Neuropathology Practice Questions

Q: Which chromosome mutation is associated with medulloblastoma?

Chromosome 17. **Explanation:** **Medulloblastoma** is the most common malignant brain tumor in children, typically arising in the cerebellum. The most characteristic cytogenetic abnormality associated with this tumor is **Isochromosome 17q (i17q)**. This mutation involves the loss of the short arm (17p) and the duplication of the long arm (17q). The loss of 17p is significant because it houses the **TP53** tumor suppressor gene (though TP53 mutations are specifically linked to the SHH subgroup), and i17q is a hallmark of the Group 3 and Group 4 molecular subtypes of medulloblastoma, carrying a poorer prognosis. **Analysis of Incorrect Options:** * **Chromosome 16:** Mutations here are more commonly associated with renal pathologies (like ADPKD - PKD1) or certain leukemias, but not classically with medulloblastoma. * **Chromosome 18:** Trisomy 18 (Edwards Syndrome) is a multisystem genetic disorder. While it increases the risk of some tumors (like Wilms tumor), it is not the primary association for medulloblastoma. * **Chromosome 19:** Codeletion of 1p/19q is the diagnostic molecular marker for **Oligodendrogliomas**, not medulloblastoma. **High-Yield Clinical Pearls for NEET-PG:** * **Location:** Always arises in the **cerebellum** (vermis in children, hemispheres in adults). * **Histology:** Characterized by **Homer-Wright Rosettes** and "small round blue cells." * **Drop Metastasis:** It has a high propensity to spread via CSF to the spinal cord [2]. * **Molecular Subgroups:** WNT (best prognosis), SHH, Group 3 (worst prognosis), and Group 4. * **Genetic Syndromes:** Associated with **Turcot Syndrome** (APC gene) and **Gorlin Syndrome** (PTCH1 gene) [1]. **References:** [1] Kumar V, Abbas AK, et al.. Robbins and Cotran Pathologic Basis of Disease. 9th ed. Neoplasia, pp. 306-307. [2] Kumar V, Abbas AK, et al.. Robbins and Cotran Pathologic Basis of Disease. 9th ed. The Central Nervous System, pp. 1314-1315.

Q: What is the characteristic finding shown in the image?

Muscular dystrophy. ***Muscular dystrophy*** - Shows characteristic **variation in muscle fiber size** with **fibrofatty replacement** and **internal nuclei** migration on muscle biopsy. - Features **necrosis and regeneration** of muscle fibers without primary inflammatory infiltrates. *Neuropathy* - Demonstrates **grouped angular atrophy** pattern where denervated muscle fibers cluster together in groups. - Shows **uniform fiber atrophy** affecting entire fascicles supplied by damaged motor neurons. *Guillain-Barré syndrome* - Primarily affects **peripheral nerves** with **demyelination**, not visible on standard muscle biopsy. - Muscle biopsy would show **neurogenic changes** similar to other neuropathies, not the dystrophic pattern seen here. *Polymyositis* - Characterized by **inflammatory cell infiltrates** (lymphocytes, macrophages) within muscle fascicles. - Shows **perifascicular atrophy** pattern with muscle fiber damage at the periphery of fascicles.

Q: A 4-year-old girl developed clumsiness and difficulty ambulating over 6 months. On physical examination, she showed difficulty with balance while walking, dysarthria, poor hand coordination, absent deep tendon reflexes, and a bilateral Babinski sign. Light touch and vibratory sensation were greatly diminished. There was no muscular weakness. Over the next 5 years, she developed congestive heart failure from hypertrophic cardiomyopathy. She also had hyperglycemia. At autopsy, there was increased perinuclear iron deposition within cardiac myocytes. Which of the following genetic abnormalities with trinucleotide repeat expansions was most likely present in this patient?

