Myasthenia

Question 1

Def

Answer 1

an autoimmune disease of the neuromuscular junction (NMJ) characterized by muscle weakness that worsens with activity and improves with rest. MG is caused by autoantibodies directed against postsynaptic molecules, most commonly acetylcholine receptors (AchR)

Question 2

Symptomes

Answer 2

The most common initial symptom is ocular muscle weakness (e.g., ptosis and/or diplopia), with progression to generalized weakness typically occurring within two years

Fatigable weakness of skeletal muscles that worsens with increased muscle use and improves with rest.

Generalized disease can involve all skeletal muscles, especially:
Eye muscles: diplopia, blurred vision [6]
Bulbar muscles: dysarthria, difficulty chewing and/or swallowing, dyspnea
Proximal muscles: difficulty standing from a chair , climbing stairs, brushing hair [6]
Respiratory muscles: dyspnea, respiratory failure
Localized disease most commonly affects the eye muscles.

Normal deep tendon reflexes
Limb weakness is typically symmetrical.
Ocular weakness (e.g., ptosis) is typically asymmetrical.

Question 3

Dx

Answer 3

confirmed by antibody testing and electromyographic evaluation

Question 4

Tx

Answer 4

acetylcholinesterase inhibitors
-pyridostigmine titrated to symptom relief
immunosuppressive drugs can be added if symptoms persist
-glucocorticoids and/or azathioprine
Acute exacerbations, as seen in myasthenic crises, are generally treated with either IV immunoglobulins or plasma exchange
Thymectomy

Question 5

Commonly co-occurence of

Answer 5

All patients with MG should be screened for thymoma with CT chest.

Consider diagnostic studies for other autoimmune disorders (e.g., Hashimoto thyroiditis, rheumatoid arthritis, SLE).

Question 6

Peak incidence

Answer 6

Peak incidence
♂ : 40–70 years
♀ : 20–40 years

Question 7

Autoantibodies directed against

Answer 7

postsynaptic acetylcholine receptors or receptor-associated proteins

-Seropositive MG (80–90% of cases): positive assays for antibodies (in blood) against the acetylcholine receptor (AChR-Ab)
-Seronegative MG (10–20% of cases): negative for AChR antibodies, but may be positive for muscle-specific tyrosine kinase antibodies (MuSK antibodies)

Question 8

Classification

Answer 8

Ocular myasthenia: only the extraocular and/or eyelid muscles
Generalized myasthenia

Question 9

Tests

Answer 9

The eyebrow of the unaffected eye is usually lower than the affected eyebrow. [5]
Ice-pack test: An ice pack placed on the affected eyelid for 5 minutes improves ptosis by ≥ 2 mm. [5][6]
Curtain sign: Lifting the more ptotic eyelid worsens ptosis in the contralateral eyelid; eyebrow elevation and furrowing of the forehead can also occur.
Cogan lid twitch sign: brief eyelid twitching when looking straight ahead after 10–20 seconds of downward gaze [5]
Simpson test: historically used to reproduce eyelid fatigue; positive if looking upward for > 1 minute (without lifting the head) provokes eyelid fatigue

Question 10

Exacerbations

Answer 10

Infection
Surgery, anesthesia
Pregnancy [5]
Medications
Antibiotics (e.g., fluoroquinolones, aminoglycosides, macrolides)
Cardiovascular drugs (e.g., procainamide, quinidine, beta blockers)
Psychiatric drugs (e.g., chlorpromazine, risperidone, lithium)
Glucocorticoids

Question 11

EMG results

Answer 11

Findings: decremental response to repetitive nerve stimulation

Question 12

Edrophonium test:

Answer 12

administration of a rapid-acting, short-duration acetylcholinesterase inhibitor to assess for symptom improvement in patients with suspected myasthenia gravis

Question 13

Diff dx

Answer 13

Lambert-Eaton myasthenic syndrome (LEMS)

Congenital myasthenic syndrome
(Presents similarly to myasthenia gravis, but typically starts during infancy or childhood)

Amyotrophic lateral sclerosis
[progressive dysfunction of both `UMN and LMN]

Chronic progressive external ophthalmoplegia (for ocular symptoms) [mtch myopathy]

Question 14

Lambert-Eaton myasthenic syndrome (LEMS)

Answer 14

neuromuscular junction disorder characterized by proximal muscle weakness and autonomic dysfunction

Paraneoplastic: associated with SCLC

autoantibodies directed against presynaptic voltage-gated calcium channels (anti-VGCC antibodies) = impaired ACh release in the NMJ

Proximal muscle weakness; muscle strength improves with repetitive or ongoing use
Reduced or absent reflexes
Autonomic symptoms
Dry mouth
Constipation
Erectile and ejaculatory dysfunction
Orthostatic dysregulation

Active muscle contraction or repeated muscle tapping increases reflex activity.
Lambert sign: hand grip strength gradually increases over several seconds
EMG: Repetitive nerve stimulation results in incremental responses.
Confirmatory test: anti-VGCC antibodies in serum
Paraneoplastic LEMS: Treat the underlying malignancy.

First-line to improve neuromuscular transmission: amifampridine [Blockade of presynaptic potassium channels]
No Response to cholinesterase inhibitors!

Question 15

Miasthenic crisis

Answer 15

acute, life-threatening exacerbation of myasthenic symptoms that leads to respiratory failure

Most commonly occurs within 3 years of disease onset

Intubate early if risk of respiratory failure is high

High-dose prednisone
PLUS IVIg or plasma exchange