Neuromuscular Pharmacology
Neuromuscular Pharmacology
What Do You Need to Know?
- MG pharmacotherapy — pyridostigmine (symptomatic), prednisone (may initially worsen), steroid-sparing agents, complement inhibitors (eculizumab), FcRn inhibitors (efgartigimod)
- Myasthenic crisis — ICU monitoring, IVIG or PLEX; 20/30/40 rule: FVC <20 mL/kg, NIF |<30| cmH2O (i.e., not more negative than −30), MEP <40 cmH2O — intubate; avoid aminoglycosides/fluoroquinolones/magnesium
- Drugs that worsen MG — aminoglycosides, fluoroquinolones, magnesium, beta-blockers, checkpoint inhibitors, telithromycin, D-penicillamine
- Lambert-Eaton — 3,4-DAP (amifampridine) first-line; pyridostigmine less effective; treat underlying malignancy
- Botulinum toxin — cleaves SNARE/SNAP-25, onset 3–7 days, duration ~3 months; used for dystonia, spasticity, chronic migraine, sialorrhea
- NMJ blockers — succinylcholine (depolarizing, hyperkalemia risk) vs rocuronium/vecuronium (nondepolarizing, reversed by sugammadex)
- Inflammatory myopathy Rx — prednisone first-line, steroid-sparing agents, IVIG (especially dermatomyositis); IBM has limited treatment response
- Neuropathy treatments — CIDP (IVIG/PLEX/steroids), GBS (IVIG or PLEX — steroids NOT effective), neuropathic pain (duloxetine, pregabalin)
🚩 Don’t Miss — Test-Day Priorities
- Pyridostigmine in MuSK MG: often poorly tolerated / less effective — cholinergic hypersensitivity is the classic clue; immunotherapy (rituximab) is the actual workhorse.
- Cholinergic crisis vs myasthenic crisis: excess pyridostigmine produces SLUDGE-M + fasciculations + miosis; edrophonium worsens cholinergic crisis — clinical context (recent dose, secretions) distinguishes.
- Steroid-induced MG worsening: high-dose prednisone can transiently worsen MG in ~10–20% — bridge with IVIG or PLEX before starting in moderate-severe disease.
- Eculizumab / ravulizumab / zilucoplan: meningococcal vaccination is MANDATORY ≥2 weeks before initiation — failure to vaccinate is a board-favorite error.
- Azathioprine + TPMT: check TPMT activity BEFORE starting — deficient patients develop life-threatening myelosuppression.
- Mycophenolate & methotrexate: both teratogenic — pregnancy is an absolute contraindication; counsel on contraception.
- Drugs to AVOID in MG: aminoglycosides, fluoroquinolones, telithromycin (black-box), IV magnesium, β-blockers, immune checkpoint inhibitors (ICI-induced myasthenia/myocarditis/myositis overlap carries high mortality).
- 3,4-DAP (amifampridine) for LEMS: first-line — blocks presynaptic voltage-gated K⁺ channels → prolongs AP → ↑ Ca²⁺ influx → ↑ ACh release.
- Tofersen: ONLY for SOD1-mutant ALS — intrathecal antisense oligonucleotide; not for sporadic ALS.
- Deflazacort vs prednisone in DMD — less weight gain and behavioral effects, but MORE cataracts (monitor eyes); standard of care alongside exon-skipping ASOs (eteplirsen-51, golodirsen/viltolarsen-53, casimersen-45).
- IVIG in IgA-deficient patients: risk of anaphylaxis — use IgA-depleted product; also watch for thromboembolism, aseptic meningitis, headache.
