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Neurology > Neuropathology II > Flashcards

Neuropathology II Flashcards

1
Q

What is demyelination?

A

Preferential damage to the myelin sheath = relative preservation of axons

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2
Q

What are the causes of primary demyelination?

A

Multiple sclerosis, acute disseminated encephalomyelitis, acute haemorrhagic leukoencephalitis

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3
Q

What are the causes of secondary demyelination?

A 
Viral = progressive mulitfocal leukoencephalopathy 
Metabolic = central pontine myelinosis 
Toxins = cyanide, carbon monoxide
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4
Q

What is the most common demyelinating disease?

A

Multiple sclerosis = 2x more common in women, peak incidence in 20-30s

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5
Q

What is multiple sclerosis?

A

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

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6
Q

How is multiple sclerosis diagnosed clinically?

A 
Two distinct neurological defects occurring at different times 
Neurological deficit implicating one neuro-anatomical site and an MRI appreciated defect at another site
Multiple distinct (usually white matter) lesions on MRI
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7
Q

How is multiple sclerosis diagnosed supportively?

A

Visual evoked potentials

IgG oligoclonal bands in CSF

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8
Q

What are the clinical features of multiple sclerosis with optic nerve lesions?

A

Optic neuritis = unilateral visual impairment

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9
Q

What are the features of multiple sclerosis with spinal cord lesions?

A

Motor/sensory deficit in trunk and limbs

Spasticity and bladder dysfunction

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10
Q

What are the features of MS with brainstem lesions?

A

Cranial nerve signs, ataxia, nystagmus, internuclear opthalmoplegia

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11
Q

What is the disease course like in multiple sclerosis?

A

Acute or insidious onset

Relapsing and remitting, later becoming progressive

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12
Q

What are the brain features of MS?

A

Principally white matter disease
Exterior surface of brain typically appears normal
Cut surface shows plaques

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13
Q

What are some features of plaques?

A

Well circumscribed and demarcated
Irregular shaped surface
Glossy almost translucent appearance
Vary from small to very large

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14
Q

What kind of distribution do plaques display?

A

Non-anatomical distribution

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15
Q

What are some common areas for plaques to develop?

A

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

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16
Q

What are shadow plaques?

A

May reflect degree of remyelination = demonstrate thinned-out myelin sheath at edge of lesion which results in less well defined lesion

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17
Q

What are some features of active (acute) plaques?

A

Perivascular inflammatory cells, microglia and ongoing demyelination
Demyelinating plaques are yellow/brown with and ill defined edge that blends into surrounding white matter

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18
Q

What are some features of inactive (chronic) plaques?

A

Gliosis, little remaining myeinated axons and oligodendrocytes and axons reduced in number
Well demarctaed grey/brown lesions in white matter
Classically situated around lateral ventricles

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19
Q

What are the environmental and genetic factors implicated in multiple sclerosis?

A 
Environmental = associated with latitude and vitamin D deficiency, may have viral trigger
Genetic = 15x risk if affected 1st degree relative, genetic linkage with HLA DRB1
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20
Q

What is the immune pathogenesis of multiple sclerosis?

A

Lymphocytic infiltration in histology
Oligoclonal IgG bands in CSF
T cell and humeral factors involved
Anti B cell therapies reduce relapses and frequency

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21
Q

What are some degenerative diseases that affect the cerebral cortex?

A

Alzheimer’s disease, Pick disease, CJD

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22
Q

What are some degenerative diseases that affect the basal ganglia and brainstem?

A

Parkinson disease, progressive supranuclear palsy, multiple system atrophy, Huntington’s disease

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23
Q

What is a degenerative disease that affects the spinocerebellar tract?

A

Spinocerebellar ataxia

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24
Q

What characterises the pathology of degenerative diseases?

A

Simple neuronal atrophy and subsequent gliosis

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25
Q

What is dementia?

A

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

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26
Q

What is the underlying pathology of dementia?

