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Flashcards in Demyelination and Dementia Deck (60):
1

what is demyelination

preferential damage to the myelin sheath with relative preservation of axons

2

what is the role of myelination

Locally confining neuronal depolarisation
Protecting axons
Forming nodes of Ranvier (precipitate rapid saltatory conduction)

3

what cell myelinates

oligodendrocytes

4

what does myelin damage cause

disrupts neuronal conduction

5

what are the acute causes of demyelination

-MS
-acute disseminates encephalomyelitis
-acute haemorrhagic leukoencephalitis

6

what are the secondary causes of demyelination

viral
-progressive mulitofcal leukoencephalopathy
metabolic insults
-central pontine myelinosis
toxic
-CO, organic solvents, cyanide

7

what is the epidemology of MS

1/1000
F:M 2:1
peak incidence 20-30yrs
association with latitude

8

what is MS

auto immune demyelinating disorder characterised by distinct episodes of neurological deficits, separated in time and which correspond to spatially separated foci of neurological injury

9

what is needed for a clinical diagnosis of MS

Two distinct neurological defects occurring at different times
A neurological defect implicating one neuro‐anatomical site, and a MRI appreciated defect at another neuro‐anatomical site
Multiple distinct (usually white matter) CNS lesions on MRI

Also supportive
Visual evoked potentials (evidence of slowed conduction)
IgG oligoclonal bands in CSF

10

what is seen on MRI in MS

areas of hyperintensity - plaques

11

what are the clinical features of MS

presentation typically with a focal neurological deficit
-optic neuritis (unilateral vision loss painful)
-spinal cord lesions (motor/ sensory deficit in trunk and limbs , spasticity, bladder dysfunction)
-brain stem lesions (CN nerve signs, ataxia, nystagmus, internuclear ophthalmoplegia)

acute/ insidious onset
relapsing and remitting / progressive

12

what type of matter does MS principally affect

white matter (axons)
cut surface of brain shows plaques, surface (grey) is normal

13

what do MS plaques look like

well circumscribed, well demarcated, irregular shaped, glassy
non anatomical and non symmetrical distribution

14

where in CNS typically gets plaques in MS

adjacent to lateral ventricles
corpus callosum
optic nerves and chiasm
brainstem
ascending and descending tracts
cerebellum
spinal cord

15

what is the histology of an active MS plaque

perivascular inflammatory cells
recruitment of microglia
ongoing demyelination

are yellow/ brown with ill defined edge

16

what is the histology of inactive plaques

gliosis
little remaining myelinating axons
oligodendrocytes and axons both reduced in numbers

grey/ brown well demarcated lesions, typically around lateral ventricles

17

what are shadow plaques in MS

reflects a degree of myelination

18

what are the risk factors for MS

lattitude
vit D deficiency
viral trigger? (EBV)
genetics- familial, HLA DRB1

19

what is the immune pathogenesis of MS

t cells
- TH1 cells – IFN‐g activating macrophages
-TH17 cells – recruiting and activating damaging leukocytes
- lymphocytic infiltration

humeral factors
-oligoclonal IgG bands on CSF

20

why is MS classed as an immune mediated disease

Lymphocytic infiltration in histology
Oligoclonal IgG bands in CSF
Genetic linkage to HLA DRB1

21

what are the degenerative diseases of the cerebral cortex

alzheimers disease
pick disease
CJD (prion disease)

22

what are the main degenerative diseases of the basal ganglia and brain stem

parkinsons, huntingtons

23

what is a degenerative diseases of the spinocerebellar

spinocerebellar ataxias

24

what are the degenerative diseases of the motor neurones

MND

25

what is the pathology of degenerative diseases

simple neuronal atrophy and subsequent gliosis

26

what is dementia

an acquired and persistent generalised disturbance of higher mental functions in an otherwise fully alert person

27

where do neurodegenerative diseases typically affect

functionally related neuronal groups

28

is dementia part of the normal ageing process

no

29

what are the primary dementias

alzheimers
lewy body
picks disease (fronto-temporal dementia)
huntingtons

30

what are the secondary dementias

other disorders that give rise to dementia:
-multi infarct (vascular)
-infection (HIV/syphilis)
-trauma
-metabolic

drugs and toxins (alcohol)
vit B12 def
paraneoplastic syndromes
intracranial SOL
chronic hydrocephalus

31

what are the most common subtypes of dementia

alzheimers
vascular
lewey body
frontotemporal (picks)

32

what is the epidemiology of alzheimers

F:M 2;1
1% in 60-65
40%+ in >85s
1% familial (amyloid precursor proteins presenilin 1 &2)
increased incidence in trisomy 21

33

what happens to symptoms of alzheimers when onset later

is more severe

34

what is the presentation of alzherimers

insidious impairment of higher intellectual function with alterations in mood and behaviour

