Pots Flashcards
What’s an oedematous hemisphere?
distorted and swollen
What’s the falx cerebri?
the fold of dura mater which lies between the cerebral hemispheres
What’s subfalcine herniation?
The most common cerebral herniation pattern, is characterised by displacement of the brain (typically the cingulate gyrus) beneath the free edge of the falx cerebri due to raised intracranial pressure.
Where do meningiomas occur?
Meningiomas may be attached to the inner aspect of the dura anywhere within the skull. Since the spinal cord is also enveloped by meningeal coverings, meningiomas may also occur in the intravertebral canal.
Grade of meningiomas
WHO grade I, benign
Although there are very rare examples of malignant meningiomas (WHO grade III). There is an intermediate group of tumours which have histological features that are associated with an increased risk of local recurrence (e.g. necrosis, mitotic activity, nuclear pleomorphism) which are termed atypical meningiomas (WHO grade II). The invasion of the bone is not uncommonly seen, and this is not an indicator of malignancy. There are several histological subtypes of meningiomas, some of which have a worse prognosis.
What proportion of primary intracranial tumours are meningiomas?
20%
Are meningiomas more common in men or women?
Women, which may be related to the expression of hormone (progesterone) receptors by many of these tumours.
Risk factors for meningiomas
Age
meningiomas may occur at an earlier age in those with a hereditary predisposition, such as neurofibromatosis type 2 (NF-2)
Treatment of choice for meningiomas
Surgery which is difficult at some sites such as the skull base where the tumour can infiltrate around cranial nerves. What is important to be aware of is that although these tumours are biologically benign, they can behave in a malignant manner, in that they can have devastating clinical sequelae. This is easy to understand if you consider that the brain has a limited opportunity for expansion within the bony skull. An enlarging tumour mass will compress the surrounding brain and related structures, such as cranial nerves, arteries, and dural venous sinuses, and will ultimately displace the brain once it has attained a significant size, resulting in herniation.
From what cell type to meningiomas arise?
Arachnoid cap cells
Where might a meningioma be to present with loss of smell?
Olfactory groove where it compresses the olfactory nerve.
Where might a meningioma be to present with behavioural changes?
Parasagittal tumours that compress the frontal lobes
From which region is it difficult to resect meningiomas? And what can you do to treat them?
The skull base as there are vital structures present, and surgical access is more difficult.
Radiotherapy
What’s the tumour?
- neoplastic cells are arranged in meningothelial whorls and have pink (eosinophilic) cytoplasm with uniform nuclei
- scattered psammoma bodies - circular dark purple deposits of calcium
Meningioma
What’s the tumour?
several circumscribed mass lesions scattered throughout the brain, the cut surfaces of which show focal haemorrhage and crumbly white areas of necrosis.
Metastatic colon cancer
What’s the most common type of brain tumour in the UK?
metastatic tumours
The most common primary sites are the lung (accounting for 50% of metastatic brain tumours), breast, gastrointestinal (GI) tract, skin (melanoma) and kidney. Carcinomas are the most common tumour type to metastasise to the brain, but lymphoma can also do so. Metastatic deposits are blood-borne, and are often multiple.
What’s meningeal carcinomatosis?
When tumours metastasise via the bloodstream to the meninges, where they seed the subarachnoid space.
may be present in 1-8% of cancer patients
Cancers that have a greater propensity to form meningeal carcinomatosis (or malignant meningitis)
- lung
- lobular carcinoma (a subtype of adenocarcinoma) of the breast
- GI tract
- melanoma
- Lymphomas may also spread in this manner (lymphomatous meningitis)
Presentation of a meningeal carcinomatosis
- confusion
- focal neurology secondary to cranial nerve involvement (especially cranial nerves III, V, VI)
- symptoms and signs of raised intracranial pressure
- hydrocephalus, due to obstruction to the flow of cerebrospinal fluid (CSF) in the subarachnoid space
What does it mean for a tumour to be occult?
Unknown origin
What should you do if you suspect a meningeal carcinomatosis?
CSF examination is important for diagnosis in these cases as malignant cells may be seen on cytological examination of the CSF.
