Eduovisual
Nervous System & Special Senses
Lambert-Eaton myasthenic syndrome
— Paraneoplastic LEMS (~50–60%): almost always small cell lung cancer (SCLC); neurologic symptoms often precede cancer diagnosis by months to years.
— Autoimmune (non-paraneoplastic) LEMS: associated with other autoimmunity (vitiligo, thyroid disease, type 1 DM), younger patients, female predominance.
— Middle-aged or older smoker with proximal lower-extremity weakness, dry mouth, and areflexia that improves transiently after exercise.
— Patient referred for "fatigue and difficulty climbing stairs," found to have autonomic complaints (erectile dysfunction, constipation, orthostasis).
— A patient with known SCLC developing new proximal weakness — always consider LEMS before attributing to deconditioning or chemotherapy neuropathy.
Board pearl: The classic Step 3 trigger phrase is "weakness improves with sustained effort" plus autonomic dysfunction plus smoking history — this combination should immediately push LEMS above myasthenia gravis on your differential, and trigger a workup for occult SCLC even if the chest x-ray is unremarkable.
Step 3 management framing: Suspecting LEMS is not just a neurology call — it is a cancer screening trigger. The ambulatory diagnosis obligates you to pursue CT chest and, if negative, FDG-PET, and to repeat surveillance every 3–6 months for up to 2 years.
— Proximal muscle weakness (legs > arms, "waddling gait," trouble rising from a chair)
— Autonomic dysfunction (dry mouth is the most common; also impotence, constipation, orthostatic hypotension, decreased sweating)
— Hyporeflexia or areflexia that transiently improves after brief exercise (post-exercise facilitation)
— Smoking history (pack-years), occupational exposures, weight loss, hemoptysis, night sweats — SCLC screening.
— Dry mouth, dry eyes, constipation, erectile dysfunction, lightheadedness on standing — autonomic survey.
— Personal/family history of autoimmune disease (vitiligo, Hashimoto, type 1 DM, pernicious anemia).
— Medication review: aminoglycosides, fluoroquinolones, magnesium, beta-blockers, calcium-channel blockers can unmask or worsen weakness.
Key distinction: In MG, sustained or repeated activity worsens symptoms (fatigable weakness, worse later in the day, ptosis after sustained upgaze). In LEMS, a few seconds of maximal effort transiently improves strength and reflexes — the Lambert sign when grip strength augments over the first few seconds of squeezing.
Board pearl: A man in his 60s with a 40-pack-year history complaining of "I can't get out of my recliner, my mouth is always dry, and sex doesn't work anymore" is LEMS until proven otherwise — and your next move is a CT chest, not a neuromuscular referral alone.
— Symmetric proximal weakness, lower extremities more than upper; hip flexors and quadriceps most affected.
— Gowers maneuver may be positive (uses arms to push off thighs when rising).
— Waddling, "myopathic" gait.
— Distal strength, neck flexors, and cranial nerves are relatively preserved early.
— Deep tendon reflexes are diminished or absent at rest.
— After 10–15 seconds of sustained maximal voluntary contraction of the tested muscle, reflexes reappear or augment — post-exercise facilitation, pathognomonic on exam.
— Dry oral mucosa, decreased lacrimation.
— Orthostatic vitals: drop in SBP ≥20 or DBP ≥10 within 3 minutes of standing without compensatory tachycardia (sympathetic and parasympathetic dysfunction).
— Pupillary sluggishness; rarely tonic pupils.
— Bedside single-breath count, forced vital capacity if available, accessory muscle use.
— Severe respiratory weakness is uncommon at presentation but can occur, especially in paraneoplastic disease or with concurrent infection/drug exposure.
Step 3 management: When you document "reflexes 0/4 at rest, 2/4 after 15 seconds of isometric contraction" in a smoker with proximal weakness, the very next orders are anti-P/Q VGCC antibody, EMG with repetitive nerve stimulation, and CT chest with contrast — written together, not sequentially, to compress the diagnostic timeline.
