Case 5

Question 1

what do the internal carotid arteries bifurcate into?

Answer 1

the anterior cerebral artery, middle cerebral artery and the posterior communicating artery on each side of the head

Question 2

what does the anterior cerebral artery supply?

Answer 2

 Medial portions of the frontal lobes (including medial sensorimotor cortex).
 Superior medial parietal lobes.
 Anterior four-fifths of the corpus callosum.
 Anterior portions of the basal ganglia and internal capsule.
 Olfactory bulb and tract.

Question 3

the anterior cerebral passes forward to travel in what?

Answer 3

the interhemispheric fissure (median longitudinal fissure) as it sweeps back and over the corpus callosum

Question 4

what are the two major branches of the anterior cerebral artery?

Answer 4

1. Pericallosal artery – this forms an anastomosis with the posterior cerebral artery.
2. Callosomarginal artery

Question 5

the middle cerebral artery turns laterally to enter what? where it bifurcates into what?
what branches does it give off?

Answer 5

the depths of the Sylvian fissure
here, it usually bifurcates into the superior and inferior divisions

• The branches of the middle cerebral artery form loops as they pass over the insula (insular branches) and then around and over the operculum (opercular branches) to exit the Sylvian fissure onto the lateral convexity.

Question 6

what does the superior division of the MCA supply?

Answer 6

the cortex above the Sylvian fissure, including the lateral frontal love and usually including the peri-Rolandic cortex

Question 7

what does the inferior division of the MCA supply?

Answer 7

the cortex below the Sylvian fissure, including the lateral frontal lobe and a variable portion of the parietal lobe

Question 8

what does the MCA thus supply?

Answer 8

most of the cortex on the dorsolateral convexity of the brain

Question 9

describe the path of the posterior cerebral artery. what are its territories?

Answer 9

it curves back after arising from the top of the basilar and sends branches over the inferior and medial termporal lobes and over the medial occipital cortex

territories therefore include inferior and medial temporal and occipital cortex

Question 10

what are the vascular territories of arteries supplying deep cerebral structures?

Answer 10

• Lenticulostriate arteries - arise from the initial portions of the middle cerebral artery before it enters the Sylvian fissure, and they supply large regions of the basal ganglia and internal capsule.
• Anterior choroidal artery - arises from the internal carotid artery. Its territory includes portions of the globus pallidus, putamen, thalamus, and the posterior limb of the internal capsule.
- Thus, lacunar infarction in either the lenticulostriate or anterior choroidal territories often causes contralateral hemiparesis.
• Recurrent artery of Heubner - arises from the initial portion of the anterior cerebral artery to supply portions of the head of the caudate, anterior putamen, globus pallidus, and internal capsule.
• Small, penetrating arteries that arise from the proximal posterior cerebral arteries near the top of the basilar artery include the thalamoperforator arteries which supply the thalamus and sometimes extend to a portion of the posterior limb of the internal capsule.

Question 11

what are the different types of stroke?

Answer 11

1. Ischaemic stroke – this occurs when the flow of blood is prevented by a thrombus or an embolus, either from the heart or a large vessel (such as the carotid artery). Thromboembolic infarction is the cause of 80% of strokes.
2. Haemorrhagic stroke – this results from rupture of a cerebral artery wall.

Question 12

what are risk factors for a stroke?

Answer 12

• Asian and black African populations
• Age (above 40 years of age)
• Male
• Hypertension
• Hypercholesterolemia
• Diabetes
• Cigarette smoking
• Positive family history
• Cardiac disease

Question 13

Give definitions for:

• stroke
• completed stroke
• stroke-in-evolution
• minor stroke
• transient ischaemic attack (TIA)

Answer 13

• Stroke – Stroke is defined as a syndrome of rapid onset of cerebral deficit (usually focal) lasting > 24 hours or leading to death, with no cause apparent other than a vascular one.
• Completed Stroke – means the deficit has become maximal, usually within 6 hours.
• Stroke-In-Evolution – describes progression during the first 24 hours.
• Minor Stroke – Patients recover without significant deficit, usually within a week.
• Transient Ischaemic Attack (TIA) - means a sudden focal deficit lasting from seconds to 24 hours with complete recovery. This definition is unsatisfactory as after 1 hour ischaemic damage has already occurred. TIAs have a tendency to recur, and may herald thromboembolic stroke.
Focal Neurological Deficit – this is a problem with nerve, spinal cord, or brain function. It affects a specific location, such as the left side of the face, right arm, or even a small area such as the tongue.

Question 14

when does ischaemic stroke occur?

Answer 14

when inadequate blood supply to a region of the brain lasts for enough time to cause infarction of brain tissue

Question 15

what can ischaemic stroke be a result of? what is the difference?

Answer 15

• It can be caused as a result of a thrombus (thrombolic infarct) or an embolus (embolic infarct).
• Embolic infarcts are considered to occur suddenly, with maximal deficits at onset, while thrombotic infarcts may have a more stuttering course.

Question 16

what are small-vessel infarcts? what’s another name for them? what structures are affected?

Answer 16

lacunar infarcts = involve the small, penetrrating vessels that supply the deep structures

• The deep structures of the cerebral hemispheres these include the basal ganglia, thalamus, and internal capsule, while in the brainstem these include the medial portions of the midbrain, pons, and medulla.

• Lacunar stroke (stroke is less than a cm in diameter on the scan – due to small penetrating arteries being affected)

Question 17

what are lacunar infarcts usually associated with?

Answer 17

small-vessel disease (lipohyalinotic thickening) caused by chronic hypertension

Question 18

in addition to focal neurological deficits, what else can ischaemic stroke be associated with?

Answer 18

headaches or, less commonly, seizures

• Headache occurs in 30% of ischemic strokes. When headache is unilateral, it is more commonly on the side of the infarct. Seizures occur in 10% of stroke patients.

Question 19

is stroke a big cause of death worldwide?

Answer 19

second most common, after ischaemic heart disease

Question 20

what is the death rate following stroke?

Answer 20

20-25%

Question 21

what are the main causes of stroke?

Answer 21

Thromboembolic infarction (80%), cerebral and cerebellar haemorrhage (10%) and subarachnoid haemorrhage (SAH) (about 5%) are the main causes; arterial dissection and arteriovenous malformations also contribute.

Question 22

describe the development of ischaemic damage

Answer 22

• Immediate area - Ischaemia leads to the death of cells in the immediate area that is supplied by the blood vessels.
The tissue in the immediate area die within minutes to hours and this tissue cannot be repaired.
• Penumbra - The area surrounding the immediate are of infarct is known as the penumbra.
Here, the blood supply is compromised but not cut off.
The cells are under ‘threat’ but not dead.
There is the potential for rescue and repair.
It is crucial that treatment is administered early to prevent further damage to the penumbra.

Question 23

what are the three things that cause ischaemic damage?

Answer 23

1. Neurotransmitters – glutamate
2. Ions – calcium and sodium
3. Free Radicals – abnormal oxygen molecules (e.g. superoxide)

Question 24

what are the different mechanisms that cause ischaemic damage?

