Myasthenia Gravis

Populations and Risk Factors

Bimodal age distribution — women most commonly diagnosed before age 40 (early-onset MG); men most commonly after age 60 (late-onset MG); overall female:male ratio approximately 2:1 in early-onset, equalizes in late-onset
Approximately 75% of patients have thymic abnormalities — thymic hyperplasia (especially in young women) or thymoma (especially in older patients); thymectomy improves symptoms in many patients
Autoimmune comorbidity cluster — MG patients have increased incidence of other autoimmune diseases (thyroid disease, rheumatoid arthritis, lupus)
No clear genetic inheritance pattern, but familial clustering exists; HLA associations identified
Drug interactions — aminoglycoside antibiotics, beta-blockers, calcium channel blockers, magnesium, neuromuscular blocking agents, and certain anesthetics can precipitate or worsen MG; critical for MT to know because medication changes can destabilize a previously stable patient
Triggers for symptom worsening include overexertion, emotional stress, heat exposure, infections, menstruation, and surgery

Causes and Pathophysiology

Autoimmune Attack on the Neuromuscular Junction

In normal neuromuscular transmission, a motor nerve action potential triggers release of ACh from the presynaptic terminal into the synaptic cleft. ACh binds to nicotinic receptors on the postsynaptic motor end plate, generating a muscle fiber action potential and contraction. Acetylcholinesterase (AChE) rapidly breaks down ACh to terminate the signal.
In MG, the immune system produces IgG autoantibodies (anti-AChR antibodies in ~85% of cases) that attack the postsynaptic ACh receptors through three mechanisms:

Receptor blockade: Antibodies physically occupy the ACh binding site, preventing ACh from docking
Accelerated receptor internalization: Antibody-receptor complexes are endocytosed and degraded faster than normal (complement-mediated)
Complement-mediated destruction: The antibody-receptor complex activates the complement cascade, destroying the postsynaptic membrane architecture and flattening the junctional folds

The combined result is approximately 70–80% reduction in available ACh receptors before clinical symptoms appear. This "safety factor" explains why MG develops gradually and why initial symptoms are subtle.

The Fatigability Mechanism

With fewer available receptors, the first few nerve impulses in a contraction sequence generate adequate muscle fiber action potentials — the remaining receptors are sufficient for initial effort. However, as ACh is released repeatedly with sustained or repetitive activity, the limited receptor population becomes progressively saturated and the safety margin is overwhelmed. Subsequent impulses fail to generate sufficient postsynaptic depolarization, and muscle fibers drop out of the contraction — producing the characteristic progressive weakness with sustained effort.
Rest restores function because during rest, ACh clearance by AChE allows the limited receptors to reset, and the safety margin is temporarily restored. This rest-recovery cycle is the defining clinical feature that distinguishes MG from all other causes of weakness.

Thymic Involvement

The thymus gland is thought to be the site of initial autoimmune activation — it contains myoid cells that express ACh receptors, potentially serving as the antigen that triggers the autoimmune response. Thymic hyperplasia or thymoma is present in ~75% of patients, and thymectomy improves or remits symptoms in many cases.

Anti-MuSK Antibodies

Approximately 5–10% of MG patients have antibodies against muscle-specific kinase (MuSK) instead of AChR. MuSK-positive MG tends to affect bulbar muscles preferentially (face, jaw, throat), produces more prominent facial and respiratory weakness, and responds differently to treatment.

Signs and Symptoms

Ocular MG (Earliest Presentation)

Ptosis — drooping of one or both eyelids; often the first symptom; worsens throughout the day and with sustained upward gaze; improves after rest or sleep
Diplopia — double vision from extraocular muscle weakness; variable and fluctuating; may shift from one eye to the other
Approximately 50% of patients who present with isolated ocular MG progress to generalized MG within 2 years

