Neuroscience

Question 1

List a few risk factors for ischemic stroke.

Answer 1

• Older (>65 years old)
• Male sex
• History of transient ischemic attack
• Atherosclerosis
• Systemic Arterial Hypertension
• Cardiovascular heart disease
• Hypercoagulable states (e.g. pregnancy, hyperhomocysteinemia, protein C and S deficiency, cancer or malignancy)

Question 2

How does atrial fibrillation increases the risk of stroke?

Answer 2

During atrial fibrillation, the blood becomes stagnant, this promotes blood clotting (Virchow’s Triad), and blood clot is formed in the left atrial appendage. This blood clot then embolism into the cerebral circulation / blood vessels towards the brain, resulting in ischemic stroke.

Question 3

Name 3 common sites of thrombotic stroke.

Answer 3

Carotid bifurcation
Basilar artery
Origin of middle cerebral artery

Question 4

Name 4 clinical features you will see in MCA infarcts?

Answer 4

Contralateral hemipararesis and loss of sensation in the lower half of the face and upper limbs

Contralateral homonymous hemianopia without macular sparing

Eye gaze to the side of lesion (ipsilateral)

Aphasia

Broca’s Area (left inferior anterior gyrus)
Wernicke’s Area (left superior temporal gyrus)

Contralateral hemineglect

Question 5

How do you quantify the severity of stroke?

Answer 5

Using the National Institute of Health (NIH) Stroke Scale

Normal: 0
Mild: 1-6
Moderate: 7-12
Severe: >12
Max: 42

Question 6

How do you know imaging is highly suggestive of stroke instead of tumour or lesions?

Answer 6

When there is a straight line boundaries, which is indicative of the vascular boundaries.

Question 7

Name the first line imaging modality used for detecting stroke.

Answer 7

Head CT (computed tomography) without contrast

Question 8

Are Head CT with contrast contraindicated in stroke? What is the other contraindication?

Answer 8

Yes, they are contraindicated in patients with stroke, and intracranial haemorrhage.

Question 9

What would you see on neuroimaging from MCA infarcts?

Answer 9

Hyperdense (brighter) MCA dot sign (usually after 90 mins)

Hypodense (darker) brain tissue (can be due to oedema)

Loss of “insular ribbon sign” (loss of grey-white matter differentiation)

Obscuration of lentiform nucleus (loss of basal ganglia)

Question 10

What are the advantages of Head CT over MRI?

Answer 10

Faster / quick to perform, so to shorten the time before administrating thrombolytic drugs

Easier to obtain compared to MRI (logistically)

More affordable (MRI is more expensive)

Able to detect haemorrhage better than MRI

Can be performed by anyone

Reproducible

Question 11

What are the criteria (indications) for thrombolytic therapy (e.g. tissue plasminogen activator, tPA)?

Answer 11

Dagnosis of acute stroke
Age > or equal to 18 years old
Onset of symptoms < 4.5 hours before tPA administration (best is <3 hours)
Head CT confirming no contraindications (e.g. haemorrhage and large stroke)

Question 12

What are the contraindications for thrombolytic therapy (e.g. tissue plasminogen activator, tPA)?

Answer 12

Recent head trauma
Large stroke
Intracranal haemorrhage
Bleeding Diathesis
Recent surgery or procedure
Recent MI 
Recent GI bleed / malignancy
Pregnancy
Improving symptoms
Seizure at onset

Question 13

What is the necrosis that occurs with infarction of brain tissue?

Answer 13

Liquefactive necrosis

Note: coagulative necrosis are seen after infraction in other organs.

Question 14

What are the causes of subarachnoid haemorrhage?

Answer 14

Traumatic: head trauma

Non-traumatic: rupture cerebral (saccular, berry) aneurysm

Question 15

Name 3 risk factors for subarachnoid haemorrhage.

Answer 15

Hypertension
Smoking
Positive Family History

Question 16

Describe the clinical features of subarachnoid haemorrhage.