Causes of intracerebral haemorrhage
- hypertension
- arteriovenous malformations
- head trauma
- brain tumour
Which tumour is known to metastasise early to the brain and at a stage when the primary lung tumour may not be visible on imaging
small cell carcinoma of the lung
Presentation and diagnosis of brain tumours
- seizures (can be partial or generalised)
- focal neurological signs
- signs and symptoms of raised intracranial pressure (e.g. papilloedema, headache, vomiting)
The diagnosis is then made on imaging (with confirmatory biopsy performed occasionally). In some cases there may only be a single deposit, and the patient may not have a history of a primary tumour. In these cases a biopsy of the lesion, or examination of the surgically resected lesion, will enable histological confirmation of the diagnosis. The tumour deposit may also present acutely as a result of intratumoural haemorrhage.
What is subfalcine herniation of the cingulate gyrus?
displacement of the cingulate gyrus beneath the free edge of the falx cerebri due to raised intracranial pressure
Cell of origin of GBM
Thought to be astrocytes
Most common brain tumours in adults
GBM
How do GBMs migrate?
GBM is a highly aggressive tumour that has usually spread widely along nerve fibre tracts through the white matter of the brain at the time of presentation
If an astrocytic tumour that spreads through the corpus callosum results in….
a butterfly glioma
Do gliomas spread outside the CNS?
Rarely and this is usually only seen in conjunction with surgery such as the placement of a ventriculoperitoneal shunt for alleviation of raised intracranial pressure in association with the tumour.
Treatment of GBM
temozolamide (an alkylating chemotherapeutic agent) several years ago (2005) just under a quarter of patients survive for two years and approximately 10% of patients for three years.
Surgical resection/debulking of the tumour mass to relieve symptoms is possible in some sites of the brain such as the frontal lobe, but this type of surgery is limited to areas of the brain which can be removed without incurring significant neurological dysfunction. This is not a curative procedure.
Primary GBM
de novo
usually seen in the older population
Secondary GBM
Progression from a lower grade glioma, i.e. WHO grade II or III astrocytoma (secondary GBM).
Risk factors for GBM
- peak incidence between 45-70 yrs of age
- increased incidence of gliomas in patients with neurofibromatosis type 1 (von Recklinghausen’s disease); more commonly optic nerve gliomas, but an increase in the incidence of GBMs are also seen.
neurofibromatosis type 1 aka…
von Recklinghausen’s disease
What is uncal herniation of the brain?
In uncal herniation, a common subtype of transtentorial herniation, the innermost part of the temporal lobe, the uncus, can be squeezed so much that it moves towards the tentorium and puts pressure on the brainstem, most notably the midbrain.
What’s Duret’s haemorrhage?
Duret haemorrhages are small lineal areas of bleeding in the midbrain and upper pons of the brainstem. They are caused by a traumatic downward displacement of the brainstem that lacerates the penetrating veins.
What’s transtentorial herniation?
herniation of the medial temporal lobes/hippocampus through the tentorial notch
What’s the tentorium?
a dural membrane that separates the posterior fossa from the middle cranial fossa
Cystic, with a peripheral nodule
pilocytic astrocytoma (WHO grade 1)
Typical site for pilocytic astrocytoma
cerebellum
Pilocytic astrocytoma most commonly occur in…
children or young adults
Most common childhood glioma
pilocytic astrocytoma; cured by surgical excision
How can you die from a pilocytic astrocytoma?
herniation of the cerebellar tonsils into the foramen magnum at the skull base resulting in compression of the brainstem, in which the vital cardiorespiratory centres are found, by the cerebellar tonsils.
There’s a brown tumour nodule attached to a nerve in the region of the cerebellopontine angle. What is it?
vestibular (or acoustic) schwannoma (often referred to as an acoustic neuroma)
Cell of origin of vestibular schwannomas
Schwann cells
In addition to the 8th cranial nerve, schwannomas can also be found in…
the skin and rarely in other sites such as the gastrointestinal tract
Intracranial schwannomas arise on…..
most commonly arise from the VIIIth cranial nerve. They occasionally arise from the Vth, IXth, and Xth cranial nerves. These tumours favour sensory nerve roots.
Treatment of schwannomas
surgically removed and cured
What syndrome is associated with the development of bilateral schwannomas?
pathognomic of neurofibromatosis type 2
Inheritance pattern of neurofibromatosis
autosomal dominant pattern, although up to 50% cases of NF are due to new mutations
Associated with NF1
patients have:
- multiple neurofibromas
- Lisch nodules (hamartomas of the iris)
- cafe au lait spots
- optic nerve gliomas
- phaeochromocytomas
What is a Lisch nodule?
a pigmented hamartomatous nodular aggregate of dendritic melanocytes affecting the iris
What is a hamartoma?
mostly benign, focal malformation that resembles a neoplasm in the tissue of its origin
Associated with NF2
patients develop:
- bilateral vestibular schwannomas
- peripheral schwannomas
- meningiomas (often multiple) and ependymomas (CNS tumours derived from ependymal cells)
- neurofibromas in these patients are rare
Frequency of neurofibromatosis (NF)
NF 1 is more common than NF 2 (1:3000, compared with 1:40 000)
Which chromosomes are the NF genes on?
