Lambert-Eaton Myasthenic Syndrome (LEMS)¶

VERSION: 1.1 CREATED: January 30, 2026 REVISED: January 30, 2026 STATUS: Draft - Pending Review

DIAGNOSIS: Lambert-Eaton Myasthenic Syndrome (LEMS)

ICD-10: G73.1 (Lambert-Eaton syndrome), C34.90 (Malignant neoplasm of unspecified part of unspecified bronchus or lung - for paraneoplastic LEMS), G70.80 (Other specified myoneural disorders)

SYNONYMS: Lambert-Eaton myasthenic syndrome, LEMS, Lambert-Eaton syndrome, Eaton-Lambert syndrome, paraneoplastic Lambert-Eaton syndrome, autoimmune Lambert-Eaton syndrome, VGCC antibody syndrome, P/Q-type calcium channel antibody syndrome, presynaptic neuromuscular junction disorder, paraneoplastic neuromuscular junction disorder, voltage-gated calcium channel antibody disease, myasthenic syndrome

SCOPE: Diagnosis and management of Lambert-Eaton myasthenic syndrome in adults, including both paraneoplastic (P-LEMS, ~60% associated with small cell lung cancer) and autoimmune (A-LEMS) subtypes. Covers VGCC antibody testing, DELTA-P score calculation for paraneoplastic risk stratification, electrodiagnostic evaluation (repetitive nerve stimulation), cancer screening protocols, symptomatic treatment with 3,4-diaminopyridine, immunotherapy, and long-term monitoring. Excludes myasthenia gravis (separate template), botulism, and congenital myasthenic syndromes.

DEFINITIONS: - P-LEMS: Paraneoplastic LEMS, associated with underlying malignancy (~60% SCLC) - A-LEMS: Autoimmune LEMS, no associated malignancy (non-paraneoplastic) - VGCC: Voltage-gated calcium channel (P/Q-type antibodies are diagnostic) - DELTA-P Score: Dutch-English LEMS Tumor Association Prediction score for paraneoplastic risk - Lambert sign: Hyporeflexia that improves or normalizes after brief maximal voluntary contraction (post-exercise facilitation) - CMAP facilitation: >100% increment in compound muscle action potential amplitude after high-frequency (50 Hz) repetitive nerve stimulation or after 10-second maximal voluntary contraction

DELTA-P SCORE (Paraneoplastic Risk Stratification):

Feature	Points
D - Dysarthria or Dysphagia at onset	1
E - Erectile dysfunction (males)	1
L - Loss of weight (>5% in 6 months)	1
T - Tobacco use (current or recent)	1
A - Age at onset >50 years	1
P - Positive bulbar involvement	1

Interpretation: - Score 0-1: Low risk of malignancy (~0-2%); likely autoimmune LEMS - Score 2: Intermediate risk (~15-25%); cancer screening recommended - Score >=3: High risk of malignancy (~83-96%); intensive cancer screening mandatory; SCLC most common

Note: DELTA-P score >=3 has sensitivity ~96% and specificity ~99% for paraneoplastic LEMS (Titulaer et al. J Neurol Neurosurg Psychiatry 2011).

PRIORITY KEY: STAT = Immediate | URGENT = Within hours | ROUTINE = Standard | EXT = Extended/atypical cases | - = Not applicable to this setting

═══════════════════════════════════════════════════════════ SECTION A: ACTION ITEMS ═══════════════════════════════════════════════════════════

1. LABORATORY WORKUP¶

1A. Essential/Core Labs¶

Test	ED	HOSP	OPD	ICU	Rationale	Target Finding
CBC with differential (CPT 85025)	STAT	STAT	ROUTINE	STAT	Baseline before immunotherapy; infection screen; paraneoplastic cytopenias	Normal
CMP (CPT 80053)	STAT	STAT	ROUTINE	STAT	Renal/hepatic function baseline; electrolytes; pre-treatment assessment	Normal
P/Q-type VGCC antibody (CPT 86255)	URGENT	URGENT	ROUTINE	URGENT	Primary diagnostic test; positive in ~85-90% of LEMS (both P-LEMS and A-LEMS); sensitivity highest for P/Q-type	Negative (<0.02 nmol/L); positive confirms LEMS in appropriate clinical context
N-type VGCC antibody	URGENT	URGENT	ROUTINE	URGENT	May be co-positive with P/Q-type; less specific but supportive	Negative
SOX1 antibody	URGENT	URGENT	ROUTINE	URGENT	Paraneoplastic marker highly specific for SCLC (~64% sensitivity in P-LEMS); helps distinguish P-LEMS from A-LEMS	Negative (positive strongly suggests underlying SCLC)
ESR (CPT 85652)	URGENT	ROUTINE	ROUTINE	URGENT	Inflammatory/autoimmune screen; cancer screening	Normal
CRP (CPT 86140)	URGENT	ROUTINE	ROUTINE	URGENT	Inflammatory marker; infection screen	Normal
TSH (CPT 84443)	URGENT	ROUTINE	ROUTINE	URGENT	Thyroid disease as autoimmune comorbidity; hypothyroidism worsens weakness	Normal
Blood glucose (CPT 82947)	STAT	STAT	ROUTINE	STAT	Pre-steroid baseline; autonomic dysfunction assessment	Normal
HbA1c (CPT 83036)	-	ROUTINE	ROUTINE	-	Glycemic status before corticosteroid initiation	<5.7%
Magnesium (CPT 83735)	STAT	STAT	ROUTINE	STAT	Hypomagnesemia worsens neuromuscular transmission	Normal (1.7-2.2 mg/dL)
Calcium (CPT 82310)	STAT	STAT	ROUTINE	STAT	Calcium channel function directly relevant to LEMS pathophysiology	Normal (8.5-10.5 mg/dL)
Phosphorus (CPT 84100)	STAT	STAT	ROUTINE	STAT	Baseline electrolyte panel	Normal
PT/INR (CPT 85610)	STAT	STAT	-	STAT	Coagulation baseline before procedures	Normal
Urinalysis (CPT 81003)	STAT	ROUTINE	ROUTINE	STAT	Infection screen; baseline	Negative
LDH (CPT 83615)	URGENT	ROUTINE	ROUTINE	URGENT	Tumor marker; baseline before immunotherapy	Normal