Answer 24

1. Excitotoxicity
2. Reperfusion injury
3. Free Radical Formation (oxidative stress)
4. Apoptosis
5. Inflammation
6. Peri-infarct depolarizations

Question 25

what is excitotoxicity? describe the process

Answer 25

= process of cell death

• Glutamate is the major excitatory transmitter in the body = essential for normal function (e.g. with memory)
• But if it’s produced in excess then it kills cells
• By process of excitotoxicity
• It over-activates receptors in the membrane
• Which allows calcium to go into the cell and other process to be triggered
• Glutamate antagonists as a treatment for stroke failed in trials – mainly due to side effects as the receptors are also needed for normal function

• Hypoxia leads to an inadequate supply of ATP, which in turn leads to failure of membrane pumps.
• This causes an increased release of the excitatory neurotransmitter glutamate into the extracellular fluid.
• This causes a repaid influx of calcium (mainly) and sodium ions into the cells in the immediate area.
• The ‘calcium overload’ in the cells triggers a wide range of processes including, eventually leading to the formation of free radicals.
• The processes that occur inside the cell, leading to free radical formation, are:
 Mitochondrial injury
 Increased production of nitric oxide
 Protease activation
 Phospholipase activation
• These processes result in cell death, mostly through necrosis.

Question 26

what is reperfusion injury?

Answer 26

• Restoration of blood flow to an area of the brain, previously rendered ischaemic by a thrombotic blockade of a key artery (thrombus/embolus), results in:
 Inflammation
 Oxidative stress
• This causes the death of more neurons.

Question 27

free radical formation

• how formed
• what does it cause

Answer 27

Free Radical Formation (Oxidative Stress)
• This is induced in the brain.
• There is formation of superoxide and nitric oxide, which combine together to form superoxynitrate.
• The formation of these radicals results in:
 Lipid peroxidation
 Protein oxidation
 DNA damage

Question 28

apoptosis

• when does it occur
• how does it occur

Answer 28

• Exocitotoxicity results in ‘necrosis’ at the onset of injury.
• ‘Apoptosis’ is programmed cell death that occurs much later than the onset of injury.
• It occurs in the following way:
 Oxidative stress causes mitochondrial injury.
 This causes release of cytochrome C from the mitochondria.
 Cytochrome C activates the paracaspases into caspases (caspase9 and 3).
 This leads to DNA damage and cell death (apoptosis).
• This is a complex process due to the integration between anti-apoptotic proteins (Bcl-2) and pro-apoptotic proteins.

Question 29

the normal physiology heavily dependent on?

Answer 29

the correct effects of neurotransmitters such as glutamate. In the normally functioning body, glutamate is involved in transport of ions and the homeostasis of free radicals in the brain.

Question 30

does inflammation normally take place in the brain?

Answer 30

no - therefore it is a key therapeutic target

Question 31

why does inflammation occur in the brain?

Answer 31

Inflammation occurs due to a potent inflammatory response as a result of brain damage.
 This occurs as a response of immune system to infection.
 The blood-brain barrier is compromised thus leading to infection.

Question 32

what is inflammation characterised by?

Answer 32

	Heat (calor)
	Redness (rubor)
	Swelling (tumor)
	Pain (dolor)
	Loss of function (function laesa)

Question 33

where does the potent inflammatory response occur? what does it involve in each area?

Answer 33

The potent inflammatory response occurs throughout the body, causing inflammation of the brain and vascular inflammation.

Central inflammation:
 This occurs in the brain and involves microglia.
 This causes the degradation of the extracellular matrix in the brain, leakage of the blood-brain barrier and the activation of the endothelial cells in the brain.

Peripheral inflammation:
 The liver becomes activated due to the release of chemokines from the brain.
 It causes the liver to express acute phase proteins and other chemokines and cytokines.
 These cause an increased production of neutrophils (which contain IL-1).
 Due to the leakage of the blood-brain barrier, the neutrophils infiltrate the brain.

Question 34

when is the outcome following stroke very poor?

Answer 34

if patient already had an ‘inflammatory condition’ such as obesity and arthritis

Question 35

what is the simple examination used for diagnosing strokes?

Answer 35

 Face – sudden weakness of the face
 Arm – sudden weakness of one or both arms
 Speech - difficulty speaking, slurred speech
 Time - the sooner treatment can be started, the better

Question 36

what is the purpose of investigations in stroke?

Answer 36

 To confirm the clinical diagnosis and distinguish between haemorrhage and thromboembolic infarction.
 To look for underlying causes and to direct therapy.
 To exclude other causes, e.g. tumour.

Question 37

what imaging is used in acute stroke? what used for what?

Answer 37

1. Non-contrast CT – demonstrate haemorrhage immediately but cerebral infarction is often not detected or only subtle changes are seen initially.
2. MRI – shows changes in early infarction and a later MRI shows the full extent of the damaged area or penumbra.
3. Diffusion-weighted MRI (DWI) – can detect cerebral infarction immediately but is as accurate as CT for the detection of haemorrhage.

Question 38

the stroke most commonly seen is caused by what? what causes a similar picture?

Answer 38

infarction in the internal capsule following thromboembolism in a middle cerebral artery branch

a similar picture is caused by internal carotid occlusion

Question 39

what are clinical features of stroke? (most common stroke and internal carotid occlusion?)

Answer 39

• The stroke most commonly seen is caused by infarction in the internal capsule following thromboembolism in a middle cerebral artery branch. A similar picture is caused by internal carotid occlusion.
• Limb weakness on the opposite side to the infarct develops over seconds, minutes or hours (occasionally longer).
• There is a contralateral hemiplegia or hemiparesis with facial weakness.
 Hemiplegia/ Hemiparesis – paralysis of one side of the body.
• Aphasia is usual when the dominant hemisphere is affected. [in this case the left hemisphere is damaged (this is the dominant hemisphere in regards to language)]
• Weak limbs are at first flaccid and areflexic.
• Headache is unusual.
• Consciousness is usually preserved.
• After a variable interval, usually several days, reflexes return, becoming exaggerated. An extensor plantar response appears.
• Weakness is maximal at first; recovery occurs gradually over days, weeks or many months.

Question 40

describe the process of diagnosing a stroke

Answer 40

• This begins with a detailed patient history and exam, including questions about stroke risk factors, and continues with a number of diagnostic tests.
• Blood flow in the major cranial and neck vessels should be assessed with Doppler ultrasound. This is particularly important in suspected internal carotid artery stenosis (a carotid bruit would be heard), since carotid endarterectomy may be required.
• The possibility of a cardioembolic source should be investigated with an electrocardiogram, to look for evidence of cardiac ischemia or arrhythmias, and an echocardiogram, to look for structural abnormalities or thrombi.
• Blood tests for cardiac enzymes to detect myocardial infarction are also performed on most patients admitted for acute stroke.

Question 41

what is treatment for stroke? (ischaemic)

Answer 41

• Drugs for hypertension, heart disease, diabetes, other medical conditions.
• Endarterectomy
• Speech therapy, dysphagia care, physiotherapy, occupational therapy.
• Specific issues, e.g. epilepsy, pain, incontinence
• Anticoagulation (warfarin/ heparin)
• Antiplatelet agents
• Thrombolysis has been shown to improve outcome and should be used immediately if there are no contraindications.
 Once a hemorrhage has been ruled out by CT, the thrombolytic agent tissue plasminogen activator (tPA) is administered within 4.5 hours of stroke onset.
 Following administration of tPA, patients are typically watched closely in an intensive care unit setting for at least 24 hours before transfer to the regular patient floor.
 In patients with stroke who are not eligible for tPA or in patients who have had a TIA, acute administration of the antiplatelet agent aspirin can reduce the risk of early recurrent stroke.

• Internal Carotid Endarterectomy – this is a surgical procedure to remove the atheromatous plaque material, or any occlusive material, in the lining of an artery constricted by the buildup of soft/hardening deposits.

Question 42

what is treatment for haemorrhagic stroke?