Board pearl: Areflexia that augments with brief exercise is the single most LEMS-specific bedside finding tested on Step 3.
— Anti-P/Q-type VGCC antibodies: positive in ~85–95% of LEMS patients; the cornerstone confirmatory test.
— Anti-N-type VGCC: less specific, may be positive in paraneoplastic cerebellar degeneration and other syndromes.
— SOX1 antibodies: present in ~65% of paraneoplastic LEMS; strong marker for underlying SCLC even when initial imaging is negative.
— Send AChR (acetylcholine receptor) and MuSK antibodies if MG is on the differential; coexistence is rare but reported.
— CBC, CMP, LDH, calcium (paraneoplastic hypercalcemia), sodium (SIADH from SCLC).
— Consider NSE and ProGRP if SCLC suspicion is high (institution-dependent).
— CT chest with IV contrast is the initial study in every newly diagnosed LEMS patient regardless of smoking status.
— If CT is negative and clinical/serologic suspicion remains high (especially SOX1+, older smoker), proceed to whole-body FDG-PET/CT.
— If still negative, repeat imaging every 3–6 months for up to 2 years; tumor often emerges later.
Key distinction: A positive P/Q VGCC antibody is highly supportive but not sufficient on its own — paraneoplastic cerebellar degeneration and even some healthy controls can be positive. Diagnosis requires clinical syndrome + serology + electrodiagnostics, ideally with a cancer evaluation.
CCS pearl: On the CCS interface, after "advance clock" reveals weakness and dry mouth in a smoker, order CT chest, anti-VGCC antibodies, and neurology consult on the same screen, then advance to electrodiagnostics — bundling orders mirrors real outpatient workflow and avoids penalty for delay.
— Low baseline compound muscle action potential (CMAP) amplitudes at rest (often <50% of normal) in clinically affected muscles — reflects reduced ACh release.
— Normal sensory studies.
— Normal or mildly slowed conduction velocities.
— Low-frequency RNS (2–3 Hz): further decrement in CMAP amplitude (>10%) — also seen in MG, not specific.
— High-frequency RNS (20–50 Hz) or post-exercise CMAP: incremental response of >60–100% in CMAP amplitude — highly specific for LEMS.
— Practically, brief (10-second) maximal voluntary contraction followed by repeat stimulation is better tolerated than tetanic stimulation and yields the same diagnostic increment.
— Proximal weakness with autonomic features and hyporeflexia
— Post-exercise CMAP facilitation >60% on RNS
— Positive anti-P/Q VGCC antibody
— Variables: Dysarthria, dysphagia, dysphonia; Erectile dysfunction; Loss of weight; Tobacco use; Age >50; Performance status (Karnofsky <70). Score ≥3 → high SCLC risk → expedited PET and bronchoscopy.
Board pearl: The "incremental response on high-frequency stimulation" waveform graphic is a near-guaranteed Step 3 image stem — recognize the rising staircase pattern and pair it with dry mouth + areflexia to lock in LEMS.
Step 3 management: If electrodiagnostics confirm LEMS but VGCC antibodies are negative, do not drop the cancer workup — seronegative LEMS still warrants aggressive SCLC screening with PET and pulmonology referral.
— Track 1 — Symptomatic neuromuscular treatment to restore strength and quality of life.
— Track 2 — Treat the underlying cause: aggressive workup and treatment of SCLC (if paraneoplastic) often produces the most durable neurologic improvement.
— Paraneoplastic LEMS + confirmed SCLC: prioritize oncologic therapy (chemo ± radiation/immunotherapy). Tumor-directed treatment alone frequently improves neurologic symptoms substantially.
— Non-paraneoplastic (autoimmune) LEMS: longer-term immunosuppression is more central since there is no tumor to treat.
— Severe weakness, respiratory compromise, bulbar involvement: escalate to IVIG or plasmapheresis for rapid effect, similar to myasthenic crisis management.
