Central Nervous System Question and Answers

Central Nervous System

Question 1. Write a note on Prion diseases.
Answer:

• Prions: Abnormal forms of a cellular protein that cause rapidly progressive neurodegenerative disorders

Examples (in humans)

• Creutzfeldt-Jakob disease
• Gerstmann-Sträussler-Speaker syndrome
• Fatal familial insomnia
• Kuru

Read and Learn More Preparatory Manual of Pathology Question and Answers

Pathogenesis and Molecular Genetics

• Degenerative disorders, caused by the “spreading” of misfolded proteins
• The disease occurs when PrP undergoes a conformational change from its normal
• α-helix-containing isoform (PrPc) to an abnormal -pleated sheet isoform, usually termed PrPsc
• Accumulation of PrPSc in neural tissue results in disease
• How this accumulation is brought about?
• α-helical PrPc may spontaneously shift to α-sheet PrPsc conformation, due to germ-line PrP mutations
• Propagation: PrPSc converts other molecules of PrPc into PrPsc, resulting in the formation of PrPsc aggregates

Question 2. Write a note on Creutzfeldt-Jakob disease.
Answer:

Creutzfeldt-Jakob disease (CJD)

• The most common Prion disease
• Familial forms are caused by mutations in PRNP
• Age group: Seventh decade, with an average survival of 7 months

Variant Creutzfeldt-Jakob disease

• Most common in young adults
• Due to the consumption of bovine spongiform encephalopathy agent in contaminated foods or blood transfusion

Morphology

• Pathognomonic finding: Spongiform transformation of the cerebral cortex

Microscopy

• Small, microscopic empty vacuoles within the neuropil and in neurons
• Advanced cases: Severe neuronal loss, reactive gliosis, expansion of vacuolated areas into cyst-like spaces (“status spongiosis”)

Question 3. Write a note on Parkinson’s disease.
Answer:

Parkinson’s disease (PD)

• A neurodegenerative disease characterized by prominent hypokinetic movement disorder

Etiology

• Loss of dopaminergic neurons in the substantia nigra

Clinical features

• Diminished facial expression (masked facies), stooped posture, slowing of voluntary movement, festinating gait (progressively shortened, accelerated steps), rigidity, and “pill-rolling” tremor
• Triad of parkinsonism tremor, rigidity, and bradykinesia

Molecular Genetics and Pathogenesis

1. α-synuclein aggregation results in autosomal dominant PD

• α-synuclein aggregates are toxic to neurons
• These aggregates have been termed Lewy bodies and Lewy neurites

Morphology

• A characteristic finding is pallor of substantia nigra, due to loss of pigmented, catecholaminergic neurons
• Lewy bodies: Single or multiple cytoplasmic, eosinophilic, round to elongated inclusions that often have a dense core surrounded by a pale halo
• Lewy bodies are composed of α-synuclein

Question 4. What are Negri bodies?
Answer:

Negri bodies

• Pathognomonic microscopic finding in rabies
• These are cytoplasmic, round to oval, eosinophilic inclusions
• Found in pyramidal neurons of the hippocampus and Purine cells of the cerebellum

Question 5. Write a note on cerebrospinal fluid (CSF) findings in pyogenic meningitis.
Answer:

CSF examination in pyogenic meningitis

• Appearance: turbid or purulent
• Leukocytes: Increased (>1000/microliter), mainly neutrophils
• Proteins (mg/dl): Increased (50–1500)
• Glucose (mg/dl): Decreased (<40)

Question 6. Write a note on cerebrospinal fluid (CSF) findings in tuberculous meningitis.
Answer:

CSF examination in tuberculous meningitis

• Appearance: Clear or cloudy
• Leukocytes: Increased (100–600/microliter), mainly lymphocytes
• Proteins (mg/dl): Increased (45–300)
• Glucose (mg/dl): Decreased (10–45)

Question 7. Write a note on pilocytic astrocytoma.
Answer:

Pilocytic astrocytes

• Seen in children and young adults
• Site: Cerebellum (most commonly) followed by optic chiasm and brain stem

Pathogenesis

• Associated with neurofibromin gene mutation, in NF-1 patients
• BRAF mutations

Morphology

• Tumors are often cystic
• Composed of bipolar cells with long, thin “hair-like” processes, and shows GFAPpositivity
• Rosenthal fibers and eosinophilic granular bodies are seen

Question 8. Write a note on glioblastoma multiform.
Answer:

Glioblastoma (glioblastoma multiform)

Sites

• Cerebral hemispheres in adults
• Cerebellum and brain stem in children

Salient features

• Cytoplasmic and nuclear pleomorphism, increased mitosis
• Vascular/endothelial cell proliferation producing glomeruli like vessels (glomerular body), due to VEGF production by the malignant astrocytes
• Geographic pattern of necrosis: Tumor cells collect along the edges of the necrotic regions (pseudo-palisading pattern)

Question 9. Write a note on medulloblastoma.
Answer:

Medulloblastoma (WHO, grade IV)

• Most commonly affects children
• Most common site: Cerebellum

Molecular genetics

• Loss of chromosome 17p material
• MYC amplification is associated with aggressive clinical course

Morphology

Gross

• Well-circumscribed, gray, friable mass in the cerebellum

Microscopy

• Sheets of small cells with scant cytoplasm, ill-defined cell borders, and hyperchromatic nuclei, which are angular or ovoid shape
• Mitosis is abundant
• Tumor cells can form Homer Wright rosettes and express GFAP positivity

Question 10. Write a note on the morphology of meningiomas.
Answer:

Meningiomas

• Benign dual-band tumors of adults, that arise from the meningothelial cells of the arachnoid

Morphology

Gross

• Encapsulated, dual-band tumor
• Can spread in a sheet-like fashion along the dural surface

Microscopy: The following patterns are recognized

1. WHO Grade I/IV

• Syncytial: Whorled clusters of cells, with indistinct cell membranes, pseudo inclusions, cellular whorls, and psammoma bodies
• Fibroblastic: Spindle-shaped cells and a fascicular or storiform architecture
• Transitional: Features of syncytial and fibroblast types
• Psammomatous: Composed of psammoma bodies, formed from the calcification of syncytial nests of meningothelial cells
• Secretory: PAS-positive intracytoplasmic droplets
• Microcystic: With a loose, spongy appearance

2. Atypical meningiomas (WHO grade II/IV)

• Aggressive tumors
• High rate of recurrence

Examples: Clear cell and choroid meningioma

3. Anaplastic (malignant) meningioma (WHO grade III/IV)

• Highly aggressive tumors
• High mitotic rates (>20 mitoses per 10 high power fields)

Examples: Papillary and rhabdoid meningioma

Eye

Question 1. Write a note on retinoblastoma.
Answer:

Retinoblastoma

• The most common primary intraocular malignancy of children
• Inherited cases: Occurs in individuals who inherit a germ line mutation of one RB allele
• Sporadic cases: In individuals with no germ line mutations, loss of Rb genes occurs following Knudson’s two-hit hypothesis

Morphology

• Tumor cells appear as collections of small, round cells with hyperchromatic nuclei
• Viable tumor cells are found encircling the blood vessels
• Cleaner-Wintersteiner rosettes can be seen
• Foci of dystrophic calcification is a characteristic feature