5.5 CNS pathology Flashcards
What is this neural tube malformation describing?
failure of one or more vertebrae to close properly, from asymptomatic (occulta) to meningoceles or myelomeningoceles
spinal bifida
what is this neural tube malformation called?
protrusion of meninges through parietal foramina or abnormal bony openings of the skull
cranial defects- from absent skill bones (acrania) to cranial meningoceles
[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
downward displacement of one or both cerebellar tonsils
[Malformation of neuroaxis]
What is this condition describing?
- group of neuro-oculo-cutaneous syndromes or neurocutaneous disorders involving structures arising from the embryonic ectoderm
Phakomatoses
[Malformation of neuroaxis]
What is this condition describing?
- formation of various small tumours from neuroectoderm in the eye, skin or internal organs
Neurofibromatosis type I (NF-1)
how is the brain injured from secondary trauma related injury?
- 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
What is inflammation of the meninges called?
meningitis
what is inflammation of the brain parenchyma, most often of viral origin called?
encephalitis
what is inflammation of the spinal cord called?
myelitis
what is simultaneous inflammation of the brain parenchyma (encephalitis) and the meningitis (meningitis) called?
Meningoencephalitis
What are abnormally folded proteins, specific causative agent in the brain, leading to spongiform encephalopathy (CJD called?
Prions
What is this autoimmune disease that leads to destruction of myelin?
Multiple sclerosis
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?
Leukodystrophy
Tay-Sachs disease (progressive neurodegeneration due to _____________)
intracellular accumulation of GM2 gangliosides
In descending order, ranked the sensitivity to nervous system cells to decreased oxygen
Neurones > oligodendrocytes > astrocytes > endothelial cells
What is the neuronal response in within 12 hours of an irreversible hypoxic-ischemic insult in an acute injury?
shrinkage of the cell body, pyknosis of nucleus, disappearance of nucleolus, loss of Nissl substance and intense eosinophilia of the cytoplasm (“red neurons”)
What is the neuronal response in within 12 hours of an irreversible hypoxic-ischemic insult in an axonal injury?
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
What are the intracellular inclusions seen in Herpes?
Cowdry bodies
What are the intracellular inclusions seen in Rabies infection?
Negri bodies
What is accumulated in neurones during normal aging, thought to play a role in development of neurodegenerative disorders?
Lipofuscin
What is the abnormal protein seen in Alzheimer’s disease?
Neurofibrillary tangles
What is the abnormal protein see in Parkinson’s?
lewy bodies
What is the response to astrocytes in response to injury?
- 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
What is the response to microglial cells in response to injury?
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
what is the mechanism behind cytotoxic oedema seen in tumours and infections?
- May follow generalised hypoxic, ischaemic or exposure to certain toxins
- Increased in intracellular fluid secretion secondary to neuronal and glial cell injury
What is the mechanism seen in vasogenic oedema?
- May proliferate around infarcts, tumours or part of an inflammatory response
- Defect in blood brain barrier, allowing fluid to shift from the vascular component to the extracellular spaces of the brain
What is global cerebral ischaemia caused by?
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
Which part of the brain is most sensitive to a drop in blood pressure?
o Watershed infarction – border areas of arterial territory (e.g. between ACA and MCA)
- Purkinje cells of cerebellum and laminar cortical necrosis
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
circle of Willis;
basal ganglia and internal capsule are
- ____________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
Penumbra
What are the common extra cranial sites for formation of thrombi thrombi?
– common carotid artery bifurcation, vertebral artery origin (near branching sites
what are common intra cranial sites for formation of arterial thrombi?
circle of Willis, middle cerebral artery origin, basilar artery
what are common intra cranial sites for formation of venous thrombi?
superior sagittal sinus
which artery is most affected by emboli?
middle cerebral artery?
what is the timescale of infarction when there is: No changes on gross or light microscopy
< 12 hours
what is the timescale of infarction when there is: Earliest light microscopy changes in the form of ischemic cells (red dead neurons)
12 to 24 hours
what is the timescale of infarction when there is: Neutrophil with vascular response
24 to 48 hours
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
48 hours
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
48 hours to 2/3 weeks
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)
From 1st week
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
hypertension;
smaller penetrating arteries
Venous infarcts – superior sagittal sinus thrombosis, a difficult clinical diagnosis
- Risk factors – hypercoagulable states (dehydration, phlebitis, pregnancy, birth control pill)
- Typically, ______________
frontal lobe haemorrhagic infarctions
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
hypertension (most common);
deep white matter or deep grey matter, brainstem and cerebellum;
Lipohyalinosis;
cortical and leptomeningeal arteries
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
MCA > ACA > PCA;
high output congestive heart failure;
tangled network of wormlike vascular channels
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
Sac-like dilatation;
branch points in circle of Willis
