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52 Cards in this Set
- Front
- Back
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Diffential diagnosis for patients with dementia
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• Causes of dementia can include:
Vascular disease (including multi-infarct dementia) Parkinson’s disease Pick’s disease Huntington’s disease Normal pressure hydrocephalus Metabolic diseases, including Vitamin B12 deficiency, Chronic drug intoxication, hypothyroidism, and alcoholism Infectious causes, including HIV, neurosyphilis, and bacterial meningitis Major depression •The clinical diagnosis of Alzheimer’s disease can be made with 85% to 90% accuracy. |
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What is depicted at the arrow?
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Acute infarct
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What is depicted at the arrow?
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Healed cerebral infarct
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What is depicted at the arrow?
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cerebral cortical spongiform encephalopathy
Ex. Prion disease, where loss of neurons (see image below) leads to dementia. Champagne bubbles characteristic of Prion disease can be seen in Spongiform Encephalopathy |
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What disease is depicted here?
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Spongiform encephalopathy
Ex. Prion disease, where loss of neurons (see image below) leads to dementia. Champagne bubbles characteristic of Prion disease can be seen in Spongiform Encephalopathy |
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What disease did this patient have?
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Alzheimer's Disease
Alzheimer’s disease is a pathological diagnosis characterized grossly by cortical atrophy and microscopically by neurofibrillary tangles (NFT’s) and senile plaques (SP’s) |
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What hallmark of which disease is depicted here?
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Neurofibrillary tangle in AD
NFT’s are intracellular lesions of Alzheimer’s disease and develop from accumulation of hyperphosphorylated tau protein Remains of damaged neuronal microtubules (as the intermediate filaments of the neuronal skeleton break down, tau protein is accumulated) - tau is a microtubule-associated protein. NFT are not specific just for AD, this is also seen in Progressive Supranuclear Palsy and post trauma ex. football players therefore they are NOT pathognomonic for AD |
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What disease is depicted here? What is depicted at the arrows?
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Intracellular inclusion bodies consisting of paired helical filaments that appear in a characteristic double- helix shape
Are resistant to degradation by acid and alkali Seen in AD as part of neurofibrillary tangles |
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What are neurofibrillary tangles?
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-Intracellular inclusion bodies consisting of paired helical filaments that appear in a characteristic double-helix shape
-Filaments appear to be composed of a hyperphosphorylated microtubule-associated protein called tau -Remains of damaged neuronal microtubules |
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What is depicted here?
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Cortical Senile Plaques
Only really seen in AD Central core of amyloid |
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What is depicted here? Which disease is this?
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Senile Plaques, pathognomonic for AD. Extracellular lesions that develop from accumulation of amyloid protein
Red: Central core of amyloid (Made of beta sheets) Yellow: sprouting neurite processes which seem to be a failed attempt at neuronal generation This is AD |
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Which part of the brain is this?
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Hippocampus
Location where senile plaques in AD are first seen usually. The entorhinal cortex (gateway to hippocampus) and amygdala |
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What is this? Which disease is it indicative of?
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It is a Hirano Body, made of actin
Found in AD Aggregates of broken down actin filaments found in neuronal cytoskeleton |
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What is this depicting? Where is it found?
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These are ACTIN FILAMENTS found in HIRANO BODIES in AD
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What is seen here? What disease is this?
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Granulo-vacuolar degeneration with tubulin aggregates, found in AD
Described as birds-eye looking intracellular inclusions that are made up of tubulin (type of intermediate filament) |
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What is the relevance of Down's Syndrome to a discussion of Alzheimer's? What is shown in this picture?
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In Down's there are plaques, tangles and brain abnormalities; originally it was thought that AD could originate on the same chromosome as Down's because it also leads to plaques and tangles
Chromosome 21 codes for a protein called Amyloid Precursor Protein [APP] (transmembrane protein, involved in fast axonal transport - beta portion gets clipped and accumulates in AD) |
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What is shown here?
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Congo red positive plaques in Down's Syndrome
Patients with Down’s syndrome are more at risk of developing NFT’s and Senile Plaques at a much younger age because of their chromosomal trisomy |
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What is shown here?
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Plaques with amyloid core - as in AD
Patients with Down’s syndrome are more at risk of developing NFT’s and Senile Plaques at a much younger age because of their chromosomal trisomy |
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What is shown here?
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Abnormalities in the basal forebrain (in particular the basal nucleus of Meynert) seen in AD
There is a decreased cell density of the cholinergic neurons here Hypothesis is that cell death in the nucleus basalis may be the reason for cortical atrophy in AD |
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What is shown here? Which is abnormal?
