Neuropathology

Question 1

A 33-year-old man presents with anxiety and depression. Soon he develops rapidly progressive cognitive impairment with myoclonus, ataxia and eventually akinetic mutism. Characteristic pathological change expected in brain autopsy, in this case, is

Select one:
1. Lewy bodies
2. Extensive vacuole formation
3. Ventricular dilatation
4. Lack of gliosis
5. Eosinophilic extraneuronal deposits

Answer 1

Extensive vacuole formation

The description suggests CJD. Microscopically CJD shows a spongiform encephalopathy secondary to
neuropil vacuolisation.

Question 2

The neuropathological findings in Punch Drunk syndrome include which of the following changes?

Select one:
1. Knife blade gyri
2. Basal ganglia enlargement
3. Neurofibrillary tangles
4. Caudate hypertrophy
5. Pulvinar signs

Answer 2

Neurofibrillary tangles

Dementia pugilistica (DP) is a type of neurodegenerative disease that can affect around 15% of boxers who suffer concussions after 12-16 years of boxing on average. Symptoms and signs of DP develop
progressively over a long latent period.Histological changes in Punch Drunk syndrome (Dementia Pugilistica) would include neuronal loss and neurofibrillary tangles. Thinning of the corpus callosum, perforation of the septum pellucidum and ventricular enlargement is also seen in this condition.

Question 3

Depigmentation of the substantia nigra is seen in which of the following disorders?

Select one:
1. Creutzfeldt-Jakob Disease
2. Huntington’s disease
3. Dandy-Walker malformation
4. Alzheimers disease
5. Parkinson’s disease

Answer 3

Parkinson’s disease

The macroscopic changes in idiopathic Parkinsons disease would include depigmentation of the substantia nigra, particularly the zona compacta, and depigmentation of the locus coereleus and diffuse cortical atrophy.

The histological changes in idiopathic Parkinsons disease would include Reactive astrocytosis, neuronal loss, Presence of Lewy bodies in different areas such as the substantia nigra, locus cereleus, dorsal motor nucleus of the vagus, hypothalamus, nucleus basalis of meynert, Edinger-Westphal nucleus nd raphe nuclei.

Question 4

The immunological staining used in detection of Pick’s disease is

Select one:
1. Glycosaminoglycan
2. Amyloid P
3. Basic fibroblast growth factor antibodies
4. Anti-tau antibodies
5. Heparan sulfate

Answer 4

Anti-tau antibodies

A variety of stains can be used to visualise Pick bodies and Pick cells, but the most efficient and highly
specific method is to use immunohistochemical staining with anti-tau and anti-ubiquitin antibodies. The neurofibrillary tangles of Alzheimer’s can be stained with antibodies to basic fibroblast growth factor, amyloid P, and heparan sulfate glycosaminoglycan.

Question 5

Which of the following is correct concerning white matter hyperintensities seen in mood disorders?

Select one:
1. Best seen in T1 images of MRI
2. Seen only in bipolar patients
3 .Associated with good recovery from mood episodes
4. Associated with vascular risk factors
5. Seen more often in younger patients

Answer 5

Associated with vascular risk factors

A strong association between mood disorder and the number and severity of focal signal hyperintensities
on T2-weighted images has been established. These white matter hyperintensities (WMH) occur
particularly in the deep subcortical white matter and to a lesser extent in the basal ganglia and
periventricularly. They are seen in excess in bipolar and unipolar mood disorder, with an odds ratio of 3 to 7.

In major depression, WMH are particularly common in elderly subjects, where they are linked to risk factors
for, and the presence of, vascular disease.

Question 6

Which one of the following is a protective factor against Alzheimer’s disease?

Select one:
1. Down’s syndrome
2. Apolipoprotein e2 allele
3. Head injury
4. Post menopausal estrogen decline
5. Age

Answer 6

Apolipoprotein e2 allele

Apolipoprotein e2 allele is a proven protective factor against Alzheimer’s disease. Other possible protective
factors are smoking, NSAIDs, oestrogen, premorbid intelligence and education.

