Degenerative conditions affecting the nervous system

Question 1

demyelination definition?

Answer 1

preferential destruction of myelin sheath around axon
Relative preservation of axons themselves
disease of myelin or oligodendrocyte/Schwann cell

Question 2

what cells produce Myelin in the CNS?

-effect of demyelination?

Answer 2

• oligodendrocytes

- disruption of electrical conductivity within the CNS

Question 3

Demyelination:

-what are the different types? (4) give examples

Answer 3

Primary 
(MS)
Secondary 
(central pontine myelinolysis, progressive multifocal leucoencephalopathy, sub-acute sclerosing pan encephalitis, AIDS, axonal degeneration) 
Metabolic 
Toxic
(cyanide, CO, solvents)

Question 4

Multiple sclerosis 
-definition?
-pattern?
-what are the common manifestations? (6)
-what factors might contribute to pathogenesis?
-what is seen on MRI?
-morphology (external and cut?) what is seen in white matter? distribution?
where is affected? (4)

Answer 4

• episodes of neurological deficit separated by time, brain and spinal cord lesions disseminated in both time and space, ned to have different areas involved
• relapsing and remitting with flare-up episodes

-Visual disturbance, parasthesia,
spasticity of one or more of the extremities, speech disturbance,
gait abnormalities.
May develop cognitive impairment

-environmental, genetic (HLA gene), immune

-areas of demyelination, myelinated areas in brain are normally dark
tends to radiate out from the corpus colossum in patches

-external- appears normal
cut- see multiple areas of demyelination termed plaques
As white matter disease
well-demarcated plaques (acute the soft and pink)
non anatomical distribution,
optic nerve, periventricular white matter, corpus callosum, brain stem and spinal cord
might act as a SOL (rarely)

Question 5

what are the different types of MS plagues? (4)

• what are the features of each?
• describe the appearance of acute and chronic MS plaques
• what are the 3 major features of an MS plaque?

Answer 5

acute active plaques
(ongoing myelin breakdown, abundant macrophages, inflammatory cells including both lymphocytes and monocytes, mostly as perivascular cuffs.
small active lesions often entered around veins.)

Chronic inactive plaques
(centre of an inactive plaque contains little or no myelin
astrocytic proliferation and gliosis are prominent)

Chronic active plaques
relapse on the same part of the brain as has been previously affected

Shadow plaques
border between normal and affected white matter is not clearly defined. some abnormally thinned out myelin sheaths can be identified, especially at the outer edges

-Acute
demyelinated plaques are yellow/brown with an ill defined edge which blends into surrounding white matter

chronic
well demarcated grey/brown lesions in white matter, classically situated around lateral ventricles

-demyelination
inflammation
Gliosis

Question 6

Dementia

• definition?
• is it normal?
• what are the 2 main groups?

Answer 6

• Nuerodegenerative disorder: an impairment of previously acquired occupational or social functioning due to development of acquired and persistent memory impairment associated with impairment of intellectual function in the presence of normal consciousness
• nooope, always pathological

-Primary dementias
Alzheimers disease (most common), diffuse Lewy body disease, Huntington's disease, Pick's disease

Secondary dementias
other disorders resulting in secondary changes in the CNS resulting in dementia such as; vascular, metabolic, infection and trauma

Question 7

Alzheimer’s disease

• present when?
• penetrance?
• genetic variations that might contribute? (3)
• presentation?
• What macroscopic pathology seen? (6)
• microscopic features? (4)
• appearance in MRI?

Answer 7

• over 60s
• sporadic occurrence, slight familial tendency
• amyloid precursor protein (APP) gene found on chromosome 21, presenilin 1 gene on chromosome 14 and presenilin 2 gene on chromosome 8.

-insidious impairment of higher intellectual function, with alterations in mood and behaviour
Later- progressive disorientation, memory loss and aphasia = severe cortical dysfunction
can eventually result in profound disability, muteness and immobility

-decreased size and weight of brain
widening of sulci
narrowing of gyri
compensatory dilatation ventricles and secondary hydrocephalus
frontal, temporal and parietal lobes affected
brainstem and cerebellum normal

-Intracytoplasmic neurofibrillary tangles
AB amyloid plaques (extracellular or neuritic plaques) amyloid angiopathy
extensive neuronal loss with astrocytosis

• sulk wider, gyri narrower, increased space between brain and cranium

Question 8

What are neurofibrillary tangles?

What are amyloid plaques?
stain?

what is Amyloid angiopathy?

Answer 8

-bundles of filaments in the cytoplasm of the neurons that displace or encircle the nucleus. Major component is tau protein, a micro-tubule associated protein, which is abnormally phosphorylated in Alzheimer’s disease.
use silver stains to see

-focal, spherical collections of dilated, tortuous, neuritic processes surrounding a central amyloid core. Often surrounded by peripheral reactive astrocytes and microglia.
Occur most frequently in hippocampus, cerebral cortex and deep grey matter.
CONGO RED!!

– perivascular amyloid deposition, derived from abnormally cleavage of APP.

Question 9

Dementia with Lewy bodies

• presentation? (3)
• pathological features? (4)
• how are lewy bodies detected?

Answer 9

-progressive, hallucination and fluctuating levels of attention
can develop features of parkinson disease
Fluctuation of severity of condition day to day

-degeneratin of the substance nigra
remaining nerve cells contain lewy bodies
degeneration of the cortical areas of the brain as seen in Alzheimers
formation of cortical lewy bodies

-by immunochemical staining for the protein ubiquitin

Question 10

Huntington’s disease

• onset & definition?
• inheritance?
• triad of what?
• presentation?
• microscopic changes? (2)

Answer 10

• neuropsychiatric dosorder, onset between 35-50
• autosomal dominant (huntington gene of chromosome 4p)
• emotional, cognitive and motor disturbance

-chorea, myoclonus, clumsiness, slurred speech, depression, irritability, apathy
dementia develops later

-loss of neurones in caudate nucleus and cerebral cortex accompanies by reactive fibrillary gliosis

Question 11

Pick’s disease

• definition?
• onset?
• pathological signs? (2)
• histological findings? (2)
• Symptoms? (4)
• pattern?

Answer 11

• progressive dementia, characterised by slowly progressing changes in character and social deterioration leading to impairment of intellect, memory and language
• 50-60

-extreme atrophy of cerebral cortex in frontal and temporal lobes
neuronal loss and astrocytosis

-Pick’s cells (swollen neurones) and intracytoplasmic filamentous inclusions known as Pick’s bodies

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

rapidly progressive, mean length 7 years

Question 12

Multi infarct Dementia

• definition?
• onset?
• associated with what?
• what features distinguish it from Alzheimers? (4)

Answer 12

• deterioration in mental functioning due to changes or damage to the brain tissue from hypoxia or anoxia as a result of multiple blood clots within vessels supplying the brain
• after age 60, also in middle aged hypertensives
• depression and anxiety, as sufferers aware of mental deficits

-abrupt onset
stepwise progression
Hx hypertension/stroke
evidence to stroke on CT or MRI