Answer 42

1. Anticonvulsants – to prevent seizure recurrence
2. Antihypertensive - to reduce BP and other risk factors of heart disease
3. Osmotic diuretics - to decrease intracranial pressure in the subarachnoid space

• Often related to high BP
• Obviously not thrombolysed
• Management of clotting if abnormal (e.g. on anticoagulants – 10-20%)
• Active management of BP
• Consider high level care (e.g. NHDU, ICU)
• Research findings on minimally invasive surgery awaited
• Space occupying lesion – putting pressure on brain, herniation – often die very early – due to these
  Reverse anticoagulants:
  PCC (replaces clotting factors that warfarin has depleted) – if on warfarin
  Other ones used more often now - anti-10A blockers??

Question 43

what is long-term management for stroke patients?

Answer 43

• Medical therapy – risk factors identified and addressed.
• Antihypertensive therapy – recognition and control of high blood pressure is the major factor in primary and secondary stroke prevention.
• Antiplatelet therapy – long-term soluble aspirin (75mg daily) or clopidogrel reduces substantially the incidence of further infarction following thromboembolic TIA or stroke. (Aspirin 300mg 14 days then clopidogrel 75mg - on acute stroke unit)
• Anticoagulants – heparin and warfarin should be given if there is atrial fibrillation and cardiomyopathies. Brain hemorrhage must be excluded by CT/MRI.

• Recovery and rehabilitation from stroke is a remarkable process with variable outcome. Functional neuroimaging studies have demonstrated that over time other brain areas can “take over” the functions previously carried out by the infarcted regions of brain tissue.

Question 44

what is prognosis for stroke?

Answer 44

• About 25% of patients die within 2 years of a stroke, nearly 10% within the first month.
• Recurrent strokes are, however, common (10% in the first year) and many patients die subsequently from myocardial infarction.
Of initial stroke survivors, some 30–40% remain alive at 3 years.

Question 45

transient ischaemic attack (TIA)

• what is it
• is it an emergency
• what happens
• what is amaurosis fungax
• what is transient global amnesia

Answer 45

• This is a focal neurologic deficit lasting less than 24 hours, caused by temporary brain ischemia.
• TIAs are a neurologic emergency.
• TIAs cause sudden loss of function, usually within seconds, and last for minutes or hours.
• Amaurosis fungax – sudden loss of vision in one eye. This is due to an embolus in the retinal arteries.
• Transient global amnesia – episodes of amnesia/confusion lasting several hours, occurring principally in people over 65 and followed by complete recovery. This is presumed to be due to posterior circulation ischaema.

Question 46

lacunar infarction

• what are they
• what commonly present with it
• what does it usually cause
• symptoms

Answer 46

• Lacunes are small (<1.5cm3) infarcts seen on MRI or at autopsy.
• Hypertension is commonly present.
• Minor strokes (e.g. pure motor stroke, pure sensory stroke, sudden unilateral ataxia and sudden dysarthria with a clumsy hand) are syndromes caused typically by single lacunar infarcts.
• Lacunar infarction is often symptomless.

Question 47

can there be improvement in neurological functions after a stroke

Answer 47

over a period of 3-6 months following a stroke some patients regain some neurological functions (even if reduced).

Question 48

Stroke triggers physiological and structural changes in neuronal circuits adjacent to the infarct. These changes affect stroke recovery and can be manipulated to lead to neural repair.
What do these changes include?
What is a key aspect of neural repair after stroke?

Answer 48

1. Axonal sprouting – formation of new connections in the cortex adjacent to the stroke site.
2. Neurogenesis – formation of new neurons and their migration to the area of injury.
3. Angiogenesis in the peri-infarct area.
4. Growth Factor regulation - such as FGFs and EPO – to promote recovery.
5. Oligodendrocyte precursor cells, OPCs – recruitment and differentiation of immature forms of glial cells.
6. Post-stroke hypoexcictability – physiological changes in response or cortical circuits

• A key aspect of neural repair after stroke is that these cellular and molecular events are not occurring in isolation.
• Injury to the nervous system induces expression of both growth-promoting and growth-inhibiting genes which together determine the location and degree of axonal sprouting.
• In post-stroke neurogenesis, migrating immature neurons associate with angiogenic blood vessels. Neurogenesis and angiogenesis are integrated tissue reorganization processes after stroke.

ENDOGENOUS REPAIR MECHANISMS

1. Restoration of the neuronal network – neuroplasticity/neurogenesis
2. Restoration of the blood supply – angiogenesis
3. Neurorepair role of brain immune cells (microglia – type of neuroglia located throughout the brain and spinal cord – account for 10-15% of all cells found within brain – resident macrophage cells, so they act as first and main form of active immune defence in the CNS – (neuroglia are non-neuronal cells in the CNS and PNS – they maintain homeostasis, form myelin, and provide support and protection for neurons – they include oligodendrocytes, astrocytes, ependymal cells and microglia, in CNS, and Schwann and satellite cells in the PNS)
4. Protection of non-injured brain structures by glial scarring

Question 49

what is neuroplasticity? what does it include?

Answer 49

Brain plasticity (neuroplasticity) refers to the extraordinary ability of the brain to modify its own structure and function following changes within the body or in the external environment.

Neuroplasticity ranges from cellular changes to large-scale changes involved in cortical remapping following an injury.

Question 50

which part of the brain is particularly neuroplastic?

Answer 50

the cortex

Question 51

brain plasticity underlies normal brain function, such as what?

Answer 51

our ability to learn and modify our behaviour

Question 52

what is synaptic pruning? what is important about it?

Answer 52

• One of the fundamental principles of how neuroplasticity functions is linked to the idea of synaptic pruning.
• This theory states that weaker synaptic contacts are eliminated while stronger connections are kept and strengthened. Experience (in the form of which connections are activated most frequently) determines which are kept and which are pruned.
• This theory thus explains how the brain can adapt itself and mould to its environment.

Question 53

which cerebral artery are infarcts and ischaemic events more common?

Answer 53

in the middle cerebral artery (most common site of stroke) than in the anterior or posterior cerebral arteries

Question 54

what do anterior cerebral artery infarcts typically produce?

what are dominant and non-dominant ACA strokes sometimes associated with?

what may there also be a variable degree of?

Answer 54

Occlusion: paralysis and sensory loss in contralateral leg and perineum

• ACA infarcts typically produce upper motor neuron-type weakness and cortical-type sensory loss affecting the contralateral leg more than the arm or face.

• Dominant ACA strokes sometimes are associated with transcortical motor aphasia, and nondominant ACA strokes can produce contralateral neglect.
 Contralateral neglect - This is a disorder that renders the sufferer of the stroke unable to acknowledge his/her left side. Not only does the victim neglect the left side of his/her own body, but they don’t acknowledge the left side of anything.

• There may also be a variable degree of frontal lobe dysfunction depending on the size of the infarct.
• Such dysfunction may include a grasp reflex, impaired judgment, flat affect, apraxia, abulia, and incontinence.

Question 55

posterior cerebral artery

• what do PCA infarcts typically cause
• what may smaller infarcts that don’t involve the whole PCA territory
• sometimes what are involved - leading to what
• what else

Answer 55

occlusion: blindness

                     * PCA infarcts typically cause a contralateral homonymous hemianopia.  * Smaller infarcts that do not involve the whole PCA territory may cause smaller homonymous visual field defects.  * Sometimes the small, penetrating vessels that come off the proximal PCA are involved, leading to infarcts in the thalamus or posterior limb of the internal capsule.  * The result can be a contralateral sensory loss; contralateral hemiparesis; or even thalamic aphasia if the infarct is in the dominant (usually left) hemisphere, thereby mimicking features of MCA infarcts.  * PCA infarcts that involve the left occipital cortex and the splenium of the corpus callosum can produce alexia (inability to recognise or read written words or letters) without agraphia (inability to write).