🔍 Buzzwords & Pathognomonic FindingsMechanism · Adverse effects · Use / monitoring
Mechanism
- Pyridostigmine / neostigmine / edrophonium → reversible AChE inhibitor — ↑ ACh at NMJ
- Azathioprine → purine synthesis inhibitor (6-MP prodrug)
- Mycophenolate mofetil → IMPDH inhibitor — blocks de novo purine synthesis in lymphocytes
- Methotrexate → dihydrofolate reductase inhibitor (folate antagonist)
- Cyclosporine / tacrolimus → calcineurin inhibitors — block IL-2 transcription
- Rituximab → anti-CD20 mAb — B-cell depletion
- Eculizumab / ravulizumab / zilucoplan → terminal complement (C5) inhibitors — block MAC assembly
- Efgartigimod / rozanolixizumab → FcRn antagonists — accelerate IgG catabolism
- 3,4-DAP (amifampridine / Firdapse) → presynaptic voltage-gated K⁺ channel blocker → ↑ ACh release
- Riluzole → glutamate release inhibitor / Na⁺ channel blocker
- Edaravone → free-radical scavenger (oxidative stress in ALS)
- Tofersen → SOD1 antisense oligonucleotide (intrathecal)
- Nusinersen / risdiplam → SMN2 splicing modifiers (SMA); onasemnogene abeparvovec (Zolgensma) → AAV9 SMN1 gene replacement
- Eteplirsen / golodirsen / viltolarsen / casimersen → exon-skipping ASOs (DMD exons 51, 53, 53, 45); delandistrogene moxeparvovec (Elevidys) → AAV micro-dystrophin gene therapy for AMBULATORY DMD only; 2025 FDA boxed warning for acute serious liver injury / acute liver failure; ataluren → nonsense-mutation readthrough — NOT FDA-approved; EU conditional marketing authorization NOT renewed in March 2025 (historical / non-US)
Adverse effects
- SLUDGE-M + fasciculations + miosis → cholinergic crisis (pyridostigmine excess)
- Myelosuppression in TPMT-deficient patient → azathioprine
- Teratogenicity / pregnancy contraindication → mycophenolate, methotrexate
- Pulmonary fibrosis + hepatotoxicity → methotrexate (give folic acid; leucovorin rescue)
- PRES + nephrotoxicity + HTN + tremor + gingival hyperplasia / hirsutism → cyclosporine / tacrolimus (calcineurin inhibitors)
- Meningococcal sepsis risk → eculizumab / ravulizumab / zilucoplan (vaccinate first)
- Hepatitis B reactivation + PML (rare) → rituximab
- Anaphylaxis in IgA deficiency + thromboembolism + aseptic meningitis → IVIG
- Hypotension + coagulopathy + citrate-related hypocalcemia → PLEX
- LFT elevation → riluzole (monitor transaminases)
- Chronic corticosteroids in DMD → weight gain (less with deflazacort vs prednisone) but MORE cataracts with deflazacort — monitor eyes
- Myasthenia + myocarditis + myositis overlap (high mortality) → immune checkpoint inhibitor irAE
Use / monitoring / drug-to-avoid
- First-line symptomatic MG → pyridostigmine (less useful in MuSK MG)
- First-line LEMS → 3,4-DAP / amifampridine (Firdapse)
- Refractory AChR-positive generalized MG → eculizumab / ravulizumab / zilucoplan or efgartigimod / rozanolixizumab
- MuSK-positive MG, refractory AChR MG, NMOSD, PCNSV → rituximab
- MG crisis → IVIG or PLEX (steroids may transiently worsen; bridge first)
- GBS → IVIG or PLEX (steroids NOT effective)
- CIDP → IVIG, PLEX, or steroids (efgartigimod SC now approved)
- Drugs that worsen MG (AVOID): aminoglycosides, fluoroquinolones, telithromycin (black-box), macrolides (caution), IV magnesium, β-blockers, CCBs, lithium, procainamide, quinine/quinidine, D-penicillamine, ICIs
- Pre-azathioprine → check TPMT activity; monitor CBC + LFTs
- Pre-eculizumab → meningococcal vaccine ≥2 weeks prior (± prophylactic antibiotics)
- SOD1-mutant familial ALS → tofersen (intrathecal) — not for sporadic ALS
- ALS disease-modifying → riluzole (oral) + edaravone (IV/oral cycles)
- DMD standard of care → deflazacort (preferred) ± mutation-specific exon-skipping ASO ± AAV gene therapy
- SMA infants <2 yr → onasemnogene abeparvovec (single IV dose); nusinersen (intrathecal) or risdiplam (oral) for ongoing therapy