1. Amifampridine (3,4-diaminopyridine, 3,4-DAP) — first-line symptomatic therapy.
2. Add pyridostigmine for modest additive benefit (less effective than in MG).
3. Immunosuppression (prednisone + steroid-sparing agent like azathioprine) for inadequate response.
4. IVIG or plasma exchange for severe or refractory disease, or as bridge before surgery/chemo.
5. Rituximab for refractory autoimmune LEMS.
— Avoid neuromuscular-blocking drugs: aminoglycosides, fluoroquinolones, macrolides, magnesium (including IV Mg for preeclampsia or laxatives), beta-blockers, calcium-channel blockers, iodinated contrast in high doses.
— Alert anesthesia: patients are exquisitely sensitive to both depolarizing and non-depolarizing neuromuscular blockers.
Step 3 management: The single most impactful intervention for a paraneoplastic LEMS patient is diagnosing and treating the SCLC — neurologic improvement often parallels tumor response. Never let symptomatic therapy distract from completing the oncology workup.
Board pearl: A "MedicAlert bracelet for LEMS" plus a written anesthesia precaution letter is a high-yield ambulatory discharge intervention.
— Mechanism: blocks presynaptic voltage-gated potassium channels → prolongs nerve terminal depolarization → enhanced calcium influx → increased ACh release.
— FDA-approved for adults and children ≥6 years with LEMS (Firdapse, Ruzurgi historically).
— Dosing: start 15–20 mg/day divided TID–QID, titrate by 5 mg every 3–4 days to symptom response; max 80 mg/day (single dose ≤20 mg).
— Adverse effects: perioral and digital paresthesias (most common, dose-related), nausea, abdominal pain, insomnia, seizures at high doses or in predisposed patients, QT prolongation.
— Contraindications: history of seizures, congenital long QT, concurrent QT-prolonging drugs (fluoroquinolones, ondansetron, methadone, certain antipsychotics).
— Monitoring: baseline and periodic ECG; symptom diary; renal function.
— Acetylcholinesterase inhibitor; modest benefit in LEMS (much less than in MG).
— Useful as adjunct to amifampridine, particularly for autonomic symptoms (dry mouth, constipation).
— Dose 30–60 mg PO TID–QID; watch for cholinergic side effects (cramps, diarrhea, bradycardia).
— Prednisone 1 mg/kg/day, taper after response; pair with calcium, vitamin D, PPI, PJP prophylaxis if ≥20 mg ≥4 weeks, bone density monitoring.
— Azathioprine 2–3 mg/kg/day as steroid-sparing agent; check TPMT activity before starting; monitor CBC and LFTs.
— Alternatives: mycophenolate mofetil, methotrexate, rituximab for refractory cases.
— IVIG 2 g/kg over 2–5 days; benefit lasts weeks.
— Plasma exchange (PLEX) 5 sessions over 1–2 weeks; useful preoperatively or in severe weakness.
Step 3 management: Before titrating amifampridine, always obtain a baseline ECG and seizure history — these two screens prevent the most common drug-related adverse events on the boards and in practice.
Board pearl: Perioral tingling in a LEMS patient is amifampridine — not a stroke, not progression — and is managed with dose reduction, not drug discontinuation.
— Limited-stage SCLC: concurrent chemoradiation (platinum + etoposide + thoracic RT); consider prophylactic cranial irradiation if response.
— Extensive-stage SCLC: platinum + etoposide + PD-L1 inhibitor (atezolizumab or durvalumab) per current oncology guidelines.
— Caveat: immune checkpoint inhibitors can exacerbate paraneoplastic neurologic syndromes including LEMS — coordinate closely with neurology; weigh oncologic benefit vs. neurologic flare risk.
— Rituximab 375 mg/m² weekly × 4 or 1 g × 2 doses; screen for hepatitis B and TB before infusion; expect benefit at 1–3 months.
— Mycophenolate 1 g BID; monitor CBC; teratogenic — REMS program for women of reproductive potential.
— Maintenance IVIG every 4–6 weeks for severely affected, immunosuppression-intolerant patients.
— Aminoglycosides (gentamicin, tobramycin), fluoroquinolones, macrolides, clindamycin, tetracyclines at high doses.
