A 58-year-old man from rural Maharashtra presents with a 3-year history of progressive tremor at rest, rigidity, and bradykinesia. He reports difficulty initiating gait and frequent falls. Examination reveals a stooped posture, masked facies, and a pill-rolling tremor. MRI brain shows no structural lesion. What is the most likely pathological finding in the substantia nigra?

Explanation

## Diagnosis: Parkinson's Disease **Key Point:** Parkinson's disease (PD) is characterized by selective loss of dopaminergic neurons in the substantia nigra pars compacta, with the pathognomonic hallmark being **Lewy bodies** — intracytoplasmic inclusions composed primarily of α-synuclein. ### Pathological Features of PD | Feature | Details | |---------|----------| | **Primary site** | Substantia nigra pars compacta (SNpc) | | **Neuronal loss** | 50–70% depletion of dopaminergic neurons | | **Lewy bodies** | α-synuclein–rich cytoplasmic inclusions with halo | | **Lewy neurites** | Dystrophic processes containing α-synuclein | | **Consequence** | Striatal dopamine depletion → motor dysfunction | ### Clinical Correlation The classic **tetrad** of PD—resting tremor, rigidity, bradykinesia, and postural instability—results from dopaminergic denervation of the striatum. The stooped posture and masked facies reflect brainstem involvement beyond the SNpc. **High-Yield:** Lewy bodies are NOT specific to PD; they also occur in Lewy body dementia and Parkinson's dementia complex. However, in the context of **isolated motor parkinsonism with SNpc pathology**, Lewy bodies are diagnostic. **Clinical Pearl:** The absence of structural lesion on MRI rules out secondary parkinsonism (vascular, traumatic, toxic) and supports idiopathic PD. ### Lewy Body Composition 1. **Core:** α-synuclein (major component) 2. **Halo:** Ubiquitin, neurofilament proteins 3. **Electron microscopy:** 10–20 nm filaments in concentric arrays [cite:Robbins 10e Ch 28]