- Inflammatory myopathies (DM/PM/IMNM) → steroids first-line + IVIG (esp. dermatomyositis) + MTX/AZA/MMF steroid-sparing; rituximab refractory; IBM → poor response to immunotherapy
- Neonatal transient MG → supportive care ± temporary AChEI / PLEX
Myasthenia Gravis Pharmacology
Overview of MG Treatments
| Drug | Class / Mechanism | Role | Key Considerations |
|---|---|---|---|
| Pyridostigmine | AChE inhibitor — increases ACh at NMJ | First-line symptomatic therapy | Cholinergic side effects (diarrhea, cramping, salivation); less effective in MuSK-positive MG |
| Prednisone | Corticosteroid | First-line immunotherapy for moderate–severe MG | Initial worsening in ~10–20% (higher with rapid high-dose initiation); start low, go slow; long-term side effects require steroid-sparing agents |
| Azathioprine | Purine synthesis inhibitor | Steroid-sparing; onset 6–12 months | Check TPMT before starting; risk of myelosuppression |
| Mycophenolate | IMPDH inhibitor | Steroid-sparing; onset 6–12 months | GI side effects; teratogenic; RCTs negative but widely used |
| Rituximab | Anti-CD20 — B-cell depletion | Refractory MG; especially effective in MuSK-positive MG | Screen for hepatitis B; risk of PML (rare) |
| Eculizumab / Ravulizumab | Terminal complement (C5) inhibitor | Refractory generalized AChR-positive MG | Must vaccinate against Neisseria meningitidis before starting |
| Efgartigimod | FcRn inhibitor — accelerates IgG degradation; lowers IgG but does NOT affect IgM or IgA (selective class effect) | Generalized AChR-positive MG | Reduces total IgG levels; cyclic dosing (4 weekly infusions per cycle) |
| Efgartigimod SC (Vyvgart Hytrulo) | FcRn inhibitor — SC formulation with hyaluronidase | Generalized AChR-positive MG; also CIDP indication (FDA 2024) | SC alternative to IV efgartigimod; same MOA |
| Rozanolixizumab (Rystiggo) | FcRn inhibitor — SC | AChR+ AND MuSK+ generalized MG (FDA 2023) | First FcRn inhibitor approved for MuSK-positive disease |
| Zilucoplan (Zilbrysq) | SC daily anti-C5 peptide (complement inhibitor) | AChR-positive generalized MG (FDA 2023) | Self-administered SC daily; meningococcal vaccination required |
| IVIG | Pooled immunoglobulins | Acute exacerbations, crisis, pre-thymectomy | Check IgA level (anaphylaxis risk in IgA deficiency) |
| Plasmapheresis (PLEX) | Removes circulating antibodies | Myasthenic crisis, rapid stabilization | Requires central access; effects are temporary |
Thymectomy
- Indicated for: thymoma (regardless of MG severity) and non-thymomatous generalized AChR-positive MG (MGTX trial)
- Less beneficial in: MuSK-positive MG, late-onset MG (>50 years), purely ocular MG
Board Pearl
Eculizumab requires meningococcal vaccination before initiation. It blocks terminal complement (C5), which is also the defense against Neisseria. Efgartigimod works by blocking FcRn, which normally recycles IgG — blocking it accelerates IgG catabolism, lowering pathogenic antibody levels. FcRn inhibitors selectively lower IgG; they do NOT affect IgM or IgA — an increasingly board-relevant distinction.
Myasthenic Crisis Management
Approach to Crisis
- Definition: MG exacerbation with respiratory failure requiring intubation or noninvasive ventilation
- Monitoring: serial FVC and NIF every 2–4 hours
- 20/30/40 rule: FVC <20 mL/kg, NIF |<30| cmH2O (i.e., not more negative than −30), MEP <40 cmH2O — intubate
- Treatment: IVIG (0.4 g/kg/day × 5 days) or PLEX (5 exchanges) — equally effective
- Hold pyridostigmine initially (excess secretions complicate airway management)
- Identify triggers: infection (#1), medication changes, surgery
- Distinguish from cholinergic crisis (excess AChE inhibitor) — salivation, diarrhea, miosis, bradycardia
Board Pearl
In myasthenic crisis, follow FVC, not oxygen saturation. SpO2 drops late in neuromuscular respiratory failure. FVC <20 mL/kg is the key threshold. Infection is the #1 trigger for crisis.