GAA repeats in the frataxin gene. ### **Explanation** The clinical presentation describes **Friedreich Ataxia (FA)**, the most common inherited ataxia. It typically manifests before age 20 with progressive limb and gait ataxia, dysarthria, and loss of deep tendon reflexes (due to peripheral neuropathy). **Why Option D is Correct:** Friedreich Ataxia is an **autosomal recessive** trinucleotide repeat disorder characterized by **GAA repeats** in the **FXN gene** on chromosome 9. This gene encodes **frataxin**, a mitochondrial protein involved in iron homeostasis. * **Pathophysiology:** Deficiency of frataxin leads to mitochondrial iron overload, causing oxidative stress and damage to the posterior columns (loss of vibration/proprioception), spinocerebellar tracts (ataxia), and corticospinal tracts (Babinski sign). * **Systemic Involvement:** The "classic triad" for exams includes **neurological deficits**, **Hypertrophic Cardiomyopathy** (the leading cause of death, often showing iron deposition in myocytes), and **Diabetes Mellitus/Hyperglycemia**. **Why Other Options are Incorrect:** * **Option A (CAG):** Associated with **Huntington Disease**. Presents with chorea and dementia in adults; it involves atrophy of the caudate nucleus. * **Option B (CGG):** Associated with **Fragile X Syndrome**. Presents with intellectual disability, macroorchidism, and long face/large ears. * **Option C (CTG):** Associated with **Myotonic Dystrophy**. Presents with "CTG" (Cataracts, Toupee/early balding, Gonadal atrophy) and myotonia (delayed muscle relaxation). **NEET-PG High-Yield Pearls:** * **Inheritance:** Autosomal Recessive (unique among most trinucleotide repeat disorders which are often Dominant). * **Mnemonic for GAA:** **G**ait **A**taxia **A**lways. * **Cardiac finding:** Hypertrophic Cardiomyopathy (HCM) is seen in 90% of patients. * **Skeletal findings:** Kyphoscoliosis and Pes Cavus (high arched feet) are common associations.

Q: Glioma of the optic nerve is usually?

Pilocytic. **Explanation:** Optic nerve gliomas are most commonly **Pilocytic Astrocytomas** (WHO Grade I). These are slow-growing, relatively benign tumors that typically occur in children and young adults [1]. **Why Pilocytic is correct:** Pilocytic astrocytomas have a predilection for the optic pathway (optic nerve, chiasm, and hypothalamus). When associated with **Neurofibromatosis Type 1 (NF1)**, they are frequently bilateral. Histologically, they are characterized by "hair-like" bipolar cells, **Rosenthal fibers** (eosinophilic corkscrew-shaped inclusions), and eosinophilic granular bodies. **Analysis of Incorrect Options:** * **Gemistocytic Astrocytoma:** This is a variant of diffuse astrocytoma (Grade 2) characterized by large, eosinophilic cell bodies with eccentric nuclei. It has a high rate of progression to glioblastoma and is not typical for the optic nerve. * **Fibrillary Astrocytoma:** This refers to the most common subtype of low-grade diffuse astrocytoma. It typically involves the cerebral hemispheres in adults [2], not the optic nerve in children. * **Lamellar:** This is not a recognized histological subtype of glioma. **High-Yield Clinical Pearls for NEET-PG:** * **Association:** 15–30% of children with NF1 develop optic pathway gliomas. * **Imaging:** Classic "fusiform" enlargement of the optic nerve on MRI. * **Histology Keyword:** Rosenthal fibers (made of GFAP and heat shock proteins). * **Prognosis:** Excellent; these are Grade I tumors and often remain stable for years [1]. **References:** [1] Kumar V, Abbas AK, et al.. Robbins and Cotran Pathologic Basis of Disease. 9th ed. The Central Nervous System, pp. 1319-1320. [2] Cross SS. Underwood's Pathology: A Clinical Approach. 6th ed. Common Clinical Manifestations Of Central And Peripheral Nervous System Disease, pp. 725-726.

Q: Which of the following conditions is characterized by localized regional cerebral atrophy?

