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Neurology > Demyelination and dementia > Flashcards

Demyelination and dementia Flashcards

1
Q

What is demyelination?

A

Preferential damage to the myelin sheath

Relative preservation of the axons

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2
Q

What is the function of oligodendrocytes?

A

Locally confining neuronal depolarisation
Protecting axons
Forming nodes of ranvier

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3
Q

What are examples of primary demyelinating disorders?

A

MS
Acute disseminated encephalomyelitis
Acute haemorrhagic leukoencephalitis

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4
Q

What are examples of secondary demyelinating disorders?

A

Viral: PML
Metabolic: central pontine myelinolysis
Toxic: CO, organic solvents, cyanide

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5
Q

What is MS?

A

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

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6
Q

What is required for the clinical diagnosis of MS?

A

Two distinct neurological deficits occurring at different times
A neurological deficit implicating one neuro-anatomical site and a MRI appreciated deficit at another neuro-anatomical site
Multiple distinct CNS lesions on MRI

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7
Q

What are tests that can be run in MS to support the diagnosis?

A

Visual evoked potentials; evidence of slowed conduction

IgG oligoclonal bands in CSF

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8
Q

What are the clinical features of MS?

A

Optic neuritis
Spinal cord lesions; motor or sensory deficit in trunk and limbs, spasticity, bladder dysfunction
Brain stem lesion: CN sign, ataxia, nystagmus, INO

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9
Q

Whatare the different types of MS?

A

Acute or insidious

Relapsing and remitting

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10
Q

What does MS look like morphologically?

A

White matter disease

Cut surface shows plaques

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11
Q

What are plaques in MS?

A 
Well circumscribed, well demarcated
Irregular shaped areas
Glassy, translucent appearance
Vary from small to large
Non-anatomical distribution
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12
Q

What are frequently affected locations in MS?

A 
Adjacent to lateral ventricles
Corpus callosum
Optic nerves and chiasm
Brainstem
Ascending and descending fibre tracts
Cerebellum
Spinal cord
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13
Q

What will active plaques show?

A

Perivascular inflammatory cells
Microglia
Ongoing demyelination

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14
Q

What will inactive plaques show?

A

Gliosis
Little remaining myelinated axons
Oligodendrocytes and axons reduced in number

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15
Q

Where are acute lesions commonly found?

A

Surrounding white matter

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16
Q

Where are chronic lesions commonly found?

A

Around lateral ventricles

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17
Q

What are the environmental factors of MS?

A

Assoc with latitude
Relationship with vit D deficiency
EBV viral trigger

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18
Q

What are the genetic risk factors for MS?

A

HLA DRB1

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19
Q

Why is MS classified as an immune mediated disease?

A

Lymphocytic infiltration in histology
Oligoclonal IgG bands in CSF
Genetic linkage to HLA DRb1

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20
Q

What are degenerative diseases of the cerebral cortex?

A

Alzheimer’s
Pick Disease
CJD

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21
Q

What are degenerative diseases of the basal ganglia and brain stem?

A

PD
Progressive supranuclear palsy
Multiple system atrophy
Huntington’s disease

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22
Q

What are degenerative diseases of the spinocerebellar system?

A

Friedreich Ataxia

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23
Q

What are degenerative diseases of the motor neurons?

A

MND

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24
Q

What is the pathogenesis of degenerative diseases?

A

Simple neuronal atrophy and subsequent gliosis

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25
Q

What is dementia?

A

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

26
Q

What are the primary dementias?

A

Alzheimer’s
Lewy body
Pick’s disease
Huntington’s

27
Q

What are the secondary dementias?

A 
Vascular dementia
Infection; HIV, syphilis
Tauma, metabolic
Alcohol
B1 
Paraneoplastic syndromes
SOL
Chronic hydrocephalus
28
Q

What is the commonest dementia?

A

Alzheimer’s

29
Q

What genes are implicated in alzheimer’s?

A

Amyloid precursor protein (APP) - chromosome 21
Presenilin 1 - chromosome 14
Presenilin 2 - chromosome 1

30
Q

What are the clinical features of alzheimer’s disease?

A

Insidious impairment of higher intellectual function with alterations in mood and behaviour
Later: progressive disorientation, memory loss and aphasia

31
Q

What can be seen macroscopically in alzheimer’s disease?