Question 7

The enzyme involved in the metabolism of amyloid precursor protein that prevents amyloid formation is

Select one:
1. Protein kinase
2. Delta-secretase
3. Gamma-secretase
4. Alpha-secretase
5. Beta-secretase

Answer 7

Alpha-secretase

Alpha secretases are a family of proteolytic enzymes that cleave amyloid precursor protein in its
transmembrane region. In conditions like Alzheimer’s disease, when amyloid precursor protein is processed
by beat-secretase and gamma secretase, it gives rise to beta amyloid peptide, which plays a crucial role in
the pathogenesis of Alzheimer’s dementia.

Question 8

A 40-year-old woman was found wandering on streets after the recent funeral of her husband. She can give
her personal demographic details and has no past psychiatric history. She has no physical injuries. Which
of the following deficits is likely? (June 2008)

Select one:
1. Loss of semantic memory
2. Loss of new learning capacity
3. Continuous anterograde amnesia
4. Loss of procedural memory
5. Loss of memory of personal events well rehearsed

Answer 8

Loss of memory of personal events well rehearsed

This is characteristic of dissociative amnesiWell rehearsed personal events are lost (such as the fact that her husband was ill before death, for example).

Question 9

Which of the following structures is larger on the left side compared to the right hemisphere in healthy right
handed subjects?

Select one:
1. Cingulate cortex
2. Planum temporale
3. Superior colliculus
4. Thalamus
5. Amygdala

Answer 9

Planum temporale

The planum temporale shows a marked leftward volume asymmetry that is related to the degree of righthandedness; this is more marked in males (nearly ten times asymmetrical on the left in males)

Question 10

Neurofibrillary tangles seen in Alzheimer’s disease are made up of

Select one:
1. Hypophosphorylated tau protein
2. Amyloid fibrils
3. Actin filaments
4. Synaptophysin
5. Hyperphosphorylated tau protein

Answer 10

Hyperphosphorylated tau protein

Neurofibrillary tangles are composed of cytoskeletal elements, primarily abnormally hyperphosphorylated
tau protein. Tau is a peptide required for microtubule assembly. Microtubules are essential to transport of
materials down axons. Hyperphosphorylation of Tau proteins can result in the self-assembly of tangles of
paired helical filaments and straight filaments, which are involved in the pathogenesis of Alzheimer’s
disease.

Question 11

Autopsy of an elderly man who suffered from marked tremors and a progressive cognitive decline shows
cells negative for tau protein. What is the likely diagnosis?

Select one:
1. Lewy body dementia
2. Vascular dementia
3. Alzheimer’s dementia
4. CJD
5. Frontal lobe degeneration

Answer 11

Lewy body dementia

Lewy bodies that are seen in diffuse Lewy body disease (dementia), rarely have any tau protein deposits.

They are primarily made of alpha synuclein and ubiquitin which are tau negative.

Question 12

Neurofibrillary tangles are most commonly present in which of the following locations in Alzheimer’s?

Select one:
1. Brain stem
2. Auditory association cortex
3. Hippocampus
4. Prefrontal cortex
5. Insula

Answer 12

Hippocampus

Neurofibrillary tangles occur with ageing and in all the other conditions listed above. NFTs are found in the
hippocampus (Ammons horn) and are also found in the Amygdala, parahippocampal gyrus, neocortex,
locus coereleus, and nucleus of meynert and Raphe nuclei. Senile Plaques are found in the same sites as
those of NFTs. Plaques include extra cellular Amyloid as a component, and beta A-4 protein is a major
biochemical component of plaque Amyloid.

Question 13

Marked atrophy of the caudate nucleus is seen in which of the following disorders?