1B. Extended Workup (Second-line)¶

Test	ED	HOSP	OPD	ICU	Rationale	Target Finding
AChR binding antibody (CPT 86235)	-	URGENT	ROUTINE	-	MG overlap screen; ~15% of LEMS patients have concurrent MG antibodies	Negative
AChR modulating antibody (CPT 86235)	-	URGENT	ROUTINE	-	MG overlap; increases sensitivity for coexistent MG	Negative
GAD65 antibody	-	ROUTINE	ROUTINE	-	Autoimmune overlap (stiff person syndrome, cerebellar ataxia, type 1 diabetes)	Negative
ANNA-1 (anti-Hu) antibody	-	ROUTINE	ROUTINE	-	Paraneoplastic marker for SCLC; sensory neuropathy overlap	Negative
CRMP-5 (anti-CV2) antibody	-	ROUTINE	ROUTINE	-	Paraneoplastic marker; associated with SCLC, chorea, neuropathy	Negative
Amphiphysin antibody	-	ROUTINE	ROUTINE	-	Paraneoplastic marker; stiff person spectrum; breast/lung cancer	Negative
Anti-Zic4 antibody	-	ROUTINE	ROUTINE	-	Paraneoplastic marker; cerebellar degeneration with SCLC	Negative
ANA (CPT 86235)	-	ROUTINE	ROUTINE	-	Autoimmune overlap screen (SLE, Sjogren)	Negative or low titer
Hepatitis B surface antigen (CPT 80074)	-	ROUTINE	ROUTINE	-	Screen before rituximab/immunosuppression (reactivation risk)	Negative
Hepatitis B core antibody	-	ROUTINE	ROUTINE	-	Screen for prior HBV before rituximab	Negative
Hepatitis C antibody (CPT 80074)	-	ROUTINE	ROUTINE	-	Screen before immunosuppression	Negative
HIV (CPT 87389)	-	ROUTINE	ROUTINE	-	Screen before immunosuppression	Negative
Quantitative immunoglobulins (IgG, IgA, IgM)	-	ROUTINE	ROUTINE	-	Baseline before IVIg; monitor on immunosuppression	Normal
TB test (QuantiFERON-Gold or PPD)	-	ROUTINE	ROUTINE	-	Screen before immunosuppression	Negative
Vitamin D (25-OH) (CPT 82306)	-	ROUTINE	ROUTINE	-	Immune modulation; deficiency common in autoimmune disease	>30 ng/mL
PSA (males >50) (CPT 84153)	-	ROUTINE	ROUTINE	-	Malignancy screen in paraneoplastic workup	Normal
CEA (CPT 82378)	-	ROUTINE	ROUTINE	-	Tumor marker screen; lung and GI malignancies	Normal (<5 ng/mL)
NSE (neuron-specific enolase)	-	ROUTINE	ROUTINE	-	SCLC tumor marker; elevated in ~60% of SCLC	Normal
ProGRP (pro-gastrin-releasing peptide)	-	ROUTINE	ROUTINE	-	SCLC-specific tumor marker; more specific than NSE	Normal

1C. Rare/Specialized (Refractory or Atypical)¶

Test	ED	HOSP	OPD	ICU	Rationale	Target Finding
VGKC-complex antibody (LGI1, CASPR2)	-	EXT	EXT	-	Autoimmune encephalitis overlap; if cognitive or autonomic features prominent	Negative
Paraneoplastic antibody comprehensive panel	-	EXT	EXT	-	If initial antibodies negative but paraneoplastic syndrome suspected	Negative
SPEP with immunofixation (CPT 86334)	-	ROUTINE	EXT	-	Paraproteinemic neuropathy screen in atypical cases	Normal
Free light chains (serum)	-	EXT	EXT	-	Light chain disease screen	Normal ratio
Ganglionic AChR antibody	-	EXT	EXT	-	Autoimmune autonomic ganglionopathy if prominent autonomic features	Negative
Anti-Purkinje cell antibody (PCA-Tr/DNER)	-	EXT	EXT	-	Paraneoplastic cerebellar degeneration overlap with LEMS	Negative
Muscle biopsy	-	EXT	EXT	-	If diagnosis uncertain; rule out inflammatory myopathy	Normal
Genetic testing (CACNA1A, CACNB4)	-	-	EXT	-	Familial hemiplegic migraine/episodic ataxia with calcium channelopathy overlap; very rare	Normal

2. DIAGNOSTIC IMAGING & STUDIES¶

2A. Essential/First-line¶

Study	ED	HOSP	OPD	ICU	Timing	Target Finding	Contraindications
CT chest with contrast (CPT 71260)	URGENT	URGENT	ROUTINE	URGENT	Within 24-48h of diagnosis; primary malignancy screen	No lung mass, mediastinal lymphadenopathy, or thymoma	Contrast allergy, renal insufficiency
Chest X-ray (PA and lateral) (CPT 71046)	STAT	STAT	ROUTINE	STAT	Immediate; initial screen for lung mass	No mass lesion, no hilar adenopathy	None significant
PET/CT (FDG) (CPT 78816)	-	URGENT	ROUTINE	-	Within 1-2 weeks of diagnosis; most sensitive for occult SCLC if CT chest negative; recommended for all LEMS patients	No FDG-avid lesion; SCLC can be very small and CT-occult	Uncontrolled diabetes (glucose >200); pregnancy
ECG (12-lead) (CPT 93000)	STAT	ROUTINE	ROUTINE	STAT	At presentation; autonomic dysfunction assessment	Normal sinus rhythm; no QTc prolongation	None

2B. Electrodiagnostic & Specialized Studies¶

Study	ED	HOSP	OPD	ICU	Timing	Target Finding	Contraindications
Repetitive nerve stimulation (RNS) - low rate (2-3 Hz) (CPT 95937)	-	URGENT	ROUTINE	-	During workup; test multiple nerves including proximal muscles	Decremental response >10% at 2-3 Hz (similar to MG but typically more pronounced; test hand and shoulder muscles)	Pacemaker (relative)
Repetitive nerve stimulation (RNS) - high rate (20-50 Hz) (CPT 95937)	-	URGENT	ROUTINE	-	Immediately after low-rate RNS; DIAGNOSTIC hallmark of LEMS	Incremental response >100% (often >200%) at high-frequency stimulation; this distinguishes LEMS from MG	Pacemaker (relative); painful - consider post-exercise facilitation instead
Post-exercise facilitation testing (CPT 95937)	-	URGENT	ROUTINE	-	10 seconds of maximal voluntary contraction then immediate repeat CMAP; preferred over high-rate RNS (less painful)	>100% increment in CMAP amplitude post-exercise; characteristic of presynaptic NMJ disorder	None significant
Baseline CMAP amplitude assessment	-	URGENT	ROUTINE	-	Before RNS; record resting CMAP amplitudes in multiple nerves	Low resting CMAP amplitudes (typically <5 mV in hand muscles); hallmark of LEMS	None
Standard EMG/NCS (CPT 95886, 95907-95913)	-	ROUTINE	ROUTINE	-	Complete electrodiagnostic evaluation; rule out concurrent neuropathy/myopathy	Low CMAP amplitudes at rest; normal sensory responses; no active denervation (unless cancer-related neuropathy)	None significant
Single-fiber EMG (SFEMG) (CPT 95872)	-	ROUTINE	ROUTINE	-	If RNS non-diagnostic; increased jitter with improvement at higher firing rates (opposite of MG pattern)	Increased jitter that improves with increased firing rate (presynaptic pattern)	Requires experienced electromyographer
Autonomic function testing (CPT 95921-95924)	-	ROUTINE	ROUTINE	-	If autonomic symptoms present; quantifies autonomic involvement	Abnormal sudomotor, cardiovagal, or adrenergic responses; supports LEMS diagnosis	None significant

2C. Cancer Screening Protocol¶

Study	ED	HOSP	OPD	ICU	Timing	Target Finding	Notes
CT chest/abdomen/pelvis with contrast	-	URGENT	ROUTINE	-	If initial CT chest negative and clinical suspicion high (DELTA-P >=2)	No occult malignancy	Annual screening required for at least 2 years
PET/CT (repeat if initial negative)	-	-	ROUTINE	-	Every 6 months for 2 years if DELTA-P >=3 and initial PET negative	No FDG-avid lesion	SCLC may be delayed in presentation; continuous vigilance
CT chest (low-dose screening)	-	-	ROUTINE	-	Every 6 months for 2 years from diagnosis; then annually for 2 more years (total 4 years screening)	No new lung nodules or mass	Per EFNS/PNS guidelines; P-LEMS risk persists for years
MRI brain with contrast (CPT 70553)	-	ROUTINE	ROUTINE	-	If neurological symptoms suggest brain metastases or paraneoplastic cerebellar degeneration	No metastases; no cerebellar atrophy	Gadolinium allergy, GFR <30, pacemaker
Bronchoscopy with biopsy	-	ROUTINE	-	-	If CT/PET shows suspicious pulmonary lesion	Tissue diagnosis; SCLC vs NSCLC	Coagulopathy; severe respiratory compromise
Mammography (females)	-	-	ROUTINE	-	As part of comprehensive malignancy screen	No malignancy	Per age-appropriate screening guidelines
Colonoscopy (age-appropriate)	-	-	ROUTINE	-	If no lung cancer found; screen for other malignancies	No malignancy	Bowel prep; coagulopathy

Note: Cancer screening protocol based on Titulaer et al. recommendations. If initial comprehensive screening is negative, repeat CT chest every 6 months for 2 years. If DELTA-P score >=3, repeat PET/CT at 3-6 months. ~3-5% of patients initially classified as A-LEMS are later diagnosed with cancer, usually within 2 years.

