369.4 ð ç« æ«éèš Summary
369.4.1 ð äžå¥è©±çžœçµ
Weakness = loss of muscle strength; distinguish from fatigue/asthenia/deconditioning; localize along motor pathway â (1) UMN cortex/internal capsule/brainstem/spinal cord (spasticity + hyperreflexia + Babinski + minimal atrophy + no fasciculations); (2) LMN anterior horn cell + nerve root + plexus + peripheral nerve (flaccid + hyporeflexia + early atrophy + fasciculations + downgoing plantar); (3) NMJ (fatigable normal reflexes); (4) Muscle myopathy (proximal symmetric + â CK + normal reflexes early); mixed UMN + LMN in ALS (anterior horn + corticospinal), cervical spondylosis (UMN below + LMN at level), subacute combined degeneration B12, HTLV-1 myelopathy; distribution clues â hemiparesis (cortical/subcortical stroke, internal capsule lacune, brainstem with crossed signs, spinal cord Brown-Séquard); paraparesis (spinal cord thoracolumbar level + cauda equina + parasagittal); quadriparesis (high cervical above C5 + brainstem + diffuse); distal symmetric (peripheral neuropathy, length-dependent feet first); proximal symmetric (myopathy + CIDP/AIDP + NMJ); asymmetric/multifocal (mononeuritis multiplex vasculitis/DM/HIV/leprosy + multifocal motor neuropathy + polyradiculopathy); cranial/bulbar (NMJ MG + brainstem stroke + bulbar-onset ALS + cranial neuropathies); time course â sudden (stroke + spinal cord trauma/infarct + hypokalemic periodic paralysis + transverse myelitis), hours-days (GBS ascending areflexia after URI/GI Campylobacter + tick paralysis + botulism descending bulbar + diphtheria + periodic paralysis), days-weeks (MG fatigable + polymyositis/DM â CK + CIDP + vasculitic neuropathy + hypothyroid myopathy + drug-induced steroid/statin), months-years (ALS combined UMN+LMN no sensory + muscular dystrophies + MS + hereditary neuropathies CMT + spinal cord compression); MRC strength grading 0-5; workup â EMG/NCS (key for localization) + CK + electrolytes (K+, Mg2+) + TSH + B12 + autoimmune panels (ANA, anti-Jo-1, anti-AChR, anti-MuSK, anti-VGCC, anti-HMG-CoA reductase) + paraneoplastic + MRI brain/cord/plexus/muscle + LP/CSF (GBS, CIDP) + muscle/nerve biopsy + genetic testing; MG details â fatigable weakness ocular/bulbar/generalized + AChR antibodies (85%)/MuSK (5-10%)/seronegative + RNS decremental + ice pack test + pyridostigmine + immunosuppression + thymectomy; MG newer therapies 2021-2024: efgartigimod Vyvgart (FcRn) + rozanolixizumab Rystiggo + zilucoplan Zilbrysq (C5) + ravulizumab Ultomiris (C5); LEMS: proximal weakness improves with use + autonomic + VGCC antibodies + paraneoplastic SCLC + 3,4-DAP + IVIG; GBS: ascending + areflexia + albuminocytologic dissociation + IVIG or plasma exchange (NOT steroids) + monitor respiratory; polymyositis/dermatomyositis: proximal + â CK + anti-Jo-1 + DM skin (heliotrope, Gottron) + cancer risk in DM + steroids + IS; periodic paralysis (hypokalemic most common AD + hyperkalemic + Andersen-Tawil + thyrotoxic in Asian males with hyperthyroidism) + acetazolamide; AFM (acute flaccid myelitis): pediatric enterovirus D68/A71 + asymmetric flaccid + polio-likeã
369.4.2 ð æ²»çç²ŸèŠ (è©³èŠ Ch383 ç¥ç¶èè chapter)
- GBSïŒIVIG 0.4 g/kg/d à 5 days OR plasma exchange (5 sessions) â equivalent efficacy; NOT steroids (no benefit, may harm); respiratory monitoring NIF + FVC + early intubation if FVC < 15-20 mL/kg