Question 56

what does ‘watershed’ refer to?

Answer 56

those areas of the brain that receive dual blood supply from the branching ends of two large arteries

Question 57

what are watershed zones?

Answer 57

• When the blood supply to two adjacent cerebral arteries is compromised, the regions between the two vessels are most susceptible to ischemia and infarction.
• These regions between cerebral arteries are called watershed zones.

Question 58

which watershed infarcts can occur with severe drops in systemic blood pressure?

Answer 58

bilateral watershed infarcts in both the ACA-MCA and MCA-PCA watershed zones

Question 59

what can cause an ACA-MCA watershed infarct?

Answer 59

a sudden occlusion of an internal carotid artery or a drop in blood pressure in a patient with carotid stenosis

Question 60

what symptoms can watershed infarcts produce?

Answer 60

Watershed infarcts can produce proximal arm and leg weakness (“man in the barrel” syndrome).

 In the dominant hemisphere, watershed infarcts can cause transcortical aphasia syndromes.

Question 61

what can MCA-PCA watershed infarcts cause?

Answer 61

disturbances of higher-order visual processing

Question 62

what are the different types of intracranial haemorrhage?

Answer 62

 Intracerebral and cerebellar hemorrhage
 Subarachnoid hemorrhage
 Subdural and extradural hemorrhage/haematoma

Question 63

subarachnoid haemorrhage

• what is it
• symptoms
• risk factors

Answer 63

• Subarachnoid Hemorrhage – sudden bleeding into the subarachnoid space surrounding the brain, which causes severe headache with stiffness of the neck.
• Symptoms – patients may describe this as the “worst headache of my life” or as feeling like the head is suddenly about to explode.
• Risk Factors for aneurysmal rupture include hypertension, cigarette smoking, alcohol consumption, and situations causing sudden elevation in blood pressure.

Question 64

what are the causes of subarachnoid haemorrhage?

Answer 64

the usual cause of a subarachnoid hemorrhage is a cerebral aneurysm that has burst.
 Saccular (berry) aneurysms develop within the circle of Willis and adjacent arteries.
 Common sites are at the arterial junctions:
 Between posterior communicating and internal carotid artery – posterior communicating artery aneurysm.
 Between anterior communicating and anterior cerebral artery – anterior communicating and anterior cerebral artery aneurysm.
 At the trifurcation or a bifurcation of the middle cerebral artery – middle cerebral artery aneurysm.

Question 65

which of the meninges are vascularised?

Answer 65

dura and pia mater are highly vascularised

Question 66

subarachnoid haemorrhage

• investigations
• diagnosis
• clinical effects
• treatmetn

Answer 66

• Investigations – CT scan performed within the first 3 days after rupture can detect the haemorrhage. CT is better than MRI for detecting acute subarachnoid haemorrhage, although after about 2 days subarachnoid haemorrhage may no longer be visible on CT. Lumbar puncture should be performed in suspected subarachnoid haemorrhage with a negative CT.
• Diagnosis – the diagnosis is confirmed by a CT scan or by finding blood-stained CSF at lumbar puncture.
 Identification of the site of the aneurysm, upon which decisions about treatment will be based, is achieved by cerebral angiography.
• Clinical Effects – range form headache and meningeal irritation, causing nuchal rigidity (inability to flex neck forward) and photophobia, to cranial nerve and other focal neurologic deficits, to impaired consciousness, coma and death.
• Treatment – bed rest and either neurosurgical placement of a clip across the neck of the aneurysm or interventional neuroradiology to place detachable coils within the aneurysm.

Question 67

subdural haematoma (SDH)

• what is it
• symptoms
• risk factors

Answer 67

• Subdural Haematoma (SDH) means accumulation of blood in the subdural space following rupture of a vein. (below the meningeal layer of dura)
• Symptoms – headache, drowsiness and confusion. The interval between injury and symptoms can be days, or extend to weeks or months.
• Risk Factors – age (common in elderly), alcoholics, blunt trauma, shaken baby, predisposing factors – brain atrophy, shaking, whiplash).

Question 68

SDH

• cause
• investigations
• clinical effects
• treatment

Answer 68

• Cause – rupture of bridging veins (cross subdural space). Slow venous bleeding (less pressure = haematoma develops over time)
• Investigations – CT scan shows a crescent-shaped haemorrhage that crosses suture lines. Gyri are preserved, since pressure is distributed equally. Cannot cross falx, tentorium.
• Clinical Effects – focal deficits (e,g, hemiparesis or sensory loss) develops. Epilepsy occasionally occurs. Stupor, coma and coning may follow.
• Treatment – surgical evacuation, except for small to moderate-sized chronic subdural hematomas, which, depending on the severity of symptoms, can be followed clinically because some will resolve spontaneously.

Question 69

extradural haematoma (EDH)

• what is it
• symptoms
• cause
• investigations
• treatment

Answer 69

• Extradural Haematoma (EDH) means accumulation of blood in the extradural space (between the inner surface of the skull and the outer layer of the dura mater).
• Symptoms – initially there are no symptoms (lucid interval). Within in a few hours the patient develops an ipsilateral dilated pupil and contralateral hemiparesis, with rapid transtentorial coning. Bilateral fixed dilated pupils, tetraplegia and respiratory arrest follow.
• Cause – rupture of middle meningeal artery (branch of maxillary artery), often secondary to fracture of temporal bone. There is rapid expansion under systemic arterial pressure, leading to a transtentorial herniation.
• Investigations – CT scan shows a lens-shaped biconvex that does not cross suture lines. The haematoma can cross the falx and tentorium.
• Treatment – requires urgent neurosurgery: if it is performed early, the outcome is excellent.

Question 70

carotid stenosis

• what causes it
• what can they cause
• what does this result in
• what is another mechanism for infarction with carotid stenosis
• investigations
• treatment

Answer 70

• Atherosclerotic disease commonly leads to stenosis of the internal carotid artery just beyond the carotid bifurcation.
• Thrombi formed on a stenotic internal carotid artery can embolize distally, giving rise to TIAs or infarcts of various carotid branches, especially the MCA, ACA, and ophthalmic artery.
• This results in the following pathologies:
 MCA – contralateral face-arm or face-arm-leg weakness, contralateral sensory changes, contralateral visual field defects, aphasia and neglect.
 ACA – contralateral leg weakness.
 Ophatlamic artery – amaurosis fugax
• Another mechanism for infarction with carotid stenosis is a sudden drop in systemic blood pressure, leading to infarction in the ACA-MCA watershed territory.
• Investigations – a stethoscope, placed just below the angle of the jaw, will pick up a whooshing sound (bruit). The severity of carotid stenosis can be estimated with Doppler ultrasound and Magnetic resonance angiography (MRA).
• Treatment – carotid endarterectomy.

Question 71

what are the components of a motor exam?

Answer 71

1. Tone
2. Strength
3. Reflexes

Question 72

what is muscle tone?

Answer 72

the continuous and passive partial contraction of the muscles, or the muscle’s resistance to passive stretch during resting state

Question 73

how is muscle tone assessed?

Answer 73

Muscle tone is tested by measuring the resistance to passive movement of a relaxed limb.

