Neuropathology 3: Raised, ICP, SOLs and Trauma

Question 1

Normal ICP?

Answer 1

5-13 mmHg

Question 2

Progression of rise in ICP?

Answer 2

Some blood / CSF must escape from the cranial vault to avoid the rise in ICP

Once this is saturated, venous sinuses are flattened and there is little / no CSF

Any further increase in brain volume results in an increased ICP

Question 3

Causes of raised ICP?

Answer 3

Hydrocephalus

SOL

Diffuse lesion in the brain, e.g: oedema

Increased venous V

Physiological causes, e.g: hypoxia, hypercapnia, pain

Question 4

Define hydrocephalus?

Answer 4

Accumulation of excessive CSF within the ventricular system of the brain

Question 5

Normal production and turnover of CSF?

Answer 5

Choroid plexus, in the lateral and 4th ventricles of the brain, produce the CSF

It is absorbed by arachnoid granulations

Question 6

Constituents of CSF?

Answer 6

Lymphocytes <4 cells / ml

0 neutrophil cells

Protein <0.4g / l

Glucose >2.2 mmol/l

There are no rbcs

Question 7

Causes of hydrocephalus?

Answer 7

CSF flow obstruction, e.g: inflammation, pus and tumours

Decreased resorption of CSF, e.g: post-SAH or meningitis

Over-production of CSF, e.g: tumours of choroid plexus (very rare), congenital abnormalities

Question 8

Classifications of hydrocephalus?

Answer 8

Non-communicating - obstruction to CSF flow within the ventricular system

Communicating - obstruction to CSF flow outside the ventricular system, e.g: in the sub-arachnoid space or arachnoid granulations
This may be post SAH or infective bacterial meningitis

Question 9

Timing of hydrocephalus development with relation to closure of cranial sutures?

Answer 9

If hydrocephalus develops before closure of cranial sutures, then cranial enlargement occurs

If hydrocephalus develops after closure of the cranial suture the there is expansion of the ventricles and increased ICP

Question 10

What is hydrocephalus ex vacuo?

Answer 10

DOES NOT involve an increased in CSF pressure within the ventricles; rather, there is loss of brain parenchyma and this leads to expansions of the ventricles and CSF pool (to accomodate change in intracranial volume left by loss of parenchymal volume

Dilatation of the ventricular system and a compensatory increase in CSF volume secondary to a loss of brain parenchyma (e.g. in Alzheimer’s Disease)

Question 11

Effects of raised ICP?

Answer 11

Intracranial shifts and herniations; often this is a tonsillar herniation (AKA coning)

Midline shift

Distortion and P on CNs and vital neurologic centres

Impaired cerebral blood flow, as CPP = MAP - ICP

Reduced LoC

Question 12

Types of herniations?

Answer 12

1. Subfalcine herniation -
   unilateral (asymmetric) expansion of cerebral hemisphere displaces the cingulate gyrus under the falx cerebri
2. Tentorial herniation - medial aspect of temporal lobe herniates over the tentorium cerebelli

Compression of ipsilateral third cranial nerve and its parasympathetic fibres -> pupillary dilation and impairment of ocular movements on the side of the lesion.

3. Tonsillar herniation -
   displacement of cerebellar tonsils through the foramen magnum.

Life-threatening as it causes brainstem compression and compromises vital respiratory centres in medulla oblongata.

4. Transcalvarium – swollen brain will herniate through any defect in the dura and skull
   Reduction in level of consciousness
   Dilatation of pupil on same side as mass lesion
   Bradycardia, increase in pulse pressure and increase in mean arterial pressure,
   Cheyne-Stokes respiration

Question 13

Consequences of subfalcine herniation?

Answer 13

There is assoc. compresison of the ACA, leading to:

• Weakness and/or sensory loss in leg (due to ischaemic of primary motor and somatosensory cortex in these areas)

Question 14

Consequence of tentorial herniation?