Generalized MG

Fatigable weakness — the hallmark: muscles are strongest after rest and weakest after sustained effort; a patient may start eating normally and progressively lose jaw strength during the meal; voice may start clear and become nasal or slurred after talking
Bulbar involvement: Dysphagia (difficulty swallowing — risk of aspiration), dysarthria (nasal or slurred speech), difficulty chewing (jaw weakness during meals), weak facial expression ("myasthenic snarl" when attempting to smile)
Proximal limb weakness: Difficulty raising arms overhead (hair brushing, reaching), difficulty climbing stairs; greater in proximal than distal muscles
Fluctuating pattern: Symptoms worsen throughout the day (worst in evening), after exertion, in heat, during illness, and with emotional stress; improve after rest and sleep
Sensation is completely intact — MG affects only motor transmission at the NMJ; no sensory, autonomic, or reflex abnormalities
Reflexes are normal — this is a critical distinguishing feature from GBS (areflexia) and ALS (hyperreflexia)

Myasthenic Crisis vs. Cholinergic Crisis

Feature	Myasthenic Crisis	Cholinergic Crisis
Cause	Undertreated MG; infection, surgery, or medication trigger	Overmedication with anticholinesterase drugs
Weakness	Profound respiratory and limb weakness	Weakness plus excessive secretions
Pupils	Normal	Miotic (constricted)
Secretions	Dry mouth	Excessive salivation, lacrimation, bronchial secretions (SLUDGE signs)
Fasciculations	Absent	May be present
Emergency action	Intubation, IV immunoglobulin or plasmapheresis	Withhold anticholinesterase medication; intubation if needed

Both are life-threatening emergencies. If a patient with MG develops sudden respiratory difficulty, do not treat — call emergency services immediately.

Assessment Profile

Subjective Presentation

Chief complaint: "My eyelids droop, especially later in the day"; "I can't finish a meal without my jaw getting tired"; "My voice gets weaker the longer I talk"; "I'm fine in the morning but by afternoon I can barely lift my arms"; the temporal fluctuation pattern is the most important diagnostic clue
Pain quality: MG does not typically produce pain — the primary complaint is weakness and fatigue; however, secondary muscular aching may develop in compensatory muscles (cervical extensors from holding drooping head, lumbar extensors from trunk weakness); no neuropathic pain
Onset: Insidious; ocular symptoms (ptosis, diplopia) are usually first; gradual progression to generalized weakness over weeks to months; may be triggered by infection, surgery, pregnancy, or medication change
Aggravating factors: Sustained or repetitive effort (key feature); heat exposure; emotional stress; illness or infection; afternoon and evening hours; specific medications (aminoglycosides, beta-blockers, magnesium)
Easing factors: Rest rapidly restores strength (minutes to hours); sleep; cooler environment; anticholinesterase medication (pyridostigmine) temporarily improves strength; morning hours are typically best
Red flags: Respiratory difficulty (shortness of breath, weak cough, inability to count to 20 in one breath, use of accessory muscles) → possible myasthenic crisis; emergency referral; do not treat. Sudden worsening after medication change → possible cholinergic crisis or medication interaction. New-onset dysphagia with coughing on liquids → aspiration risk; medical referral.

Observation

Local inspection: Ptosis (unilateral or bilateral) — may worsen during the assessment as the patient maintains upward gaze; "myasthenic snarl" (the patient's attempt to smile produces a grimace because the upper lip elevates but the lower face cannot follow); visible jaw drop after sustained chewing; no muscle atrophy in early or moderate disease (atrophy is a late finding)
Posture: Head may be tilted back to compensate for ptosis (chin elevation); forward head posture from neck extensor fatigue; drooping shoulders from deltoid and upper trapezius weakness; overall posture may appear normal at the start of assessment and visibly deteriorate during the session
Gait: Normal early in the session; progressive waddling or unsteady gait with sustained walking as proximal hip muscles fatigue; no steppage gait, no spasticity, no ataxia — the gait deterioration is purely from progressive muscular fatigue

Palpation

Tone: Normal or mildly hypotonic — MG does not produce spasticity (no UMN lesion), rigidity, or the flaccidity of denervation (LMN intact); tone is normal at rest and decreases only with sustained effort; compensatory muscles (cervical extensors, lumbar extensors) may be hypertonic from chronic overwork
Tenderness: No primary tenderness from MG itself; secondary tenderness in compensatory muscles — cervical extensors and upper trapezius (compensating for weak head/neck muscles), lumbar paraspinals (compensating for trunk weakness), forearm extensors (compensating for grip fatigue); trigger points in chronically overworked compensatory muscles
Temperature: Normal — MG does not affect vasomotor control. However, heat exposure worsens symptoms by accelerating ACh degradation as described in Pathophysiology. Heat modalities are contraindicated.
Tissue quality: Muscle bulk is preserved in early and moderate disease — palpation reveals normal muscle architecture. In long-standing severe MG, disuse atrophy may develop. Fascial quality is normal. No pseudohypertrophy (distinguishes from MD) and no fibrotic changes (distinguishes from chronic inflammatory conditions).