Answer 16

Thunderclap headache: often described as the worst headache in patients’ lives

Impaired consciousness

Mass effect

Meningeal signs

Prodromal symptoms

Question 17

What would you see on CT without contrast for subarachnoid haemorrhage?

Answer 17

Hyperdense (whitish, brighter, blood) lesion in the subarachnoid space

Question 18

Briefly describe the 3 classification of subdural haemorrhage.

Answer 18

Acute SDH: symptoms onset <3 days

Subacute SDH: symptoms onset 4-20 days

Chronic SDH: symptoms onset >21 days

Question 19

What are the causes of SDH?

Answer 19

Rupture or tear of the bridging veins which can occur secondary to any of the following:

Head trauma
Shaken baby syndrome
Acceleration-deceleration injury
Cerebral atrophy
Alcohol use disorder
Advanced age and very young
Hyponatremia

Question 20

Why are elderly has an increased risk of subdural haemorrhage?

Answer 20

Elderly (advanced age) are prone to cerebral atrophy. When there is cerebral atrophy, there is an enlargement of the subdural space, which results in an increased length that bridging vein has to transverse. The bridging veins are more vulnerable to shearing force

Question 21

Why does alcohol abuse increase the risk of subdural haemorrhage?

Answer 21

Alcohol -> thins the veins and increased risk for thrombocytopenia, easier to rupture.

Question 22

Describe how a SDH would appear in Head CT without contrasts.

Answer 22

Crescent-shaped (concave) hyperdense (blood) lesion

Cross the suture line

Does not cross the midline (due to the presence of flax cerebri)

Ventricular and sulcal effacement

If the mass is large enough, it can cause a midline shift to the contralateral side due to mass effect

Radiodensity of the lesion on CT depends on the timeline of SDH.

Acute: usually hyperdense
Subacute: isodense
Chronic: hypodense

Question 23

What is the cause of epidural haemorrhage?

Answer 23

Rupture or tear to the middle meningeal artery (branch of maxillary artery)

Question 24

Where is the most common site of rupture? Explain why.

Answer 24

The pterion is the most common site of rupture, as it is the thinnest part of the skull, and where the middle meningeal artery lies in close proximity to the skull\

Question 25

Which region of the brain does blood usually pool in EDH?

Answer 25

Temporal or tempo-parietal region

Question 26

What kind of herniation does EDH result in? Why does it occur?

Answer 26

Transtentorial uncal herniation. Due to increased intracranial pressure.

Question 27

Describe the classical presentation of EDH.

Answer 27

1. Initial sudden loss of consciousness 2. Lucid interval: temporary restoration of consciousness with normal or near-normal neurological function 3. Renewed decline in neurological status and onset of symptoms due to hematoma (e.g. mass effect)

Question 28

Explain why there is a period of restoration of consciousness with normal or near-normal neurological function.

Answer 28

Due to the venous shunting of blood out from the epidural space.

Question 29

Describe how EDH would appear in Head CT without contrast

Answer 29

Lenticular-shaped (biconvex) hyperdense (typically) lesion Does not cross the suture lines Crosses the midline (EDH can cross the dural attachment sites) Ventricular and sulcal effacement If the mass is large enough, it will cause a midline shift to the contralateral side (mass effect)

Question 30

What are the red flags of Headache?

Answer 30

Mnemonics: SNOOPP S: Systemic signs & symptoms (fever, weight loss) N: neurological deficits/dysfunction (altered mental status, seizure) O: onset of headache is abrupt O: older age (>50y/o) with new or progressive headache P: papilloedema, and other signs of increased intracranial pressure P: progressive headache

Question 31

What are the indication for brain imaging in headache?

Answer 31

Mnemomics: I WARN P I: incapacitating headache W: worst headache in patient’s life A: abrupt onset R: recent onset in patients > 50 years old N: new onset of nocturnal headache P: papilloedema, pattern change in headache, post-traumatic headache, pituitary dysfunction, elevated pressure in eye or intracranially

Question 32

Describe the pathophysiological mechanism contributing to Alzheimer Disease.

