5.5 CNS pathology

Question 1

What is this neural tube malformation describing?

failure of one or more vertebrae to close properly, from asymptomatic (occulta) to meningoceles or myelomeningoceles

Answer 1

spinal bifida

Question 2

what is this neural tube malformation called?

protrusion of meninges through parietal foramina or abnormal bony openings of the skull

Answer 2

cranial defects- from absent skill bones (acrania) to cranial meningoceles

Question 3

[Malformation of brain: Chiari malformation]

• structural defect in the cerebellum, characterized by a ______________ through the foramen magnum
• Can sometimes lead to non-communicating hydrocephalus as a result of obstruction of cerebrospinal fluid (CSF) outflow

Answer 3

downward displacement of one or both cerebellar tonsils

Question 4

[Malformation of neuroaxis]

What is this condition describing?

• group of neuro-oculo-cutaneous syndromes or neurocutaneous disorders involving structures arising from the embryonic ectoderm

Answer 4

Phakomatoses

Question 5

[Malformation of neuroaxis]

What is this condition describing?

• formation of various small tumours from neuroectoderm in the eye, skin or internal organs

Answer 5

Neurofibromatosis type I (NF-1)

Question 6

how is the brain injured from secondary trauma related injury?

Answer 6

• Brain may be damaged from secondary injury – due to acceleration and deceleration causing brain to hit the skull
• Shearing forces may lead to diffuse axonal injury, leading to neuronal death, disability or haemorrhage

Question 7

What is inflammation of the meninges called?

Answer 7

meningitis

Question 8

what is inflammation of the brain parenchyma, most often of viral origin called?

Answer 8

encephalitis

Question 9

what is inflammation of the spinal cord called?

Answer 9

myelitis

Question 10

what is simultaneous inflammation of the brain parenchyma (encephalitis) and the meningitis (meningitis) called?

Answer 10

Meningoencephalitis

Question 11

What are abnormally folded proteins, specific causative agent in the brain, leading to spongiform encephalopathy (CJD called?

Answer 11

Prions

Question 12

What is this autoimmune disease that leads to destruction of myelin?

Answer 12

Multiple sclerosis

Question 13

What is the condition where there is specific gene abnormality that leads to abnormal development or destruction of the white matter (myelin sheath) of the brain?

Answer 13

Leukodystrophy

Question 14

Tay-Sachs disease (progressive neurodegeneration due to _____________)

Answer 14

intracellular accumulation of GM2 gangliosides

Question 15

In descending order, ranked the sensitivity to nervous system cells to decreased oxygen

Answer 15

Neurones > oligodendrocytes > astrocytes > endothelial cells

Question 16

What is the neuronal response in within 12 hours of an irreversible hypoxic-ischemic insult in an acute injury?

Answer 16

shrinkage of the cell body, pyknosis of nucleus, disappearance of nucleolus, loss of Nissl substance and intense eosinophilia of the cytoplasm (“red neurons”)

Question 17

What is the neuronal response in within 12 hours of an irreversible hypoxic-ischemic insult in an axonal injury?

Answer 17

cell body enlargement and rounding, peripheral displacement of the nucleus, enlargement of the nucleolus, and peripheral dispersion of Nissl substance (central chromatolysis

o Wallerian degeneration – degeneration of myelin and axons distal to injury

Question 18

What are the intracellular inclusions seen in Herpes?

Answer 18

Cowdry bodies

Question 19

What are the intracellular inclusions seen in Rabies infection?

Answer 19

Negri bodies

Question 20

What is accumulated in neurones during normal aging, thought to play a role in development of neurodegenerative disorders?

Answer 20

Lipofuscin

Question 21

What is the abnormal protein seen in Alzheimer’s disease?

Answer 21

Neurofibrillary tangles

Question 22

What is the abnormal protein see in Parkinson’s?

Answer 22

lewy bodies

Question 23

What is the response to astrocytes in response to injury?