Select one:
1. Huntington’s disease
2. Punch drunk syndrome
3. Alcoholic dementia
4. Creutzfeldt-Jakob Disease
5. Lewy Body dementia

Answer 13

Huntington’s disease

Macroscopic findings in Huntington’s disease include 1. Small brain with reduced mass
2. Marked atrophy of the corpus striatum, particularly the caudate nucleus
3. Marked atrophy of the cerebral cortex, particularly
the frontal lobe gyri
4. Dilatation of the lateral and third ventricles.

Histological changes in Huntington’s disease would include neuronal loss in the cerebral cortex and neuronal loss in the corpus striatum and astrocytosis in the affected regions.

Question 14

In those with Mild Cognitive Impairment, which of the following biomarkers can detect worsening cognitive
function?

Select one:
1. Decreased tau protein in CSF
2. Increased Tau-to-Amyloid ratio in CSF
3. Decreased Ubiquitin-to-Amyloid ratio in CSF
4. Decreased Tau-to-Amyloid ratio in CSF
5. Increased beta amyloid in CSF

Answer 14

Increased Tau-to-Amyloid ratio in CSF

Individuals with early Alzheimer’s dementia have reduced CSF beta-amyloid and increased levels of CSF
tau and phosphorylated tau. The CSF tau/amyloid beta ratio is nearly 5 times higher in those who later
convert to full-blown Alzheimer’s dementia compared to non-converters. Increased CSF tau/A-beta
(amyloid) ratios show strong promise as a preclinical biomarker to predict future dementia in cognitively
normal older adults.

Question 15

Which of the following is correct with respect to planum temporale?

Select one:
1. It is present only on dominant cerebral hemisphere
2. It is normally larger on left side
3. It specialises in visual processing
4. In schizophrenia left More than right asymmetry is noted
5. It is situated in anterior temporal surface

Answer 15

It is normally larger on left side

The planum temporale, the posterior superior surface of the superior temporal gyrus, is a highly lateralized
brain structure involved with language. In schizophrenic patients, a consistent reversal of the normal left larger- than- right asymmetry of planum temporale surface area is noted ( Planum temporale asymmetry reversal in schizophrenia)

Question 16

Knife blade atrophy is seen in

Select one:
1. Pick’s disease
2. Alzheimer’s disease
3. Lewy body dementia
4. CJD
5. Progressive supranuclear palsy

Answer 16

Pick’s disease

Knife-blade type atrophy refers to the marked atrophy of the frontal and temporal lobes with relative sparing
of parietal and occipital lobes in patients with Pick’s disease.

Question 17

Hirano bodies are seen in brain autopsy of a patient who had a history of cognitive impairment. Which of
the following diagnosis is most likely?

Select one:
1. Vascular dementia
2. Wilson disease
3. Crutzfeld Jakob disease
4. Alzheimer’s dementia
5. Lewy body dementia

Answer 17

Alzheimer’s dementia

Hirano bodies are rod-shaped eosinophilic bodies in the cytoplasm of neurons that may be set free in the
extracellular space if the neuron dies. Hirano bodies seen in Alzheimer’s are intracellular aggregates of
actin and actin-associated proteins. They are frequently seen in hippocampal pyramidal cells

Question 18

The macroscopic changes seen in Alzheimer’s disease includes

Select one:
1. Senile plaques
2. Neuronal loss
3. Ventricular enlargement
4. Vacuolisation
5. Neurofibrillary tangles

Answer 18

Ventricular enlargement

The macroscopic changes in Alzheimers disease would include Enlargement of the lateral and third
ventricles, global brain atrophy, reduction in brain weight and sulcal widening. Neuronal loss, senile
plaques, neurofibrillary tangles, reactive astrocytosis and shrinking of dendritic branching are the
microscopic changes seen in the cerebral cortex in Alzheimers disease. Cerebral atrophy and ventricular
enlargement are macroscopic changes.

