A 65-year-old woman is being evaluated for Parkinson's disease. She has asymmetric rest tremor, cogwheel rigidity, and bradykinesia for 2 years (Hoehn & Yahr stage 2). She also complains of constipation and anosmia preceding motor symptoms by 5 years. Which Braak stage of Parkinson disease pathology does the clinical sequence of anosmia and constipation PRECEDING motor symptoms suggest?
- A Braak stage 3 (substantia nigra pars compacta involvement, onset of motor symptoms)
- B Braak stages 1–2 (olfactory bulb and dorsal vagal nucleus involvement before substantia nigra) ✓
- C Braak stages 5–6 (neocortical involvement with dementia)
- D Braak stage 4 (temporal mesocortex and allocortex involvement)
Explanation
Braak's staging hypothesis for Parkinson disease proposes that alpha-synuclein pathology begins in the olfactory bulb and dorsal motor nucleus of the vagus nerve (Braak stages 1–2), before ascending to the substantia nigra (stage 3, when motor symptoms emerge) and eventually reaching the neocortex (stages 5–6, correlating with dementia). This 'bottom-up' spread explains the prodromal non-motor features of PD: hyposmia (olfactory bulb involvement, stage 1), constipation and autonomic symptoms (dorsal vagal and enteric nervous system involvement), REM sleep behaviour disorder, and depression — which commonly precede the classic motor syndrome by years. This patient's 5-year prodrome of anosmia and constipation is classic for Braak stages 1–2 preceding stage 3.
Reference: Harrison's Principles of Internal Medicine, 21st ed.
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