2D. Bedside Clinical Tests¶

Test	ED	HOSP	OPD	ICU	Timing	Target Finding	Notes
Deep tendon reflex testing (pre- and post-exercise)	STAT	STAT	ROUTINE	STAT	Initial exam; Lambert sign assessment	Hyporeflexia or areflexia at rest that improves after 10 sec maximal contraction (Lambert sign); pathognomonic for LEMS	Compare reflexes before and after 10-second isometric contraction
Manual muscle testing (proximal emphasis)	STAT	STAT	ROUTINE	STAT	Initial exam	Proximal weakness legs > arms; hip flexors and quadriceps most affected; may improve briefly with initial contraction	Use MRC grading scale; document post-exercise augmentation
Grip strength testing (pre- and post-exercise)	STAT	STAT	ROUTINE	STAT	Serial assessment	Reduced grip at baseline; may improve after initial maximal effort (post-exercise facilitation)	Dynamometer preferred for objective measurement
Forced vital capacity (FVC)	STAT	STAT	-	STAT	At presentation and serially if respiratory symptoms	>20 mL/kg (>1.5 L)	Respiratory failure rare in LEMS but can occur, especially with cancer treatment or crisis
Negative inspiratory force (NIF/MIP)	STAT	STAT	-	STAT	At presentation and serially	More negative than -40 cm H2O	Monitor if worsening weakness or peri-treatment
Orthostatic vital signs	STAT	STAT	ROUTINE	STAT	Initial assessment; autonomic dysfunction quantification	No orthostatic hypotension (drop >20 systolic or >10 diastolic on standing)	Common in LEMS due to autonomic involvement
Pupillary examination	STAT	STAT	ROUTINE	STAT	Initial exam	Normal pupillary responses; sluggish pupils may suggest autonomic involvement	Distinguish from botulism (fixed dilated pupils)
Dry mouth assessment (visual analog scale)	-	ROUTINE	ROUTINE	-	Each visit; autonomic symptom tracking	No xerostomia	Dry mouth is one of the earliest and most common autonomic features

3. TREATMENT¶

3A. Acute/Emergent¶

Treatment	Route	Indication	Dosing	Contraindications	Monitoring	ED	HOSP	OPD	ICU
IVIg (intravenous immunoglobulin) (CPT 96365)	IV	Acute LEMS exacerbation with significant functional impairment; rapid symptom control; pre-treatment or perioperative optimization	0.4 g/kg :: IV :: daily x 5 days :: 0.4 g/kg/day IV x 5 days (total 2 g/kg) OR 1 g/kg/day x 2 days; infuse over 4-6 hours; slow initial rate per protocol	IgA deficiency (check IgA level first); recent thrombotic event; renal failure (use sucrose-free formulation)	Pre-infusion: IgA level, renal function, CBC; during: vital signs q15 min first hour then q1h; headache; aseptic meningitis; thrombosis risk; renal function post-infusion	STAT	STAT	-	STAT
Plasma exchange (PLEX) (CPT 36514)	IV	Acute LEMS exacerbation; alternative to IVIg; LEMS crisis with respiratory compromise; pre-thymectomy optimization if concurrent thymoma	1-1.5 plasma volumes :: IV :: every other day x 5-7 exchanges :: 5-7 exchanges over 10-14 days; exchange 1-1.5 plasma volumes per session every other day; albumin replacement preferred	Hemodynamic instability; sepsis; central line contraindication; heparin allergy	BP during exchange; electrolytes (Ca, K, Mg); coagulation studies; fibrinogen; line site infection; hypotension	STAT	STAT	-	STAT
Normal saline IV	IV	Volume resuscitation for orthostatic hypotension from autonomic dysfunction	500-1000 mL :: IV :: bolus then maintenance :: 500-1000 mL NS bolus then 75-125 mL/hr maintenance as needed for orthostatic symptoms	Heart failure; volume overload	I/O; BP; orthostatic vitals; weight	STAT	STAT	-	STAT

3B. Symptomatic Treatments¶

Treatment	Route	Indication	Dosing	Contraindications	Monitoring	ED	HOSP	OPD	ICU
3,4-Diaminopyridine (amifampridine/Firdapse)	PO	First-line symptomatic treatment for LEMS; enhances presynaptic acetylcholine release by blocking potassium channels; improves strength and autonomic symptoms	5 mg :: PO :: TID :: Start 5 mg TID; increase by 5 mg per dose every 3-5 days; usual effective dose 15-20 mg TID-QID; max 80 mg/day (max 20 mg per single dose); take with food	Seizure history (lowers seizure threshold); concurrent use of drugs that lower seizure threshold; QT prolongation	ECG at baseline and after dose changes; seizure precautions; QTc monitoring; paresthesias (perioral, digital); GI upset	URGENT	URGENT	ROUTINE	URGENT
3,4-Diaminopyridine phosphate (Ruzurgi)	PO	Alternative formulation of amifampridine for LEMS; enhances presynaptic acetylcholine release by blocking potassium channels; improves strength and autonomic symptoms	5 mg :: PO :: TID :: Start 5 mg TID; increase by 5 mg per dose every 3-5 days; usual effective dose 15-20 mg TID-QID; max 80 mg/day (max 20 mg per single dose); take with food	Seizure history (lowers seizure threshold); concurrent use of drugs that lower seizure threshold; QT prolongation	ECG at baseline and after dose changes; seizure precautions; QTc monitoring; paresthesias (perioral, digital); GI upset	URGENT	URGENT	ROUTINE	URGENT
Pyridostigmine (Mestinon)	PO	Adjunctive symptomatic treatment; enhances postsynaptic acetylcholine effect; less effective in LEMS than in MG but may provide modest additional benefit when combined with 3,4-DAP	30 mg :: PO :: TID :: Start 30 mg TID; increase by 30 mg per dose every 2-3 days; usual effective dose 60 mg q4-6h; max 120 mg per dose; less effective as monotherapy in LEMS than MG	Mechanical GI/GU obstruction; uncontrolled asthma	Cholinergic side effects: diarrhea, cramping, salivation, bradycardia	-	ROUTINE	ROUTINE	-
Guanfacine	PO	Refractory dry mouth from autonomic dysfunction not responsive to 3,4-DAP; off-label use	1 mg :: PO :: daily :: Start 1 mg daily; may increase to 2 mg daily; used off-label for autonomic dry mouth	Hypotension; bradycardia; renal impairment	BP; HR; sedation	-	-	ROUTINE	-
Midodrine	PO	Orthostatic hypotension from autonomic dysfunction in LEMS	2.5 mg :: PO :: TID :: Start 2.5 mg TID; titrate by 2.5 mg per dose every 1-2 weeks; max 10 mg TID; avoid dosing within 4 hours of bedtime	Supine hypertension; urinary retention; severe organic heart disease; pheochromocytoma	Supine BP (check 1 hour after first dose); avoid supine position for 4h after dosing	-	ROUTINE	ROUTINE	-
Fludrocortisone	PO	Orthostatic hypotension refractory to midodrine; volume expansion	0.1 mg :: PO :: daily :: Start 0.1 mg daily; may increase to 0.2 mg daily; max 0.3 mg daily	Heart failure; hypertension; edema	Electrolytes (hypokalemia); weight; BP; edema; supine hypertension	-	ROUTINE	ROUTINE	-
Polyethylene glycol 3350 (MiraLAX)	PO	Constipation from autonomic dysfunction in LEMS	17 g :: PO :: daily :: 17 g (1 capful) dissolved in 8 oz liquid once daily; adjust frequency to bowel response	Known bowel obstruction	Bowel habits; electrolytes if prolonged use	-	ROUTINE	ROUTINE	-
Senna	PO	Constipation from autonomic dysfunction; adjunct to osmotic laxative	8.6 mg :: PO :: qHS :: 8.6-17.2 mg PO qHS; may increase to BID if needed; max 34.4 mg/day	Bowel obstruction; acute abdominal pain	Bowel habits; avoid long-term use if possible	-	ROUTINE	ROUTINE	-
Artificial tears/saliva substitutes	TOP	Dry eyes and dry mouth from autonomic dysfunction	1-2 drops :: TOP :: q2-4h PRN :: Artificial tears q2-4h PRN for dry eyes; saliva substitute spray or lozenges PRN for dry mouth	None significant	Symptom relief assessment	-	ROUTINE	ROUTINE	-
Sildenafil	PO	Erectile dysfunction from autonomic dysfunction in LEMS	25 mg :: PO :: PRN :: Start 25 mg PO 1 hour before sexual activity; may increase to 50-100 mg; max 100 mg/day	Concurrent nitrates (CONTRAINDICATED); severe cardiovascular disease; recent stroke/MI within 6 months	BP; cardiac status; vision changes; priapism	-	-	ROUTINE	-