— Magnesium (IV for preeclampsia/asthma, oral laxatives, antacids).
— Beta-blockers, non-dihydropyridine CCBs, procainamide, quinidine.
— Iodinated contrast in large volumes (rare exacerbations reported).
— Botulinum toxin is absolutely contraindicated.
— Communicate diagnosis to anesthesia; succinylcholine and non-depolarizing blockers cause prolonged paralysis — sugammadex is preferred for rocuronium reversal.
— Consider preoperative IVIG or PLEX for major surgery in moderately/severely affected patients.
CCS pearl: On the CCS case, after confirming SCLC in a LEMS patient, simultaneously order oncology consult, neurology consult, PFTs, brain MRI for staging, and a written anesthesia/medication-avoidance list in the chart — multidisciplinary parallel processing is rewarded.
Key distinction: Unlike MG, immunosuppression alone rarely produces dramatic improvement in LEMS; symptomatic therapy with amifampridine plus treatment of the tumor does the heavy lifting.
— Higher baseline risk of falls from proximal weakness and orthostasis — initiate PT, home safety evaluation, and assistive device early.
— Polypharmacy review essential — many older patients are on beta-blockers, CCBs, statins (myopathy overlap), and PPIs (magnesium depletion or magnesium-containing antacids).
— Cognitive screening before starting immunosuppression and steroids; steroids can precipitate delirium or psychosis.
— Bone health: DEXA scan, calcium 1200 mg/day, vitamin D 800–1000 IU/day, consider bisphosphonate if starting chronic prednisone.
— Amifampridine is renally cleared; in moderate–severe renal impairment start at the lowest dose (5 mg) and titrate slowly, with closer ECG and seizure monitoring.
— Pyridostigmine dose reduction in CKD; cholinergic side effects amplified.
— Azathioprine/6-MP: reduce dose; monitor cytopenias closely.
— IVIG: caution — risk of acute kidney injury (osmotic nephrosis from sucrose-containing formulations), volume overload, and thromboembolism. Use sucrose-free preparations, slow infusion, ensure hydration.
— Amifampridine metabolized via N-acetyltransferase 2 (NAT2); slow acetylators have higher exposure — start low.
— Azathioprine: monitor LFTs; avoid if active liver disease.
— Mycophenolate: generally safe but monitor LFTs.
— Weigh aggressive immunosuppression against infection risk; vaccinate (inactivated influenza yearly, pneumococcal series, RSV, shingles recombinant, COVID-19) before starting immunosuppressants when possible.
— Discuss goals of care, including advance directives and code status, particularly when SCLC is confirmed.
Step 3 management: In a frail 78-year-old with newly diagnosed LEMS and SCLC, the highest-yield ambulatory orders are fall prevention referral, home oxygen assessment, vaccination catch-up before steroids, and palliative care consultation — all alongside oncology and neurology.
Board pearl: Always check TPMT activity before azathioprine — deficiency causes life-threatening myelosuppression.
— Pregnancy itself does not consistently worsen LEMS; data are limited.
— Magnesium sulfate is contraindicated for eclampsia/preterm labor — use alternative regimens (e.g., levetiracetam or phenytoin for seizure prophylaxis after multidisciplinary discussion); use calcium gluconate antidote if Mg was inadvertently given.
— Amifampridine: limited human data; weigh risk/benefit; some experts continue at lowest effective dose.
— Pyridostigmine: generally considered acceptable.
— Avoid mycophenolate and methotrexate (teratogenic); switch to azathioprine preconception (relatively safer) or IVIG.
— Prednisone acceptable at lowest effective dose; monitor for gestational diabetes and hypertension.
— Anesthesia plan for delivery: regional preferred over general; communicate diagnosis early; avoid neuromuscular blockers if possible.
— Neonatal transient LEMS from transplacental antibodies has been reported rarely — monitor newborn for hypotonia and feeding difficulty.
— Very rare; usually autoimmune (non-paraneoplastic); look for associated autoimmune disease.