Answer 23

• astrocytes are the principal cells responsible for repair and scar formation on the brain during gliosis
• In response to injury, astrocytes undergo both hypertrophy and hyperplasia
• Cytoplasm expands and takes on a bright pink hue, and the cell extends multiple stout, ramifying processes (gemistocytic astrocytes)
• Astrocytes proliferate and fill up the defect, leading to a glial scar

Question 24

What is the response to microglial cells in response to injury?

Answer 24

resident macrophages of the CNS, phagocytic function
o After an injury, they become activated and elongated (rod cells), aggregating around the injured area, forming microglial nodules
o Neurophagia – microglial cells surround and phagocytose dead or dying neurones

Question 25

what is the mechanism behind cytotoxic oedema seen in tumours and infections? - May follow generalised hypoxic, ischaemic or exposure to certain toxins

Answer 25

- Increased in intracellular fluid secretion secondary to neuronal and glial cell injury

Question 26

What is the mechanism seen in vasogenic oedema? | - May proliferate around infarcts, tumours or part of an inflammatory response

Answer 26

- Defect in blood brain barrier, allowing fluid to shift from the vascular component to the extracellular spaces of the brain

Question 27

What is global cerebral ischaemia caused by?

Answer 27

Widespread cerebral ischemia not due to vascular occlusion - Severe hypotension with global hypoperfusion – usually in the setting when systolic blood pressure falls below 50 mmHg e.g. cardiac arrest or shock - This leads to Diffuse brain swelling and injury – when the insult is mild, there may be only a transient post-ischaemic confusional state, with eventual complete recovery

Question 28

Which part of the brain is most sensitive to a drop in blood pressure?

Answer 28

o Watershed infarction – border areas of arterial territory (e.g. between ACA and MCA) - Purkinje cells of cerebellum and laminar cortical necrosis

Question 29

Ischaemic stroke - Considerations – reduction of blood flow in a specific artery will affect the area that it supplies, presenting with characteristic neural deficits -Collateral flow through ____________ may limit the damage in an ischaemic stroke – linkage of carotid and vertebral-basilar systems o However, there are anatomical variants of the circle of Willis – communication arteries may vary in diameter and position o Marked atherosclerosis may result in luminal narrowing, reducing blood flow - Some parts of the brain are supplied by perforating arteries – end arteries with no collateral flow o Some areas such as the ________________ supplied by such arteries – poorer outcome

Answer 29

circle of Willis; basal ganglia and internal capsule are

Question 30

- ____________area – may remain viable for several hours after an ischemic event due to the collateral arteries o Such areas are often closer to collateral vessels between the anterior, middle and posterior cranial arteries o Goal of stroke therapy is to revive this area – a higher volume of penumbra around a cerebral infarction means a greater volume of potentially salvageable brain matter by thrombolysis and thrombectomy

Answer 30

Penumbra

Question 31

What are the common extra cranial sites for formation of thrombi thrombi?

Answer 31

– common carotid artery bifurcation, vertebral artery origin (near branching sites

Question 32

what are common intra cranial sites for formation of arterial thrombi?

Answer 32

circle of Willis, middle cerebral artery origin, basilar artery

Question 33

what are common intra cranial sites for formation of venous thrombi?

Answer 33

superior sagittal sinus

Question 34

which artery is most affected by emboli?

Answer 34

middle cerebral artery?

Question 35

what is the timescale of infarction when there is: No changes on gross or light microscopy

Answer 35

< 12 hours

Question 36

what is the timescale of infarction when there is: Earliest light microscopy changes in the form of ischemic cells (red dead neurons)

Answer 36

12 to 24 hours

Question 37

what is the timescale of infarction when there is: Neutrophil with vascular response

Answer 37

24 to 48 hours

Question 38

what is the timescale of infarction when there is: Soft swollen (vasogenic and cytotoxic edema) surrounding oedema and midline shift – increased intracranial pressure and risk of herniation