Motion Assessment

AROM: The diagnostic pattern — initial movements are performed with near-normal strength and range, but repeated or sustained effort produces progressive weakness and range loss. Have the patient perform 10 repetitions of shoulder abduction or sustained upward gaze — progressive deterioration confirms fatigability. Compare morning vs. afternoon function if possible.
PROM / end-feel: Normal — joints are not affected; end-feel is normal elastic-muscular; PROM equals AROM at rest (critical distinction from capsular or structural conditions); PROM exceeds AROM only during fatigued state, and the difference increases with sustained activity
Resisted testing: Progressive weakness with repetition — initial MMT may grade 4/5 or 5/5, declining to 2/5 or 3/5 after sustained contraction or repeated testing; proximal muscles fatigue before distal; facial and ocular muscles fatigue most rapidly; rest 1–2 minutes and retest — improvement confirms fatigability rather than fixed weakness

Special Test Cluster

MG is diagnosed medically (anti-AChR antibody testing, EMG repetitive nerve stimulation, Tensilon test). The MT assessment cluster focuses on documenting the fatigability pattern, ruling out other causes of weakness, and screening for crisis.

Test	Positive Finding	Purpose
Sustained upward gaze test (CMTO)	Ptosis develops or worsens within 30–60 seconds of sustained upward gaze; resolves after brief rest	Demonstrate ocular fatigability — the most accessible clinical test for MG; can be performed at every session
Repetitive movement fatigue test (CMTO)	Progressive weakness with 10 repetitions of shoulder abduction, grip, or jaw opening; strength partially recovers after 1–2 minutes rest	Confirm the fatigability-recovery pattern that defines MG; documents current functional status
Deep tendon reflexes (CMTO)	Normal (2+)	Critical rule-out: normal reflexes distinguish MG from GBS (areflexia), ALS (hyperreflexia), and spinal cord lesions
Respiratory function screen (CMTO)	Reduced ability to count to 20 in one breath; weak cough; use of accessory respiratory muscles	Crisis screening — respiratory decline is the most dangerous complication; any deterioration warrants immediate medical referral
Ice pack test (supplementary)	Ptosis improves after applying an ice pack to the closed eyelid for 2 minutes (cold slows AChE, temporarily increasing ACh at the receptor)	Non-pharmacological confirmation of NMJ dysfunction; simple bedside/clinic test; supplements the Tensilon test concept

Tensilon (edrophonium) test concept: Tensilon is a rapid-acting acetylcholinesterase inhibitor. IV administration produces transient improvement in MG weakness within 30 seconds, confirming the diagnosis. This is a physician-administered test but is frequently tested on the CMTO exam — know the concept (blocking ACh breakdown temporarily increases ACh at the depleted receptor population).

Differential Diagnoses

Condition	Key Distinguishing Feature
Lambert-Eaton Myasthenic Syndrome (LEMS)	Presynaptic disorder (antibodies against voltage-gated calcium channels); weakness improves transiently with repeated effort (opposite of MG); strong association with small cell lung cancer; hyporeflexia
Guillain-Barre Syndrome	Areflexia (MG has normal reflexes); ascending pattern; acute onset after infection; sensory symptoms present; no fatigability pattern
Amyotrophic Lateral Sclerosis (ALS)	Combined UMN and LMN signs (hyperreflexia + fasciculations + atrophy); progressive without fluctuation; no recovery with rest; no ocular involvement
Botulism	Descending paralysis (cranial nerves first); dilated pupils (MG has normal pupils); autonomic dysfunction; history of contaminated food or wound
Thyroid ophthalmopathy (Graves' disease)	Proptosis (bulging eyes) rather than ptosis; restricted extraocular movement from fibrotic muscles, not fatigue; thyroid function abnormalities