Answer 14

Compression of ipsilateral CN III and its parasympathetic fibres:
• Pupillary dilatation
• Impaired ocular movements

These signs are present IPSILATERALLY

Question 15

Consequences of cerebellar herniation?

Answer 15

Brainstem compresion so LIFE-THREATENING, due to vital resp centres in the medulla

Question 16

Clinical signs of raised ICP?

Answer 16

Papilloedema (pressure on CN II)

Headache (worse o lying own, coughing, sneezing and straining)

N&v (pressure on vomiting centres in pon and medulla)

Neck sitffness (due to pressure on dura around cerebellum and brainstem)

Question 17

Types of SOLs?

Answer 17

Tumours:
• Primary tumours
• Metastases (common)

Abscess (single / multiple)

Haematomas

Localised brain swelling, e.g: swelling and oedema around a cerebral infarct

Question 18

Clinical presentation of tumours?

Answer 18

Facial symptoms

Headache

Vomiting

Seizures

Visual disturbances

Question 19

Signs of tumours?

Answer 19

Focal deficit and papilloedema

Question 20

Location of brain tumours, according to age?

Answer 20

In CHILDREN, 70% of tumours arise BELOW the tentorium cerebelli

In ADULTS, 70% of tumours arise ABOVE the tentorium cerebelli (2 As)

Question 21

Most common cancers that metastasise to the brain?

Answer 21

Breast, lung, kidney, thyroid and colon carcinomas

Malignant melanomas also

Question 22

Location of metastases to the brain?

Answer 22

Often seen at the BOUNDARIES between the grey and white matter

Mets can be single or multiple BUT multiple intracerebral tumours are far more likely to be metastatic

Question 23

Why are brain tumours thought of as SOLs?

Answer 23

Distinction between benign and malignant is far less important

Even when benign, tumours can be very infiltrative and difficult to resect; the most benign lesions can even kill, depending on where they are

And yet some high grade brain tumours do not metastasise

Question 24

Influence of oedema on an SOL?

Answer 24

Increases the influence of the SOL

Question 25

Most common type of brain tumour according to age

Answer 25

Adults - astrocytoma (a type of glioma); meningiomas are also common Children - medulla blastoma, although low grade astrocytomas are not uncommon

Question 26

WHO astrocytoma grading?

Answer 26

Pilocytic (grade I) - occur in childhood and are benign with no progression Well-differentiated (grade II) - tends to progress and become more anaplastic and aggressive; difficult to resect Anaplastic (grade III) Glioblastoma (grade IV) - can be: • Primary (assoc. with EGFR amp, PTEN loss and p53 mutations) • Secondary (to a well-differentiated or anaplastic astrocytoma)

Question 27

Histological appearance of a glioblastoma?

Answer 27

Numerous mitoses Anaplasia (marked nuclear atypia and poorly differentiated) Necrosis with surrounding palisading Neoangiogenesis - VEFG secretion by the tumour leads to increased vascularity in the high grade lesions

Question 28

Occurrence of medulloblastomas?

Answer 28

2nd most common tumour in children, after pilocytic astrocytoma

Question 29

Histological appearance of medulloblastoma?

Answer 29

Poorly differentiated / embryonal, i.e: they look like primitive, undifferentiated embryonal cells

Question 30

Location of medulloblastoma?

Answer 30

Tend to occur below the tentorium cerebelli, in the midline of the cerebellum

Question 31

Treatment of medulloblastoma?

Answer 31

Very RADIOSENSITIVE Good survival with resection and radiotherapy

Question 32

Consequences of a medulloblastoma?

Answer 32

Occlusion of CSF flow, perhaps at the 4th ventricle, leads to hydrocephalus and increased head size

Question 33

Pituitary tumours?

Answer 33

????????

Question 34

Cause of single abscesses

Answer 34

1. Local extension, e.g: from a mastoiditis 2. Direct implantation, e.g: following a skull fracture or penetrating injury They tend to occur adjacent to the source

Question 35

Cause of multiple abscesses?