NF 1 gene is on chromosome 17
NF 2 gene is on chromosome 22
What’s a CVA?
Cerebrovascular accident
How do sagittal sinus thrombosis (and thrombosis of other intracranial venous sinuses) often present?
headache
seizures
What can occlusion of the venous return from the brain due to thrombus within the venous sinus result in?
oedema of the brain with raised intracranial pressure and patchy ischaemia affecting the cortex and the white matter
There may be haemorrhage from the vessels in the cortex and white matter due to occlusion of the blood flow
signs and symptoms of raised intracranial pressure
HPV!
headache
papilloedema
vomiting
The development of cerebral sinus thrombosis is seen in a variety of clinical settings, which include the following:
- Infection, particularly the extension of infection from the paranasal sinuses. This may also be associated with meningitis.
- Pregnancy and the puerperium.
- Any disorder that predisposes to a hypercoagulable state, such as antiphospholipid syndrome, protein C & S deficiencies. Also dehydration, pregnancy, the oral contraceptive.
- Chronic inflammatory diseases such as inflammatory bowel disease.
- Following trauma.
What is an epidural (extradural) haemorrhage?
The blood is in the space between the dura and the skull.
What is associated with a fracture of the temporal bone?
Tearing of the dura away from the bone to which it is normally closely apposed. The middle meningeal artery has consequently been torn as it runs between the dura and the skull in the floor of the middle cranial fossa. The blood is arterial in origin, so the systemic blood pressure forces blood between the external layer of the dura which is normally tightly adherent to the periosteum, and the bone, resulting in the formation of an epidural haematoma.
Clinical presentation of an epidural haemorrhage
loss of consciousness immediately following the impact, followed by a lucid period
The mass effect of the accumulating blood eventually results in drowsiness and coma several hours later, as a consequence of raised intracranial pressure. Immediate evacuation of the blood clot can be life saving.
What’s a contrecoup lesion?
In head injury, a coup injury occurs under the site of impact with an object, and a contrecoup injury occurs on the side opposite the area that was hit.
If there is an impact on the left side of the brain that results in a epidural haemorrhage then this is the coup lesion. A subarachnoid haemorrhage on the right would be the contrecoup lesion. The impact on the left results in shift of the brain within the cranium, with impact of the brain on the right (opposite the site of impact) against the skull. The brain is then rapidly thrust away from this site of impact on the right, resulting in tearing of the vessels in this area. This causes tiny haemorrhages within the cortex which are referred to as a contusion (a ‘bruise’ to the surface of the brain) with focal intracerebral haematoma formation. This, together with the tearing of overlying vessels, results in bleeding locally into the subarachnoid space.
Why can survivors of subarachnoid haemorrhage develop hydrocephalus?
Due to resorption of the blood in the subarachnoid space, and fibrosis with subsequent blockage of the flow of CSF.
Why can meningitis result in hydrocephalus?
In meningitis, there may be fibrosis within the subarachnoid space as a result of the resolution of the inflammation.
Sudden onset, severe headache
subarachnoid haemorrhage (SAH)
What’s the cause of subdural haemorrhage?
Tearing of the bridging veins as they pass from the superior surface of the cerebral hemisphere into the sagittal sinus.
What is gliosis?
The necrotic tissue has subsequently been removed by macrophages, which has left a space. Over time scar tissue may be formed by the astrocytes, this process is known as gliosis. The scar is composed of glial tissue, not fibrous tissue as you see elsewhere in the body.
Risk of hypertension on the brain
intracerebral haemorrhage and infarction
What’s a lacunar infarct?
Lacunar stroke or lacunar infarct (LACI) is the most common type of stroke, and results from the occlusion of small penetrating arteries that provide blood to the brain’s deep structures.
Cause of lacunar infarcts and slit haemorrhages
Long standing hypertension
Where are lacunar infarcts and slit haemorrhages likely to occur?