 In the upper limbs, tone is assessed by rapid pronation and supination of the forearm and flexion and extension at the wrist.
 In the lower limbs, while the patient is supine the examiner’s hands are placed behind the knees and rapidly raised; with normal tone the ankles drag along the table surface for a variable distance before rising, whereas increased tone results in an immediate lift of the heel off the surface

Question 74

what is muscle strength?

Answer 74

this is the maximum amount of force that a muscle can exert against some form of resistance in a single effort

Question 75

how is muscle strength tested?

Answer 75

Muscle strength is tested using the MRC grading scale:
 0/5: No contraction
 1/5: Muscle flicker, but no movement
 2/5: Movement possible, but not against gravity (test the joint in its horizontal plane)
 3/5: Movement possible against gravity, but not against resistance by the examiner
 4 – = movement against a mild degree of resistance
 4 = movement against moderate resistance
 4+ = movement against strong resistance
 5/5: Normal strength

Question 76

what is a muscle reflex?

Answer 76

this is the ability of a muscle to contract in response to a stimulus (e.g. stretch)

Question 77

what are deep tendon reflexes often rated according to?

Answer 77

Deep tendon reflexes are often rated according to the following scale:

 0: Absent reflex
 1+: Trace, or seen only with reinforcement
 2+: Normal
 3+: Brisk
 4+: Nonsustained clonus (i.e., repetitive vibratory movements)
 5+: Sustained clonus

clonus = associated with upper motor neurone pathologies
fasciculations = associated with lower motor neurone pathologies

Question 78

what are lower motor neurones controlled by?

Answer 78

 ‘Directly’ by local circuit neurons within the spinal cord and brainstem that coordinate individual muscle groups.
 ‘Indirectly’ by upper motor neurons in higher centres that regulate those local circuits.

Question 79

what is the motor neurone-muscle relationship?

Answer 79

• Each lower motor neuron innervates muscle fibres within a single muscle.
• All the motor neurons innervating a single muscle (The motor neuron pool for that muscle) are grouped together into rod-shaped clusters that run parallel to the long axis of the cord for one or more spinal cord segments.

Question 80

where are the motor neurone pools that innervate the arm located?

Answer 80

in the cervical enlargement of the spinal cord

Question 81

where are the motor neurone pools that innervate the leg located?

Answer 81

in the lumbar enlargement of the spinal cord

Question 82

where are the neurones that innervate the axial musculature located?

Answer 82

medially in the spinal cord - lateral to these cells groups are motor neurone pools innervating muscles located progressively more laterally in the body

• These pathways terminate primarily in the medial region of the spinal cord, which is concerned with postural muscles, whereas other pathways terminate more laterally, where they have access to the lower motor neurons that control movements of the distal parts of the limbs.

Question 83

what do spinal cord segments that innervate a large amount of muscles have?

Answer 83

a ventral horn that appears swollen

Question 84

what are intrafusal muscle fibres?

Answer 84

Intrafusal muscle fibres are skeletal muscle fibres that serve as specialised sensory organs (proprioceptors), called muscle spindles, which detect the amount and rate of change in length of a muscle

Question 85

what motor neurones innervate intrafusal muscle fibres? what is their function? what else are they innervated by?

Answer 85

small y-motor neurones

• The intrafusal muscle fibres are also innervated by sensory axons that send information to the brain and spinal cord about the length and tension of the muscle.
• The function of the γ motor neurons is to regulate this sensory input by setting the intrafusal muscle fibres to an appropriate length.

Question 86

what innervates the extrafusal muscle fibres?

Answer 86

α-motor neurons innervate the extrafusal muscle fibres, which are the muscle fibres that actually generate the forces needed for posture and movement.

Question 87

what are extrafusal muscle fibres?

Answer 87

Extrafual muscle fibres are skeletal muscle fibres that generate muscle tension by contracting, thereby allowing for posture and skeletal movement

Question 88

where are motor neurones responsible for control of muscles in the head and neck lcoated?

Answer 88

• in the brainstem
• The latter neurons are distributed in the motor nuclei of the cranial nerves in the medulla, pons, and midbrain.
• Somewhat confusingly, but quite appropriately, these motor neurons in the brainstem are also called lower motor neurons.

Question 89

what are the two types of lower motor neurones? what is each involved with?

Answer 89

alpha and gamma

• alpha innervate extrafusal muscle fibres and so are involved with the strength and power of a muscle
• gamma neurones innervate intrafusal muscle fibres, and so are involved with muscle tone and muscle tension

Question 90

what constitutes the smallest unit of force that can be activated to produce movement?

Answer 90

a single alpha motor neurone and its associated muscle fibres - because an action potential generated by a motor neurone normally brings to threshold all of the muscle fibres it contacts

Question 91

what is a ‘motor unit’?

Answer 91

a single α motor neuron and all the muscle fibres it innervates

Question 92

how do motor units and alpha motor neurones vary in size?

Answer 92

 Small α motor neurons innervate few muscle fibres and form motor units that generate small forces.
 Large α motor neurons innervate larger, more powerful motor units.

Question 93

slow twitch muscle fibres

• what innervated by
• what motor unit
• describe them
• what imporant for

Answer 93

Slow Twitch Muscle Fibres (Type I, Red Muscle – “slow oxidative fibres”)

• Innervated by small α motor neurons, and so form part of SMALL (S) MOTOR UNITS.
• Rich blood supply (rich capillary beds).
• Rich myoglobin – makes the muscle appear ‘red’.
• Greatly increased number of mitochondria.
• Resistant to fatigue.

• These muscle fibres are especially important for activities that require sustained muscular contraction, such as the maintenance of an upright posture.

Question 94

intermediate muscle fibres

• describe them
• what motor unit
• how do they compare to the other types
• how can they generate ATP

Answer 94

Intermediate Muscle Fibres (Type IIA – “fast oxidative-glycolytic fibres”)

• FAST FATIGUE-RESISTANT (FR) MOTOR UNITS are of intermediate size and are not quite as fast as FF units.
• They generate more force than a slow motor unit and, are substantially more resistant to fatigue than an FF unit.
• They can generate ATP by substrate-level phosphorylation (glucose > lactic acid).

Question 95

fast twitch muscle fibres

• what innervated by
• what motor unit
• describe them

Answer 95

Fast Twitch Muscle Fibres (Type IIB, White Muscle – “fast glycolytic fibres”)

• Innervated by large α motor neurons, and so form part of FAST FATIGABLE (FF) MOTOR UNITS.
• Large fibres for great strength of contraction.
• Extensive sarcoplasmic reticulum for rapid release of calcium ions to initiate contraction.
• Large amounts of glycolytic enzymes for rapid release of energy by the glycolytic process.
• Less extensive blood supply.
• Fewer mitochondria.
• Easily fatigued.

Question 96

can athletic training change the proportions of fast and slow twitch muscles that an individual has?

Answer 96

• Some people have considerably more fast-twitch than slow-twitch fibres, and others have more slow-twitch fibres; this could determine to some extent the athletic capabilities of different individuals.
• Athletic training has not been shown to change the relative proportions of fast-twitch and slow-twitch fibres however much an athlete might want to develop one type of athletic prowess over another. Instead, this seems to be determined almost entirely by genetic inheritance.

Question 97

what are the different motor unit types? describe each, what is each used for?

Answer 97

small motor units:

• type I fibres
• small, slow, fatigue resistant
• red muscle (anti-gravity, posture)
• mixed, pale muscle
• standing, walking

fast fatigue-resistant motor units:

• type IIa fibres
• fast, fatigue resistant
• mixed, pale muscle
• running

fast fatigable motor units:

• type IIb fibres
• large, fast, fatiguing
• mixed, pale muscle
• jumping

Question 98

what is the size principle (in terms of motor units)?