Answer 32

Enzymatic cleavage of transmembrane amyloid precursor protein (APP) by beta-secretase and gamma-secretase, results in the formation of insoluble beta-amyloid monomers. Beta-amyloid monomers aggregates to form beta-amyloid plaques, which deposits outside the neuron Extracellular beta-amyloid initiate the activation of intracellular kinase, which results in the phosphorylation of tau protein in the microtubule. Hyperphosphorylate tau protein results in the formation of neurofibrillary tangles in the neuron, which damages the microtubules via apoptosis, and result in Alzheimer Disease.

Question 33

Name the 3 genetic factors that predispose to Alzheimer Disease.

Answer 33

- Amyloid Precursor Protein (APP) gene on Chromosome 21. People with trisomy 21 have an overpression of APP gene, predisposing them to Alzheimer Disease. - Apo ε gene on chromosome 19. Apo ε breaks down beta-amyloid. The lack of ApoE, predispose individuals to Alzheimer Disease. - Presenilin-1 and -2 (PSEN-1 and PSEN-2) gene, on chromosome 14 and chromosome 1, respectively. PSEN gene mutation results in gamma secretes to change location, forming plaques.

Question 34

Describe the microscope findings of the brain in Alzheimer Disease.

Answer 34

- pink or red beta-amyloid plaques in the interneuronal space of the brain under Congo Red stain - green birefringent of beta-amyloid plaques under polarised light - Gallyas stain of neurofibrillary tangles (aggregated of hyperphosphorylated tau protein)

Question 35

Name 3 complications of Alzheimer Disease

Answer 35

Infection: aspiration pneumonia Malnourishment/dehydration Intracerebral haemorrhage (due to increased risk of cerebral amyloid angiopathy)

Question 36

Parkinson disease primarily affects individual of which age?

Answer 36

>45 years old

Question 37

Name a contributing genetic factor to Parkinson Disease

Answer 37

α-Synuclein (SNCA) gene, which results in the accumulation of lewy bodies

Question 38

Describe the pathophysiology of Parkinson Disease.

Answer 38

α-Synuclein (SNCA) gene -> accumulation of lewy bodies -> progressive dopaminergic neuron degeneration in the substantia nigra (part of the basal ganglia) -> decrease dopaminergic neuron -> dopamine deficiency -> movement disorder

Question 39

Describe the clinical features of Parkinson Disease

Answer 39

Triad of Parkinsonism 1. Bradykinesia (slow movement) 2. Resting tremor (pill-rolling tremor) 3. Rigidity (Cogwheel rigidity)

Question 40

Describe how the brain will look like grossly in Parkinson Disease.

Answer 40

The loss of pigmentation in the substantia nigra

Question 41

Describe the microscopic findings of the brain in Parkinson DIsease

Answer 41

Lewy bodies (aggregates of misfolded α-Synuclein (SNCA) in the neural cell bodies of substantia nigra

Question 42

Describe the genetic factor of Hutington disease

Answer 42

Mutation of hutington gene on chromosome 4 Autosomal dominant

Question 43

Describe the pathogenesis of Hutington disease.

Answer 43

Mutation of hutington gene on chromosome 4 -> increased CAG trinucleotide repeats -> increased glutamine -> increased Hutington protein -> accumulation of Hutington protein which aggregates in the neuronal cells of dorsal striatum (cudate & putamen) -> over activation of NMDA receptors -> atrophy and neuronal cell death -> increased dopamine, decreased GABA and acetylcholine -> movement disorder

Question 44

Describe the clinical features of Hutington disease.

Answer 44

Early stage: - hyperkinesia - chorea (involuntary, sudden, irregular, nonrepetitive arrhythmic movments of the limbs, neck, head, and/or face) Late stage: - Hypokinetic (dystonia, rigidity, bradykinesia) - Akinetic (inability to move or speak) - Cognitive decline and behaviour/personality changes

Question 45

Why does subsequent generation have an earlier onset and more severe presentation of Hutington disease?

Answer 45

Hutington disease can be due to the autosomal dominant mutation of hutington gene. Because of "anticipation" genetic phenomenon, there is an increased in the number of CAG repeats (repeat expansion) in subsequent generation