Answer 35

Haematogenous spread, e.g: from a: • Bronchopneumonia • Bacterial endocarditis These tend to occur at grey and white matter boundaries

Question 36

Symptoms of abscess?

Answer 36

Fever Raised ICP Symptoms of underlying cause

Question 37

Ix for abscesses?

Answer 37

CT or MRI scan

Question 38

Treatment of abscesses?

Answer 38

Aspiration for culture and treatment Requires weeks of antibiotics

Question 39

Define bacterial meningitis?

Answer 39

Inflammation of the leptomeninges and CSF, within the subarachnoid space

Question 40

Consequences of

Answer 40

Severe oedema and raised ICP Arachnoiditis, which can cause lack of CSF reabsorption and hydrocephalus (contributing to raised ICP)

Question 41

CSF contents in bacterial meningitis?

Answer 41

Abundant polymorphs Decreased glucose

Question 42

Culprit bacterial in meningities of different age groups?

Answer 42

Neonates - E. coli Infants and children - H. influenzae Adolescents and young adults - N. meningitidis Older adults or children - S. pneumoniae Older adults - L. monocytogenes

Question 43

Types of traumatic head injury?

Answer 43

Missile (penetrating) or non-missile (blunt)

Question 44

Consequences of head trauma?

Answer 44

Skull fractures Parenchymal and vascular injury

Question 45

Mechanism of a penetrating injury?