3C. Second-line/Refractory¶

Treatment	Route	Indication	Dosing	Contraindications	Monitoring	ED	HOSP	OPD	ICU
Prednisone	PO	Autoimmune LEMS (A-LEMS) with inadequate response to 3,4-DAP alone; bridge to steroid-sparing agent; NOT first-line for P-LEMS (treat cancer first)	10-20 mg :: PO :: daily :: Start 10-20 mg daily; increase by 10 mg every 5-7 days to 0.5-1 mg/kg/day; maintain 4-8 weeks then taper by 5-10 mg/month to lowest effective dose	Active untreated infection; uncontrolled diabetes; psychosis history	Glucose; BP; mood/sleep; weight; bone density; GI prophylaxis	-	ROUTINE	ROUTINE	-
IVIg (maintenance)	IV	Chronic immunomodulation for LEMS with ongoing functional impairment despite 3,4-DAP and oral immunotherapy	1 g/kg :: IV :: every 4 weeks :: 1 g/kg IV every 4 weeks (may adjust to 0.4-1 g/kg based on response); infuse over 4-6 hours	IgA deficiency; recent thrombotic event; renal failure	Renal function; IgA level; vital signs during infusion; headache; thrombosis risk	-	ROUTINE	ROUTINE	ROUTINE
Plasma exchange (maintenance)	IV	Chronic LEMS refractory to IVIg and oral immunotherapy	1 plasma volume :: IV :: every 2-4 weeks :: Single volume exchange every 2-4 weeks; adjust frequency based on clinical response and antibody levels; albumin replacement	Hemodynamic instability; line complications	BP; electrolytes; coagulation; line site	-	ROUTINE	-	-

3D. Disease-Modifying / Immunosuppressive Therapies¶

Treatment	Route	Indication	Dosing	Pre-Treatment Requirements	Contraindications	Monitoring	ED	HOSP	OPD	ICU
Azathioprine (Imuran)	PO	Steroid-sparing agent for A-LEMS; long-term immunosuppression to reduce VGCC antibody production; onset 6-18 months	50 mg :: PO :: daily :: Start 50 mg daily; increase by 50 mg every 1-2 weeks to target 2-3 mg/kg/day (typically 150-250 mg/day); onset 6-18 months	TPMT genotype/activity BEFORE starting (mandatory); CBC; LFTs; hepatitis B/C screen; TB test	TPMT deficiency (homozygous); concurrent allopurinol (reduce dose by 75%); pregnancy (relative); active infection	TPMT genotype before starting; CBC q1-2 weeks during titration then monthly; LFTs monthly; amylase/lipase if abdominal pain; lymphocyte count target 600-1000	-	ROUTINE	ROUTINE	-
Mycophenolate mofetil (CellCept)	PO	Steroid-sparing agent for A-LEMS; alternative to azathioprine; onset 6-12 months	500 mg :: PO :: BID :: Start 500 mg BID; increase to 1000 mg BID after 2 weeks; target 2000-3000 mg/day; onset 6-12 months	CBC; LFTs; hepatitis B/C screen; pregnancy test (females); TB test	Pregnancy (Category D - teratogenic); concurrent azathioprine; active infection	CBC q2 weeks x 3 months then monthly; LFTs; GI side effects (diarrhea, nausea); lymphopenia; REMS pregnancy prevention	-	ROUTINE	ROUTINE	-
Rituximab (Rituxan)	IV	Refractory A-LEMS not responding to conventional immunosuppressants; may be used earlier in severe cases; less evidence than in MG but reported efficacy	375 mg/m2 :: IV :: weekly x 4 weeks :: 375 mg/m2 IV weekly x 4 weeks; OR 1000 mg IV x 2 doses 14 days apart; re-dose when CD19/CD20 recover or clinical worsening; onset 3-6 months	HBV serology (HBsAg, anti-HBc, anti-HBs); hepatitis C screen; HIV test; CBC; immunoglobulins; TB test; vaccinations up to date	Active hepatitis B; active infection; severe immunodeficiency; PML history	CD19/CD20 counts q3-6 months; immunoglobulins q6 months; PML risk (very rare); infusion reactions (premedicate with acetaminophen, diphenhydramine, methylprednisolone)	-	ROUTINE	ROUTINE	-
Cyclosporine (Sandimmune/Neoral)	PO	Alternative steroid-sparing agent for A-LEMS; faster onset than azathioprine (2-6 months)	2-3 mg/kg/day :: PO :: BID :: Start 2-3 mg/kg/day divided BID; target trough 100-150 ng/mL; onset 2-6 months	Renal function; BP; electrolytes; hepatitis screen; TB test	Uncontrolled hypertension; renal impairment; concurrent nephrotoxic drugs	Trough levels; renal function q2 weeks then monthly; BP; electrolytes (K, Mg); lipids; gingival hyperplasia; hirsutism	-	-	ROUTINE	-
Cyclophosphamide	IV	Severe refractory LEMS not responding to other immunosuppressants; reserved for life-threatening or disabling disease	500-1000 mg/m2 :: IV :: monthly x 6 months :: Pulse IV 500-1000 mg/m2 monthly x 6 months; OR oral 1-2 mg/kg/day; reserved for refractory cases; MESNA uroprotection with IV dosing	CBC; renal function; hepatitis screen; pregnancy test; fertility counseling	Pregnancy; active infection; bone marrow suppression; hemorrhagic cystitis history	CBC weekly during treatment; urinalysis (hemorrhagic cystitis); fertility counseling; malignancy risk	-	EXT	EXT	EXT
Oncology-directed chemotherapy (cisplatin/etoposide)	IV	Standard first-line for SCLC in P-LEMS; treatment of underlying malignancy is the primary therapy for paraneoplastic LEMS; neurological symptoms often improve with cancer treatment	Per oncology protocol :: IV :: per oncology :: Cisplatin 60-80 mg/m2 day 1 + etoposide 100-120 mg/m2 days 1-3 q21d x 4-6 cycles; defer to oncology for specific regimen	Oncology staging; LEMS diagnosis confirmation; LEMS-specific caution: avoid neuromuscular blocking agents if surgery needed	Per oncology assessment	Neuromuscular function during treatment; FVC if respiratory symptoms; electrolytes; renal function; myelosuppression	-	ROUTINE	ROUTINE	-
Radiation therapy (SCLC)	EXT	Limited-stage SCLC with or without concurrent chemotherapy; palliative radiation for extensive-stage	Per radiation oncology protocol :: EXT :: per oncology :: Concurrent chemoradiation for limited stage; palliative for extensive stage; prophylactic cranial irradiation per oncology	Radiation oncology staging; treatment planning	Per radiation oncology assessment	Neurological function; esophagitis; pneumonitis	-	ROUTINE	ROUTINE	-
Immune checkpoint inhibitors (with extreme caution)	IV	SCLC maintenance (atezolizumab, durvalumab); CRITICAL WARNING: may worsen LEMS or trigger myasthenic crisis; only under joint neuro-oncology management	Per oncology protocol :: IV :: per oncology :: Per oncology; MUST be administered with close neuromuscular monitoring; have IVIg/PLEX available	Baseline FVC; neuromuscular assessment; joint neuro-oncology plan	Pre-existing myasthenic crisis; uncontrolled LEMS; use only with neuromuscular specialist co-management	FVC before each cycle; MG-ADL equivalent assessment; creatine kinase; troponin (myocarditis); monitor for rapid neurological deterioration	-	EXT	EXT	EXT

