Neuropathology 2 Flashcards
(131 cards)
1
Q
What do oligodendrocytes do?
A
Insultate axons
Locally confine neuronal depolarisation
Protect axons
Form nodes of Ranvier
2
Q
What do nodes of ranvier precipitate?
A
Rapid saltatory conduction
3
Q
What does damage to oligodendrocytes do?
A
Damaged neuronal conduction
4
Q
What is demyelination?
A
Preferential damage to the myelin sheath, with relative preservation of axons
5
Q
Demyelinating disorders can be either?
A
Primary or secondary
6
Q
Name 3 primary demyelinating disorders.
A
- Multiple Sclerosis.
- Acute disseminated encephalomyelitis. (post-infectious AI disorder, mild, self-limiting, kids)
- Acute haemorrhagic leukoencephalitis. (post-infectious AI disorder, rapidly fatal, adults)
7
Q
Outline 3 secondary demyelinating disorders.
A
- Viral – progressive multifocal leukoencephalopathy (PML).
- Metabolic – central pontine myelinosis.
- Toxic – CO, organic solvents, cyanide.
8
Q
What is the most common demyelinating disease?
A
MS
9
Q
What is the female to male ratio in MS?
A
2:1
10
Q
What is the peak age incidence in MS?
A
20-30 years old
11
Q
What does MS have a well known association with?
A
Latitude
12
Q
What is MS defined as?
A
An auto-immune demyelinating disorder, characterised by distinct episodes of neurological deficits, separated in time, and which correspond to spatially separated foci of neurological injury
13
Q
For a clinical diagnosis of MS, what is needed?
A
- 2 distinct neurological defects occurring at different times
- A neurological defecting implicating one neuro-anatomical site, and a MRI-appreciated defect at another neuro-anatomical site
- Multiple distinct (usually white matter) CNS lesions on MRI
14
Q
What also supports a diagnosis of MS?
A
- Visual evoked potentials (evidence of slowed conduction)
* IgG oligoclonal bands in CSF
15
Q
What would be seen in the CSF of a patient with MS?
A
IgG oligoclonal bands
16
Q
Where is presentation of MS usually?
A
Within a focal neurological deficit
17
Q
Give an example of a focal neurological deficit.
A
Optic nerve lesions - optic neuritis
- unilateral visual impairment
18
Q
Onset of MS is?
A
Acute OR Insidious
19
Q
Describe the complications of a spinal cord lesion.
A
- motor or sensory deficit in trunk and limbs.
- spasticity.
- bladder dysfunction
20
Q
Describe the complications of a brain stem lesion.
A
- cranial nerve signs.
- ataxia.
- nystagmus.
- internuclear ophthalmoplegia.
21
Q
Describe the course of MS.
A
Can be relapsing and remitting, later becoming progressive
22
Q
In areas corresponding to white matter, what does demyelination show up as on an MRI?
A
Hyperintense regions on T2 weighted MRI scans
23
Q
What is MS a disease of?
A
WHITE matter
24
Q
Therefore, how does the external surface of the brain appear?
A
NORMAL
25
What does the cut surfaces of the brain in MS show?
Plaques
26
Describe the appearance of plaques in MS.
Well circumscribed, well-demarcated.
Irregularly shaped areas.
Glassy, almost translucent appearance.
Vary from small to large lesions.
27
What is the distribution of plaques in MS like?
Non-anatomical
28
List areas which are frequently affected by plaques.
* Adjacent to lateral ventricles
* Corpus callosum
* Optic nerves and chasm
* Brainstem
* Descending and ascending fibre tracts
* Cerebellum
* Spinal cord
29
Describe the histology of active plaques.
* Perivascular inflammatory cells
| * Ongoing demyelination
30
Describe the histology of inactive plaques.
* Gliosis
* Little remaining myelinated axons
* Oligodendrocytes and axons reduced in numbers
31
What may 'shadow' plaques represent?
A degree of RE-myelination
32
What do shadow plaques demonstrate at the edge of lesions?
Thinned out myelin sheaths
33
What do shadow plaques result in?
Less well defined lesions
34
Macroscopically, how do active plaques appear?
Demyelinating plaques are yellow/brown, with an ill-defined edge which blends into surrounding white matter
35
Describe the macroscopic appearance of inactive plaques.
* Well-demarcated grey/brown lesions in white matter
| * Classically situated around lateral ventricles
36
What environmental factors may MS be associated with?
* Latitude
* Vit D deficiency - lack of sun
* Viral trigger remains hypothesised (ie. EBV)
37
What does MS have a genetic linkage to?
HLA DRB1
| IL-2 and IL-7
38
Outline how MS is an immune-mediated disease.
* Lymphocytic infiltration in histology
* Oligoclonal IgG bands in CSF
* Genetic linkage to HLA DRB1
* T cell factors
39
What therapy reduces relapses and frequency of demyelinating disorders?
Anti- B cel
40
Give examples of degenerate disorders affecting the cerebral cortex.
Alzheimer’s Disease
Pick Disease
CJD
41
Give examples degenerate disorders affecting the basal ganglia and brainstem.