35

what are the late features of alzheimers

progressive disorientation, memory loss, aphasia = indicates severe cortical dysfunction

profound disability, muteness and immobility

36

what causes death in alzheimers

secondary cause e,g, bronchopneumonia

37

what is the pathology of alzheimers

decrease in size and weight of brain due to cortical atrophy - in frontal, temporal and parietal lobes

widening of sulci and narrowing of gyri

compensatory dilatation of the ventricles, 2ndary hydrocephalus ex vacuo

38

what parts of brain are spared in Alzheimers

occipital lobe, brainstem, cerebellum

39

what are the microscopic features of alzheimers

extensive neuronal loss with associated astrocyte proliferation - simple neuronal atrophy and gliosis

neurofibrillary tangles - esp in hippocampus and temporal lobe

neuritic plaques - Abeta amyloid plaques, surrounded by astrocytes and microglia

amyloid angiopathy

40

what is the importance of amyloid Abeta in alzheimers

Abeta is produced by the cleavage of amyloid precursor protein APP (central element of neuritic plaques)

APP is on chromosome 21- early onset alzheimers in trisomy 21 (down s)

mutations of presenilin linked in familial alzheimers

apolipoprotein E- allele e4

41

what do Abeta oligomers activate

NMDA receptors causing excitotoxicity which causes neuronal damage in alzheimers

42

what are the histological features of amyloid angiopathy

extracellular eosinophillic accumulation

polymerised beta pleated sheats formed by Abeta

stains with congo red

disrupts BBB- serum leaking, oedema, local hypoxia

43

what are the clinical features of lewy bodies dementia

progressive dementia
hallucinations
fluctuating levels of attention/ cognition (on day to day basis)
memory affected later than in alzheimers
features of parkinsonism present at onset or emerge shortly after

44

what are the clinical features of parkinsonism

Loss of facial expression, stooping, shuffling gait, slow initiation of movements, stiffness and pill rolling tremor

45

what conditions do you get parkinsonism in

ones where the nigro-striatial dopaminergic pathways are affected
-parkinsons
-lewy body dementia
-drugs
-trauma
-multi system atrophy
-progressive supranuclear palsy
-cortico-basal degeneration

46

what are the pathological features of lewy bodies dementia

degeneration of the substantia nigra - pallor

47

what is seen microscopically in lewy bodies dementia

loss of pigmented neurones
reactive gliosis, microglial accumulation

remaining neurones may show lewy bodies
-Single / multiple intracytoplasmic, eosinophillic, round/ elongated bodies that have a dense core and a surrounding pale halo
(Aggregates of a‐synuclein and ubiquitin)

48

what are the clinical features of huntingtons disease

relentlessly progressive neuropsychiatric disorder
onset usually 35-50
emotional, cognitive and motor disturbance
-chorea
-myoclonus
-clumsiness
slurred speech
-depression
-irritability
-apathy

develop dementia later

49

what is the inheritance pattern of huntingtons

AD
on chromosome 4P (additional CAG repeats- disease penetrant when >35 repeats)

50

what is seen pathologically in huntingtons

atrophy of basal ganglia, caudate nucleus and putamen
cortical atrophy occurs later
compensatory expansion in the ventricles

51

what is seen histologically in huntingtons

simple neuronal atrophy
pronounced astrocytic gliosis

52

what is fronto-temporal dementia

(picks disease)
progressive dementia commencing in middle life (50-60s) characterised by progressive changes in character and social deterioration causing impairment of intellect, memory and language

53

what are the symptoms of fronto-temporal dementia

personality and behavioural change
speech and communication problems
changes in eating habits
reduced attention span

duration of disease usually 2-10 years

54

what is seen pathologically in fronto-temporal dementia

extreme atrophy of cerebral cortex in frontal the temporal lobes
neuronal loss and gliosis

55

what is seen histologically in fronto-temporal dementia

pick cells (swollen neurones)
intracytoplasmic filamentous inclusions (picks bodies)

56

what is multi-infarct dementia (MID)

disorder involving a deterioration in mental functioning due to cumulative damage to the brain through hypoxia or anoxia as a result of multiple blood clots within the blood vessels supplying the brain

Successive, multiple cerebral infarctions cause increasingly larger areas of cell death and damage. When a sufficient area of the brain is damaged, dementia results.

57

who gets MID

men
middle age hypertensives
>60s

58

why are patients with MID so prone to depression and anxiety

as have insight- aware of their mental deficits

59

how do you distinguish MID from alzheimers

abrupt onset
stepwise progression
history of hptx or stroke
evidence of stroke will be seen on CT/ MRI

60

what are the pathological findings of MID

large vessel infarcts
-more common
-scattered through hemispheres
-atheroma of large cerebral arteries provoke thromboembolsim

small vessel (lacuna) infarcts)
-rarer
-central, subcortical distribution
-related to long standing hypertension and arteriosclerosis of small vessels