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Top: Normal Cholinergic Neurons in the Basal Nucleus of Meynert
Bottom: Abnormal Cholinergic Neurons in AD Hypothesis is that cell death in the nucleus basalis may be the reason for cortical atrophy in AD Drugs (eg. Aricept) that improve cholinergic integrity in this system help give 6-12 months of better functioning, but patients seem to become refractory to them |
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What has genetic research on AD told us?
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- Research has produced evidence of a link between Alzheimer’s disease and chromosomes 1,10,14,19 and 21
-Chromosomes 1,14,and 21 have been linked with early-onset Alzheimer’s disease, an extremely rare form of the disease -ApoE4 gene located on chromosome 19 has been associated with late-onset Alzheimer’s disease, the most common form of the disease, so has Beta-Catenin gene on chromosome 10. Patients homozygous for the apolipoprotein E4 allele have a 60% increase in risk of developing early-onset Alzheimer’s disease. Chromosomes 1, 14: single point mutation in the PRESENILIN genes will cause 100% AD Hereditary form of Alzheimer's only makes of 10% The overwhelming majority is sporadic= 90% |
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What is PIck's Disease?
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-frontotemporal dementia
-Progressive dementia in middle or late life -Higher incidence in males -Cerebral gyral atrophy of frontal and temporal lobes, sparing posterior 2/3 of the superior gyrus -Pick bodies and “balloon” cells |
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What disease is this? Which lobes are effected
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Pick's disease
Affects both frontal and temporal lobes Pick’s disease presents with “knife-blade”, “wind-swept” atrophy of the frontotemporal regions of the brain Cerebral gyral atrophy of frontal and temporal lobes, sparing posterior 2/3 of the superior temporal gyrus The early deficits in Pick’s disease are often in personality, while higher cognition often remains intact |
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What disease is this?
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Pick's disease
Affects both frontal and temporal lobes Pick’s disease presents with “knife-blade”, “wind-swept” atrophy of the frontotemporal regions of the brain Cerebral gyral atrophy of frontal and temporal lobes, sparing posterior 2/3 of the superior temporal gyrus The early deficits in Pick’s disease are often in personality, while higher cognition often remains intact |
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What is shown here?
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Silver stain showing Pick Bodies
cause it to become spherical and “balloon” cells, also strain with tau-antibody |
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What is shown here?
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Left: nucleus
Right: pick body Pick bodies (intraneuronal inclusions) which cause it to become spherical and “balloon” cells, also strain with tau-antibody |
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Parkinson's disease: clinical features, pathology, and related syndromes
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-Relatively common (1:1000) Older people
-Clinical features: Tremor, bradykinesia, rigidity,instability of posture and gait, mask- like facies -Pathology: loss of neuromelanin-bearing nerve cells; formation of Lewy bodies -PARKINSONIAN SYNDROME: Carbon monoxide, drugs (e.g.phenothiazines), manganese, arteriosclerosis (?), encephalitis (esp. von Economo’s disease), ALS-PD |
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What disease is this? Is the top or bottom abnormal?
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Top: loss of neuromelanin- Parkinson's
Bottom: normal The histological hallmark of Parkinson’s disease is depigmentation of the substantia nigra in the midbrain loss of dopaminergic neurons |
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What is shown here?
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A Lewy body in a dying neuron
Lewy bodies: intracellular, eosinophilic inclusion with surrounding clear halos- are often seen in the midbrain of Parkinson’s patients (HALLMARK OF PD) |
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What is shown here?
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Lewy body with halo in PD
Lewy bodies: intracellular, eosinophilic inclusion with surrounding clear halos- are often seen in the midbrain of Parkinson’s patients (HALLMARK OF PD) |
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What disease is this?
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Diffuse Lewy Body disease
Second-most common cause of dementia (second to AD) in the United States Comorbid with AD: 30% with AD also have diffuse lewy body disease (both are diseases of aging) Lewy bodies not just in substantia nigra but throughout brain |
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What is progressive supranuclear palsy?
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-Postural instability, dysphagia/dysarhria, supranuclear gaze palsy, marked axial rigidity
-Neurofibrillary tangles in many subcortical structures (accumulation of tau protein) -Resistant to treatment with antiparkinsonian agents |
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What is depicted here?
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This is supranuclear palsy: Substantia nigra degeneration like Parkinson’s, but Neurofibrillary tangles rather than Lewy bodies
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What is depicted here?
