Demyelination and Dementia NeuroPathology Flashcards
What 2 structures are damaged during the process of demyelination?
Myelin sheath itself
oligodendrocytes/ schwann cells which form myelin sheaths
What is the main Primary demyleinating disease process in adults?
Multiple Sclerosis (MS)
What Primary demyelinating diseases are more common in children?
Acutedisseminatedencephalomyelitis (self-limiting)
Acutehaemorrhagicleukoencephalitis (rapidly fatal)
What are the secondary causes of demyelination?
- Viral e.g. Progressivemultifocalleukoencephalopathy(PML) •Metabolic e.g. centralpontinemyelinosis
- Toxic agents e.g. carbon monoxide
Why does MS present as hyperintense lesions in the white matter on MRI?
Most axons are concentrated in the white matter
What CSF sign is indicative of MS?
IgGoligoclonalbandsinCSF
What focal neurological signs do patients with MS present with if they have optic nerve lsions?
opticneuritis
=> Unilateralvisualimpairment
What focal neurological signs do MS patients present with if they have lesions in the spinal cord?
- Motororsensorydeficitintrunkandlimbs
- Spasticity
- Bladderdysfunction
What focal neurological signs are present in MS patients with brainstem lesions?
- Cranialnervesigns
- Ataxia
- Nystagmus
- Internuclearopthalmoplegia
Describe the appearance of plaques in MS
- Wellcircumscribed
- Irregularshaped
- Glassy/translucentappearance
- Varyin size
- Non‐anatomicaldistribution
What areas of the brain are plaques normally found in?
- Adjacenttolateralventricles
- Corpuscallosum
- Opticnerves
- Brainstem
- Cerebellum
Explain the histological findings in an acute active MS lesion
- Microglia (digest myelin like macrophage)
- Inflammatorycells around blood vessels
Plaques grow in a perivascular distribution
Describe the histological findings in a chronic or inactive MS lesion
Gliosis (proliferation of glial cells)
Less oligodendrocytes and myelinated axons present
What is the difference in the macroscopic appearance of active and inactive MS lesions
Active = ill defined edge Inactive = well demarcated
Give examples of degenerative diseases of the cerebral cortex?
Alzheimer’sDisease
CJD
What neurodegenerative diseases originate in the basal ganglia and brainstem?
ParkinsonDisease
ProgressiveSupranuclearPalsy
HuntingtonDisease
Where else can neurodegenerative diseases present aside from the cerebral cortex, brainstem and basal ganglia?
Cerebellum (Freidrich's ataxia) Motor neurones (MND)
Dementia is an ageing process and not pathological. TRUE/FALSE?
FALSE
DementiaisNOTpartofthenormalageingprocess,itisalways pathological
Give examples of Primary Dementia
- Alzheimer’sdisease
* Lewybodydementia
Give examples of causes of secondary dementia
Multi‐infarct(vascular)dementia
•Infection(HIV,syphilis)
•Trauma
•Metabolic
What symptoms can alzheimers progress to show in the later stages?
- disorientation
- worsened memoryloss
- aphasia
- profounddisability/immobility
Patient’s with alzheimers usually die of the disease. TRUE/FALSE?
FALSE
Deathusuallyoccursduetoasecondarycause,like bronchopneumonia
Describe the macroscopic appearance of the brain in alzheimers dementia
•cortical atrophy
=> in frontal,temporalandparietallobes
(Occipital, brainstemand cerebellumspared)
•Wideningofsulci / Narrowingofgyri
•Dilatationof ventricles
What microscopic features are typical of Alzheimers disease?
- neuronalloss (+astrocyteproliferation = gliosis)
- neurofibrilliary tanngles (in hippocampus and temporal lobe)
- neuritic plaques due to amyloid angiopathy
Why is alzheimers disease thought to be more common in those with Down Syndrome (Trisomy 21)?
Genetically have more of amyloid protein precursor (on chromosome 21)
=> more at risk of amyloid angiopathy
Describe the microscopic appearance of amyloid angiopathy
- Extracellulareosinophils
- Polymerisedbetapleated sheats
- StainswithCongoRed
- Disruptsbloodbrainbarrier => local oedema
What is Lewy Body dementia?
- progressivedementia
- hallucinations
- fluctuating levelsofattention/cognition
- Fluctuationonaday‐to‐daybasis
- FeaturesofParkinsonism
What are the clinical features of Parkinson’s disease
- Lossoffacialexpression
- stooping
- shufflinggait
- slowinitiationof movements
- tiffness
- pillrollingtremor
Where in the brain does Lewy Body dementia cause degeneration?
In the substantia nigra (similar to parkinson’s)
Describe how Lewy Body Dementia appears microscopically
- Lossofpigmentedneurons
- Reactivegliosis
- RemainingneuronsmayshowLewybodies:
When are patient’s with huntington’s disease usually diagnosed and when does dementia develop?
Usually diagnosed between 35-50
dementia presents later in disease process
How does huntington’s dementia appear macroscopically in the brain?
Atrophyofbasalganglia:
-caudate nucleus andputamen
Corticalatrophyoccurslater
How does Huntington’s disease appear microscopically in the brain?
- Atrophyofstriatal neuronesthebasalganglia
- astrocyticgliosis
What condition is responsible for Fronto-Temporal dementia?
Pick’s disease
When does Pick’s disease usually present?
commencinginmiddlelife(usuallybetween50and60years)
What symptoms do patients with Pick’s disease get (relating to damage of frontal/temporal lobes)?
- Personalityandbehaviouralchange •Speechandcommunicationproblems •Changesineatinghabits
- Reducedattentionspan
Pick’s disease is rapidly progressive. How many years do patient’s normally live with this disease?
2-10 years
av. = 7
How does Pick’s disease appear macroscopically?
Extremeatrophyofcerebral cortexinfrontalandlaterin temporallobes
•Brainweight<1Kg
How does pick’s disease appear microscopically and what are the hallmark’s of this disease?
•Neuronallossandgliosis
Histologicalhallmarks:
•Pick’scells(swollenneurons)
•Intracytoplasmicfilamentous inclusions(Pick’s bodies)
What groups of patient’s are most likely to get multi-infarct dementia?
Men >women
>60 = common
BUTalsoseeninmiddle‐aged hypertensives
What clues can help to distinguish multi-infarct dementia from alzheimer’s disease
- Abruptonset
- Stepwiseprogression
- Historyofhypertensionorstroke
- Evidenceofstroke onCTorMRI
