Degenerative Toxic and Metabolic Disorders of CNS Flashcards
What is dementia?
Gradual decline in cognitive function
Memory defects, aphasia, apraxia, agnosia, loss of abstract though, behavior/personality change, impaired judgment
Alzheimer’s
Inheritance
10% are familial (early onset)
90% are sporadic
Alzheimer’s
What genes may be involved in early onset?
Mutations in APP, presenilin 1 or 2
Down Syndrome increases risk
apoE4 increases risk
apoE2 decreases risk
Alzheimer’s
What is the basic pathogenesis?
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
Alzheimer’s
Gross appearance of brain
Atrophic gyri, enlarged sulci
Enlarged ventricles due to atrophy (Hydrocephalus ex vacuole)
Alzheimer’s
What are neurofibrillary tangles?
Inclusions of hyperphosphorylated tau bunched up inside the neurons
They are neurotoxic when they build up
Alzheimer’s
Where do amyloid plaques build up?
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
Lewy Body Disease
What are Lewy bodies?
Symptoms?
Aggregates of alpha-synuclein
Initially get dementia and visual hallucinations, followed by Parkinsonian symptoms
Frontotemporal lobar degeneration
Symptoms
Destruction of frontal and temporal lobes
Change in personal and social conduct, often with disinhibition and language changes
Frontotemporal lobar degeneration
Caused by…?
Degeneration of frontal and temporal lobes linked to mutations in tau protein gene on chr 17
Pick’s Disease
Symptoms
Frontal and temporal lobe destruction
Presents with aphasia, goes on to have dementia later
Pick’s Disease
What is seen on histology?
Pick bodies – aggregates of cytoplasmic inclusions (tau protein) in hippocampus and cortex
Parkinson’s Disease
Inheritance
Mostly sporadic
Some cases due to familial inheritance with mutations in alpha-synuclein gene
Parkinson’s Disease
Clinical Definition
Fluctuating cognition
Visual hallucinations
TRAP –resting tremor (pill rolling), Cogwheel rigidity, Akinisia/bradykinisia, Postural instability and gait ataxia
Parkinson’s Disease
What is seen on histology?
Lewy bodies in the neurons, composed of alpha-synuclein
Loss of dopaminergic pigmented neurons in substantia nigra
Huntington’s Disease
Cause
Autosomal dominant disorder caused by (CAG) trinucleotide repeats inserted in huntingtin gene on chr 4
Huntington’s Disease
What is seen on gross imaging?
Degeneration of the caudate nucleus, thus impairing the indirect pathway and causing excess movement
Huntington Disease
Symptoms
Chorieform movements
Psychiatric symptoms progressing to dementia and cachexia
Multiple System Atrophy
Symptoms
Parkinsonism
Cerebellar ataxia
Autonomic dysfunction
Multiple System Atrophy
Pathology
Glial cytoplasmic inclusions containing alpha-synuclein
ALS
Symptoms
See both UMN (spasticity and hyperreflexia) and LMN (atrophy and muscle weakness) signs
Muscle atrophy
ALS
Inheritance
Most cases are sporadic
Familial cases may be related to mutation in superoxide dismutase gene on chr 21
ALS
What might be seen on spinal cord histology?
Degeneration of CSTs
Loss of LMNs in anterior horns
Werdnig Hoffman Disease
Inheritance
Autosomal recessive
Werdnig Hoffman Disease
Symptoms
“Floppy baby”
Degeneration of LMNs and anterior horn cells leads to neurogenic atrophy of distal muscles
Friedreich Ataxia
Cause
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
Friedreich Ataxia
Symptoms
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
Friedreich Ataxia
What other condition is it associated with?
Hypertrophic cardiomyopathy
What is Vascular Dementia?
Multifocal infarction and injury due to HTN, atherosclerosis, or vasculitis
Wernicke Korsakoff Syndrome
Describe the two phases
Acute Wernicke encephalopathy (nystagmus, ophthalmoplegia, cerebellar dysfunction, altered mental status)
Chronic Korsakoff psychosis (confabulation, amnesia)
How should Wernicke encephalopathy be treated?
Thiamine supplementation
What gross changes may be seen in the brain in Wernicke’s encephalopathy?
Mammillary body hemorrhage and atrophy
Acute–scattered petechial hemorrhages on mamm bodies
Chronic – mamm bodies shrunken and discolored
Methanol Toxicity
What does it cause?
Global hypoxic injury leading to white matter necrosis and hemorrhages/hemorrhagic infarction of putamen and claustrum
Carbon Monoxide Poisoning
What does it cause?
Cerebral edema
White matter petechial hemorrhages
Hemorrhagic necrosis of globus pallidus
Subacute Combined Degeneration
Caused by…?
Vitamin B12 deficiency
-Pernicious anemia, chronic gastritis, surgical resection, tumors, strict veggie diet
Subacute Combined Degeneration
Symptoms
Megaloblastic anemia
Weakness, paresthesias of hands and feet, loss of vibration sense, ataxia
Central Pontine Myelinolysis
Caused by…? What is seen on histology of pons?
Caused by too rapid correction of hyponatremia
See large triangular lesion with myelin loss in pons
Hepatic encephalopathy
What kinds of cells are seen? Caused by…?
Alzheimer type II astrocytes (nuclei are large and clear appearing)
Caused by hyperammonemia (liver failure)