Parkinson Disease
Progressive Supranuclear Palsy
Multiple System Atrophy
Huntington Disease
42
Give examples of degenerate disorders affecting spinocerbellar areas
Spinocerebellar ataxias (ie. Friedereich Ataxia).
43
Give examples of degenerate disorders affecting motor neurones
MND
44
What are degenerate disorders characterised by?
Simple neuronal atrophy, and subsequent gliosis
45
What is dementia?
An acquired and persistent generalised disturbance of higher mental functions in an otherwise fully alert person
46
What are neurodegenerative disorders characterised by?
* Progressive loss of neurons.
| * Typically affecting functionally related neuronal groups.
47
Name the 4 primary dementias.
* Alzheimer’s disease
* Lewy body dementia
* Pick’s disease (fronto-temporal dementia)
* Huntington’s disease
48
What are secondary dementias?
Disorders that give rise to dementia
49
What is the most common subtype of dementia?
Alzheimers
50
What is the 2nd most common subtype of dementia?
Vascular dementia
51
List causes of multi-infarct (vascular) dementia.
```
Infection (HIV, syphilis)
Trauma
Metabolic
Drugs and toxins (alcohol)
Vitamin deficiencies (Vitamin B1)
Paraneoplastic syndromes
Intracranial space occupying lesions
Chronic hydrocephalus
```
52
What is the female to male ratio of Alzheimers?
2:1
53
Why does Alzheimers most commonly arise?
Usually sporadic
54
What genes may be found in Alzheimers?
* Amyloid precursor protein (APP)
| * Presenilin 1 + 2.
55
What is there an increased incidence of Alzheimers in?
Trisomy 21 - amyloid precursor protein
56
Describe clinically, what Alzheimers is like at the beginning?
Insidious impairment of higher intellectual function with alterations in mood and behaviour
57
What happens later in Alzheimers? What does this indicate?
Progressive disorientation, memory loss, aphasia
| SEVERE CORTICAL DYSFUNCTION
58
How does death in Alzheimers usually occur?
Due to secondary cause e.g pneumonia
59
What happens to the size of the brain in Alzheimers?
DECREASES - due to cortical atrophy
60
What areas of the brain are most commonly affected by atrophy in Alzheimers?
Frontal, temporal and parietal lobe atrophy
61
What happens to sulci in Alzheimers?
They become wider
62
What happens to gyri in Alzheimers?
They become more narrow
63
How is the ventricular system in Alzheimers affected?
There is compensatory dilatation of the ventricles, and secondary hydrocephalus ex vacuo
64
What areas are normal/spared in Alzheimers?
The occipital lobe, brainstem and cerebellum
65
What are the 4 main microscopic features of Alzheimers?
* Extensive neuronal loss, with associated astrocyte proliferation - simple neuronal atrophy and gliosis
* Neurofibrillary tangles
* Neuritic plaques
* Amyloid angiopathy
66
Where in the brain are Neurofibrillary Tangles found?
In the hippocampus and temporal lobe
67
Are neurofibrillary tangles extra or intracytoplasmic?
Intracytoplasmic
68
What, associated with microtubules, is seen in Alzheimers and other degenerate diseases?
Tau protein
69
What are Aß amyloid plaques also called?
Neuritic plaques
70
What do Aß amyloid plaques surround?
Astrocytes and microglia
71
What is Aß amyloid the central element of?
Neuritic plaques
72
What is Aß produced by?
Cleavage of amyloid precursor protein (APP)
73
What is trisomy 21 associated with the early onset of?
Alzheimers
74
What is trisomy 21 associated with?
Amyloid precursor protein (APP) is on chromosome 21
75
What mutations are implicated in familial Alzheimers?
* Point mutations in APP
* Presenilin 1
* Presenilin 2
76
What chromosome is the gene for Presenilin i) 1 ii) 2 located on?
i) 14
| ii) 1
77
What is the commonest familial cause of Alzheimer’s? What does this do?
Apolipoprotein E e4 allele – dysregulates APP
78
What are thought to be the main toxic lesions in Alzheimers?
Abeta Oligomers
79
What are neuritic plaques composed of?
Amyloid, formed from oligomerisation of Ab oligomers
80
What do Ab oligomers promote?
Hyper-phosphorylation and mis-localisation of TAU
81
What does the mislocation of TAU appear to do?
Enhance the excitotoxicity affect of Abeta oligomers
82
What do fibrillary tangles arise due to?
Abnormal organisation of the cytoskeleton; hyperphosphorylated TAU protein is insoluble in vivo
83
What lesion does Alzheimers demonstrate?
Cerebral amyloid angiopathy
84
What is the amyloid that accumulates in cerebral amyloid angiopathy in Alzheimers?
Ab, which accumulates in the wall of arterioles
85
What colour does amyloid stain?
Congo red
86
What is the effect of the accumulation of Ab?
Stiffens and thickens vessel walls, disrupting the BBB
87
What does Stiffens and thickens vessel walls, disrupting the BBB lead to?
* Serum leaking
* Oedema
* Local hypoxia
88
What accumulated extracellular in amyloid angiopathy?