Question 19

A 55-year-old lady is a known alcoholic. She drinks in binges and presents with deficits in new learning
though she could retain messages long enough to hold a conversation. The most prominent pathology in
this patient will be seen in

Select one:
1. Hippocampus
2. Dorsolateral prefrontal cortex
3 .Hypothalamus
4. Dorsal medial thalamus
5. Cerebellum

Answer 19

Dorsal medial thalamus

Wernicke’s encephalopathy is characterized by degenerative changes including gliosis and small
hemorrhages in structures surrounding the third ventricle and aqueduct (i.e. the mamillary bodies,
hypothalamus, mediodorsal thalamic nucleus, colliculi, and midbrain tegmentum), as well as cerebellar
atrophy.

Question 20

Selective cerebellar atrophy as a neuropathological change is likely to be seen in which of the following
dementias?

Select one:
1. Lewy body dementia
2. Creutzfeldt-Jakob Disease
3. Alzheimer’s dementia
4. Normal Pressure Hydrocephalus
5. Parkinson’s disease dementia

Answer 20

Creutzfeldt-Jakob Disease

In Creutzfeldt - Jakob disease, macroscopic changes would include generalised cerebral atrophy,
sometimes a selective cerebellar atrophy and ventricular enlargement. Histological changes would include status spongiosus, neuronal degeneration without inflammation and astrocytic proliferation. There is a nerve cell loss, gliosis and spongiform changes.

Question 21

A 10 year old child in a special school has challenging behaviour associated with aggression and
stereotyped motor activity. Which of the following seen in MRI is associated with autism?

Select one:
1. Cerebral atrophy
2. Hypoplastic cerebellum
3. Medial temporal atrophy
4. Caudate atrophy
5. White matter hyperintensities

Answer 21

Hypoplastic cerebellum

Hypoplasia of cerebellar vermis and to some extent the cerebellar hemispheres is documented.

Question 22

Which disease can be studied by inducing ‘autoimmune encephalomyelitis’?

Select one:
1. Acquired brain injury
2. Parkinson’s disease
3. Huntington’s disease
4. Multiple sclerosis
5. Alzheimer’s disease

Answer 22

Multiple sclerosis

Experimental autoimmune encephalomyelitis (EAE) is a laboratory model used to study the efficacy of
potential agents treating multiple sclerosis (MS). EAE is also used to investigate the pathogenesis of
autoimmunity, CNS inflammation and demyelination.

Question 23

In which of the following conditions both balloon cells and Hirano bodies are seen?

Select one:
1. Alzheimer’s disease
2. HSE encephalitis
3. Neurosyphilis
4. CJD
5. Pick’s disease

Answer 23

Pick’s disease

Hirano bodies are fusiform or spheroidal eosinophilic bodies, that are commonly observed in the
hippocampi of the elderly and are especially numerous in patients with various dementias or degenerative
diseases.

Balloon cells (BCs) are specific pathological marker of cortical malformations during brain development. Both Hirano bodies and Balloon cells are seen together in Pick’s disease.

Question 24

Arteriosclerotic changes in major arteries are most commonly found in which of the following types of
dementia?

Select one:
1. Multi-infarct dementia
2. Lewy body dementia
3. Alzheimer’s dementia
4. Parkinson’s disease dementia
5. Normal Pressure Hydrocephalus

Answer 24

Multi-infarct dementia

In multi-infarct dementia, brain damage due to multiple cerebral infarcts leads to local or general brain atrophy and ventricular enlargement. The presence of arteriosclerotic changes is commonly noted.

Question 25

You have noticed some degree of cognitive decline and weight loss in an intravenous drug user. The most
probable diagnosis is

Select one:
1. Neurosyphilis
2. Alzheimer’s dementia
3. CADASIL
4. Binswanger’s disease
5. HIV dementia

Answer 25

HIV dementia

One of the common sources of acquiring HIV infection is intravenous drug use. Subcortical dementia is
common in patients with HIV in late stages of their illness

Question 26

Which of the following is a true statement concerning human HIV disease?

