384.3 🏥 內科專科考前版

384.3.1 Mechanistic Deep Dive

384.3.1.1 α-Synuclein in DLB

  • Lewy bodies cortical + brainstem (vs PD mostly brainstem early)
  • Diffuse cortical spread
  • Often + AD co-pathology

384.3.1.2 Antipsychotic Sensitivity Mechanism

  • D2 receptor blockade in already depleted dopaminergic system
  • Severe EPS, mutism, rigidity

384.3.1.3 Subcortical Ischemic Vascular Disease (SIVD)

  • Lipohyalinosis of small penetrating arteries
  • Lacunes + white matter changes
  • Chronic ischemia
  • Often HTN-related

384.3.2 Recent Trials & Updates

384.3.2.1 Pimavanserin for DLB Psychosis

  • Selective 5HT-2A inverse agonist
  • Avoids dopaminergic blockade
  • FDA-approved for PD psychosis (off-label for DLB)
  • HARMONY trial

384.3.2.2 Lewy Body RT-QuIC

  • α-synuclein seed amplification assay
  • CSF, skin biopsy
  • High accuracy for synucleinopathies
  • Distinguishes DLB from AD

384.3.2.3 Plasma Biomarkers

  • Phosphorylated α-synuclein
  • Emerging

384.3.3 High-Yield Specialist Points

384.3.3.1 Lewy Body Pathology Spread (Braak)

  • Brainstem → limbic → cortex
  • DLB has prominent cortical involvement
  • PD typically more brainstem early

384.3.3.2 Cingulate Island Sign

  • FDG-PET DLB
  • Preserved posterior cingulate
  • Surrounded by reduced metabolism (especially precuneus)

384.3.3.3 Occipital Hypometabolism

  • DLB
  • Less in AD
  • Helpful imaging feature

384.3.3.4 REM Sleep Behavior Disorder Importance

  • Strong predictor of synucleinopathy
  • 80%+ develop within 15 years (PD, DLB, MSA)
  • Counsel patients

384.3.3.5 Differential of Visual Hallucinations

  • DLB (well-formed, animals, people, often non-threatening)
  • Drug-induced (anticholinergics, dopaminergics)
  • Delirium (variable)
  • Charles Bonnet (visual loss)
  • Schizophrenia (less well-formed in elderly)
  • AD with psychosis

384.3.3.6 Charles Bonnet Syndrome

  • Visual loss → vivid hallucinations
  • Insight preserved
  • Not DLB
  • Sensory deprivation phenomenon

384.3.3.7 Sundowning in DLB

  • Worsening evening/night
  • Similar to AD

384.3.3.8 Cognitive Fluctuations Distinguishing

  • DLB classical
  • Delirium (acute, identifiable cause)
  • Sleep disorders (especially OSA)
  • Medication side effects

384.3.3.9 Vascular Cognitive Impairment Imaging

  • White matter hyperintensities
  • Lacunar infarcts
  • Cortical infarcts
  • Microbleeds
  • CAA features

384.3.3.10 Hypertensive Encephalopathy

  • Severe HTN
  • Confusion, seizures, vision changes
  • PRES on MRI
  • Treat HTN

384.3.3.11 CADASIL Details

  • NOTCH3 mutation
  • Cysteine substitution
  • Granular osmiophilic material on skin biopsy
  • White matter (anterior temporal characteristic)
  • Migraine + recurrent strokes + cognitive
  • Genetic testing

384.3.3.12 CARASIL

  • AR
  • HTRA1 mutation
  • Asian populations
  • Similar to CADASIL

384.3.3.13 Fabry Disease

  • α-galactosidase
  • White matter changes
  • Strokes
  • Renal, skin, cardiac

384.3.4 Pearls

  • DLB: 4 core (fluctuation, visual hallucinations, RBD, parkinsonism)
  • DLB vs PDD: timing distinction
  • DLB: severe antipsychotic sensitivity — AVOID typical antipsychotics
  • Rivastigmine, donepezil: very effective in DLB
  • Pimavanserin for psychosis
  • VCI: stepwise (multi-infarct) or gradual (subcortical)
  • Mixed dementia very common
  • NPH: wet, wobbly, wacky → shunt
  • CADASIL: AD, NOTCH3, anterior temporal white matter