Eosinophils
89
What does Ab form?
Polymerised beta sheets
90
What does Ab form?
Polymerised beta pleated sheets
91
Name important features of Lewy Body dementia.
* Progressive dementia.
* Hallucinations.
* Fluctuating levels of attention/cognition.
* Fluctuation in severity on a day-to-day basis.
* Features of Parkinsonism are present at onset, or emerge shortly after.
92
Lewy body dementia can show an overlap with Parkinson's. What are the differences?
* Characterised by fluctuating cognitive dysfunction, including attention.
* MEMORY is affected LATER in the course of the disease
93
What are the clinical features of Parkinson's?
* Loss of facial expression. (hypomimia)
* Stooping.
* Shuffling gait.
* Slow initiation of movements.
* Stiffness and pin rolling tremor.
94
What is hypomimia?
Loss of facial expressions
95
Most cases of Parkinson's are ______
IDIOPATHIC
96
What is the pathology of lewy body dementia?
Degeneration of the substantia nigra
97
In what condition can you also see degeneration of the substantia nigra?
Parksinson's
98
Macroscopically, what is seen in lewy body dementia?
Pallor in the substantia nigra, where pigmented dopaminergic neurones run
99
You get MORE cortical lewy bodies in Dementia
FALSE - LESS
100
What are the microscopic features of lewy body Dementia?
* Loss of pigmented neurones.
* Reactive gliosis and microglial accumulation.
* Remaining neurones may show Lewy bodies:
- “Single / multiple intracytoplasmic, eosinophillic, round to elongated bodies that have a dense core and a surrounding pale halo”
- Aggregates of a-synuclein and ubiquitin
101
What is Huntington's disease?
A relentlessly progressive neuropsychiatric disorder
102
When does onset of Huntington's occur?
Most commonly between the ages of 35-50, but can occur at any time.
103
What is the triad of clinical features in Huntington's?
A triad of emotional, cognitive and motor disturbance
104
What are the symptoms of Chorea?
* Chorea (dance-like movements).
* Myoclonus.
* Clumsiness.
* Slurred speech.
* Depression.
* Irritability.
* Apathy.
105
When do people with Huntington's develop dementia?
Later on in the course of the disease
106
What is the inheritance pattern on Huntington's?
Autosomal dominant
107
What chromosome is the Huntington's gene on?
4p
108
Genetically, when does Huntington's occur?
CAG repeats .... CAG CAG CAG CAG
<28 = normal
>35 = Huntington's
109
Describe the macroscopical pathology of Huntington's.
* Atrophy of basal ganglia: caudate nucleus, putamen.
| * Cortical atrophy occurs later
110
Describe the microscopic pathology of Huntington's.
* Simple neuronal atrophy of striatal neurones of the basal ganglia.
* Pronounced astrocytic gliosis.
111
What is Pick's disease also known as?
Fronto-temporal dementia
112
What is Pick's disease?
A progressive dementia, commencing in middle life (usually between 50 and 60 years) characterised by progressive changes in character and social deterioration leading to impairment of intellect, memory and language
113
What are the symptoms of Pick's disease?
Sx related to frontal and temporal lobes:
* Personality and behaviour change.
* Speech and communication problems.
* Change in eating habits.
* Reduced attention span
114
Picks disease is a ______ ________ illness
RAPIDLY, PROGRESSIVE
115
How long does Pick's disease last?
Between 2 to 10 years.
| - the mean length of illness is ~ 7 years
116
What happens to the frontal and temporal lobes in Pick's disease?
EXTREME atrophy - frontal lobe first then temporal
117
What does the weight of the brain end up being in Pick's disease?
<1kg
118
What are the histological hallmarks of Pick's?
* Pick’s cells – swollen neurones.
| * Intracytoplasmic filamentous inclusions, known as Pick’s bodies.
119
What is vascular dementia?
Disorder involving a deterioration in mental functioning due to cumulative damage to the brain through hypoxia or anoxia (lack of oxygen) as a result of multiple blood clots within the blood vessels supplying the brain.
120
What is vascular dementia also called?
Multi-infarct dementia
121
What do successive, multiple, cerebral infarctions cause?
Increasingly larger areas of cell death and damage
122
What happens when a significant area of the brain is damaged?
Dementia results
123
Who is vascular dementia more common in?
MEN
124
Who gets vascular dementia?
Commonly after the age of 60
| AND MIDDLE AGED HYPERTENSIVES
125
Sufferers of vascular dementia are aware of their mental defects, what can therefore happen?
Depression and anxiety
126
What is vascular dementia difficult to distinguish from?
Alzheimer's
127
What clues help to diagnose vascular dementia from Alzheimer's?
* Abrupt onset.
* Stepwise progression.
* Hx of hypertension or stroke.
* Evidence of stroke will be seen on CT or MRI.
128
Steadily progressing deterioration is?
Alzheimer's
129
Step-wise deterioration, due to episodic vascular induced brain infarction is?
Vascular dementia
130
What provokes thromboembolism in vascular dementia?
Atheroma of large cerebral arteries
131
What would be seen in MID?
Large vessel infarcts
