17. CNS Disorders & Intracranial Tumours

Question 1

Dementia has a prevalence of ...% increasing to ...% in over 80yo. It is characterised by the ...(55%) or ... (45%) of the ... system of the brain. The most common degenerative cause is ..., which is a ... that affects more of older females. ...% at age 65 develop symptoms of ... and ...% of population at age 85 have .... Younger individuals can also get dementia due to ... (prion disease), ... (hereditary) and ... toxicity.
Symptoms of dementia includes:
* Complex processing problems - ..., ..., ..., ...
* ... loss
* ... change
* Slower ...
Dementia is the ... leading cause of death (~... years from diagnosis to death)

Answer 1

Dementia has a prevalence of 5% increasing to 20-40% in over 80yo. It is characterised by the degeneration(55%) or infarct (45%) of the Limbic system of the brain. The most common degenerative cause is Alzhiemer's disease (AD), which is a neurone degeneration that affects more of older females. 15% at age 65 develop symptoms of AD and 35% of population at age 85 have AD. Younger individuals can also get dementia due to Cretzfeldt-Jakob (prion disease), Picks disease (hereditary) and alcoholic toxicity.
Symptoms of dementia includes:
* Complex processing problems - confusion, delirium, hallucination, impaired judgements
* Memory loss
* Personality change
* Slower motor capacity
Dementia is the 6th leading cause of death (~8 years from diagnosis to death)

Question 2

What is the limbic system of the brain?

Answer 2

A group of interconnected nuclei that mediate emotions, learning and memory. These nuclei also produce ACh, bDNF

Question 3

What is bDNF?

Answer 3

bDNF = brain derived neurotrophic factor is a protein that promotes neuronal survival, assists nerve growth, maturation and differentiation. Important for neural plasticity, role in learning/ memory.

Question 4

Alzheimer’s disease is a ... degeneration that expresses as ... and leads to .... ... is a protein that exists in healthy brains and help ....
In AD phosphorylation, ..., this therefore causes ... and cause reduction in bDNF. This forms ....
In AD, ... accumulates in the extracellular space to form .... These are ... protein that causes ... of the CNS.
In AD, reduction in ... can be seen due to ....

Answer 4

Alzheimer’s disease is a neuronal degeneration that expresses as tangles/plaque and leads to neural apoptosis. Tau is a protein that exists in healthy brains and help stabilise microtubules.
In AD phosphorylation, tau becomes toxic, this therefore causes tubules to breakdown and lose its structure and cause reduction in bDNF. This forms neurofibrillary tangles.
In AD, beta-amyloid accumulates in the extracellular space to form plaques. These are neurotoxic protein that causes apoptosis of the CNS.
In AD, reduction in grey and white matter can be seen due to neurocortical degeneration.

Question 5

Limbic system loss in Alzheimer’s leads to downstream:
CNS → ..., ..., enlarged ...
Sensory → ... due to reduction in ...
* Outcome = ... (memory/ speech) and ... loss.

Answer 5

Limbic system loss in Alzheimer’s leads to downstream:
CNS → cortical atrophy, shinkage of brain mass, enlarged ventricles
Sensory → apoptosis due to reduction in bDNF
* Outcome = dementia (memory/ speech) and visual processing loss.

Question 6

What is the current definitive diagnosis of Alzheimer’s disease?

Answer 6

Post-mortem amyloid beta plaques

Question 7

What are the ocular signs of Alzheimer’s disease? How are these measured?

Answer 7

• Retinal nerve fibre layer thinning via peripapillary scans on OCT
• Macula GCIPL/GCC (ganglion cell inner plexiform layer/ ganglion cell complex) thinning on OCT
• Deposits of amyloid beta plaques in the retina (& brain) - using curcumin staining

Question 8

Myelin is needed to facilitate .... Myelination starts in the ... during the ...th month of gestation. Myelin reaches the ... at ...th month and stops at the ... at term. Myelin may sometimes enter the eye and appear as ... nerves. This may disappear with ... or ....

Answer 8

Myelin is needed to facilitate inter-nodal atonal conduction. Myelination starts in the LGN during the 5th month of gestation. Myelin reaches the chiasm at 6th month and stops at the lamina cribrosa at term. Myelin may sometimes enter the eye and appear as feathery white medullated nerves. This may disappear with multiple sclerosis or optic neuropathy.

Question 9

What are the causes of demyelination? (3 causes + details)

Answer 9

• Multiple sclerosis = most common
• Toxicity - CO poisoning, metabolic problems (Vit B deficiency)
• Inflammation - Guillian-Barre syndrome, Fisher’s syndrome, Devic’s disease

Question 10

Of 20% of multiple sclerosis cases, ... is the presenting sign. 85% of MS cases experience .... Optic neuritis is the inflammation of ... or .... There are two presentations:
* ... - visible at lamina (orbital)
* ... - retrobulbar to orbit

Answer 10

Of 20% of multiple sclerosis cases, optic neuritis is the presenting sign. 85% of MS cases experience optic neuritis. Optic neuritis is the inflammation of optic nerve fibres or retinal NFL. There are two presentations:
* Papillitis - visible at lamina (orbital)
* Retrobulbar neuritis - retrobulbar to orbit

Question 11

How would optic neuritis appear on OCT initially and in the long term?