— Amifampridine approved down to age 6; consider lymphoma and neuroblastoma screening in rare paraneoplastic pediatric cases.
— Growing population — ICIs can induce de novo LEMS or exacerbate existing disease.
— Workup new proximal weakness in any ICI-treated patient with VGCC antibodies and EMG.
— Management: hold ICI, start high-dose steroids, neurology and oncology co-management; consider IVIG/PLEX.
— Screen for thyroid disease, type 1 DM, pernicious anemia, vitiligo in non-paraneoplastic LEMS.
Key distinction: A pregnant LEMS patient with preeclampsia is a board emergency — never give magnesium sulfate without weighing severe neuromuscular blockade risk; consult MFM and neurology before delivery.
Step 3 management: Before any elective surgery or planned pregnancy in a LEMS patient, optimize with IVIG or PLEX, and document a clear anesthesia plan in the chart.
— Respiratory failure — uncommon at presentation but possible during disease flares, infections, or after exposure to neuromuscular-blocking medications.
— Aspiration pneumonia from bulbar weakness (less common than in MG but still occurs).
— Falls and fractures from proximal lower-extremity weakness and orthostatic hypotension.
— Autonomic crises: severe orthostasis, ileus, urinary retention, sexual dysfunction; contribute substantially to morbidity.
— Deconditioning and sarcopenia from chronic weakness.
— Amifampridine: seizures (dose-related), QT prolongation, paresthesias.
— Pyridostigmine: cholinergic crisis (rare at LEMS doses) — diarrhea, bradycardia, bronchospasm.
— Corticosteroids: hyperglycemia, hypertension, osteoporosis, avascular necrosis, cataracts, weight gain, mood changes, infection risk including PJP.
— Azathioprine: myelosuppression, hepatotoxicity, pancreatitis, increased lymphoma risk.
— Mycophenolate: GI intolerance, cytopenias, teratogenicity, PML (rare).
— IVIG: AKI, thromboembolism (DVT, PE, MI, stroke), aseptic meningitis, anaphylaxis in IgA deficiency, volume overload.
— PLEX: central line complications, hypotension, citrate-induced hypocalcemia, coagulopathy, infection.
— Rituximab: infusion reactions, hepatitis B reactivation, PML, late neutropenia.
— Direct tumor effects, chemotherapy toxicity, immune checkpoint inhibitor–related LEMS exacerbation.
— Paraneoplastic overlap syndromes: cerebellar degeneration, sensory neuronopathy, limbic encephalitis can coexist.
Board pearl: A LEMS patient on IVIG who develops sudden chest pain or focal neurologic deficit — think IVIG-related thromboembolism (MI, stroke, PE), particularly in dehydrated elderly patients. Aspirin prophylaxis and hydration are mitigating strategies.
Step 3 management: Annual DEXA, fasting glucose/A1c, lipid panel, BP monitoring is required for any LEMS patient on chronic corticosteroids, alongside vaccination catch-up.
— Forced vital capacity (FVC) <20 mL/kg, negative inspiratory force (NIF) less negative than –30 cm H₂O, or maximum expiratory pressure <40 cm H₂O — the "20/30/40 rule" borrowed from MG crisis applies.
— Bulbar weakness with aspiration risk — inability to handle secretions.
— Hemodynamic instability from autonomic failure.
— Respiratory distress with rising PaCO₂ — do not wait for hypoxia; intubate based on mechanics and clinical trajectory.
— New or rapidly progressive weakness over days
— Initiation of IVIG or PLEX in a fragile patient
— Severe dysphagia requiring NG feeding evaluation
— Concurrent infection in a moderately affected patient
— Exposure to a contraindicated medication with worsening weakness
— Neurology — diagnosis and immunotherapy planning
— Pulmonology — bronchoscopy if SCLC suspected, PFTs
— Oncology — staging and treatment of SCLC
— Anesthesia (preoperative) — drug avoidance and reversal planning
— Physical and occupational therapy
— Social work / case management for home support, DME
— Hold all contraindicated medications (aminoglycosides, fluoroquinolones, magnesium, beta-blockers when feasible).