- small penetrating arteries and arterioles of the basal ganglia
- deep white matter
- brainstem
What are Charcot–Bouchard aneurysms?
Charcot–Bouchard aneurysms (also known as miliary aneurysms or microaneurysms) are aneurysms of the brain vasculature which occur in small blood vessels (less than 300 micrometre diameter)
Most common cause of intracerebral haemorrhage
Hypertension
What structures are close to the uncus and what can happen during raised IC pressure?
- the third cranial (oculomotor) nerve
- the posterior cerebral artery.
Compression of both cerebral arteries may lead to bilateral occipital infarcts in the setting of raised intracranial pressure.
What is cryptococcosis?
fungal infection caused by Cryptococcus neoformans (in the past it was referred to as torulosis)
Cryptococcosis is more commonly seen in….
immunocompromised patients
thickened leptomeninges and soap bubbles
Cryptococcal meningitis
What are ‘soap bubbles’?
expansion of the perivascular spaces (the so-called Virchow-Robin spaces) by collections of fungal organisms that are seen on imaging
What’s the second most common tumour of the sellar region (after pituitary adenoma) and the most common suprasellar neoplasm in children?
Craniopharyngiomas
Presentation of Craniopharyngiomas
- headache
- visual changes
Appearance of Craniopharyngiomas
complex cystic and solid tumours with brown cyst contents often described as ‘machine oil’.
Whilst they are benign tumours histologically complete surgical resection is difficult to achieve without risking significant hypothalamic dysfunction, psychological abnormalities as well as hypopituitarism. Recurrence is common.
What is Chiari Type II (Arnold Chiari malformation)?
A complex malformation and combines the herniation of the cerebellar vermis with malformation and downward displacement of the brainstem.
What is Chiari Type II associated with?
lumbosacral myelomeningocele and the majority (80%) have hydrocephalus at birth
What has been documented if fetal surgery to repair the myelomeningocele are performed in utero in Chiari II malformations prior to hydrocephalus?
Chiari II malformations completely resolved after the closure of the caudal defect. If further studies confirm this observation it may indicate that Chiari II malformations are secondary to the myelomeningocele.
A 19 year old man with learning difficulties, has numerous small rubbery nodules on his chest and back, freckles in his axilla, small nodules on his irises and some irregular light-brown patches on his flank. What gene mutation is he likely to carry?
NF1
Atypical mitotically active astrocytes with central necrosis and palisading necrosis is characteristic of…
GBM
densely packed small round blue cells forming rosettes is characteristic of…
Medulloblastoma
Whorls of meningiothelial cells which have regular nuclei and eosinophilic cytoplasm are typicl features of
Meningiomas
Epithelioid cells in brain tumours
Cerebral metastasis as epitheloid cells are not normally present in the CNS.
A 24 year old man complained of headaches, unsteady gait, nausea and vomiting over a two month period. An MRI scan of his head showed a circumscribed cystic lesion in the cerebellum. Histological analysis the lesion was composed of showed some thin-walled blood vessels and numerous small capillary channels. He had had a similar lesion excised some years ago. His father had renal clear cell carcinoma at age 43, and his brother had had a similar cerebellar lesion to himself. Further his uncle had a pheochromocytoma. What genetic mutation does he carry?
VHL
Mutation associated with: Cerebellar haemangioblastomas, pheochromocytomas and renal clear cell carcinoma
Von Hippel Lindau syndrome
Li-Fraumeni syndrome (germline p53 mutations) has a predisposition to
gliomas
N-myc mutations are associated with
a poorer prognosis in neuroblastoma
Mutation associated with:
parathyroid hyperplasia, pituitary and pancreatic adenomas
MEN-1
Presentation of HD
- hyperkinesias
- psychiatric symptoms
- dementia
Inheritance of HD
autosomal fashion and shows anticipation (earlier onset and greater severity in successive generations) due to expansion of a CAG triplet repeat in the HD gene on Chromosome 4
Pathogenesis of HD
The mutated Huntingdon’s gene shows a toxic gain of function that causes degeneration of the cortico-striatal loop, seen macroscopically as atrophy of the head of the caudate nucleus.
Presentation of parkinsons
tremor, bradykinesia and rigidity and may respond to L-DOPA therapy
Tau protein deposition in the cortex
Alzheimer’s disease
What is motor neuron disease?
aka Amyotrophic lateral sclerosis; ALS is due to selective degeneration of the motor neurons in the anterior motor pools of the spinal column.