Drugs That Worsen Myasthenia Gravis
| Drug / Class | Mechanism of NMJ Impairment | Clinical Note |
|---|---|---|
| Aminoglycosides | Block presynaptic Ca²⁺ channels and postsynaptic AChR | Most dangerous antibiotic class in MG; can precipitate crisis |
| Fluoroquinolones | Pre- and postsynaptic NMJ blockade | FDA black box warning for MG exacerbation |
| Telithromycin | NMJ blockade (mechanism not fully elucidated) | Boxed warning; contraindicated in MG; fatal cases reported |
| Magnesium (IV) | Competes with Ca²⁺ at presynaptic terminal | Avoid IV magnesium; caution with oral supplementation |
| Beta-blockers | Impair NMJ transmission | Ophthalmic beta-blockers (timolol) also worsen MG |
| Procainamide, quinidine, quinine | Class Ia antiarrhythmics — block NMJ ion channels | Established MG-worsening drugs; avoid |
| Lithium | Substitutes for Na/K at NMJ; impairs ACh release | Can unmask or worsen MG |
| Statins (rare) | May unmask or worsen MG (mechanism unclear) | Rare; do not withhold if clinically indicated, but monitor |
| Calcium channel blockers (caution) | Reduce Ca²⁺ influx at presynaptic terminal | Caution only (not strict avoidance); verapamil/diltiazem > dihydropyridines |
| D-Penicillamine | Induces autoimmune MG (anti-AChR antibodies) | Drug-induced MG; usually reversible after discontinuation |
| Checkpoint inhibitors | Immune dysregulation → de novo or unmasked MG | PD-1/PD-L1 (pembrolizumab, nivolumab) and CTLA-4 (ipilimumab) can trigger MG + myositis + myocarditis (often overlap); high mortality |
| Botulinum toxin | Blocks presynaptic ACh release (SNARE cleavage) | Relative contraindication; systemic spread risk |
| Neuromuscular blockers | Direct NMJ blockade | MG patients exquisitely sensitive to nondepolarizing agents |
Board Pearl
Telithromycin is absolutely contraindicated in MG — fatal respiratory failure reported even with a single dose. D-penicillamine causes drug-induced MG with positive AChR antibodies. Checkpoint inhibitors can cause a devastating triad of MG + myositis + myocarditis.
Lambert-Eaton Myasthenic Syndrome Treatment
Pharmacotherapy
- 3,4-Diaminopyridine (amifampridine): first-line; blocks presynaptic K⁺ channels → prolongs AP → increased Ca²⁺ influx → more ACh release (Firdapse — amifampridine phosphate, FDA-approved 2018; Ruzurgi previously approved for pediatrics, withdrawn)
- Pyridostigmine: modest benefit; less effective than in MG (presynaptic defect = reduced ACh release)
- Immunotherapy: prednisone, azathioprine, IVIG, or PLEX for refractory cases
- Treat underlying malignancy: ~60% associated with SCLC; tumor treatment often improves LEMS
- Cancer screening: CT chest (with FDG-PET if negative) every 3–6 months for 2 years (per Titulaer/DELTA-P)
Clinical Pearl
3,4-DAP prolongs the presynaptic action potential, allowing more Ca²⁺ entry through antibody-reduced P/Q-type channels. It directly addresses LEMS pathophysiology. Seizures are the main dose-limiting side effect.
Botulinum Toxin
Formulations
| Product | Type | SNARE Target | Key Note |
|---|---|---|---|
| OnabotulinumtoxinA (Botox) | Type A | SNAP-25 | Most widely used; doses NOT interchangeable between products |
| AbobotulinumtoxinA (Dysport) | Type A | SNAP-25 | Higher unit ratio vs onabotulinum (~2.5–3:1) |
| IncobotulinumtoxinA (Xeomin) | Type A | SNAP-25 | Free of complexing proteins; lower immunogenicity |
| PrabotulinumtoxinA (Jeuveau) | Type A | SNAP-25 | Cosmetic glabellar lines only |
| DaxibotulinumtoxinA (Daxxify) | Type A | SNAP-25 | Longer duration (~6 months) via peptide excipient |
| RimabotulinumtoxinB (Myobloc) | Type B | Synaptobrevin (VAMP) | Used for type A–resistant dystonia; more dry mouth |
Mechanism, Pharmacokinetics, and Indications
- Mechanism: internalized into presynaptic terminal → light chain cleaves SNARE proteins → blocks vesicle fusion → no ACh release
- Onset: 3–7 days (up to 2 weeks for full effect); Duration: ~3 months (axonal sprouting restores transmission)
- Resistance: neutralizing antibodies develop with frequent/high-dose injections; switch to type B or Xeomin
- Dystonia: cervical dystonia (first-line), blepharospasm, limb and laryngeal dystonia
- Spasticity: focal spasticity in stroke, MS, TBI, cerebral palsy
- Chronic migraine (PREEMPT protocol): onabotulinumtoxinA; ≥15 headache days/month; 155 units total (31 fixed sites in 7 muscles); optional follow-the-pain up to 195 U
- Sialorrhea: ALS, Parkinson disease; injected into parotid and submandibular glands
Board Pearl
Botulinum toxin type A cleaves SNAP-25; type B cleaves synaptobrevin. Doses are NOT interchangeable between formulations. IncobotulinumtoxinA (Xeomin) lacks complexing proteins and may have lower immunogenicity. Use type B (Myobloc) for patients with antibody resistance to type A.
