380.4 📋 章末速蚘 Summary

380.4.1 🔑 䞀句話瞜結

Parkinson disease (PD) = 2nd most common neurodegenerative (after AD), ~ 1% > 60 yo, 5% > 85, mean onset 60; clinical hallmark TRAP — Tremor (rest, asymmetric, pill-rolling 4-6 Hz) + Rigidity (cogwheel) + Akinesia/Bradykinesia (slowness + decreased amplitude + decreased automatic movements arm swing/blinking + masked facies + micrographia + hypophonia + festinating gait) + Postural instability (later — falls); non-motor features critical — REM behavior disorder (RBD prodromal — 80% develop synucleinopathy within 15 yr) + hyposmia (very early) + constipation + orthostatic hypotension + urinary urgency + sexual dysfunction + sialorrhea + depression + anxiety + cognitive decline (MCI → PD dementia ~ 80% over time) + ICDs with DA agonists (gambling, hypersexuality, eating, shopping) + psychosis + sleep disorders + pain + fatigue; pathology α-synuclein aggregation (Lewy bodies) + loss of dopaminergic neurons in substantia nigra pars compacta + Braak staging (lower brainstem → midbrain → cortex); MDS clinical diagnostic criteria 2015: bradykinesia + (rest tremor or rigidity) + supportive (good levodopa response, levodopa-induced dyskinesia, rest tremor of limb, MIBG-cardiac sympathetic denervation) + no absolute exclusion + no red flags for atypical parkinsonism; red flags atypical parkinsonism (rapid progression + early falls < 1 yr + severe autonomic failure + severe bulbar dysfunction + inspiratory stridor + cerebellar signs + supranuclear gaze palsy + symmetric onset + poor levodopa response); DaT-SCAN (123I-FP-CIT SPECT) abnormal in PD/MSA/PSP/DLB + normal in essential tremor/vascular parkinsonism/drug-induced/psychogenic; emerging biomarkers — skin biopsy phosphorylated α-synuclein in peripheral nerves + CSF/plasma α-synuclein RT-QuIC; treatment — levodopa/carbidopa (Sinemet) GOLD STANDARD + dopamine agonists pramipexole (Mirapex) + ropinirole (Requip) + rotigotine patch (Neupro) + apomorphine SC rescue (ICDs warn!) + MAO-B inhibitors selegiline + rasagiline (Azilect) + safinamide (Xadago glutamate modulator) + COMT inhibitors entacapone (with each levodopa) + opicapone (Ongentys once daily FDA 2020) + amantadine (reduces dyskinesias, ER Gocovri FDA-approved) + anticholinergics (trihexyphenidyl, benztropine — limited use cognitive SEs); non-motor treatment — rivastigmine FDA-approved for PD dementia + pimavanserin (Nuplazid) selective 5HT-2A inverse agonist FDA-approved for PD psychosis + quetiapine/clozapine (AVOID typical antipsychotics) + SSRIs/SNRIs/TCAs depression + droxidopa (Northera) for orthostatic hypotension + midodrine + pyridostigmine + botulinum toxin sialorrhea + melatonin/clonazepam RBD + fiber/laxatives/lubiprostone/prucalopride constipation; advanced therapies for motor fluctuations + dyskinesias — deep brain stimulation (DBS) STN (most common) + GPi + Vim (tremor) + levodopa-carbidopa intestinal gel (LCIG, Duopa) duodenal infusion via PEG-J + foslevodopa-foscarbidopa (Vyalev) continuous SC infusion FDA 2024 (less invasive alternative to LCIG) + apomorphine SC pump + sublingual film (Kynmobi) + inhaled levodopa (Inbrija) for OFF rescue + focused ultrasound MRgFUS (thalamotomy FDA 2018 for tremor + pallidotomy FDA 2021 for dyskinesias) non-invasive; no disease-modifying therapy yet — multiple trials of α-synuclein-targeted antibodies (prasinezumab PASADENA + cinpanemab disappointing) + GLP-1 agonists (exenatide promising, lixisenatide LIXIPARK 2024) + LRRK2 inhibitors + GBA-targeted approaches; genetic PD 10-15% — LRRK2 (most common AD) + GBA (risk allele, more aggressive cognitive decline) + PARKIN/PINK1/DJ-1 (AR, young-onset) + SNCA (rare AD); mimics — vascular parkinsonism (lower body, stepwise, normal DaT) + drug-induced (antipsychotics, antiemetics, VPA) + Wilson disease (young + KF rings + ceruloplasmin) + hepatocerebral degeneration + manganism。