A

Cortical atrophy in frontal, temporal and parietal lobes
Widening of sulci and narrowing of gyri
Hydrocephalus ex vacuo

32
Q

What areas of the brain tend to be spared in alzheimer’s disease?

A

Occipital
Brainstem
Cererbellum

33
Q

What are the microscopic features of alzheimer’s disease?

A

Extensive neuronal loss with assoc astrocyte proliferation
Neurofibrillary tangles
Neuritic plaques

34
Q

What are neurofibrillary tangles?

A

TAU protein, assoc with microtubules

Intracytoplasmotic

35
Q

Where can neurofibrillary tangles be found?

A

Hippocampus and temporal lobes

36
Q

Are neurofibrilary tangles a good indicator of disease severity?

A

No

37
Q

What are neuritic plaques?

A

A-beta amyloid plaques

38
Q

Where can neuritic plaques be found?

A

Surrounding astrocytes and microglia

39
Q

How is A-beta amyloid produced?

A

Cleavage of amyloid precursor protein

40
Q

What will amyloid stain with?

A

Congo red

41
Q

What is the impact of amyloid angiopathy in the brain?

A

Serum leaking
Oedema
Local hypoxia

42
Q

What is lewy body dementia?

A

Progressive dementia along with hallucinations and fluctuating levels of attention and cognition
PARKINSONISM

43
Q

Is memory affected at the start of lewy body dementia?

A

No

44
Q

What are the classical features of parkinson’s?

A 
Loss of facial expression
Stooping
Shuffling
Bradykinesia
Stiffness
Pill rolling tumour
45
Q

What can cause parkinsonism?

A 
Idiopatic PD 
Lewy body dementia
Drugs; phenothiazines
Trauma; dementia pugilistica
Multi-system atrophy 
Progressive supranuclear palsy
Cortio-basal degeneration
46
Q

What is the pathogenesis of parkinson’s?

A

Loss of dopaminergic neurons in the substantia nigra

47
Q

What is seen macroscopically in lewy body dementia?

A

Pallor in substantia nigra where the pigmented dopaminergic neurones should run

48
Q

What is seen microscopically in lewy-body dementia?

A

Loss of pigmented neurones
Reactive gliosis
Microglial accumulation
Aggregates of alpha-synuclein and ubiquitin

49
Q

What are the classical clinical features of huntington’s disease?

A

Emotional
Cognitive
Motor disturbance; chorea

50
Q

What is the inheritance of huntington’s disease?

A

Chromosome 4
CAG repeats
Shows genetic anticipation

51
Q

What is seen macroscopically in huntington’s disease?

A

Atrophy of striatum

Frontal and parietal atrophy occurs later

52
Q

What is seen microscopically in huntington’s disease?

A

Simple neuronal atrophy of striatal neurones

Pronounced astrocytic gliosis

53
Q

What is Pick’s disease (frontotemporal dementia)?

A

Progressive dementia commencing in middle life characterised by changes in character and social deterioration leading onto impairment of intellect, memory and language

54
Q

What are the symptoms of frontotemporal dementia?

A

Personality and behavioural change
Speech and communication problems
Changes in eating habits
Reduced attention span

55
Q

What can be seen macroscopically in frontotemporal dementia?

A

Extreme atrophy of cerebral cortex in frontal and later in temporal lobes

56
Q

What is seen microscopically in frontotemporal dementia?

A

Neuronal loss and gliosis
Pick’s cells (swollen neurones)
Intracytoplasmic filamentous inclusions known as Pick’s bodies

57
Q

What is multi-infarct dementia?

A

Disorder involving a deterioration in mental function 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

58
Q

Who is most likely affected by vascular dementia?

A

Men after age of 60

Middle-aged hypertensives

59
Q

How can alzheimer’s and MID be differentiated?

A

Abrupt onset
Stepwise progression
History of hypertension or stroke
Evidence of stroke seen on CT or MRI

60
Q

What is the morphological appearance of MID?

A

Large vessel infarcts
Atheroma of large cerebral arteries
Lacunar infarcts; related to longstanding hypertension and arteriosclerosis of small vessels

Neurology (48 decks)

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