Demyelination and dementia

Question 1

What is demyelination?

Answer 1

Preferential damage to the myelin sheath

Relative preservation of the axons

Question 2

What is the function of oligodendrocytes?

Answer 2

Locally confining neuronal depolarisation
Protecting axons
Forming nodes of ranvier

Question 3

What are examples of primary demyelinating disorders?

Answer 3

MS
Acute disseminated encephalomyelitis
Acute haemorrhagic leukoencephalitis

Question 4

What are examples of secondary demyelinating disorders?

Answer 4

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

Question 5

What is MS?

Answer 5

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

Question 6

What is required for the clinical diagnosis of MS?

Answer 6

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

Question 7

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

Answer 7

Visual evoked potentials; evidence of slowed conduction

IgG oligoclonal bands in CSF

Question 8

What are the clinical features of MS?

Answer 8

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

Question 9

Whatare the different types of MS?

Answer 9

Acute or insidious

Relapsing and remitting

Question 10

What does MS look like morphologically?

Answer 10

White matter disease

Cut surface shows plaques

Question 11

What are plaques in MS?

Answer 11

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

Question 12

What are frequently affected locations in MS?

Answer 12

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

Question 13

What will active plaques show?

Answer 13

Perivascular inflammatory cells
Microglia
Ongoing demyelination

Question 14

What will inactive plaques show?

Answer 14

Gliosis
Little remaining myelinated axons
Oligodendrocytes and axons reduced in number

Question 15

Where are acute lesions commonly found?

Answer 15

Surrounding white matter

Question 16

Where are chronic lesions commonly found?

Answer 16

Around lateral ventricles

Question 17

What are the environmental factors of MS?

Answer 17

Assoc with latitude
Relationship with vit D deficiency
EBV viral trigger

Question 18

What are the genetic risk factors for MS?

Answer 18

HLA DRB1

Question 19

Why is MS classified as an immune mediated disease?

Answer 19

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

Question 20

What are degenerative diseases of the cerebral cortex?

Answer 20

Alzheimer’s
Pick Disease
CJD

Question 21

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

Answer 21

PD
Progressive supranuclear palsy
Multiple system atrophy
Huntington’s disease

Question 22

What are degenerative diseases of the spinocerebellar system?

Answer 22

Friedreich Ataxia

Question 23

What are degenerative diseases of the motor neurons?

Answer 23

MND

Question 24

What is the pathogenesis of degenerative diseases?

Answer 24

Simple neuronal atrophy and subsequent gliosis

Question 25

What is dementia?

Answer 25

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

Question 26

What are the primary dementias?

Answer 26

Alzheimer's Lewy body Pick's disease Huntington's

Question 27

What are the secondary dementias?

Answer 27

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

Question 28

What is the commonest dementia?

Answer 28

Alzheimer's

Question 29

What genes are implicated in alzheimer's?

Answer 29

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

Question 30

What are the clinical features of alzheimer's disease?

Answer 30

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

Question 31

What can be seen macroscopically in alzheimer's disease?

Answer 31

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

Question 32

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

Answer 32

Occipital Brainstem Cererbellum

Question 33

What are the microscopic features of alzheimer's disease?

Answer 33

Extensive neuronal loss with assoc astrocyte proliferation Neurofibrillary tangles Neuritic plaques

Question 34

What are neurofibrillary tangles?

Answer 34

TAU protein, assoc with microtubules | Intracytoplasmotic

Question 35

Where can neurofibrillary tangles be found?

Answer 35

Hippocampus and temporal lobes

Question 36

Are neurofibrilary tangles a good indicator of disease severity?

Answer 36

No

Question 37

What are neuritic plaques?

Answer 37

A-beta amyloid plaques

Question 38

Where can neuritic plaques be found?

Answer 38

Surrounding astrocytes and microglia

Question 39

How is A-beta amyloid produced?

Answer 39

Cleavage of amyloid precursor protein

Question 40

What will amyloid stain with?

Answer 40

Congo red

Question 41

What is the impact of amyloid angiopathy in the brain?

Answer 41

Serum leaking Oedema Local hypoxia

Question 42

What is lewy body dementia?

Answer 42

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

Question 43

Is memory affected at the start of lewy body dementia?

Answer 43

No

Question 44

What are the classical features of parkinson's?

Answer 44

``` Loss of facial expression Stooping Shuffling Bradykinesia Stiffness Pill rolling tumour ```

Question 45

What can cause parkinsonism?

Answer 45

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

Question 46

What is the pathogenesis of parkinson's?

Answer 46

Loss of dopaminergic neurons in the substantia nigra

Question 47

What is seen macroscopically in lewy body dementia?

Answer 47

Pallor in substantia nigra where the pigmented dopaminergic neurones should run

Question 48

What is seen microscopically in lewy-body dementia?

Answer 48

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

Question 49

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

Answer 49

Emotional Cognitive Motor disturbance; chorea

Question 50

What is the inheritance of huntington's disease?

Answer 50

Chromosome 4 CAG repeats Shows genetic anticipation

Question 51

What is seen macroscopically in huntington's disease?

Answer 51

Atrophy of striatum | Frontal and parietal atrophy occurs later

Question 52

What is seen microscopically in huntington's disease?

Answer 52

Simple neuronal atrophy of striatal neurones | Pronounced astrocytic gliosis

Question 53

What is Pick's disease (frontotemporal dementia)?

Answer 53

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

Question 54

What are the symptoms of frontotemporal dementia?

Answer 54

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

Question 55

What can be seen macroscopically in frontotemporal dementia?

Answer 55

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

Question 56

What is seen microscopically in frontotemporal dementia?

Answer 56

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

Question 57

What is multi-infarct dementia?

Answer 57

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

Question 58

Who is most likely affected by vascular dementia?

Answer 58

Men after age of 60 | Middle-aged hypertensives

Question 59

How can alzheimer's and MID be differentiated?

Answer 59

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

Question 60

What is the morphological appearance of MID?

Answer 60

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