.
This can be seen in chronic bulbar MG
What is triple furrowing of the tongue
Result fromchronic bulbarMG due to functional denervation. This atrophy resolves gradually as myasthenia gravis improves. Atrophy of facial, tongue, neck extensor, and shoulder girdle muscles often normalizes after successful treatment, particularly in patients with MuSK MG.
In this seropositive Ab form of MG IgG1 and IgG3 antibodies bind the main immunogenic region, causing crosslinking, internalization, and complement-mediated membrane attack complex formation.
What is AChR Ab mechanism
This is the common MoA of the following three immunotherapies: Eculizumab, ravulizumab, zilucoplan
What is Complement inhibition
Effective therapeutic target in AChR generalized MG
Bind to C5 and block the cleavage of C5 to C5a and C5b, preventing
membrane attack complex formation in the terminal complement pathway
Zilucoplan additionally inhibits C5b-C6 binding, the initial step in membrane
attack complex formation.
In addition to experiencing clinical improvement complement inhibition allows many patients to reduce prednisone, nonsteroidal immune suppressant, and rescue therapy use
A 25yo F with MG presents to your clinic to discuss medication options as she wished to become pregnant in the near future. These three medications are contraindicated in this case.
What is Mycophenolate mofetil, methotrexate, and cyclophosphamide are teratogens
Medications considered to have the lowest fetal risk in pregnancy atminimum effective doses include oral pyridostigmine bromide, prednisone, azathioprine, and IVIg or plasma exchange for exacerbation