CMTO Exam Relevance

CMTO Appendix category A4 (neurological conditions)
Fatigable weakness is the defining feature — exam questions test whether the student can identify the "worse with effort, better with rest" pattern and distinguish it from constant weakness (MD, ALS), ascending weakness (GBS), or UMN weakness (MS, stroke)
Tensilon test concept: know that blocking AChE temporarily increases ACh availability and improves MG weakness — confirms the postsynaptic receptor deficit
Normal reflexes distinguish MG from GBS (areflexia) and ALS (hyperreflexia/fasciculations) — a frequently tested differential
Myasthenic crisis vs. cholinergic crisis — know the distinction; both are emergencies; exam questions test whether the student can identify which crisis is occurring based on secretion and pupil findings
Heat worsens symptoms (accelerates ACh degradation) — exam questions may present a scenario where the MT applies heat and the client worsens
Know the ocular presentation (ptosis, diplopia) as the most common initial presentation and that 50% progress to generalized disease

Massage Therapy Considerations

Primary therapeutic target: secondary muscle tension in compensatory muscles overworked to substitute for MG-weakened muscles — cervical extensors (compensating for head drop), lumbar paraspinals (compensating for trunk weakness), forearm extensors (compensating for grip fatigue); also psychosocial stress reduction, as stress worsens MG symptoms
Fatigability principle — the #1 MT planning rule for MG: Treatment must not fatigue the client. Muscle strength is a depletable resource in MG — any activity (including resisting massage pressure, maintaining a position, or even the effort of getting on the table) depletes available neuromuscular transmission capacity. Schedule sessions when the client is most rested (typically morning, and after taking pyridostigmine). Keep sessions shorter than standard.
Heat avoidance: Heat accelerates acetylcholinesterase activity, further reducing the already-diminished ACh available at the NMJ. All heat modalities are contraindicated — no hot packs, heated table, warm hydrotherapy, or hot stones. Maintain a cool-to-neutral treatment environment.
Intact sensation with motor vulnerability: Sensation is fully intact (the NMJ affects motor transmission only), so the client can provide accurate pressure feedback. However, muscles subjected to sustained pressure may fatigue locally — use moderate, rhythmic techniques rather than sustained deep compression.
Respiratory monitoring: Intercostal and diaphragmatic weakness may develop subtly. Monitor breathing throughout the session. If respiratory effort increases, stop treatment. Do not position supine if diaphragmatic weakness is suspected — semi-reclined or side-lying preferred.
Immunosuppressant awareness: Most MG patients take immunosuppressive medications (prednisone, azathioprine, mycophenolate). The therapist must not treat if they have an active infection. Adjust for steroid side effects (osteoporosis, easy bruising, thin skin).
Contraindications: all heat modalities; treatment during myasthenic or cholinergic crisis; aggressive or prolonged techniques that fatigue muscles; treatment by a therapist with active illness (immunocompromised client)

Treatment Plan Foundation

Clinical Goals

Reduce secondary muscle tension in compensatory overload muscles
Support general relaxation and parasympathetic activation (stress reduction directly reduces symptom burden)
Maintain fascial mobility without fatiguing weakened muscles
Monitor respiratory function and overall neuromuscular status between medical appointments

Position

Side-lying or semi-reclined preferred — minimizes respiratory demand compared to supine; avoids prone positioning which places respiratory demand on the diaphragm
Support the head and neck with adequate bolstering — cervical extensors fatigue quickly; the head should not need to be held up by the client
Room temperature cool-to-neutral — no heated table
Schedule for morning hours and after pyridostigmine dosing (peak effect 1–2 hours after dose)