Note: Treatment of underlying malignancy is the most important therapy in P-LEMS. LEMS symptoms often improve significantly with successful cancer treatment. Immunosuppressive therapy (azathioprine, mycophenolate, rituximab) should be used cautiously in P-LEMS as it may impair anti-tumor immunity. Immune checkpoint inhibitors may paradoxically worsen paraneoplastic neurological syndromes.

4. OTHER RECOMMENDATIONS¶

4A. Referrals & Consults¶

Recommendation	ED	HOSP	OPD	ICU
Neuromuscular specialist referral for diagnosis confirmation, treatment planning, and long-term management of LEMS	URGENT	URGENT	ROUTINE	URGENT
Oncology referral for cancer screening and management in all LEMS patients (mandatory given ~60% paraneoplastic association)	URGENT	URGENT	ROUTINE	URGENT
Pulmonology referral for respiratory function monitoring if FVC declining or significant weakness	-	ROUTINE	ROUTINE	URGENT
Thoracic surgery referral if lung mass identified on imaging	-	URGENT	ROUTINE	-
Radiation oncology referral if SCLC confirmed for treatment planning	-	ROUTINE	ROUTINE	-
Speech-language pathology for swallow evaluation if dysphagia or bulbar symptoms present	-	URGENT	ROUTINE	URGENT
Physical therapy for proximal strengthening, gait training, and fall prevention given proximal leg weakness	-	ROUTINE	ROUTINE	ROUTINE
Occupational therapy for ADL adaptation and energy conservation strategies	-	ROUTINE	ROUTINE	-
Urology referral for erectile dysfunction management if not responsive to first-line treatment	-	-	ROUTINE	-
Gastroenterology referral for refractory constipation from autonomic dysfunction	-	-	ROUTINE	-
Psychiatry/Psychology referral for depression, anxiety, and adjustment to chronic diagnosis with cancer risk	-	ROUTINE	ROUTINE	-
Social work consult for insurance navigation, disability evaluation, and cancer support resources	-	ROUTINE	ROUTINE	-
Pain management referral for chronic pain from sustained weakness or paraneoplastic neuropathy	-	-	EXT	-
Palliative care referral for P-LEMS with advanced malignancy for goals of care discussion and symptom management	-	ROUTINE	ROUTINE	ROUTINE
Infusion center coordination for IVIg or rituximab scheduling	-	ROUTINE	ROUTINE	-
Smoking cessation program referral given strong association between LEMS and SCLC in tobacco users	-	ROUTINE	ROUTINE	-
Cardiology referral if autonomic dysfunction includes cardiac arrhythmias or significant orthostatic hypotension	-	ROUTINE	ROUTINE	URGENT

4B. Patient Instructions¶

Recommendation	ED	HOSP	OPD
Return to ED immediately if difficulty breathing, worsening weakness preventing walking, or inability to swallow (may indicate LEMS crisis or cancer progression)	✓	✓	✓
Return to ED if new severe weakness, falls, or inability to rise from chair (proximal weakness progression)	✓	✓	✓
Take 3,4-diaminopyridine (amifampridine) exactly as prescribed; do NOT exceed 20 mg per single dose or 80 mg/day (seizure risk)	✓	✓	✓
Take 3,4-diaminopyridine with food to reduce GI side effects (nausea, abdominal discomfort)	-	✓	✓
Report any seizures, tingling around the mouth, or numbness in fingers immediately (may indicate 3,4-DAP toxicity)	✓	✓	✓
Carry LEMS medical alert identification at all times (anesthesia and medication precautions critical)	✓	✓	✓
Provide LEMS medication list to ALL healthcare providers (emergency, dental, surgical) - many medications worsen neuromuscular junction disorders	✓	✓	✓
Attend ALL scheduled cancer screening appointments even if feeling well (cancer may develop years after LEMS diagnosis)	-	✓	✓
Report any new cough, weight loss, fatigue, chest pain, or hemoptysis immediately (may indicate lung cancer)	✓	✓	✓
Rise slowly from sitting or lying position to avoid falls from orthostatic hypotension (stand at bed/chair edge for 30 seconds before walking)	-	✓	✓
Increase fluid and salt intake to help manage orthostatic hypotension from autonomic dysfunction (unless restricted by other conditions)	-	✓	✓
Plan activities for times of best strength; use energy conservation techniques; rest between tasks	-	✓	✓
Do NOT stop immunosuppressant medications abruptly without physician guidance (disease flare risk)	-	✓	✓
Avoid extreme heat, hot baths, and saunas (may worsen weakness)	-	✓	✓
Report excessive dry mouth, constipation, or urinary symptoms to neurologist (autonomic dysfunction may require treatment adjustment)	-	✓	✓
Avoid alcohol (potentiates weakness and interacts with medications)	-	✓	✓
Understand that LEMS symptoms may improve if underlying cancer is successfully treated (for P-LEMS patients)	-	✓	✓
Stop smoking immediately if current smoker (reduces cancer risk and may slow disease progression)	✓	✓	✓

4C. Lifestyle & Prevention¶

Recommendation	ED	HOSP	OPD
Smoking cessation mandatory given strong association between LEMS, SCLC, and tobacco use (reduces ongoing cancer risk)	✓	✓	✓
Low-impact exercise (swimming, stationary bike, yoga) to maintain strength and mobility without overexertion given proximal weakness	-	✓	✓
Energy conservation with scheduled rest periods to manage fatigue and optimize function throughout the day	-	✓	✓
Home safety evaluation to remove fall hazards given proximal leg weakness and orthostatic hypotension (secure rugs, install grab bars, adequate lighting)	-	✓	✓
Compression stockings (waist-high, 30-40 mmHg) for orthostatic hypotension management from autonomic dysfunction	-	✓	✓
Elevate head of bed 10-20 degrees to reduce nocturnal supine hypertension while managing orthostatic hypotension	-	✓	✓
Increase dietary fluid intake to 2-3 L/day and liberal salt intake (unless contraindicated) for orthostatic hypotension	-	✓	✓
High-fiber diet with adequate hydration for constipation management from autonomic dysfunction	-	✓	✓
Regular dental care and oral hygiene given xerostomia (dry mouth) from autonomic dysfunction (increased caries risk)	-	-	✓
Vitamin D supplementation if deficient (1000-2000 IU daily) to support immune function and bone health, especially if on chronic steroids	-	✓	✓
Calcium supplementation (1000-1200 mg daily) if on chronic corticosteroids for bone protection	-	✓	✓
Annual influenza vaccination (inactivated form) and COVID-19 vaccination as recommended; avoid live vaccines if on immunosuppression	-	✓	✓
Aspiration precautions including thickened liquids and chin tuck positioning if dysphagia present from bulbar involvement	-	✓	✓