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A globoid neurofibrillary tangle in supranuclear palsy
tangles in many subcortical structures (accumulation of tau protein), like the substantia nigra Resistant to treatment with antiparkinsonian agents |
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What are the hallmarks of Huntington's disease?
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-Chorea, neuropsychiatric disturbances, progressive dementia
-Gene linked to chromosome 4 and identified (huntingtin); “unstable repeat disease” -Atrophy of caudate and dorsal putamen -Treatment is symptomatic |
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What is depicted here?
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Huntington's disease
Note the atrophy of the caudate nuclei Damage to the caudate in Huntington’s disease usually begins with the tail (anatomically found in the temporal horn of the lateral ventricle next to the hippocampus and geniculate) and progresses to involve the head Hence, degeneration involving the head of the caudate suggests advanced disease (as seen in image below) |
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What is depicted here?
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Huntington's disease: Proliferation of large gemistocytes (reactive astrocytes) replace neurons
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What is amyotrophic lateral sclerosis?
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-Atrophic weakness of hands and forearms, slight spasticity of the legs, and generalized hyperreflexia, with normal sensation
-Degeneration of anterior horn cells and lower brainstem motor nuclei with gliosis -Loss of large myelinated fibers in motor nerves -Skeletal muscle shows denervation atrophy -Corticospinal tract degeneration |
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What disease is this? What is depicted here?
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ALS
Atrophy of the anterior spinal roots Loss of large myelinated fibers in motor nerves |
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What disease is depicted here? What does each color indicate?
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ALS
RED: Anterior horn atrophy GREEN: Lateral corticospinal tract degeneration YELLOW: Anterior part (10% of neurons) of corticospinal tract degeneration Corticospinal tract degeneration |
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What is shown here?
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Dying neurons in ALS
Loss of large myelinated fibers in motor nerves |
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What is shown here?
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Ischemic red neuron in ALS
Dying neuron |
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What is shown here?
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Muscle atrophy in ALS
Loss of neuronal stimulation= Skeletal muscles shows denervation atrophy |
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Which brain is diseased?
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Left! Note the atrophy of the olivarynucleus and pons in OLIVOPONTOCEREBELLAR ATROPHY
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What is wrong with this picture?
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Pons atrophy in OLIVOPONTOCEREBELLAR ATROPHY
Missing pons and shriveled up medullary olives and cerebellum |
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What are the symptoms and pathology of Olivopontocerebellar atrophy?
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- Ataxia: first in legs, then in arms/hands and bulbar musculature
- Some develop symptoms of Parkinsonism - Degeneration of MCP’s, cerebellar white matter, and the pontine, olivary, and arcuate nuclei; Purkinje cell loss variable - “Dying-back” of axons; secondary myelin loss- Part of “multiple system atrophy” |
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What is depicted here?
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Top: normal
Bottom: Atrophy in pons in Olivopontocerebellar atrophy Degeneration of MCP’s, cerebellar white matter, and the pontine, olivary, and arcuate nuclei |
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What is depicted here? Which is normal?
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Top: normal olive
Bottom: Glial proliferation and loss of neurons in Olivopontocerebellar atrophy Degeneration of MCP’s, cerebellar white matter, and the pontine, olivary, and arcuate nuclei |
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Which is abnormal? What disease is this?
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Top: normal pons
Bottom: Loss of myelin fibers and loss of neurons in Olivopontocerebellar atrophy Degeneration of MCP’s, cerebellar white matter, and the pontine, olivary, and arcuate nuclei |
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What is depicted here? What disease is this?
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Loss of cerebellar white matter in Olivopontocerebellar atrophy
Purkinje cells are lost in olivopontocerebellar degeneration in addition to cells of the pons and inferior olive. Purkinje cell loss is variable. Remember that Purkinje cells receive their inputs from the mossy fibers arising from the inferior olive therefore generation of the olive leads to transsynaptic degeneration of the Purkinje cells |
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What is depicted here? What disease is this?
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Swollen Purkinje cell axons = torpedoes
Loss of Purkinje fibers due to transneuronal atrophy secondary to loss of climbing fibers from the inferior olive in Olivopontocerebellar atrophy Damaged Purkinje cell filaments in olivopontocerebellar degeneration appear as “torpedoes” on microscopy “Dying-back” of axons; secondary myelin loss Part of “multiple system atrophy” |
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What disease is this?
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Friedreich's ataxia:
-Most common spastic hereditary ataxia -Gene mapped chromosome 9 but not identified (autosomal recessive inheritance) -Degeneration of posterior columns, Clarke’s nucleus, spinocerebrellar tracts (especially dorsal), distal corticospinal tracts -50% die from cardiac arrhythmias |
