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

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):

http://library.med.utah.edu/WebPath/CNSHTML/CNS102.html

Our case Normal control

Autopsy

http://library.med.utah.edu/WebPath/CNSHTML/CNS102.html

Our case Normal control

Marked pallor of substantia nigra

This is a section from the midbrain. What do you see?

Midbrain. (Click here for H&E)

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

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

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)

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 stain

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

http://neurowiki2013.wdfiles.com/local--files/individual%3Agenetic-etiology-of-parkinson-s-disease/img2.JPG