Answer 98

• As the synaptic activity driving a motor neuron pool progressively increases, low threshold S motor units are recruited first, then FR motor units, and finally, at the highest levels of activity, the FF motor units.
• As a result, this systematic relationship has come to be known as the size principle.

Question 99

muscle spindles

• what are they
• what do they consist of
• nuclei of intrafusal fibres
• what innervates what
• how do the different afferents repsond to stretch

Answer 99

• Muscle spindles are found in skeletal muscles and consist of 4-8 specialized intrafusal muscle fibres surrounded by a capsule of connective tissue.
• The intrafusal fibres are distributed among the extrafusal fibres of skeletal muscle in a parallel arrangement.
• In the largest of the intrafusal fibres, the nuclei are collected in an expanded region named the nuclear bag fibres.
• The nuclei in the remaining 2-6 smaller intrafusal fibres are lined up single file, with the result that these fibres are called nuclear chain fibres.
• Large-diameter, myelinated sensory axons, called Ia afferents, innervate muscle spindles by coiling around the central part of the intrafusal fibres.
• Secondary innervation is provided by group II axons that innervate the nuclear chain fibres and give off a minor branch to the nuclear bag fibres.
• Group Ia afferents, which preferentially innervate nuclear bag fibres, respond phasically to small stretches, while group II afferents, which innervate both fibre types, signal the level of sustained stretch by firing tonically in proportion to the degree of stretch.

Question 100

what is the monosynaptic myotatic stretch reflex the basis of? explain. what is this reflex circuit responsible for?

Answer 100

This monosynaptic myotatic stretch reflex is the basis of the knee jerk response tested;
 The tap of the reflex hammer on the tendon stretches the muscle and therefore excites an afferent volley of activity in the Ia sensory axons that innervate the muscle spindles.
 The afferent volley is relayed to the α motor neurons in the brainstem or spinal cord, and an efferent volley returns to the muscle.
 This results in rapid contraction (extrafusal fibres) of the stretched muscle and simultaneous relaxation of the antagonist muscle.
 This reflex circuit is responsible for muscle tone.

Question 101

what is a monosynaptic reflex?

Answer 101

the excitatory pathway from a spindle to the alpha motor neurones innervating the same muscle

• When the muscle is stretched, the spindle is also stretched and the rate of discharge in the afferent fibres increased.
• When the muscle shortens, however, the spindle is relieved of tension, or “unloaded,” and the sensory axons that innervate the spindle might therefore be expected to fall silent during contraction. However, they remain active.
• The γ motor neurons terminate on the contractile poles of the intrafusal fibres, and the activation of these neurons causes intrafusal fibre contraction—in this way maintaining the tension on the middle of the intrafusal fibres where the sensory axons terminate.

Question 102

how does the level of y motor neurone activity affect the sensitivity of the reflex arc?

Answer 102

• The level of γ motor neuron activity often is referred to as γ bias, or gain, and can be adjusted by upper motor neuron pathways as well as by local reflex circuitry. The larger the gain of the stretch reflex, the greater the change in muscle force that results from a given amount of stretch applied to the intrafusal fibres.
• The CNS stimulates ϒ motor neurons. This results in the contraction of intrafusal fibres at the central part of the muscle spindle, thus increasing the sensitivity of the reflex arc.

Question 103

golgi tendon organs

• what are they
• where are they
• what are they sensitive to and why
• what are they relatively insensitive to
• describe the golgi tendon circuit - what does it do

Answer 103

• Golgi tendon organs – these are neurotendinous organs that sense changes in muscle tension. It is a proprioceptive sensory receptor organ that is at the origin and insertion of skeletal muscle fibres into the tendons of skeletal muscle.
• Golgi tendon organs are in series with the extrafusal muscle fibres.
• When a muscle is passively stretched, most of the change in length occurs in the muscle fibres, since they are more elastic than the fibrils of the tendon.
• When a muscle actively contracts, however, the force acts directly on the tendon, leading to an increase in the tension of the collagen fibrils in the tendon organ and compression of the intertwined sensory receptors. As a result, Golgi tendon organs are sensitive to increases in muscle tension that arise from muscle contraction but, unlike spindles, are relatively insensitive to passive stretch.

• The Ib axons from Golgi tendon organs contact inhibitory local circuit neurons in the spinal cord (called Ib inhibitory interneurons) that synapse, in turn, with the α motor neurons that innervate the same muscle.
 The Golgi tendon circuit is thus a negative feedback system that regulates muscle tension; it decreases the activation of a muscle when exceptionally large forces are generated and this way protects the muscle.

• The Golgi tendon organ system is not a closed loop. The Ib inhibitory interneurons also receive synaptic inputs from a variety of other sources. Acting in concert, these inputs regulate the responsiveness of Ib interneurons to activity arising in Golgi tendon organs.

Question 104

in summary, what are the muscle spindle and Golgi tendon systems?

Answer 104

 The muscle spindle system is a feedback system that monitors and maintains muscle length.
 The Golgi tendon system is a feedback system that monitors and maintains muscle force/tension.

Question 105

flexion reflex pathways

• describe pathway
• what accompanied by on opposite side
• why is this also important

Answer 105

• Stimulation of nociceptive sensory fibres leads to withdrawal of the limb from the source of pain by excitation of ipsilateral flexor muscles and reciprocal inhibition of ipsilateral extensor muscles.
• Flexion of the stimulated limb is also accompanied by an opposite reaction in the contralateral limb (i.e., the contralateral extensor muscles are excited while flexor muscles are inhibited).
• This crossed extension reflex provides postural support during withdrawal of the affected limb from the painful stimulus.
• Like the other reflex pathways, local circuit neurons in the flexion reflex pathway receive converging inputs from several different sources.

Question 106

what is lower motor neurone syndrome?

Answer 106

Damage to lower motor neuron cell bodies or their peripheral axons results in:
 Paralysis or paresis of the affected muscles, depending on the extent of the damage.
 Loss of reflexes (areflexia) due to interruption of the efferent (motor) limb of the sensory motor reflex arcs.
 Loss of muscle tone, since tone is in part dependent on the monosynaptic reflex arc that links the muscle spindles to the lower motor neurons.
 Atrophy of the affected muscles due to denervation and disuse.
 Fibrillations and Fasciculations which are spontaneous twitches characteristic of single denervated muscle fibres or motor units, respectively.

Question 107

how are the lower motor neuroenes distributed in the spinal cord?

Answer 107

In the ventral horn of the spinal cord:
 The most medial part contains lower motor neuron pools that innervate axial muscles or proximal muscles of the limbs.
 The more lateral parts contain lower motor neurons that innervate the distal muscles of the limbs.

Question 108

local circuit neurones

• where do they lie
• what patterns do they make with their connections

Answer 108

• The local circuit neurons lie primarily in the intermediate zone of the spinal cord and supply much of the direct input to the lower motor neurons, are also topographically arranged.

• The patterns of connections made by local circuit neurons in the medial region of the intermediate zone are different from the patterns made by those in the lateral region:
 The medial local circuit neurons, have axons that project to many spinal cord segments. Moreover, many of these local circuit neurons also have axonal branches that cross the midline in the commissure of the spinal cord to innervate lower motor neurons in the medial part of the contralateral hemicord. This arrangement ensures that groups of axial muscles on both sides of the body act in concert to maintain and adjust posture.
 Local circuit neurons in the lateral region of the intermediate zone have shorter axons that typically extend fewer segments and are predominantly ipsilateral. This more restricted pattern of connectivity underlies the finer and more differentiated control that is exerted over the muscles of the distal extremities.