Answer 38

48 hours

Question 39

what is the timescale of infarction when there is: Macrophages start replacing neutrophils, clearing debris (phagocytosis) Infarct becomes gelatinous and friable and more defined as oedema subsides in the first week - Tissue liquefies – fluid filled cavity which expands till all of the dead tissue is removed

Answer 39

48 hours to 2/3 weeks

Question 40

what is the timescale of infarction when there is:Astrocytic glial reaction starts and continues for weeks to months, forming a gliotic scar – parts of infarct are cystic if it is large (cystic cavity with surrounding gliosis)

Answer 40

From 1st week

Question 41

Lacunar infarct – small vessel pathology - On the background of __________- underlying arteriolosclerosis, lipohyalinosis, involving _____________ - Small infarcts in deep cortex and deep nuclei – if multiple, may lead to cognitive deficits (multi-infarct dementia

Answer 41

hypertension; smaller penetrating arteries

Question 42

Venous infarcts – superior sagittal sinus thrombosis, a difficult clinical diagnosis - Risk factors – hypercoagulable states (dehydration, phlebitis, pregnancy, birth control pill) - Typically, ______________

Answer 42

frontal lobe haemorrhagic infarctions

Question 43

Intraparenchymal haemorrhage - Stroke secondary to vessel rupture – risk factors include ______________, cerebral amyloid angiopathy, arteriovenous malformations and tumours o Most common in mid to late adult life, with a peak incidence at about 60 years of age - Spontaneous haemorrhages (non-traumatic bleed) - Hypertension-related haemorrhage – massive deep brain parenchymal haemorrhage (>50% of all significant bleeds and 15% of hypertensive deaths) o Involvement of the ______________ o Putamen is involved in 50% of cases, may also involve thalamus, pons, cerebellum o Small arteries and arterioles – arteriolosclerosis of penetrating arteries can lead to slit haemorrhages o _____________ – weakening of blood vessels in accelerated atherosclerosis o Microaneurysms of Charcot Bouchard – involves vessels < 300 µm o Petechiae haemorrhages and fibrinoid necrosis in malignant hypertension - Cerebral amyloid angiopathy – another cause of parenchymal haemorrhages, more common in peripheral lobes o Massive lobar haemorrhages or small cortical haemorrhage (< 1mm), more common in the elderly (~15% of bleeds) o Due to ß-amyloid peptide deposition in __________________ o May co-exist with Alzheimer disease

Answer 43

hypertension (most common); deep white matter or deep grey matter, brainstem and cerebellum; Lipohyalinosis; cortical and leptomeningeal arteries

Question 44

Arteriovenous malformation - Vascular malformation – tangled mass of abnormal thick-walled arteries and veins, accounts for 1.5 to 4% of all brain masses, with a 2 to 4% yearly risk of bleeding o Location – _____________ o Commonly manifests in young adults of 10 to 30 years, manifests with seizures, an intracerebral haemorrhage or a subarachnoid haemorrhage o In the newborn period, large arteriovenous malformations may lead to ________________ due to blood shunting from arteries to veins - May involve subarachnoid vessels extending into brain parenchyma or occur exclusively within the brain o On gross inspection, they resemble a __________________ o Large calibre, thick-walled vessels within brain parenchyma

Answer 44

MCA > ACA > PCA; high output congestive heart failure; tangled network of wormlike vascular channels

Question 45

Saccular (Berry) aneurysms – results in subarachnoid haemorrhages - ______________ in cerebral artery – rupture accounts for 25% of cerebrovascular deaths o Annual risk of rupture – 0.05 to 2% (increases with size, 50% if >10mm), multiple aneurysms are also possible (20%) o Male to female ratio of 1:2, incidence in adults peak in the 6th decade - Occurs at ________________ – some connective tissue diseases predispose to aneurysm formation presumably involves an inherent weakness of the arterial wall exposed to the non-laminar flow pattern of blood, which is then exposed to shear stresses

Answer 45

Sac-like dilatation; branch points in circle of Willis