380.4.2 💊 治療粟芁

  • levodopa/carbidopa (Sinemet) GOLD STANDARDstart 25/100 mg TID with meals → titrate; available IR + CR + ER (Rytary) + ODT; foslevodopa-foscarbidopa SC (Vyalev) FDA 2024 continuous infusion for advanced
  • dopamine agonistspramipexole (Mirapex) 0.125-1.5 mg TID + ropinirole (Requip) 0.25-8 mg TID + rotigotine patch (Neupro) 1-8 mg/24 hr + apomorphine SC rescue; WARN ABOUT ICDs (impulse control disorders — gambling, hypersexuality, eating, shopping) + sleep attacks + edema + hallucinations + orthostatic
  • MAO-B inhibitorsselegiline 5 mg BID + rasagiline (Azilect) 0.5-1 mg/d + safinamide (Xadago) 50-100 mg/d (glutamate modulator); mild benefit
  • COMT inhibitorsentacapone (Comtan) 200 mg with each levodopa dose + opicapone (Ongentys) 50 mg once daily HS (FDA 2020); reduces wearing off
  • amantadine100 mg BID-TID + ER Gocovri 137-274 mg HS (FDA-approved for dyskinesias); side effects livedo reticularis, edema, hallucinations
  • PD dementiarivastigmine (Exelon) 1.5-6 mg BID PO or 4.6-13.3 mg/24 hr patch (only FDA-approved for PD dementia); donepezil off-label
  • PD psychosispimavanserin (Nuplazid) 34 mg/d (selective 5HT-2A inverse agonist, no dopaminergic blockade) + quetiapine 12.5-150 mg HS + clozapine (refractory, monitor WBC) + AVOID typical antipsychotics + olanzapine + risperidone (worsen motor)
  • orthostatic hypotensiondroxidopa (Northera) 100-600 mg TID + midodrine 5-10 mg TID + fludrocortisone + pyridostigmine + salt + fluid + compression stockings
  • DBSSTN (subthalamic nucleus) most common + GPi (globus pallidus internus) alternative + Vim (thalamus, tremor-predominant) — indications motor fluctuations + dyskinesias not controlled medically + good levodopa response + reasonable cognition
  • LCIG (levodopa-carbidopa intestinal gel, Duopa)duodenal infusion via PEG-J for advanced PD with fluctuations
  • focused ultrasound (MRgFUS)thalamotomy for tremor (FDA 2018) + pallidotomy for dyskinesias (FDA 2021), non-invasive, unilateral typically

380.4.3 🎯 盧醫垫的考前提醒

  1. TRAP cardinal features: Tremor (REST, asymmetric, pill-rolling 4-6 Hz) + Rigidity (cogwheel) + Akinesia/Bradykinesia + Postural instability (later — falls); ~ 30% never have tremor
  2. Non-motor features critical and often preceding motor: REM behavior disorder (RBD) — 80% develop synucleinopathy within 15 years (PD, DLB, MSA) + hyposmia very early + constipation + orthostatic hypotension + cognitive decline + depression
  3. Pathology: α-synuclein aggregation (Lewy bodies) + loss of dopaminergic neurons in substantia nigra pars compacta + Braak staging (lower brainstem → SN → cortex)
  4. MDS diagnostic criteria: bradykinesia + (rest tremor OR rigidity) + supportive + no exclusion + no red flags for atypical parkinsonism
  5. Red flags for atypical parkinsonism: rapid progression + early falls < 1 yr + severe autonomic failure (MSA) + severe bulbar dysfunction (PSP) + inspiratory stridor (MSA) + cerebellar signs + supranuclear vertical gaze palsy (PSP) + symmetric onset + poor levodopa response
  6. DaT-SCAN distinguishes PD/atypical parkinsonism (abnormal) from essential tremor + vascular parkinsonism + drug-induced + psychogenic (normal)
  7. Treatment hierarchy: levodopa/carbidopa GOLD STANDARD + dopamine agonists (pramipexole, ropinirole, rotigotine, apomorphine — WARN about ICDs!) + MAO-B inhibitors (selegiline, rasagiline, safinamide) + COMT inhibitors (entacapone with each levodopa + opicapone once daily FDA 2020) + amantadine (reduces dyskinesias)
  8. Non-motor treatments: rivastigmine (only FDA-approved for PD dementia) + pimavanserin (Nuplazid, selective 5HT-2A inverse agonist, no dopaminergic blockade) FDA for PD psychosis + quetiapine/clozapine (AVOID typical antipsychotics + olanzapine + risperidone) + droxidopa (Northera) for orthostatic hypotension
  9. Advanced therapies for motor fluctuations + dyskinesias: DBS (STN most common, GPi alternative, Vim for tremor) + LCIG (Duopa duodenal infusion) + foslevodopa-foscarbidopa (Vyalev) continuous SC infusion FDA 2024 (less invasive than LCIG) + apomorphine + focused ultrasound (thalamotomy FDA 2018, pallidotomy FDA 2021)
  10. No disease-modifying therapy yet — α-synuclein antibodies (prasinezumab PASADENA, cinpanemab) disappointing; GLP-1 agonists (exenatide, lixisenatide LIXIPARK 2024) promising + LRRK2 inhibitors + GBA-directed (ambroxol) in trials; genetic PD 10-15% (LRRK2 most common AD + GBA risk allele + PARKIN/PINK1/DJ-1 AR young-onset)