• Differences in the way upper motor neuron pathways from the cortex and brainstem terminate in the spinal cord conform to these functional distinctions between the local circuits that organize the activity of axial and distal muscle groups.

Question 109

what lesions of motor system produce an obvious deficit and which don’t?

Answer 109

• Unilateral lesions of the medial motor systems produce no obvious deficits.
• In contrast, lesions of the lateral corticospinal tract produce dramatic deficits.

Question 110

describe the vestibulospinal tract

- is it part of the lateral or medial motor system?

Answer 110

Part of medial motor system

• The vestibular nuclei are the major destination of the axons that form the vestibular division of CN VIII.
• Neurons in the medial vestibular nucleus give rise to the medial vestibulospinal tract. It terminates bilaterally in the medial ventral horn of the cervical cord, where it regulates head position by reflex activation of neck muscles in response to the stimulation of the semi-circular canals.
• Neurons in the lateral vestibular nucleus give rise to the lateral vestibulospinal tract. It courses through the anterior white matter of the spinal cord in a slightly more lateral position. The lateral vestibulospinal tract terminates among medial lower motor neuronal pools that govern proximal muscles of the limbs.

Question 111

what do other upper motor neurones in the vestibular nuclei project to?

Answer 111

Other upper motor neurons in the vestibular nuclei project to lower motor neurons in the cranial nerve nuclei that control eye movements. This pathway produces VOR.

Question 112

reticulospinal tract

• describe
• what involved in
• part of medial or lateral motor system

Answer 112

part of medial motor system

• The reticular formation of the pons and medulla gives rise to reticulospinal fibres.
 Axons arising from the pontine reticular formation descend ipsilaterally as the medial reticulospinal tract.
 Axons from the medullary reticular formation descend bilaterally in the lateral reticulospinal tracts.
• Both tracts are located in the ventral funiculus.
• Reticulospinal fibres are involved in:
 Voluntary movement, reflex activity and muscle tone by controlling the activity of both alpha and gamma motor neurons.
 Mediating pressor and depressor effects upon the circulatory system.
 The control of breathing.

Question 113

tectospinal tract

Answer 113

• Tectospinal fibres arise from the superior colliculus of the midbrain.
• Axons pass ventromedially around the periaqueductal grey matter and cross in the dorsal tegmental decussation.
• In the spinal cord, descending tectospinal fibres lie near the ventral median fissure and terminate predominantly in cervical segments.
• The superior colliculus receives visual input and the tectospinal tract is thought to mediate reflex movements in response to visual stimuli.
• Even the simplest movements are accompanied by the activation of muscles that seem to have little to do with the primary purpose of the movement.

Question 114

rubrospinal tract

Answer 114

part of lateral motor system

• The rubrospinal tract originates from the red nucleus of the midbrain tegmentum.
• It exerts control over the tone of limb flexor muscles, being excitatory to the motor neurons of these muscles.
• Axons leaving the cells of the red nucleus course ventromedially and cross in the ventral tegmental decussation, after which they descend to the spinal cord where they lie ventrolateral to, and partly intermingled with, the lateral corticospinal tract.
• The red nucleus receives afferent fibres from the motor cortex and from the cerebellum.
• The rubrospinal tract, therefore, represents a non-pyramidal route by which the motor cortex and cerebellum can influence spinal motor activity.
• The rubrospinal tract in humans is small, and its clinical importance is uncertain, but it may participate in taking over functions after corticospinal injury. It may also play a role in flexor posturing of the upper extremities.

Question 115

describe the corticospinal tract

Answer 115

• Axons from the cerebral cortex (precentral gyrus) enter the corona radiata, and descend toward the internal capsule (posterior limb).
• The internal capsule continues into the superior cerebral peduncle (midbrain).
• The corticospinal tract fibres next descend through the ventral pons (crus cerebri), where they form somewhat scattered fascicles. These collect on the ventral surface of the medulla to form the medullary pyramids.
• At this point about 85% of the pyramidal tract fibres decussate over in the pyramidal decussation to enter the lateral white matter columns of the spinal cord, forming the lateral corticospinal tract.
• The remaining ~15% of corticospinal fibres continue into the spinal cord ipsilaterally, without crossing, and enter the anterior white matter columns to form the anterior corticospinal tract.
 These fibres terminate either ipsilaterally or contralaterally, after decussating (via spinal cord commissure).
 The anterior corticospinal pathway arises primarily from regions of the motor cortex that serve axial and proximal muscles.
• The lateral corticospinal tract forms a direct pathway from the cortex to the spinal cord and terminates primarily in the lateral portions of the ventral horn and intermediate gray matter, with some axons synapsing directing on α motor neurons.
 This is restricted to the α motor neurons that supply the muscles of the forearm and hand.
 The rest of the lateral corticospinal tract terminates among local circuit neurons.
• Over 50% of the corticospinal tract fibres originate in the primary motor cortex.
• The remainder arise from the premotor and supplementary motor areas or from the parietal lobe.

Question 116

describe the corticobulbar tract

Answer 116

• Cortex (layer 5)/ Precentral Gyrus (primary motor cortex)
• Corona radiata
• Internal capsule (genu)
• Superior cerebral peduncle (crus cerebri)
• Brainstem
• Synapse with motor nuclei of cranial nerves

Question 117

what are the upper motor neurones of the primary motor cortex?

Answer 117

the pyramidal cells of the cortical layer V

Question 118

premotor cortex

• what is it
• what does it do

Answer 118

Premotor Cortex
• The premotor cortex is an area of motor cortex lying within the frontal lobe of the brain just anterior to the primary motor cortex.
• The premotor cortex uses information from other cortical regions to select movements appropriate to the context of the action.
• Lateral premotor cortex – 65% of the neurons here have responses that are linked in time to the occurrence of movements.
• Medial premotor cortex – mediates selection of movements. However, this region appears to be specialized for initiating movements specified by internal rather than external cues. Lesions reduce the number of self-initiated or “spontaneous” movements, whereas the ability to execute movements in response to external cues remains largely intact.

Question 119

what is upper motor neurone syndrome?

Answer 119

Damage to the motor cortex or the descending motor axons in the internal capsule causes:
 Weakness of the muscles on the contralateral side of the body and face.
 Increased muscle tone (spasticity)
 Hyperactive reflexes
 Clonus (sustained) (involuntary contractions and relaxations of muscles in response to muscle stretching – clonus ankle test).
 Abnormal Babinski sign

Extensive upper motor neuron lesions may also be accompanied by rigidity of the extensor muscles of the leg and the flexor muscles of the arm (called decerebrate rigidity). Spasticity is probably caused by the removal of inhibitory influences exerted by the cortex on the postural centers of the vestibular nuclei and reticular formation.
 A loss of the ability to perform fine movements.

Question 120

what is the Babinski sign?

Answer 120

The normal response in an adult to stroking the sole of the foot is flexion of the big toe, and often the other toes. Following damage to descending upper motor neuron pathways, however, this stimulus elicits extension of the big toe and a fanning of the other toes. A similar response occurs in human infants before the maturation of the corticospinal pathway.