Select one:
1. Psychosis is the most common HIV related psychiatric problem.
2. CSF viral load is the best predictor of HIV related CNS disease.
3. HIV cross the blood brain barrier using macrophages
4. CD4 count is the better indicator for severity than viral load
5. HIV does not cause programmed cell death of neurons

Answer 26

HIV cross the blood brain barrier using macrophages

In order to enter the brain, HIV-1 must cross the BBB using mechanisms that remain unclear. The generally
accepted model is the ‘Trojan Horse hypothesis’. HIV enters the CNS as a passenger in cells trafficking to
the brain via CD4 T cells or monocytes

Question 27

Which of the following best describes the difference between CJD and vCJD? The variant CJD has

Select one:
1. Earlier onset of ataxia
2. Negative tonsillar biopsy
3. Absence of florid plaques on autopsy
4. Earlier age of onset
5. Typical EEG changes

Answer 27

Earlier age of onset

In 1996, a new type of CJD called vCJD (variant CJD) was reported. Variant CJD appears to affect younger
people than the other forms of the disease, with an average age of death of 29 years. Death occurs on an
average within 14 months.

Question 28

Which of the following is a feature more likely to be seen in Pick’s disease than other dementias?

Select one:
1. Reactive astrocytosis
2. Gliosis
3. Tau proteins
4. Ventricular shrinkage
5. Knife blade gyri

Answer 28

Knife blade gyri

Pick’s disease is associated with selective asymmetrical atrophy of the frontal and anterior temporal lobes.
Patients also show knife blade gyri and ventricular enlargement. The histological changes in Picks disease
would include Pick’s bodies, neuronal loss and reactive astrocytosis, and these changes may be seen in the
cerebral cortex, substantia nigra, locus coereleus and basal ganglia. Pick bodies are round argyrophilic
intraneuronal inclusions and pick cells are swollen cortical pyramidal cells.

Question 29

Alpha-synuclein is a major constituent of which of the following?

Select one:
1. Neurofibrillary tangles
2. Pick’s bodies
3. Prion particles
4. Neuritic plaques
5. Lewy bodies

Answer 29

Lewy bodies are weakly eosinophilic, spherical, cytoplasmic inclusions. Lewy bodies in Parkinson’s disease and DLB contain accumulations of alpha-synuclein

Question 30

The pathological factor that correlates most with cognitive decline in Alzheimer’s disease is

Select one:
1. Burden of diffuse plaques
2. Burden of neurofibrillary tangles
3. Burden of neuritic plaques
4. Burden of gliosis
5. Burden of vascular amyloid load

Answer 30

Burden of neurofibrillary tangles

A staging scheme devised by Braak and Braak (1995) is widely used to describe the extent of tangle
related abnormalities (distribution from entorhinal cortex to isocortex) in AD and correlates well with the
severity of dementia. Stages V-VI operationally define AD.

Question 31

The spongiform appearance of brain tissue in CJD is due to

Select one:
1. Apoptosis of neuronal cells
2. Glial proliferation
3. Demyelination
4. Neuropil vacuolation
5. Excessive fibrosis

Answer 31

Neuropil vacuolation

Microscopically CJD shows a spongiform encephalopathy secondary to neuropil vacuolisation.

Question 32

Lewy bodies are eosinophilic, haloed, intra neuronal inclusions. They contain which of the following
materials?

Select one:
1. Glial tissue
2. Paired helical filaments
3. Dopamine metabolites
4. Synuclein
5. Amyloid substance

Answer 32

Synuclein

Lewy bodies contain synnuclein, Ubiquitin, protein neurofilaments, granular material, dense core vesicles
and microtubule assembly protein. In Lewy body dementia, the density of Lewy bodies is much higher in the cingulate gyrus, parahippocampal gyrus and temporal cortex.