Answer 45

``` Causes FOCAL damage, with lacerations potentially occurring through: • Skin • Periosteum • Dura • Meninges • Brain ``` Direct disruption and laceration of brain parenchyma is followed by haemorrhage, which acts as a SOL

Question 46

Why is it important to differentiate between high and low velocity injuries (in this case, of the penetrating type)?

Answer 46

High velocity means the extent of the injury can be far greater Also, cavitation occurs (small bubbles appearing at low pressure), e.g: fast movement of a bullet creates a field of low P and cavitation occurs, resulting in widespread surrounding damage This does not occur in low velocity injuries

Question 47

Describe non missile (blunt) injuries

Answer 47

Describes a sudden acceleration / deceleration of head; the smaller the contact time, the larger the force on the head Brain moves within the cranial cavity and makes contact with the inner aspect of the cranium and bony protrusions NOTE - even without skull fractures, the brain can become fatally damaged

Question 48

Causes of non-missule head injuries?

Answer 48

RTAs, falls, assaults, alcohol

Question 49

Pathophysiology of head injury?

Answer 49

Primary injury - neurones injured at the time of the head injury; it is irreversible but preventative measures can be used, e.g: helmets, seatbelts Secondary injury - includes haemorrhage, oedema, etc; it is potentially treatable

Question 50

Clinical hallmark of primary brain injury?

Answer 50

Immediate change in conscious level, depending upon the extent of neuronal damage

Question 51

Types of primary injury?

Answer 51

1. Shear injury to axons; this can be localised, diffuse or both 2. Contusion, due to compressive strain, cavitation or surface lacerations of the brain parenchyma

Question 52

Consequences of a primary head injury?

Answer 52

* Scalp lesions * Skull fracture * Surface contusions * Surface lacerations * Diffuse axonal injury * Diffuse vascular injury * Petechial haemorrhages

Question 53

Issues assoc. with sclap lesions?

Answer 53

Bruising, lacerations, bleeding Potential route for infection

Question 54

Types of skull fractures?

Answer 54

Linear - straight, sharp fracture line that may cross suture (AKA diastatic fracture); increases the likelihood that a clinically significant haematoma is already present Compound - assoc. with full-thickness scalp lacerations, i.e: an open fracture Depressed - most of these are also compound and carry a risk of intracranial bacterial implantation

Question 55

Issues assoc. with skull fractures?

Answer 55

Increased likelihood that there is an intracranial bleed / haemtoma This depends on where the fracture occurs, e.g: linear fracture to the squamous portion of the temporal bone can rupture the MMA and cause an extradural haematoma

Question 56

Describe base of skull fracture

Answer 56

Always regarded as COMPOUND OR OPEN, as there is a high likelihood that there is exposure to the outside world via, e.g: adjacent paranasal air sinuses having been torn

Question 57

What are surface contusions of the brain?

Answer 57

Essentially bruises caused by tissue damage following severe compressive strains Commonly occur under the surface of the temporal and frontal lobe, as there are many sharp, bony prominences here

Question 58

Types of surface contusions?

Answer 58

Coup injury - occurs at point of impact Contra-coup injury - occurs diametrically opposite to the point of impact (on the non-impact side); often WORSE THAN COUP injuries

Question 59

2 main theories that explain why contracoup injuries tend to be worse than coup injuries

Answer 59

Denser CSF moves to impact side first, forcing the brain to contra-coup side first; in this situation, the contra-coup side would have the higher energy 2nd theory involves cavitation; low P in brain moving away from zone opposite the impact side The low P creates bubbles, which damage parenchyma

Question 60

What is diffuse axonal injury?

Answer 60

Most common type of brain damage due to blunt injury There is widespread disruption of axons, due to shear strain tearing them at the immediate time of acceleration / deceleration NOTE - different areas of the brain have different mass and density and, when exposed to forces, move at different rates relative to each other, creating shear strain between structures of different density, part. at the grey-white matter interface

Question 61

Histology of diffuse axonal injury?

Answer 61

Axonal bulbing and blebbing on the truncated neurones

Question 62

Signs of diffuse axonal injury?

Answer 62

Reduces consciousness and coma Can lead to vegetative state

Question 63

Mechanisms by which secondary brain injury can occur?

Answer 63

* Intracranial haematoma * Raised ICP * Hypoxia / ischaemia * Excitotoxicity * Oedema * Infection * Electrolyte abnormalities

Question 64

Cellular events that occur in acute brain injury?

Answer 64

1. Injury to microvasculature and the BBB occurs 2. Oedema 3. Hypoxia 4. Glutamate release leads to excitotoxicity and Ca2+ influx (increased IC Ca2+) 5. Hypoxia also increases oxidative stress, causing mitochondrial injury and free radical formation 7. These processes cause apoptosis and necrosis 8. Further tissue disruption can exacerbate the situation, creating +ve feedback loops of enhancing local injury

Question 65

Types of traumatic intracranial haematomas?

Answer 65

* Extra-dural | * Intra-dural (majority) - inc. sub-dural, intracerebral haematomas, sub-arachnoid and 'burst lobe'

Question 66

What is a 'burst lobe'?

Answer 66

Gross contusion that inv. disruption of much of the frontal and temporal lobes and is assoc. with a significant degree of haemorrhage

Question 67

Cause of traumatic extradural haematomas?

Answer 67

Usually complication of | a fracture in the temporo-parietal region that inv. MMA

Question 68

Consequences of traumatic extradural haematoma?

Answer 68

Immediate brain damage is often minimal However, if untreated, there is midline shift, compression and herniation

Question 69

What is a subdural haematoma?

Answer 69

Collection of blood between the internal surface of the dura mater and arachnoid

Question 70

Cause of subdural haemorrhage?

Answer 70

Disruption of bridging veins that extend from the surface of the brain into subdural space; occurs due to any injury assoc. with a rapid change in head velocity

Question 71

Occurrence of subdural haemorrhages?

Answer 71

Part. common in head injury affecting the elderly, e.g: falls; relative age-related atrophy of the brain places more P on the bridging veins and the brain is more mobile within the cranium Infants have susceptible arteries, as they are thin

Question 72

Cause of chronic subdural haemorrhages?

Answer 72

Less frequently assoc. with a well-defined traumatic insult Often assoc. with brain atrophy

Question 73

Appearance of chronic subdural haemorrhages?

Answer 73

Composed of liquefied blood / yellow-tinged fluid separated from inner surface of the dura mater and underlying membrane by a 'neomembrane'