4D. Medications to Avoid or Use with Caution in LEMS¶

Medication/Class	Risk Level	Details	Safe Alternative (if applicable)
NEUROMUSCULAR BLOCKING AGENTS
Succinylcholine	HIGH	Unpredictable response in LEMS; may have prolonged block	Non-depolarizing agents at markedly reduced dose with sugammadex available
Non-depolarizing NM blockers (vecuronium, rocuronium, pancuronium)	HIGH	Exaggerated and prolonged response; use 1/10 to 1/5 normal dose if absolutely necessary	Sugammadex for reversal of rocuronium; neuromuscular monitoring with TOF mandatory
ANTIBIOTICS
Aminoglycosides (gentamicin, tobramycin, amikacin)	HIGH	Impair presynaptic ACh release; can precipitate respiratory failure	Non-aminoglycoside antibiotics based on culture sensitivity
Fluoroquinolones (ciprofloxacin, levofloxacin, moxifloxacin)	HIGH	NMJ blocking effect; FDA warning for neuromuscular disorders	Beta-lactams, cephalosporins (generally safe)
Macrolides (azithromycin, erythromycin)	MODERATE	Reports of NMJ worsening	Penicillins, cephalosporins
Polymyxins (colistin)	HIGH	Strong NMJ blocking effect	Alternative per culture sensitivity
CARDIOVASCULAR
Beta-blockers (propranolol, metoprolol)	MODERATE	May worsen weakness; impair NMJ transmission; worsen orthostatic hypotension	ACE inhibitors, ARBs
Calcium channel blockers (verapamil, diltiazem)	HIGH	Directly antagonize VGCC; may significantly worsen LEMS by further reducing calcium influx at nerve terminal	Amlodipine (lower risk); ACE inhibitors; avoid verapamil/diltiazem specifically
Magnesium sulfate IV	HIGH	Inhibits presynaptic ACh release; can precipitate crisis	Avoid except life-threatening hypomagnesemia; ICU monitoring required
ANESTHETIC
Volatile anesthetics (isoflurane, sevoflurane)	MODERATE	May potentiate NMJ blockade	TIVA (total intravenous anesthesia) preferred
IMMUNE/CHECKPOINT
Immune checkpoint inhibitors (nivolumab, pembrolizumab, ipilimumab)	HIGH	May worsen paraneoplastic neurological syndromes; can trigger myasthenic crisis; use only with joint neuro-oncology management	If required for cancer treatment, close neuromuscular monitoring mandatory
OTHER
Botulinum toxin	HIGH	Blocks presynaptic ACh release; CONTRAINDICATED in LEMS	Physical therapy; oral medications for spasticity
Quinine/tonic water	MODERATE	NMJ blocking effect	Avoid quinine-containing beverages

Note: LEMS patients are exquisitely sensitive to neuromuscular blocking agents due to presynaptic defect. ALL anesthesia providers must be informed of LEMS diagnosis before any surgical procedure. Calcium channel blockers (especially verapamil and diltiazem) are particularly dangerous in LEMS as they directly worsen the underlying pathophysiology.

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5. DIFFERENTIAL DIAGNOSIS¶

Alternative Diagnosis	Key Distinguishing Features	Tests to Differentiate
Myasthenia Gravis (MG)	Fatigable weakness that WORSENS with exertion (opposite of LEMS); ptosis and diplopia prominent (rare in LEMS); normal or brisk reflexes; no autonomic dysfunction; no cancer association (except thymoma)	AChR/MuSK antibodies positive; RNS shows decrement at low-rate WITHOUT significant increment at high-rate; CMAP amplitudes normal at rest
Botulism	Acute onset descending paralysis; dilated/fixed pupils; recent ingestion of contaminated food or wound; autonomic dysfunction present; NO prior NMJ disease	Stool/serum botulinum toxin assay; EMG shows BSAP pattern with incremental response similar to LEMS but acute onset
Polymyositis/Dermatomyositis	Proximal weakness without fatigability; elevated CK (often >1000); skin findings in DM (heliotrope rash, Gottron papules); no autonomic dysfunction; no NMJ abnormalities on RNS	CK; myositis antibody panel; EMG shows myopathic pattern (no NMJ findings); muscle biopsy
Inclusion Body Myositis (IBM)	Slowly progressive; finger flexor and quadriceps weakness (asymmetric); no autonomic dysfunction; older males; no NMJ findings	CK mildly elevated; EMG shows mixed myopathic/neurogenic pattern; muscle biopsy (rimmed vacuoles); anti-cN1A antibody
Motor Neuron Disease (ALS)	Progressive weakness with fasciculations; UMN signs (hyperreflexia, Babinski); no autonomic dysfunction; no fatigability pattern; EMG shows active denervation	EMG/NCS: active denervation, fasciculations, normal NMJ studies; no VGCC antibodies
Chronic Inflammatory Demyelinating Polyneuropathy (CIDP)	Progressive proximal and distal weakness; hyporeflexia/areflexia (but NO post-exercise facilitation); sensory involvement prominent; elevated CSF protein	NCS: demyelinating pattern; CSF protein elevated; no VGCC antibodies; no RNS increment
Guillain-Barre Syndrome (GBS)	Acute ascending weakness; areflexia; post-infectious; no autonomic facilitation; respiratory failure more common	CSF albuminocytologic dissociation; NCS: demyelinating or axonal pattern; no VGCC antibodies
Hypothyroid myopathy	Proximal weakness with myalgias; delayed relaxation of reflexes (NOT facilitation); fatigue; weight gain; cold intolerance	TSH elevated; free T4 low; CK may be elevated; EMG non-specific; no NMJ findings
Addison disease	Fatigue and weakness; orthostatic hypotension; hyperpigmentation; electrolyte abnormalities (hyperkalemia, hyponatremia); weight loss	Morning cortisol; ACTH stimulation test; electrolytes; no NMJ findings
Primary autonomic failure (MSA, PAF)	Prominent autonomic dysfunction; orthostatic hypotension; urinary dysfunction; NO proximal weakness pattern; NO NMJ findings on RNS	Autonomic function testing; brain MRI (MSA: hot cross bun sign); no VGCC antibodies; normal RNS
Congenital Myasthenic Syndromes (CMS)	Childhood onset; family history; seronegative; specific gene mutations; may have presynaptic, synaptic, or postsynaptic defect	Genetic testing (CMS gene panel); no VGCC antibodies; specific RNS patterns depend on CMS type
Spinal muscular atrophy (SMA)	Proximal weakness; areflexia; childhood or adult onset; fasciculations; no autonomic dysfunction; no NMJ findings	Genetic testing (SMN1 deletion); EMG shows anterior horn cell disease pattern; no VGCC antibodies
Paraneoplastic cerebellar degeneration	Ataxia rather than proximal weakness; may coexist with LEMS in ~15% of cases; anti-Purkinje cell antibodies	PCA-Tr/DNER, Yo, Hu antibodies; brain MRI showing cerebellar atrophy; VGCC may be positive (overlap)
Drug-induced neuromuscular blockade	Temporal correlation with offending medication (aminoglycosides, calcium channel blockers); reversible on drug withdrawal	Drug history review; NMJ studies normalize after drug discontinuation; no VGCC antibodies

