Degenerative Toxic and Metabolic Disorders of CNS

Question 1

What is dementia?

Answer 1

Gradual decline in cognitive function

Memory defects, aphasia, apraxia, agnosia, loss of abstract though, behavior/personality change, impaired judgment

Question 2

Alzheimer’s

Inheritance

Answer 2

10% are familial (early onset)

90% are sporadic

Question 3

Alzheimer’s

What genes may be involved in early onset?

Answer 3

Mutations in APP, presenilin 1 or 2

Down Syndrome increases risk

apoE4 increases risk

apoE2 decreases risk

Question 4

Alzheimer’s

What is the basic pathogenesis?

Answer 4

APP is normally cleaved by an alpha-secretase that creates a product that is recyclable.

When APP gets cleaved by a beta-secretase, A-Beta-amyloid builds up and cannot be degraded. Causes buildup of Lewy bodies in neurons, leading to neuronal death

Question 5

Alzheimer’s

Gross appearance of brain

Answer 5

Atrophic gyri, enlarged sulci

Enlarged ventricles due to atrophy (Hydrocephalus ex vacuole)

Question 6

Alzheimer’s

What are neurofibrillary tangles?

Answer 6

Inclusions of hyperphosphorylated tau bunched up inside the neurons

They are neurotoxic when they build up

Question 7

Alzheimer’s

Where do amyloid plaques build up?

Answer 7

Plaques of A-beta amyloid buildup extracellularly and in the vessels (amyloid angiopathy)

Get inbetween the media and adventitia, may lead to increased risk of vessel rupture

Question 8

Lewy Body Disease
What are Lewy bodies?
Symptoms?

Answer 8

Aggregates of alpha-synuclein

Initially get dementia and visual hallucinations, followed by Parkinsonian symptoms

Question 9

Frontotemporal lobar degeneration

Symptoms

Answer 9

Destruction of frontal and temporal lobes

Change in personal and social conduct, often with disinhibition and language changes

Question 10

Frontotemporal lobar degeneration

Caused by…?

Answer 10

Degeneration of frontal and temporal lobes linked to mutations in tau protein gene on chr 17

Question 11

Pick’s Disease

Symptoms

Answer 11

Frontal and temporal lobe destruction

Presents with aphasia, goes on to have dementia later

Question 12

Pick’s Disease

What is seen on histology?

Answer 12

Pick bodies – aggregates of cytoplasmic inclusions (tau protein) in hippocampus and cortex

Question 13

Parkinson’s Disease

Inheritance

Answer 13

Mostly sporadic

Some cases due to familial inheritance with mutations in alpha-synuclein gene

Question 14

Parkinson’s Disease

Clinical Definition

Answer 14

Fluctuating cognition

Visual hallucinations

TRAP –resting tremor (pill rolling), Cogwheel rigidity, Akinisia/bradykinisia, Postural instability and gait ataxia

Question 15

Parkinson’s Disease

What is seen on histology?

Answer 15

Lewy bodies in the neurons, composed of alpha-synuclein

Loss of dopaminergic pigmented neurons in substantia nigra

Question 16

Huntington’s Disease

Cause

Answer 16

Autosomal dominant disorder caused by (CAG) trinucleotide repeats inserted in huntingtin gene on chr 4

Question 17

Huntington’s Disease

What is seen on gross imaging?

Answer 17

Degeneration of the caudate nucleus, thus impairing the indirect pathway and causing excess movement

Question 18

Huntington Disease

Symptoms

Answer 18

Chorieform movements

Psychiatric symptoms progressing to dementia and cachexia

Question 19

Multiple System Atrophy

Symptoms

Answer 19

Parkinsonism

Cerebellar ataxia

Autonomic dysfunction

Question 20

Multiple System Atrophy

Pathology

Answer 20

Glial cytoplasmic inclusions containing alpha-synuclein

Question 21

ALS

Symptoms

Answer 21

See both UMN (spasticity and hyperreflexia) and LMN (atrophy and muscle weakness) signs

Muscle atrophy

Question 22

ALS

Inheritance

Answer 22

Most cases are sporadic

Familial cases may be related to mutation in superoxide dismutase gene on chr 21

Question 23

ALS

What might be seen on spinal cord histology?

Answer 23

Degeneration of CSTs

Loss of LMNs in anterior horns

Question 24

Werdnig Hoffman Disease

Inheritance

Answer 24

Autosomal recessive

Question 25

Werdnig Hoffman Disease | Symptoms

Answer 25

"Floppy baby" Degeneration of LMNs and anterior horn cells leads to neurogenic atrophy of distal muscles

Question 26

Friedreich Ataxia | Cause

Answer 26

Autosomal recessive Trinucleotide repeat (GAA) in frataxin gene on chr 9 Frataxin is involved in mitochondrial iron regulation and free radicals build up if it is not functional

Question 27

Friedreich Ataxia | Symptoms

Answer 27

Degeneration of Cerebellum leads to ataxia Degeneration of spinal cord tracts leads to loss of vibration and proprioception, muscle weakness, loss of deep tendon reflexes

Question 28

Friedreich Ataxia | What other condition is it associated with?

Answer 28

Hypertrophic cardiomyopathy

Question 29

What is Vascular Dementia?

Answer 29

Multifocal infarction and injury due to HTN, atherosclerosis, or vasculitis

Question 30

Wernicke Korsakoff Syndrome Describe the two phases

Answer 30

Acute Wernicke encephalopathy (nystagmus, ophthalmoplegia, cerebellar dysfunction, altered mental status) Chronic Korsakoff psychosis (confabulation, amnesia)

Question 31

How should Wernicke encephalopathy be treated?

Answer 31

Thiamine supplementation

Question 32

What gross changes may be seen in the brain in Wernicke's encephalopathy?

Answer 32

Mammillary body hemorrhage and atrophy Acute--scattered petechial hemorrhages on mamm bodies Chronic -- mamm bodies shrunken and discolored

Question 33

Methanol Toxicity | What does it cause?

Answer 33

Global hypoxic injury leading to white matter necrosis and hemorrhages/hemorrhagic infarction of putamen and claustrum

Question 34

Carbon Monoxide Poisoning | What does it cause?

Answer 34

Cerebral edema White matter petechial hemorrhages Hemorrhagic necrosis of globus pallidus

Question 35

Subacute Combined Degeneration | Caused by...?

Answer 35

Vitamin B12 deficiency -Pernicious anemia, chronic gastritis, surgical resection, tumors, strict veggie diet

Question 36

Subacute Combined Degeneration | Symptoms

Answer 36

Megaloblastic anemia Weakness, paresthesias of hands and feet, loss of vibration sense, ataxia

Question 37

Central Pontine Myelinolysis | Caused by...? What is seen on histology of pons?

Answer 37

Caused by too rapid correction of hyponatremia See large triangular lesion with myelin loss in pons

Question 38

Hepatic encephalopathy | What kinds of cells are seen? Caused by...?

Answer 38

Alzheimer type II astrocytes (nuclei are large and clear appearing) Caused by hyperammonemia (liver failure)