- MGïŒpyridostigmine 30-90 mg q4-6h symptomatic + immunosuppression (prednisone, azathioprine, mycophenolate) + thymectomy (especially with thymoma, generalized); newer therapies â efgartigimod (FcRn) + rozanolixizumab (FcRn) + zilucoplan (C5) + ravulizumab (C5) + eculizumab (C5) for refractory/severe; MG crisis IVIG or plasma exchange
- LEMSïŒ3,4-diaminopyridine (amifampridine) Firdapse FDA 2018 + IVIG + immunosuppression + treat underlying SCLC (paraneoplastic)
- ALSïŒriluzole 50 mg BID (modest survival benefit) + edaravone (Radicava) IV/oral + tofersen (Qalsody) SOD1 ASO FDA 2023 for SOD1-associated; supportive (NIV, PEG, multidisciplinary)
- polymyositis/dermatomyositisïŒprednisone 1 mg/kg/d + azathioprine + mycophenolate + methotrexate + IVIG for refractory + rituximab + cancer screening in DM
- periodic paralysisïŒacetazolamide 125-1000 mg/d + dietary management + KCl PO for hypokalemic + avoid triggers + treat thyrotoxic
- rhabdomyolysisïŒaggressive IV fluids (NS or LR) target urine output 200-300 mL/h + alkalinization controversial + treat underlying
369.4.3 ð¯ ç§é«åž«çèåæé
- Localize before etiology: UMN (spastic + hyperreflexia + Babinski + minimal atrophy) vs LMN (flaccid + hyporeflexia + early atrophy + fasciculations) vs NMJ (fatigable) vs Muscle (proximal symmetric + â CK)
- Mixed UMN + LMN key DDx: ALS (anterior horn cell + corticospinal tract â no sensory, no autonomic) + cervical spondylosis (UMN below + LMN at level) + subacute combined degeneration B12 (corticospinal + posterior column + peripheral nerve) + HTLV-1 myelopathy
- Distribution clues: hemi (brain) + para (spinal) + quad (high cervical) + distal symmetric (peripheral neuropathy â length-dependent feet first) + proximal symmetric (myopathy) + asymmetric multifocal (mononeuritis multiplex â vasculitis, DM, HIV, leprosy)
- Time course: sudden = stroke/spinal cord trauma, hours-days = GBS (ascending + areflexia + after Campylobacter URI/GI), days-weeks = MG (fatigable)/polymyositis/DM, months-years = ALS/MD/MS/spinal cord compression
- GBS treatment: IVIG or plasma exchange (equivalent) â NOT steroids (no benefit, may worsen); albuminocytologic dissociation in CSF; monitor respiratory NIF/FVC, intubate if FVC < 15-20 mL/kg
- MG features + treatment: fatigable weakness ocular/bulbar/generalized + AChR antibodies (85%)/MuSK (5-10%) + RNS decremental + pyridostigmine + immunosuppression + thymectomy; MG newer therapies 2021-2024 efgartigimod/rozanolixizumab/zilucoplan/ravulizumab
- LEMS: proximal weakness improves with use (opposite of MG!) + autonomic (dry mouth) + VGCC antibodies + paraneoplastic SCLC in 50%+ â 3,4-DAP + IVIG + cancer treatment
- ALS: combined UMN + LMN + no sensory + no autonomic + no cognitive (most) â riluzole + edaravone + tofersen FDA 2023 for SOD1
- Polymyositis/DM: proximal symmetric + â CK + anti-Jo-1 (and other anti-synthetase); DM has heliotrope + Gottron + cancer risk (especially ovarian, lung, GI) â steroids + IS + cancer screening
- Periodic paralysis: episodic flaccid weakness + triggers (carbs/exercise/stress) + hypokalemic (most common AD) or hyperkalemic or thyrotoxic (Asian males with hyperthyroidism) â acetazolamide + dietary + treat thyrotoxic underlying