6. MONITORING PARAMETERS¶

6A. Acute Monitoring (ED / Inpatient / ICU)¶

Parameter	Frequency	Target/Threshold	Action if Abnormal	ED	HOSP	OPD	ICU
Forced vital capacity (FVC)	Q4-6h in acute; Q shift if stable	>20 mL/kg (>1.5 L)	If <15 mL/kg or <1 L: ICU transfer and prepare for intubation; respiratory failure less common in LEMS than MG but can occur	STAT	STAT	-	STAT
Negative inspiratory force (NIF/MIP)	Q4-6h in acute; Q shift if stable	More negative than -40 cm H2O	If weaker than -20 cm H2O: intubation consideration; ICU monitoring	STAT	STAT	-	STAT
Oxygen saturation (SpO2)	Continuous in acute	>94%	Supplemental O2; BiPAP; intubation if declining	STAT	STAT	-	STAT
Orthostatic vital signs	Q shift; daily when stable	No drop >20 systolic or >10 diastolic	Increase IV fluids; add midodrine; compression stockings; hold offending medications	STAT	ROUTINE	-	STAT
Blood pressure	Q shift; more frequent during PLEX	<160/100 mmHg	Antihypertensives PRN; adjust autonomic medications	STAT	ROUTINE	-	STAT
Neurologic exam (LEMS-specific: proximal strength, reflexes with post-exercise check)	Q shift inpatient; BID in ICU	Stable or improving strength; document Lambert sign	If worsening: reassess 3,4-DAP dose; consider IVIg/PLEX; evaluate for cancer progression	STAT	ROUTINE	-	STAT
Swallow function assessment	Daily; each meal if bulbar symptoms	Safe oral intake	NPO if aspiration risk; modified diet; SLP consult	URGENT	URGENT	-	URGENT
ECG monitoring	At baseline; after 3,4-DAP dose changes	QTc <500 ms; no arrhythmia	Hold 3,4-DAP if QTc prolongation; cardiology consult for arrhythmia	STAT	ROUTINE	-	STAT
Blood glucose	Q6h during IV/high-dose steroids	<180 mg/dL	Insulin sliding scale	STAT	ROUTINE	-	STAT
Electrolytes (K, Mg, Ca, Phos)	Daily while acute	Normal ranges	Replace aggressively; calcium homeostasis especially important in LEMS	STAT	ROUTINE	-	STAT
Temperature	Q shift	Afebrile	Infection workup if febrile (infection can worsen LEMS)	STAT	ROUTINE	-	STAT
I/O and daily weight	Daily (inpatient)	Euvolemic	Adjust fluids; consider autonomic contribution to dysregulation	-	ROUTINE	-	ROUTINE

6B. Chronic/Outpatient Monitoring¶

Parameter	Frequency	Target/Threshold	Action if Abnormal	ED	HOSP	OPD	ICU
VGCC antibody titer	Every 6-12 months	Declining or stable titer	Rising titer: reassess cancer screening; consider treatment escalation	-	-	ROUTINE	-
CT chest (cancer screening)	Every 6 months for 2 years; then annually for 2 more years	No new lesion or mass	Immediate oncology referral; biopsy; staging workup	-	-	ROUTINE	-
PET/CT (if DELTA-P >=3 and initial negative)	Every 6 months for 2 years	No FDG-avid lesion	Oncology referral; biopsy	-	-	ROUTINE	-
Proximal muscle strength testing (MRC grading)	Each clinic visit	Stable or improving	Treatment escalation; reassess 3,4-DAP dose; consider immunotherapy adjustment	-	-	ROUTINE	-
Autonomic symptom assessment (dry mouth, constipation, orthostasis, ED)	Each clinic visit	Stable or improving symptoms	Adjust symptomatic medications; consider 3,4-DAP dose optimization	-	-	ROUTINE	-
Orthostatic vital signs	Each clinic visit	No significant orthostatic drop	Adjust midodrine/fludrocortisone; increase fluids/salt; compression stockings	-	-	ROUTINE	-
FVC (office spirometry)	Each visit initially; q3-6 months when stable	>80% predicted	Pulmonology referral if declining; reassess treatment	-	-	ROUTINE	-
ECG (QTc monitoring)	At baseline; after 3,4-DAP dose changes; annually	QTc <500 ms	Hold/reduce 3,4-DAP if QTc prolonging; cardiology consult	-	-	ROUTINE	-
CBC with differential	Q2-4 weeks during immunosuppressant titration; then q3 months	WBC >3000; ANC >1500	Hold/reduce immunosuppressant if cytopenic	-	-	ROUTINE	-
LFTs	Q2-4 weeks during immunosuppressant titration; then q3 months	AST/ALT <3x ULN	Reduce or hold offending agent; hepatology referral if persistent	-	-	ROUTINE	-
Renal function (BUN/Cr)	Q3 months on cyclosporine; q6 months otherwise	Normal eGFR	Dose adjustment; avoid nephrotoxins	-	-	ROUTINE	-
Fasting glucose / HbA1c	Q3 months while on steroids	HbA1c <7%	Endocrinology referral; steroid dose reduction	-	-	ROUTINE	-
DEXA scan (bone density)	Baseline if starting chronic steroids; repeat q2 years	T-score > -1.0	Bisphosphonate; calcium/vitamin D	-	-	ROUTINE	-
Immunoglobulin levels (IgG, IgA, IgM)	Q6 months if on rituximab/chronic immunosuppression	IgG >400 mg/dL	IVIg replacement if symptomatic hypogammaglobulinemia	-	-	ROUTINE	-
CD19/CD20 B-cell counts (if on rituximab)	Q3-6 months	Depleted B-cells; monitor recovery	Redose rituximab when B-cells recover and symptoms worsen	-	-	ROUTINE	-
Weight monitoring	Each clinic visit	Stable weight; no unexplained loss	Unexplained weight loss >5%: repeat cancer screening urgently	-	-	ROUTINE	-
Depression/anxiety screening (PHQ-9, GAD-7)	Each clinic visit	Minimal symptoms	Psychiatry referral; consider SSRI (safe in LEMS)	-	-	ROUTINE	-

7. DISPOSITION CRITERIA¶

Disposition	Criteria
Discharge home	Mild symptoms; stable on 3,4-DAP; adequate oral intake; no respiratory compromise (FVC >60% predicted); cancer screening plan in place; reliable follow-up within 1-2 weeks; understands return precautions
Admit to floor (general neurology)	New diagnosis requiring expedited workup; moderate proximal weakness limiting ambulation; initiating IVIg or immunotherapy; significant autonomic dysfunction requiring stabilization; new cancer diagnosis requiring coordination
Admit to step-down/telemetry	Declining FVC or NIF trending toward danger zone; moderate-severe orthostatic hypotension with syncope; starting PLEX; cardiac arrhythmias from autonomic dysfunction
Admit to ICU	FVC <30% predicted or <1 L; NIF weaker than -25 cm H2O; progressive respiratory failure; severe autonomic instability (symptomatic bradycardia, sustained hypotension); concurrent SCLC with acute complications; myasthenic crisis-like presentation
Transfer to higher level	Neuromuscular specialist not available; PLEX needed but unavailable; ICU capability needed; oncology expertise needed for SCLC management
Discharge from hospital	FVC stable and improving; adequate oral intake; stable on oral medications; cancer screening/treatment plan in place; outpatient follow-up scheduled within 1-2 weeks; patient and family educated on LEMS management and cancer screening importance