Answer 11

Initially swelling → thickening on OCT (white or pink)
Long term result in thinning on OCT (GC or RNFL retrograde degeneration)

Question 12

Retro-bulbar neuritis is characterised by ... and ... seen on OCT. Px will often experience ... vision, abnormal ..., ... anomaly or .... Systemic symptoms involve ..., ..., ..., decreased ..., poor ... and ....

Answer 12

Retro-bulbar neuritis is characterised by loss of RNFL and optic atrophy seen on OCT. Px will often experience distorted vision, abnormal visually evoked response (VER), eye movement anomaly or diplopia. Systemic symptoms involve muscle symptoms, bowel and bladder symptoms, numbness, tingling, or pain, decreased attention span, poor memory and fatigue.

Question 13

Multiple sclerosis is a ... that require multiple ... to identify. The ... is used to diagonose MS, which involves dissemination in space: ... and dissemination ... → either have to have ... or they have to have multiple episodes of ... within a period of ....

Answer 13

Multiple sclerosis is a demyelination neuropathies that require multiple lesions over multiple episodes to identify. The Macdonald criterion is used to diagonose MS, which involves dissemination in space: 3+ lesions CNS and dissemination in time → either have to have multiple lesions or they have to have multiple episodes of optic neuritis within a period of 3 months.

Question 14

... also known as neuromyelitis optica is a rare .... disorder that can also present with ..... Damages to the optic nerve produces ... and ... thus can cause .... Damage to the spinal cord causes ... in the legs or arms, loss of ..., and problems with ... and ... function. It is a ... condition. For most cases, there is an attack on the ... located within the ... and .... The antibody against ... is found in ...% of those with NMO, but not in those with MS.

Answer 14

Devic's disease also known as neuromyelitis optica is a rare autoimmune disorder that can also present with optic neuritis. Damages to the optic nerve produces swelling and inflammation thus can cause pain and loss of vision. Damage to the spinal cord causes weakness or paralysis in the legs or arms, loss of sensation, and problems with bladder and bowel function. It is a relapsing-remitting condition. For most cases, there is an attack on the aquaporin-4 (AQP4) water channel located within the optic nerves and spinal cord. The antibody against AQP4 is found in 70% of those with NMO, but not in those with MS.

Question 15

Expansive disorders are those that .... The most common diseases associated with increased IOP are ..., ..., ..., ... and ....
Other diseases that can associate with high IOP is AIDS, ... (congenital hydrocephalus), ...., inflammatory polyneuritis, lithium therapy, ..., ..., trauma.

Answer 15

Expansive disorders are those that produce increased intraocular pressure. The most common diseases associated with increased IOP are uncontrolled systemic hypertension, cranial mass, psuedotumour cerebri (PTC) idiopathic, subarachnoid haemorrhage (SAH) and intracerebral haemorrhage.
Other diseases that can associate with high IOP is AIDS, aqueductal stenosis (congenital hydrocephalus), infectious disease (meningitis), inflammatory polyneuritis, lithium therapy, spinal cord tumour, toxic/ metabolic disorders, trauma.

Question 16

Mass effect occurs when a ... expands within the confines of a ... e.g. cranial vault. This is the ... theory. As the brain is encased in a ..., any changes in volume/ .... can have a dramatic effect on the brain. In the eye, however, ... and ... are more flexible, therefore consequences are ....

Answer 16

Mass effect occurs when a space occupying lesion expands within the confines of a fixed volume e.g. cranial vault. This is the Munro-Kellie theory. As the brain is encased in a hard skull, any changes in volume/ increase in intracranial pressure can have a dramatic effect on the brain. In the eye, however, sclera and cornea are more flexible, therefore consequences are less severe.

Question 17

Mass effect gives raised ... (ICP). ICP is similar to IOP, where normative values are between ...mmHg, above ...mmHg requires treatment. Raised iCP leads to ... and .... Both increased in ICP and IOP causes .... from pain receptors around blood vessels; ... (axonal flow); and ... compromise, including .... due to low pressure venous flow. ICP abnormalities are diagnosed using ....

Answer 17

Mass effect gives raised intracranial pressure (ICP). ICP is similar to IOP, where normative values are between 5-15mmHg, above 20mmHg requires treatment. Raised iCP leads to direct compression of tissues and vascular compromise. Both increased in ICP and IOP causes pain/ headache from pain receptors around blood vessels; axoplasmic stasis (axonal flow); and vasulcar compromise, including haemorrhagic congestion due to low pressure venous flow. ICP abnormalities are diagnosed using lumbar puncture opening pressure.

Question 18

What are the neurological signs of raised ICP?

Answer 18

• Severe/ different constant headaches
• Rigidity about neck with loss of forward flexion
• Gait problems
• Projectile vomit without nausea
• Hemi-paresis, tingling, pins & needles
• Reduced state of alertness/ consciousness
• Symptoms may worsen on straining, valsalva (forced expiration), change in posture

Question 19

How do ocular symptoms arise from raised ICP? What are the ocular signs of raised ICP?