Session Sequence

General effleurage to posterior trunk — assess overall tone; establish baseline; the effleurage itself should be therapeutic (parasympathetic activation reduces MG symptom burden)
Cervical extensor and upper trapezius release — primary compensatory overload site from head drop and postural fatigue; sustained compression and gentle stripping; these muscles are typically hypertonic from chronic overwork
Gentle suboccipital release — suboccipital muscles chronically overwork to maintain head position and visual field when neck extensors fatigue; sustained finger-pad compression
Lumbar paraspinal release — compensatory tension from trunk weakness; gentle effleurage and myofascial release; avoid prolonged prone positioning
Proximal upper extremity work — deltoid, rotator cuff, and scapular stabilizers may be areas of secondary tension; use moderate rhythmic techniques; do not perform sustained resisted work — the muscles will fatigue rapidly
Light effleurage to extremities — promote circulation and relaxation; do not extend the session if the client shows signs of fatigue (drooping eyelids, slurred speech, weaker voice)

Adjunct Modalities

Hydrotherapy: All heat modalities are contraindicated (heat accelerates ACh degradation and worsens weakness). Cool-to-room-temperature applications only. A cool cloth to the face may provide comfort, particularly if ptosis is bothersome. If hydrotherapy is used, it must be at or below body temperature.
Joint mobilization: Gentle oscillatory mobilization of cervical spine (if tolerated) and thoracic spine to maintain mobility; Grade I–II; performed after soft tissue release; gentle and rhythmic to avoid fatiguing surrounding muscles; cervical mobilization only if the client can maintain head position safely
Remedial exercise (on-table): Gentle active-assisted ROM only — the therapist supports the limb while the client moves through available range; purpose is mobility maintenance, not strengthening; no resisted exercise during the treatment session — MG muscles cannot recover quickly enough; stop if the client shows increased fatigue (speech changes, eyelid drooping, weaker movements)

Exam Station Notes

Demonstrate understanding of the fatigability pattern — state that MG weakness worsens with effort and improves with rest; show that you schedule sessions accordingly (morning, post-medication)
Monitor and verbalize respiratory status — note breathing pattern at the start and periodically during treatment; state that respiratory deterioration requires stopping treatment
Show heat avoidance — state explicitly that heat modalities are contraindicated and why (accelerates ACh breakdown)
Demonstrate that reflexes are normal — this rules out GBS and ALS and confirms the NMJ-level pathology

Verbal Notes

Session timing: "I want to make sure we're treating you at your strongest. Have you taken your medication today? How are you feeling right now compared to other times of day?"
Heat avoidance: "I keep the room temperature moderate because heat can make your symptoms worse. If you start to feel warmer or notice any changes — weaker, more droopy — let me know right away."
Fatigue monitoring: "As we work, I'll be checking in with you. If you notice your eyelids getting heavier, your voice getting weaker, or you're feeling more fatigued, tell me and we'll wrap up. It's better to do a shorter session at good quality than push too long."
Post-treatment: advise rest for several hours after treatment; the session itself consumes some neuromuscular reserve that needs to be replenished

Self-Care

Energy conservation and activity pacing — plan the most demanding activities for morning (peak medication effect, highest strength reserve); break tasks into segments with rest periods; avoid sustained overhead work
Avoid heat exposure — no hot baths, saunas, prolonged sun exposure; exercise in cool environments; cool down promptly after any exertion
Infection prevention — hand hygiene, avoid crowded environments during flu season; immunosuppressive medications increase infection susceptibility
Emergency awareness — the client and caregivers must know the signs of myasthenic crisis (increasing respiratory difficulty, inability to swallow, rapid weakening) and have a plan for emergency medical access

Key Takeaways

MG is defined by fatigable weakness — strength is best after rest and worst after sustained effort; this rest-recovery pattern distinguishes MG from every other cause of weakness
Autoantibodies destroy ~70–80% of ACh receptors at the NMJ before symptoms appear; the mechanism involves receptor blockade, accelerated internalization, and complement-mediated destruction
Ptosis and diplopia are the earliest and most characteristic findings; bulbar involvement (dysphagia, dysarthria) indicates progression; respiratory failure (myasthenic crisis) is the most dangerous complication
Reflexes are normal — this single finding distinguishes MG from GBS (areflexia) and ALS (hyperreflexia/fasciculations)
Heat worsens symptoms by accelerating ACh degradation — all heat modalities are contraindicated
Myasthenic crisis (undertreated) vs. cholinergic crisis (overtreated) — both are emergencies; distinguished by secretion and pupil findings
Schedule MT sessions for morning hours after medication; keep sessions short; monitor for respiratory fatigue throughout