8. EVIDENCE & REFERENCES¶

Recommendation	Evidence Level	Source
P/Q-type VGCC antibodies diagnostic for LEMS (~85-90% sensitivity)	Class I	Lennon VA et al. N Engl J Med 1995; 332:1467-1474
LEMS association with SCLC (~60% paraneoplastic)	Class II	Titulaer MJ et al. J Clin Oncol 2011; 29:902-908
DELTA-P score for paraneoplastic risk stratification	Class II	Titulaer MJ et al. J Neurol Neurosurg Psychiatry 2011; 82:1222-1228
SOX1 antibody as SCLC biomarker in LEMS (~64% sensitivity)	Class II	Titulaer MJ et al. J Neuroimmunol 2009; 210:78-82
Repetitive nerve stimulation: >100% increment at high-rate diagnostic for presynaptic NMJ disorder	Class I	Oh SJ et al. Muscle Nerve 2005; 32:549-556
Low resting CMAP amplitudes as hallmark of LEMS	Class I	Sanders DB. Ann N Y Acad Sci 2003; 998:500-508
Post-exercise facilitation (>100% CMAP increment) equivalent to high-rate RNS	Class II	Oh SJ et al. Muscle Nerve 2005; 32:549-556
3,4-Diaminopyridine as first-line symptomatic treatment for LEMS	Class I, Level A	Wirtz PW et al. Neurology 2009; 73:1849-1854
3,4-DAP improves strength and autonomic symptoms in LEMS (randomized controlled trial)	Class I	Oh SJ et al. Muscle Nerve 2009; 40:795-800
Amifampridine (Firdapse) FDA approval for LEMS	Regulatory	FDA approval November 2018; NDA 208078
Pyridostigmine as adjunctive therapy in LEMS (less effective than in MG)	Class III	Tim RW, Sanders DB. Semin Neurol 2004; 24:49-57
IVIg effective for LEMS acute exacerbation	Class I	Bain PG et al. J Neurol Neurosurg Psychiatry 1996; 61:510-515
Plasma exchange for LEMS exacerbation	Class II	Newsom-Davis J, Murray NM. Neurology 1984; 34:480-485
Cancer treatment improves neurological symptoms in P-LEMS	Class II	Chalk CH et al. Neurology 1990; 40:1644-1645
Cancer screening every 6 months for 2 years in LEMS	Consensus	Titulaer MJ et al. J Neurol Neurosurg Psychiatry 2011; 82:1222-1228
PET/CT more sensitive than CT alone for detecting occult SCLC in LEMS	Class II	Titulaer MJ et al. Chest 2011; 139:1187-1193
Azathioprine as steroid-sparing agent in autoimmune LEMS	Class III	Newsom-Davis J. Muscle Nerve 1998; 21:1762-1768
Rituximab for refractory autoimmune LEMS (case series)	Class IV	Maddison P et al. Neurology 2011; 76:474-476
Lambert sign (post-exercise facilitation of reflexes) as clinical hallmark	Class II	Lambert EH, Eaton LM, Rooke ED. Am J Physiol 1956; 187:612-613
Autonomic dysfunction in LEMS (dry mouth, constipation, erectile dysfunction)	Class II	O'Neill JH et al. Brain 1988; 111:577-596
EFNS/PNS guidelines for LEMS management	Consensus	Titulaer MJ et al. Eur J Neurol 2011; 18:486-490
Immune checkpoint inhibitors may worsen paraneoplastic syndromes	Class III	Guidon AC et al. Neurology 2021; 97:e234-e245
Calcium channel blockers particularly dangerous in LEMS (direct pathophysiologic antagonism)	Class III	Sanders DB et al. Neurology 2000; 54:2163-2167
Neuromuscular blocking agent sensitivity in LEMS (1/10 normal dose)	Class II	Baraka A. Can J Anaesth 1992; 39:817-819
FVC and NIF monitoring for respiratory assessment in neuromuscular disease	Class I, Level B	Thomas CE et al. Neurology 1997; 48:1253-1260
Midodrine for orthostatic hypotension management	Class I	Low PA et al. JAMA 1997; 277:1046-1051
3,4-DAP seizure risk and QTc monitoring requirement	Class II	FDA prescribing information for Firdapse (amifampridine) 2018

CHANGE LOG¶

v1.1 (January 30, 2026) - Standardized all treatment table dosing to structured 4-field format: [dose] :: [route] :: [frequency] :: [full_instructions] - Fixed PLEX route from "-" to "IV" in sections 3A and 3C (enables order sentence generation) - Eliminated cross-references in Ruzurgi row ("Same as Firdapse") -- each row now self-contained with full contraindications, monitoring, and indication - Merged Section 3E (Cancer-Directed Treatment) into Section 3D with Pre-Treatment Requirements column for consistency with standard 3A-3D structure - Cleaned medication names in Treatment column (removed parenthetical descriptors from column, moved to Indication) - Fixed dose-tier listings (e.g., "5 mg TID; 10 mg TID; 15 mg TID") to single starting dose in structured format with titration in full_instructions field

v1.0 (January 30, 2026) - Initial creation - Section 1: 43 laboratory tests across 3 tiers (16 core, 19 extended, 8 rare/specialized) - P/Q-type VGCC antibody, SOX1 antibody, N-type VGCC as core diagnostics - Comprehensive paraneoplastic antibody panel (ANNA-1, CRMP-5, amphiphysin, Zic4) - Tumor markers (NSE, ProGRP, CEA, PSA) for malignancy screening - Section 2: Imaging and studies across 4 tiers plus bedside tests - 2A: CT chest, CXR, PET/CT, ECG as essential - 2B: RNS (low-rate and high-rate), post-exercise facilitation, baseline CMAP, EMG/NCS, SFEMG, autonomic testing - 2C: Cancer screening protocol (serial CT, PET/CT, bronchoscopy, mammography, colonoscopy) - 2D: Bedside tests (Lambert sign, proximal strength, grip, FVC, NIF, orthostatic vitals, pupillary exam, dry mouth) - Section 3: Treatment across 4 subsections - 3A: Acute/emergent (IVIg, PLEX, IV fluids) - 3B: Symptomatic (3,4-DAP/amifampridine, pyridostigmine, midodrine, fludrocortisone, GI treatments, artificial tears/saliva, sildenafil) - 3C: Second-line (prednisone, maintenance IVIg, maintenance PLEX) - 3D: Disease-modifying/immunosuppressive + cancer-directed (azathioprine, mycophenolate, rituximab, cyclosporine, cyclophosphamide, chemotherapy, radiation, checkpoint inhibitors) with Pre-Treatment Requirements - Section 4: Recommendations across 4 subsections - 4A: 17 referrals including oncology, smoking cessation, palliative care - 4B: 18 patient instructions with cancer screening emphasis - 4C: 13 lifestyle modifications including orthostatic management - 4D: Medications to avoid table organized by drug class with LEMS-specific risks - Section 5: 14 differential diagnoses including MG, botulism, inflammatory myopathies, CIDP, ALS - Section 6: Monitoring parameters - 6A: 12 acute monitoring parameters - 6B: 17 chronic monitoring parameters including cancer screening schedule - Section 7: Disposition criteria (6 levels) - Section 8: 28 evidence citations - DELTA-P score reference table included - LEMS-specific medication avoidance table (calcium channel blockers highlighted as particularly dangerous)