A

Progressive loss of neurons typically affecting functionally related neuronal groups

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27
Q

What are the primary dementias?

A

Alzheimer’s disease, Lewy body dementia, Pick’s disease (fronto-temporal dementia), Huntington’s disease

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28
Q

What are the secondary dementias?

A

Multi-infarct dementia, infection, trauma, metabolic causes

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29
Q

What are some general causes of dementia?

A

Drugs and toxins, vitamin B1 deficiency, paraneoplastic syndromes, intracranial space occupying lesions, chronic hydrocephalus

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30
Q

What is the most common cause of dementia in the elderly?

A

Alzheimer’s disease = more common in women

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31
Q

What are the genetic influences of Alzheimer’s disease?

A

Usually sporadic but familial in 1% = amyloid precursor protein (APP), presenillin 1 and 2
Increased incidence in trisomy 21

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32
Q

How does Alzheimer’s present?

A

Insidious impairment of higher intellectual function with alteration in mood and behaviour

33
Q

What are the features of late Alzheimer’s disease?

A

Progressive disorientation

Memory loss and aphasia indicate severe cortical dysfunction

34
Q

What is the prognosis of Alzheimer’s disease?

A

Can result in profound disability, muteness and immobility

Death usually occurs due to a secondary cause

35
Q

What are the macroscopic features of Alzheimer’s disease?

A

Cortical atrophy = decreased brain weight and size
Widening of sulci and narrowing of gyri
Compensatory dilation of ventricles = secondary hydrocephalus ex vacuo

36
Q

What parts of the brain are usually affected by Alzheimer’s disease?

A

Frontal, temporal and parietal lobes

Occipital lobe brainstem and cerebellum normal

37
Q

What is the extensive neuronal loss that occurs on Alzheimer’s associated with?

A

Astrocyte proliferation = simple neuronal atrophy and gliosis

38
Q

What are the microscopic features of Alzheimer’s disease?

A

Neurofibrillary tangles, neuritic plaques and amyloid angiopathy

39
Q

What are some features of neurofibrillary tangles?

A

Intracytoplasmic = especially hippocampus and temporal lobe
TAU protein = associated with microtubules
Non-specific feature

40
Q

Where are neuritic plaques found?

A

Surround astrocytes and microglia = also called Abeta amyloid plaques

41
Q

What produces amyloid Abeta?

A

Cleavage of amyloid precursor protein = central element of neuritic plaques

42
Q

Why is Alzheimer’s linked with Down’s syndrome?

A

Amyloid precursor protein gene is also located on chromosome 21

43
Q

What do Abeta oligomers promote?

A

Hyperphosphorylation and mislocation of TAU

44
Q

What are some features of amyloid angiopathy?

A

Extracellular eosinophilic accumulation
Polymerised beta pleated sheets formed by Abeta
Stains with congo red

45
Q

What effect does amyloid angiopathy have on the BBB?

A

Disrupts the BBB = serum leaking, oedema and local hypoxia occur

46
Q

How common is Lewy body dementia?

A

10-15% of dementias

47
Q

What is Lewy body dementia?

A

Progressive dementia = hallucinations and fluctuating levels of attention/cognition, severity varies day to day

48
Q

How can Lewy body dementia and Alzheimer’s be differentiated?

A

Memory is affected later in Lew body dementia than it is in Alzheimer’s

49
Q

When do features of Parkinsonism present in Lewy body dementia?

A

Present at onset or develop soon after

50
Q

What are the features of Parkinsonism?

A

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

51
Q

What is type of conditions display Parkinsonism?

A

Conditions that affect the nigrostriatal dopaminergic pathways

52
Q

What are some conditions that cause Parkinsonisms?

A

Idiopathic Parkinsons, Lewy body dementia, drugs, trauma, multi-system atrophy, progressive supranuclear palsy, cortico-basal degeneration

53
Q

What is the most common cause of Parkinsonism?