Neuromuscular Junction Blockers
Depolarizing vs Nondepolarizing Agents
| Feature | Depolarizing (Succinylcholine) | Nondepolarizing (Rocuronium, Vecuronium) |
|---|---|---|
| Mechanism | Persistent depolarization → desensitization block | Competitive antagonist at AChR |
| Phase I block | Fasciculations → paralysis; no fade on train-of-four | N/A |
| Phase II block | Prolonged exposure → fade on train-of-four (resembles nondepolarizing) | N/A |
| Onset / Duration | Rapid (30–60 sec); ultrashort (5–10 min) | 1–3 min onset; intermediate (30–60 min) |
| Metabolism | Plasma cholinesterase (pseudocholinesterase) | Hepatic (vecuronium); hepatic + renal (rocuronium) |
| Reversal | No reversal agent (wait for metabolism) | Sugammadex (encapsulates drug); neostigmine + glycopyrrolate |
| Major risks | Hyperkalemia (burns, denervation); malignant hyperthermia (RYR1) | Prolonged block in MG; residual paralysis |
Succinylcholine Contraindications
- Burns (after 24–48 hours through ~1 year) — upregulation of extrajunctional AChR → massive K⁺ release
- Denervation injuries (stroke, SCI, GBS) — same mechanism; avoid after 48–72 hours
- Malignant hyperthermia susceptibility — uncontrolled Ca²⁺ release from SR via RYR1; treat with dantrolene
- Pseudocholinesterase deficiency — prolonged paralysis (hours instead of minutes)
- Hyperkalemia at baseline — succinylcholine raises K⁺ by 0.5–1.0 mEq/L
Clinical Pearl
MG patients are relatively resistant to succinylcholine (fewer functional AChR) but exquisitely sensitive to nondepolarizing agents — use 1/10th to 1/5th of the normal dose. Sugammadex rapidly reverses rocuronium and is the preferred reversal agent.
Inflammatory Myopathy Treatment
Treatment by Myopathy Type
| Myopathy | First-Line | Second-Line / Steroid-Sparing | Key Notes |
|---|---|---|---|
| Dermatomyositis | Prednisone (1 mg/kg/day) | Methotrexate, azathioprine, mycophenolate, IVIG, rituximab | IVIG has best evidence for refractory DM; screen for malignancy |
| Polymyositis | Prednisone | Methotrexate, azathioprine, mycophenolate, rituximab | Ensure not IBM misclassified as PM; check for anti-synthetase syndrome |
| IMNM | Prednisone + early steroid-sparing | IVIG, rituximab, mycophenolate | Anti-SRP or anti-HMGCR Abs; statin-triggered IMNM needs immunosuppression despite statin cessation |
| Inclusion body myositis | No proven effective treatment | IVIG may provide modest benefit | Does NOT respond to steroids; most common inflammatory myopathy >50 years |
Board Pearl
IBM does not respond to immunosuppressive therapy. If a patient >50 with asymmetric weakness (finger flexors, knee extensors) and rimmed vacuoles on biopsy is not improving on steroids, the diagnosis is IBM. Anti-HMGCR myopathy requires immunosuppression even after statin discontinuation.