— Treat infections aggressively but with LEMS-safe antibiotics (e.g., cephalosporins, penicillins, doxycycline at standard doses).
CCS pearl: On a CCS case where FVC drops from 2.5 L to 1.0 L over 6 hours in a LEMS patient with pneumonia, the correct sequence is transfer to ICU → call anesthesia → intubate electively → start IVIG → cultures and broad-spectrum LEMS-safe antibiotics — do not wait for ABG to deteriorate.
Step 3 management: Document a written medication-avoidance list and a respiratory action plan with FVC thresholds when discharging a LEMS patient — this is both a quality measure and a tested safety intervention.
— Ocular and bulbar onset common; fatigable weakness worsens with activity.
— Reflexes preserved; autonomic symptoms absent.
— AChR antibodies positive in ~85% (generalized); MuSK antibodies in a subset.
— RNS shows decrement at low frequency, no facilitation at high frequency.
— Associated with thymoma (CT chest part of workup overlaps with LEMS).
— Presynaptic NMJ disorder (toxin cleaves SNARE proteins, blocking ACh release).
— Descending paralysis starting with bulbar/cranial nerves, fixed dilated pupils, dry mouth, ileus — autonomic features overlap LEMS.
— Acute onset over hours to days; history of canned food, wound, or infant honey exposure.
— EMG shows incremental response on high-frequency RNS like LEMS — distinguish by time course and bulbar/pupil findings.
— Proximal weakness like LEMS but reflexes preserved, CK markedly elevated, no autonomic features.
— EMG shows myopathic units, fibrillations; muscle biopsy diagnostic.
— Dermatomyositis may itself be paraneoplastic — also screen for malignancy.
Key distinction: Reflex behavior is the highest-yield bedside differentiator:
— Hyperreflexia → UMN process (ALS, stroke, MS)
— Normal reflexes + fatigable weakness → MG
— Areflexia with post-exercise facilitation → LEMS
— Areflexia, ascending, post-infectious → GBS
Board pearl: A patient with both bulbar weakness AND areflexia AND fixed dilated pupils is botulism, not LEMS — pupils are typically spared in LEMS.
— Ascending symmetric weakness, areflexia, post-infectious (Campylobacter, CMV, EBV, recent vaccination, COVID).
— CSF: albuminocytologic dissociation (high protein, normal cells).
— NCS: demyelinating pattern with conduction block, prolonged distal latencies.
— Autonomic involvement can mimic LEMS, but tempo is acute (days, not months) and progression is ascending.
— Hypokalemia (periodic paralysis, diuretics, GI losses): episodic flaccid weakness, ECG changes.
— Hypophosphatemia, hypermagnesemia (iatrogenic), severe hypocalcemia.
— Hypothyroidism, hyperthyroidism (thyrotoxic myopathy or periodic paralysis in Asian males).
— Cushing syndrome — proximal weakness from steroid myopathy.
— Addison disease — weakness, hypotension, hyperpigmentation.
Step 3 management: A "weakness panel" in primary care for new proximal weakness should include CBC, CMP, TSH, CK, ESR/CRP, vitamin D, vitamin B12, HbA1c, HIV, and consideration of autoimmune serologies before referral to neuromuscular specialty.
Board pearl: Areflexia + CSF albuminocytologic dissociation = GBS; areflexia + post-exercise facilitation + dry mouth = LEMS — pair the buzzwords precisely.
— Amifampridine at titrated dose, with refills and prior authorization initiated (specialty pharmacy, REMS-like access program).
— Pyridostigmine if used; instruct on cholinergic side effects.
— Prednisone with taper schedule, plus PPI, calcium, vitamin D, and PJP prophylaxis (TMP-SMX) if dose ≥20 mg/day for ≥4 weeks.
— Azathioprine or mycophenolate with monitoring schedule.
— Bone-protective therapy (bisphosphonate) if long-term steroids planned.
— Aspirin 81 mg if IVIG used in high-thrombosis-risk patients (case-by-case).