A

Idiopathic Parkinson’s = called Parkinson’s disease

54
Q

What causes Parkinson’s disease?

A

Degeneration of the substantia nigra

55
Q

What are the macroscopic features of Parkinson’s disease?

A

Pallor in the substantia nigra = this is where pigmented dopaminergic neurons run

56
Q

What are the microscopic features of Parkinson’s?

A

Loss of pigmented neurons
Fewer cortical Lewy bodies
Reactive gliosis and microglial accumulation
Remaining neurons show Lewy bodies

57
Q

How do Lewy bodies appear?

A

Single or multiple intracytoplasmic eosinophilic round/elongated bodies = have dense core and surrounding pale halo

58
Q

What are Lewy bodies?

A

Aggregates of a-synuclein and ubiquitin

59
Q

What is Huntington’s disease?

A

Relentlessly progressive neuropsychiatric disorder = onset usually between age 35-50 but can occur at any time, dementia occurs later in disease

60
Q

What is the triad of Huntington’s disease?

A

Emotional, cognitive and motor disturbance

61
Q

What are the symptoms of Huntington’s disease?

A

Chorea, myoclonus, clumsiness, slurred speech, depression, irritability, apathy

62
Q

What is the inheritance of Huntington’s disease?

A

Autosomal dominant = Huntingtin gene on chromosome 4p

63
Q

What does mutation of the Huntingtin gene cause?

A

Additional CAG repeats = disease occurs when >35 repeats occur

64
Q

What are the macroscopic features of Huntington’s disease?

A

Atrophy of the basal ganglia in caudate nucleus and putamen

Cortical atrophy occurs later

65
Q

What are the microscopic features of Huntington’s disease?

A

Simple neuronal atrophy of striatal neurons in basal ganglia

Pronounce astrocytic gliosis

66
Q

What is Pick’s dementia?

A

Progressive dementia = characterised by progressive changes in character and social deterioration, onset usually between age 50-60

67
Q

What are the symptoms of Pick’s dementia?

A

Personality and behaviour change, communication and speech problems, changes in eating patterns, reduced attention span

68
Q

What is the prognosis of Pick’s dementia?

A

May last between 2-10 years = average is 7 years

leads to impairment of intellect, memory and language

69
Q

What are the symptoms of Pick’s dementia related to?

A

Damage to the frontal and temporal lobes

70
Q

What are the macroscopic features of Pick’s dementia?

A

Extreme atrophy of the cerebral cortex in frontal and temporal lobes = brain weight <1kg
Neuronal loss and gliosis

71
Q

What are the histological hallmarks of Pick’s dementia?

A

Pick’s cells = swollen neurons

Pick’s bodies = intracytoplasmic filamentous inclusions

72
Q

What is multi-infarct dementia?

A

Disorder involving deterioration in mental functioning due to cumulative damage to brain through hypoxia or anoxia

73
Q

What causes multi-infarct dementia?

A

Result of multiple blood clots within the vessels supplying the brain

74
Q

What do successive multiple cerebral infarctions cause?

A

Increasingly larger areas of cell death and damage = dementia results when sufficient area of brain is damaged

75
Q

What is the epidemiology of multi-infarct dementia?

A

More common in men
Usually occurs after age 60
Also seen in middle aged hypertensives

76
Q

What mental health issues are multi-infarct dementia patients prone to?

A

Depression and anxiety = they are aware of their mental deficits

77
Q

How do you distinguish multi-infarct dementia form Alzheimer’s disease?

A

Multi-infarct dementia has abrupt onset, stepwise progression, history of hypertension or stroke and evidence of stoke on CT/MRI

78
Q

What are some features of large vessel cerebral infarcts?

A

More common, scattered throughout hemispheres, atheroma of large cerebral arteries provoke thromboembolism

79
Q

What are some features of small vessel (lacunar) cerebral infarcts?

A

Rarer, central with subcortical distribution, related to longstanding hypertension and arteriosclerosis of small vessels

Neurology (48 decks)

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