Neuropathy Treatments
CIDP
- First-line options (all equivalent): IVIG, PLEX, or corticosteroids
- IVIG: 2 g/kg loading over 2–5 days, then 1 g/kg maintenance every 3–4 weeks
- Subcutaneous Ig (SCIg): alternative for maintenance; better tolerability
- Key point: unlike GBS, steroids ARE effective in CIDP
GBS
- IVIG (0.4 g/kg/day × 5 days) or PLEX (5 exchanges) — equally effective; start early
- Steroids are NOT effective in GBS — critical board distinction from CIDP
- Do NOT combine IVIG + PLEX (PLEX removes the IVIG)
- Monitor FVC closely; DVT prophylaxis; autonomic monitoring
Neuropathic Pain Pharmacotherapy
| Drug | Class | FDA Indication | Key Note |
|---|---|---|---|
| Duloxetine | SNRI | Diabetic neuropathy pain | First-line per AAN; also treats comorbid depression |
| Pregabalin | α2δ Ca²⁺ channel ligand | Diabetic neuropathy, PHN, fibromyalgia | First-line; dizziness and weight gain common |
| Gabapentin | α2δ Ca²⁺ channel ligand | Postherpetic neuralgia | Widely used off-label; renal dosing required |
| TCAs (amitriptyline) | Tricyclic antidepressant | Off-label | Anticholinergic side effects; avoid in elderly |
| Capsaicin 8% patch | TRPV1 agonist | PHN, HIV neuropathy | Applied in clinic 30–60 min; repeat every 3 months |
Clinical Pearl
Steroids work in CIDP but NOT in GBS — one of the most frequently tested distinctions on neurology boards. Both respond to IVIG and PLEX. Never combine IVIG and PLEX sequentially (PLEX removes IVIG).
ALS Pharmacotherapy
Disease-Modifying Therapy
- Riluzole — Na channel blocker, glutamate antagonist; modest survival benefit ~3 months; monitor LFTs
- Edaravone (Radicava) — free radical scavenger; IV or oral suspension (2022)
- Tofersen (Qalsody) — intrathecal antisense oligonucleotide for SOD1 ALS (FDA Apr 2023, accelerated approval)
- Relyvrio (sodium phenylbutyrate + taurursodiol) — WITHDRAWN by Amylyx in 2024 after PHOENIX trial failure
Symptomatic Therapy
- Nuedexta (dextromethorphan/quinidine) — pseudobulbar affect
- Baclofen, tizanidine — spasticity
- Glycopyrrolate, botulinum toxin — sialorrhea
- Modafinil — fatigue
Spinal Muscular Atrophy (SMA)
- Nusinersen (Spinraza) — intrathecal antisense oligonucleotide; modifies SMN2 splicing to increase functional SMN protein
- Onasemnogene abeparvovec (Zolgensma) — AAV9 SMN1 gene therapy; one-time IV infusion; <2 years/weight-based dosing; hepatotoxicity, thrombotic microangiopathy (TMA), cardiac arrhythmias
- Risdiplam (Evrysdi) — oral SMN2 splicing modifier
Duchenne / Becker Muscular Dystrophy
Corticosteroids and Dissociative Steroids
- Prednisone or deflazacort (Emflaza) — standard of care; improves strength and delays loss of ambulation
- Vamorolone (Agamree) — dissociative steroid with less growth suppression and bone toxicity (FDA 2023)
Exon-Skipping Antisense Oligonucleotides
- Eteplirsen (Exondys 51) — exon 51
- Golodirsen (Vyondys 53), viltolarsen (Viltepso) — exon 53
- Casimersen (Amondys 45) — exon 45
Gene Therapy and Other
- Delandistrogene moxeparvovec (Elevidys) — AAV micro-dystrophin gene therapy for AMBULATORY DMD ONLY with confirmed DMD mutation (FDA action Nov 14, 2025 added boxed warning for acute serious liver injury / acute liver failure and revised the indication to limit use to ambulatory DMD); the prior broad "ambulatory + non-ambulatory" label is outdated
- Givinostat (Duvyzat) — HDAC inhibitor (FDA March 2024)
- ACE inhibitors + beta-blockers — for cardiomyopathy
CIDP, MMN, POEMS, Stiff Person Syndrome
CIDP (Additional)
- IVIG (Hyqvia SC, FDA 2024 for maintenance), steroids, or PLEX first-line