— Inactivated influenza annually
— Pneumococcal (PCV20 or PCV15 + PPSV23)
— RSV if ≥60
— Recombinant zoster vaccine if ≥50
— COVID-19 per current schedule
— Hepatitis B if not immune (especially before rituximab)
— Avoid live vaccines on immunosuppression
— If initial workup negative, repeat CT chest or PET every 3–6 months for 2 years, then annually.
— Smoking cessation counseling at every visit; pharmacotherapy (varenicline, bupropion, NRT) plus behavioral support.
— List aminoglycosides, fluoroquinolones, macrolides, magnesium, beta-blockers, neuromuscular blockers, botulinum toxin.
— Neurology every 3–6 months
— Oncology per cancer protocol
— PT/OT for strength and ADL training
— Dietitian for swallowing/aspiration risk and steroid weight management
— Mental health support — chronic illness and cancer diagnosis
Step 3 management: At every LEMS follow-up visit, document a "safety bundle": medication-avoidance list reviewed, fall risk assessed, vaccination status updated, and cancer surveillance imaging scheduled.
Board pearl: Smoking cessation is both cancer prevention and disease modification in LEMS — a guaranteed counseling point on any Step 3 ambulatory vignette.
— Quantitative strength testing (MRC scale, timed sit-to-stand, 6-minute walk).
— LEMS-specific quality-of-life and functional scales (e.g., QMG adapted; LEMS-FA).
— Autonomic review of systems (dry mouth, orthostatic symptoms, sexual function, bowel/bladder).
— Medication side effect screen and adherence.
— Amifampridine: baseline and periodic ECG (QTc), renal function, seizure history check.
— Pyridostigmine: symptom-based.
— Prednisone: glucose/A1c, BP, lipids, DEXA annually, ophtho for cataracts, weight.
— Azathioprine: CBC and LFTs every 1–2 weeks during titration, then every 3 months; baseline TPMT.
— Mycophenolate: CBC, LFTs monthly initially, then quarterly.
— Rituximab: CBC, immunoglobulin levels, hepatitis serologies before each cycle.
— IVIG: renal function, CBC, hydration, thrombosis screening.
— Physical therapy focusing on proximal strength, balance, and fall prevention.
— Occupational therapy for ADL adaptation, energy conservation.
— Speech therapy / swallow evaluation if bulbar symptoms.
— Pulmonary rehab for patients with SCLC and respiratory deconditioning.
— Recognize warning signs of worsening (new dyspnea, dysphagia, falls) and when to seek urgent care.
— Action plan for febrile illness — avoid contraindicated antibiotics; carry medication list.
— Travel planning — written letter for international travel, emergency contacts, medication supply.
— Education on emergency medications to avoid, signs of crisis, and how to advocate during ER visits.
CCS pearl: Scheduling "neurology in 4 weeks, oncology in 1 week, PT evaluation now, PFTs in 3 months" with return precautions for dyspnea or dysphagia at discharge is the high-yield CCS closing sequence.
Board pearl: Functional improvement in LEMS often parallels tumor response more than immunosuppression intensity — track them together.
— Off-label or limited-evidence therapies (rituximab, maintenance IVIG) require explicit discussion of risks, benefits, and alternatives; document shared decision-making.
— Immune checkpoint inhibitors in a LEMS patient with SCLC — must explicitly discuss risk of neurologic exacerbation vs. survival benefit; co-sign by oncology and neurology recommended.
— Capacity assessment in patients with severe bulbar weakness who cannot speak — use written or assistive communication; involve speech therapy and ethics if needed.
— Medication reconciliation at every transition of care — pharmacy alert for contraindicated drugs (aminoglycosides, fluoroquinolones, magnesium, neuromuscular blockers, botulinum toxin).
— MedicAlert bracelet and wallet card documenting LEMS diagnosis and medication list.
— Anesthesia preoperative notification — written communication before any planned procedure; risk of prolonged paralysis with succinylcholine and non-depolarizing blockers.