Answer 19

Ocular symptoms arise due to transmission of ICP down ONH sheath to the lamina cribrosa.
Symptoms: photophobia; short lived vision disturbance, blur or loss (5-30secs); diplopia and pupil abnormality due to brain stem downward movement; papilloedema.

Question 20

What is a highly suspicious ocular sign of raised ICP?

Answer 20

Papilloedema + at least 1 other neurological sign

Question 21

Papilloedema can occur within ... hours of raised ICP. .... ceases when IOP is above ...mmHg, but as they are not present normally in 20% of the population, it is ..... Papilloedema is always ... but often .... Papilloedema manifest in orbit by ... along ... up to region of .... Compression causes axoplasmic stasis and thus .... Venous compromise is most marked at the ... and .... This also causes ..., buried ..., peripapillary ..., ... (NFL infarcts), forward displacement of ..., and retinal (...) or choroidal folds.

Answer 21

Papilloedema can occur within 24 hours of raised ICP. Spontaneous venous pulsation ceases when IOP is above 20mmHg, but as they are not present normally in 20% of the population, it is an unreliable sign of raised ICP. Papilloedema is always bilateral but often asymmetric. Papilloedema manifest in orbit by transmission of ICP along subarachnoid spaces up to region of lamina. Compression causes axoplasmic stasis and thus RNFL swelling. Venous compromise is most marked at the inferior pole and RNFL. This also causes disc hyperaemia, buried blood vessels, peripapillary haemorrhages, cotton wool patches (NFL infarcts), forward displacement of papilla, and retinal (Patton's folds) or choroidal folds.

Question 22

What are the two types of long term papilloedema (>3 months)?

Answer 22

Types depend on the level of vascular compromise and shunt development
* Compensated = shunt established, venous flow not compromised but axoplasmic stasis is still present → clean appearance with gross intravitreal swelling of ON
* Non-compensated = shunt not established → very dirty presentation with haemorrhages and CWPs

Question 23

Foster-Kennedy syndrome is the compression of the ... by an ..., leading to .... Contralateral papilloedema arise when the .... The atrophic optic nerve ... so the papilloedema is .... Depending on the stage of optic atrophy, there can be ... in one eye with ....

Answer 23

Foster-Kennedy syndrome is the compression of the ipsilateral optic nerve by an intracranial mass, leading to optic atrophy. Contralateral papilloedema arise when the intracranial mass is big enough to elevate ICP. The atrophic optic nerve doesn't manifest the disc edema so the papilloedema is unilateral. Depending on the stage of optic atrophy, there can be atrophic disc in one eye with bilateral papilloedema.

Question 24

... is a false brain tumour, also known as .... This typically affects .... Px will have all signs and symptoms of ..., but practitioners will fail to find the cause. Most px will have ... and ...% will have severe vision loss. CN... and ... problems are commonly invovled.

Answer 24

Pseudotumour cerebri is a false brain tumour, also known as idiopathic intracranial hypertension. This typically affects premenopausal, obese women. Px will have all signs and symptoms of papilloedema, but practitioners will fail to find the cause. Most px will have headaches and 25% will have severe vision loss. CN6 and BV problems are commonly invovled.

Question 25

Aneurysm and sub-Arachnoid haemorrhage (SAH) often involve ... either present directly or through transmitted .... If the ... ruptures, it becomes a neurological emergency. ...% of SAH symptoms arise after rupture. However, there are symptoms that can give .... (~14 days). If susceptible, px should be referred urgently to .... If px has vision and neuro-ophthalmic symptoms, px may present to optometrists, especially with 30% of .... Typical symptoms include ... and ... with or without neurological symptoms.

Answer 25

Aneurysm and sub-Arachnoid haemorrhage (SAH) often involve vision or visual pathways either present directly or through transmitted ICP. If the aneurysm ruptures, it becomes a neurological emergency. 90% of SAH symptoms arise after rupture. However, there are symptoms that can give prodromi for impending aneurysmal rupture (~14 days). If susceptible, px should be referred urgently to hospital for CT scans and surgical intervention. If px has vision and neuro-ophthalmic symptoms, px may present to optometrists, especially with 30% of posterior communicating aneurysm. Typical symptoms include severe headaches and visual disturbances with or without neurological symptoms.

Question 26

Subarachnoid haemorrhage associate with recent onset of ... that do not comply with ... e.g. thunderclap, migraines etc. Px will first experience short lived losses of ..., ... or ... and .... At the end stage, px will experience rigidity about neck with ..., ... or ..., gradual ... with or without ... and change in ....

Answer 26

Subarachnoid haemorrhage associate with recent onset of constant or severe headaches that do not comply with recognised patterns e.g. thunderclap, migraines etc. Px will first experience short lived losses of vision, blur or visual field and photophobia. At the end stage, px will experience rigidity about neck with loss of forward flexion, Infraorbital haemorrhage or papilloedema, gradual ON atropy with or without cupping and change in consciousness/ alertness.