Frontotemporal dementia. **Explanation:** The hallmark of **Frontotemporal Dementia (FTD)**, specifically Pick’s disease, is **localized regional cerebral atrophy** affecting the frontal and temporal lobes. Unlike the generalized atrophy seen in other dementias, FTD presents with a characteristic "knife-edge" thinning of the gyri. This focal degeneration leads to early changes in personality, social conduct, and language, often preceding memory loss. **Analysis of Options:** * **Alzheimer’s Disease (A):** While it involves atrophy, it is typically **generalized** or starts in the hippocampus and entorhinal cortex [1, 2]. It does not show the sharp, localized "lobar" demarcation characteristic of FTD. Alzheimer's is histologically characterized by senile plaques and neurofibrillary tangles [1]. * **Progressive Multifocal Leukoencephalopathy (PML) (C):** This is a demyelinating disease caused by the **JC virus**. It presents with multifocal white matter lesions (hyperintensities on T2/FLAIR MRI) rather than primary cortical gray matter atrophy. * **Creutzfeldt-Jakob Disease (CJD) (D):** This prion disease is characterized by **rapidly progressive** dementia. MRI typically shows "cortical ribboning" or hyperintensities in the caudate and putamen (hockey-stick sign), but not localized regional atrophy. **High-Yield Pearls for NEET-PG:** * **FTD Pathology:** Associated with **Pick bodies** (silver-staining tau inclusions) and **TDP-43** protein aggregates. * **Clinical Triad:** Behavioral changes (disinhibition), primary progressive aphasia, and early preservation of visuospatial skills. * **Imaging Sign:** Look for the **"Knife-edge" atrophy** of frontal and temporal lobes on MRI. * **Genetics:** Often associated with mutations in the *MAPT* or *GRN* genes. Neurodegenerative diseases as a group are defined by pathological processes leading to specific neuronal death and progressive symptoms [3].

Question 1

All of the following are neuronal tumors, EXCEPT:

Accepted Answer

Ependymoma

Answer

Gangliocytoma

Answer

Ganglioglioma

Answer

Neurocytoma

Question 2

Which chromosome mutation is associated with medulloblastoma?

Accepted Answer

Chromosome 17

Answer

Chromosome 16

Answer

Chromosome 18

Answer

Chromosome 19

Question 3

Damage to nervous tissue is repaired by which cells?

Accepted Answer

Astrocytes

Answer

Fibroblasts

Answer

Axons

Answer

Microglia

Question 4

What is the characteristic finding shown in the image?

Accepted Answer

Muscular dystrophy

Answer

Neuropathy

Answer

Guillain-Barré syndrome

Answer

Polymyositis

Question 5

A 4-year-old girl developed clumsiness and difficulty ambulating over 6 months. On physical examination, she showed difficulty with balance while walking, dysarthria, poor hand coordination, absent deep tendon reflexes, and a bilateral Babinski sign. Light touch and vibratory sensation were greatly diminished. There was no muscular weakness. Over the next 5 years, she developed congestive heart failure from hypertrophic cardiomyopathy. She also had hyperglycemia. At autopsy, there was increased perinuclear iron deposition within cardiac myocytes. Which of the following genetic abnormalities with trinucleotide repeat expansions was most likely present in this patient?

Accepted Answer

GAA repeats in the frataxin gene

Answer

CAG repeats in the huntingtin gene

Answer

CGG repeats in the FMR1 gene

Answer

CTG repeats in the dystrophia myotonica-protein kinase gene

Question 6

A 10-year-old girl has exhibited muscular weakness since early childhood that has not worsened. She can ambulate unassisted but does not participate in strenuous physical activities. On examination, she has 4/5 motor strength in proximal muscles and 5/5 in distal muscles. There is no muscle pain on palpation. A biopsy of the deltoid muscle is obtained, and with Gomori trichrome stain, microscopic analysis shows subsarcolemmal aggregates of rod-shaped intracytoplasmic inclusions. Laboratory studies show a normal serum creatine kinase. Which of the following is the most likely form of muscle disease she has?

Accepted Answer

Congenital myopathy

Answer

Channelopathy

Answer

Glycogen storage disease

Answer

Inflammatory myopathy

Question 7

Glioma of the optic nerve is usually?

Accepted Answer

Pilocytic

Answer

Gemistocytic

Answer

Fibrillary

Answer

Lamellar

Question 8

Which of the following conditions is characterized by localized regional cerebral atrophy?

Accepted Answer

Frontotemporal dementia

Answer

Alzheimer's disease

Answer

Progressive multifocal leukoencephalopathy (PML)

Answer

Creutzfeldt-Jakob disease (CJD)

Question 9

In Alzheimer's disease, which neurotransmitter is deficient in the cortex?

Accepted Answer

Acetylcholine

Answer

Serotonin

Answer

Dopamine

Answer

Noradrenaline

Question 10

What protein is deposited in familial amyloid neuropathy?

Accepted Answer

Mutated transthyretin

Answer

Normal transthyretin

Answer

Mutated beta-2 microglobulin

Answer

Normal beta-2 microglobulin

Neuropathology — MCQs

Neuropathology — MCQs

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