A 53-year-old male with clumsiness Leonidas Arvanitis, M.D. Neuropathology Fellow, PGY-6

History The patient was a 53 year male with a 10 year history of clumsiness He initially presented with deterioration of his singing voice, clumsiness of his left hand, incoordination and spastic reflexes. The patient had no history of drug abuse or environmental exposure. An MRI of the brain was normal, but a cervical MRI revealed a small syrinx below C6-7.

History His symptoms progressed, notable for masked facies, increased muscle upper extremity muscle tone, and poor gait and arm. One year before death the patient was also noted to have dementia, the latter manifesting in cognitive difficulty, paranoia, and delusions, but improving with medications.

Autopsy An autopsy was performed and showed the following (describe midbrain section): th/CNSHTML/CNS102.html Our case Normal control

Autopsy th/CNSHTML/CNS102.html Our caseNormal control Marked pallor of substantia nigra

This is a section from the midbrain. What do you see? Midbrain. (Click here for H&E)here

This is a section from the midbrain. What do you see? Midbrain. (Click here for H&E)here

This is a section from the midbrain. What do you see? Midbrain. (Click here for H&E)here Eosinophilic cytoplasmic inclusions Decreased numbers of pigmented neurons

This is a section from the midbrain. What do you see? Midbrain. (Click here for H&E)here Pigmented-laden macrophages Reactive gliosis

Question: The intracytoplasmic neuronal inclusions are known as …

Answer …Lewy bodies

Question: Which immunohistochemical stain highlights the Lewy bodies?

Answer A-synuclein –Click here to view stainhere

Lewy bodies (a-synuclein)

Question What is the diagnosis?

Answer Parkinson’s disease

Question What is the most common cause of Parkinson’s disease?

Answer Most cases are sporadic of unknown etiology Environmental factors such as toxic exposure, infection or lifestyle have been proposed

Question Are there any gene mutations linked to Parkinson's disease?

Answer Yes. Autosomal dominant and recessive mutations –Autosomal dominant include PARK1 point mutation in a-synuclein gene and PARK5 point mutation in ubiquitin carboxyterminal hydrolase-L1 (UCH-L1) –Autosomal recessive include PARK2 mutation in the parkin gene

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