— Fall risk assessment at every visit; home safety evaluation and assistive devices.
— Hospital-to-home: ensure outpatient amifampridine refills are in hand before discharge (specialty pharmacy delays are common); bridge prescriptions if needed.
— ED encounters by covering providers: include a prominent allergy-style alert in the EHR for contraindicated medications.
— Skilled nursing facility transfers: send written medication-avoidance list and emergency action plan.
— Driving safety — patients with significant proximal weakness or autonomic instability may not be safe drivers; many states require reporting of medical conditions affecting driving (e.g., California, Pennsylvania) — counsel and document.
— Assist with disability paperwork (FMLA, SSDI) when functional impairment limits work.
— Paraneoplastic LEMS often signals advanced SCLC — early palliative care consultation improves quality of life and aligns treatment with patient values.
— Advance directives, POLST/MOLST forms, surrogate decision-makers should be addressed early.
Step 3 management: The single most impactful safety intervention at discharge is a prominently flagged EHR allergy entry for aminoglycosides, fluoroquinolones, magnesium, and neuromuscular blockers — this prevents inadvertent administration during future ED visits and surgeries.
Board pearl: If a Step 3 stem mentions "dry mouth and impotence" alongside proximal weakness in a smoker, it is LEMS, not MG, not Parkinson, not diabetic neuropathy — and the very next step is a CT chest.
"A 64-year-old man with a 50-pack-year history presents with 4 months of difficulty rising from a chair. He notes dry mouth and erectile dysfunction. On exam, hip flexors are 4/5, knee reflexes are absent at rest but reappear after 15 seconds of sustained contraction. Best next step?"
— Answer pathway: anti-P/Q VGCC antibody + EMG with RNS + CT chest.
Image of CMAP waveforms showing a low baseline amplitude with dramatic incremental response after high-frequency stimulation or exercise.
— Answer: Lambert-Eaton myasthenic syndrome.
"A patient with known LEMS undergoes cholecystectomy. After succinylcholine, paralysis persists for 6 hours."
— Teaching point: profound NMJ blocker sensitivity; need anesthesia notification and consideration of alternatives/sugammadex.
"A 32-year-old with LEMS at 34 weeks gestation develops BP 165/110 with proteinuria. The team plans IV magnesium."
— Correct answer: avoid Mg; pursue alternative seizure prophylaxis and emergent multidisciplinary planning.
"Patient diagnosed with LEMS, CT chest negative. Next step?"
— Answer: whole-body FDG-PET; if negative, repeat imaging every 3–6 months for 2 years.
"A LEMS patient is given ciprofloxacin for UTI and develops worsening weakness."
— Answer: stop fluoroquinolone, switch to a safer agent (e.g., cephalexin or nitrofurantoin if appropriate), supportive care.
Side-by-side vignette emphasizing post-exercise facilitation vs. fatigability, autonomic involvement vs. ocular onset, VGCC vs. AChR antibodies, SCLC vs. thymoma.
"Patient on atezolizumab for SCLC develops new proximal weakness and dry mouth."
— Answer: hold ICI, send VGCC antibody, EMG, start steroids, neurology/oncology co-management.
Step 3 management: When the stem offers both a diagnostic test and a therapeutic option, choose the test that simultaneously confirms the diagnosis and screens for cancer — typically anti-VGCC antibody + CT chest.
Board pearl: "Augments with exercise" in any neuromuscular vignette = LEMS until proven otherwise.
Lambert-Eaton myasthenic syndrome is a presynaptic NMJ disorder caused by anti–P/Q-type VGCC antibodies — most often paraneoplastic to small cell lung cancer — presenting with proximal weakness, autonomic dysfunction, and areflexia that paradoxically improves with brief exercise, diagnosed by VGCC antibodies plus incremental response on high-frequency RNS, and managed with amifampridine, aggressive treatment of the underlying tumor, and meticulous avoidance of NMJ-blocking medications.
Board pearl: If you remember only one sentence — proximal weakness + dry mouth + areflexia that improves with effort = LEMS = look for small cell lung cancer.