- Efgartigimod SC (Vyvgart Hytrulo) FDA 2024 for CIDP
Multifocal Motor Neuropathy (MMN)
- IVIG first-line
- Steroids contraindicated — can worsen MMN
POEMS Syndrome
- Lenalidomide
- Autologous stem cell transplant (SCT)
Stiff Person Syndrome
- High-dose diazepam, baclofen
- IVIG, rituximab, PLEX
Periodic Paralyses and Myotonia
Periodic Paralyses
- Hypokalemic periodic paralysis (HypoKPP) (CACNA1S, SCN4A): acetazolamide (sometimes worsens hyperKPP), potassium during attack; avoid carbohydrate/exertion triggers
- Hyperkalemic periodic paralysis (HyperKPP) (SCN4A): dichlorphenamide (Keveyis), thiazides; avoid fasting/cold
- Dichlorphenamide (Keveyis) — FDA-approved for both hypoKPP and hyperKPP
Myotonia
- Mexiletine (Na channel blocker) — first-line
- Ranolazine; lamotrigine; quinine off-label
Friedreich Ataxia and Statin Myopathy / IMNM
Friedreich Ataxia
- Omaveloxolone (Skyclarys) — Nrf2 activator; first FDA-approved therapy for Friedreich ataxia (Feb 2023)
Statin Myopathy / Immune-Mediated Necrotizing Myopathy (IMNM)
- Anti-HMGCR antibody — autoimmune-mediated; does NOT resolve with statin discontinuation alone
- Treatment: IVIG, steroids, rituximab; stop statin
Quick Reference
High-Yield Summary Table
| Topic | Key Fact | Board Buzzword |
|---|---|---|
| MG symptomatic Rx | Pyridostigmine; less effective in MuSK-positive | Cholinergic vs myasthenic crisis |
| MG crisis | IVIG or PLEX; intubate if FVC <20 mL/kg | Follow FVC, not SpO2 |
| Drugs worsening MG | Aminoglycosides, fluoroquinolones, Mg²⁺, telithromycin | Telithromycin = absolute contraindication |
| LEMS treatment | 3,4-DAP first-line; screen for SCLC | K⁺ channel blocker → more ACh release |
| Botulinum toxin | Type A → SNAP-25; onset 3–7 days; lasts 3 months | Xeomin = no complexing proteins |
| Succinylcholine | Depolarizing; hyperkalemia in burns/denervation; MH risk | Pseudocholinesterase deficiency → prolonged block |
| Nondepolarizing agents | Rocuronium/vecuronium; reversed by sugammadex | Use 1/10th dose in MG |
| IBM treatment | No effective immunosuppressive therapy | Does NOT respond to steroids |
| GBS treatment | IVIG or PLEX; steroids NOT effective | Steroids work in CIDP, not GBS |
| Neuropathic pain | Duloxetine + pregabalin first-line per AAN | α2δ ligands; avoid TCAs in elderly |
References
- Narayanaswami P, Sanders DB, Wolfe G, et al. International Consensus Guidance for Management of Myasthenia Gravis: 2020 Update. Neurology. 2021;96(3):114–122.
- Wolfe GI, Kaminski HJ, Aban IB, et al. Randomized Trial of Thymectomy in Myasthenia Gravis (MGTX). N Engl J Med. 2016;375(6):511–522.
- Howard JF, Utsugisawa K, Benatar M, et al. Safety and efficacy of eculizumab in refractory generalised myasthenia gravis (REGAIN). Lancet Neurol. 2017;16(12):976–986.
- Howard JF, Bril V, Vu T, et al. Safety, efficacy, and tolerability of efgartigimod in generalised myasthenia gravis (ADAPT). Lancet Neurol. 2021;20(7):526–536.
- Ropper AH, Samuels MA, Klein JP, Prasad S. Adams and Victor’s Principles of Neurology. 12th ed. McGraw-Hill; 2023.
- Preston DC, Shapiro BE. Electromyography and Neuromuscular Disorders. 4th ed. Elsevier; 2021.
- Daroff RB, Jankovic J, Mazziotta JC, Pomeroy SL. Bradley and Daroff’s Neurology in Clinical Practice. 8th ed. Elsevier; 2022.
- Dalakas MC. Inflammatory muscle diseases. N Engl J Med. 2015;372(18):1734–1747.
- Bril V, England JD, Franklin GM, et al. Evidence-based guideline: Treatment of painful diabetic neuropathy. Neurology. 2011;76(20):1758–1765.
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