Question 121

difference between spasticity and rigidity

Answer 121

spasticity - range and force dependent

rigidity - plastic-like resistance through the range of motion

Question 122

compare lower and upper motor neurone syndromes

Answer 122

upper motor neurone syndrome:

• weakness of contralateral limb muscles/facial muscles
• increased muscle tone (spasticity)
• sustained clonus
• hyperactive reflexes
• abnormal Babinski sign

lower motor neurone syndrome:

• ipsilateral weakness and wasting (atrophy) in muscles supplied by that motor neurone
• decreased muscle tone
• fasciculations/fibrillations
• areflexia

Question 123

when does anxiety become abnormal?

Answer 123

When it is: 
	Excessively intense/ disproportionate to stimulus
	Continues beyond exposure to danger
	Triggered by harmless situations
	Occurs without a cause
	Can’t be controlled
	Causes distress
	Impairs function

Question 124

anxiety disorders are associated with dysfunction of what?

Answer 124

amygdala

Question 125

give examples of different anxiety disorders

Answer 125

• panic disorder
• phobias (agoraphobia, specific phobia, social phobia)
• OCD
• generalised anxiety disorder (GAD)
• PTSD

• While each has its own characteristics and symptoms, they all include symptoms of anxiety.
 Phobia relates to a specific situation.

Question 126

what is GAD?

Answer 126

• Generalised Anxiety Disorder (GAD) – a state of inappropriate and sometimes severe anxiety, without adequate cause, that lasts for at least six months.
• GAD is a long-term condition.
• GAD is anxiety about a wide range of situations and issues, rather than one specific event.

Question 127

what is GAD characterised by?

Answer 127

 “Free floating” anxiety or apprehension not linked to a specific cause or situation.
 Excessive, uncontrollable and often irrational worry about everyday things that is disproportionate to the actual source of worry.

Question 128

what is the epidemiology of GAD?

Answer 128

 More common in females (2:1)
 Onset is most commonly in 20s (median age of onset = 30?)
 Lifetime prevalence 5% (affects 1 in 20 adults in Britain)
 Often not recognised as patients present with physical symptoms – therefore associated with increased use of healthcare services

Question 129

what is the aetiology of GAD? (risk factors?)

Answer 129

	Genetic 'makeup'
	Anxious personality
	Negative life events and Childhood traumas
	Major stress in life
	Physical illness
	Drug harm (alcohol)

Question 130

what are the symptoms of GAD (psychological, physical and behavioural)?

Answer 130

	Psychological symptoms
o	Constant worries – often intrusive
o	Pervasive feeling of apprehension or dread
o	Poor concentration
o	Frustration and irritability
o	Inability to tolerate uncertainty; you need to know what’s going to happen in the future
	Physical symptoms
o	Trembling and Sweating
o	Nausea
o	Short of breath
o	Difficulty swallowing
o	Hot flashes and Headaches
o	Muscle aches & tensions
o	Twitching and Irritability
o	Difficulty in initiation of maintenance of sleep/ Fatigue
o	Feeling on the edge/ Restlessness
	Behavioural symptoms
o	Putting things off because you feel overwhelmed
o	Avoidance e.g. leaving home, using public transport
o	Drug taking to relieve anxiety

Question 131

describe the diagnosis of GAD

Answer 131

Different systems of ‘operational diagnoses’ are used to diagnose GAD:
o Operation diagnoses is a type of psychiatric diagnosis system:
 A person must experience a certain number of symptoms:
At least a minimum specified period
The symptoms must cause: significant disease + be associated with impairment in everyday function.

o Two operational diagnostic systems are used:
 5th Edition of the Diagnostic and Statistical Manual (DSM-5) (American Psychiatric Association, 2013)
 10th Edition of the International Classification of Diseases (ICD-10) (World Health Organization)

Diagnosis of GAD:
 Excessive anxiety or worry about a range of events or activities thatis persistent i.e.
 At least 6 out of 12 diagnostic criteria in ICD-10
 Symptoms ≥6 months in DSM-IV
 Not restricted or focussed to a particular circumstance
 contrast to a phobia (specific situation)
 contrast to OCD (e.g. contamination)
 Anxiety symptoms may be physical or psychological
 GAD can co-exist with major depression and other anxiety disorders

Question 132

describe the assessment for patients who may have GAD

Answer 132

 Full psychiatric history from patient
 Collateral history (e.g. family member)
 Exclude physical causes or complicating factors
e.g. hyperthyroidism, angina, asthma, excess caffeine intake, pheochromocytoma
 Check whether using alcohol and/or drugs to self-medicate
 In addition alcohol may form part of a withdrawal state
 Assess for depression and other ‘neurotic’ illness

Question 133

what is treatment for GAD?

Answer 133

1. Exclude any underlying medical cause (eg hyperthyroidism/ hypertension)
2. Exclude any substance abuse related anxiety
3. Short-term treatment with benzodiazepines (e.g. diazepam)
4. Long-term treatment with beta-blockers/ SSRI’s (sertraline) / SNRI (Venlafaxine)
5. Long-term treatment with Pregabalin

Question 134

what is the stress response?why does it relate to anxiety?

Answer 134

the coordinated reaction to threatening stimuli (stressor)

• Some anxiety disorders have been established as genetic predispositions; others have been rooted more towards occurrence of stressful life events.

Question 135

what is the stress response characterised by?

Answer 135

 Avoidance behaviour
 Increased vigilance and arousal
 Activation of the sympathetic division of the ANS
 Release of cortisol (stress hormone) from the adrenal glands

Question 136

what is hypothalamus centrally involved in terms of the stress response?

Answer 136

The hypothalamus is centrally involved in the following responses:
 Humoral response
 Visceromotor response
 Somatic motor response

Question 137

what is the humoral response mediated by (stress response)?

Answer 137

The humoral response is mediated by the hypothalamic-pituitary-adrenal (HPA) axis.
 Cortisol (a glucocorticoid) is released from the adrenal cortex in response to an elevation in the blood level of adrenocorticotropic hormone (ACTH).
 ACTH is released by the anterior pituitary gland in response to corticotropin-releasing hormone (CRH).
 CRH is released into the blood of the portal circulation by parvocellular neurosecretory neurons in the paraventricular nucleus of the hypothalamus.

(backwards)

Question 138

what is the diathesis-stress hypothesis?

Answer 138

 Hyperactivity of the HPA axis is associated with depression and anxiety.
Blood cortisol levels are elevated, as is the concentration of corticotrophin-releasing-hormone (CRH) in the CSF.

 The activation of the hippocampal glucocorticoid receptors by cortisol normally leads to feedback inhibition of the HPA axis.
 In depressed patients, this feedback is disrupted, explaining why HPA function is hyperactive.
 A molecular basis for the diminished hippocampal response to cortisol is a decreased number of glucocorticoid receptors.
 Glucocorticoid receptors, like all proteins, are a product of gene expression.

 Childhood abuse and neglect, in addition to genetic factors, put people at risk for developing mood and anxiety disorders, and these animal findings suggest one cause.

 This hypothesis suggests that, in addition to genetic factors, elevations in brain CRH, and decreased feedback inhibition of the HPA system, may make the brain especially vulnerable to depression and anxiety.

Question 139

what are the CRH neurones of the hypothalamus regulated by?

Answer 139

• amygdala

- hippocampus

Question 140

what is critical to fear responses?

Answer 140

amygdala

Question 141

describe how amygdala is involved in the stress response and therefore anxiety and depression

Answer 141

• The amygdala is critical to fear responses.
• Sensory information enters the basolateral amygdala, where it is processed and relayed to neurons in the central nucleus (in the amygdala).
• When the central nucleus of the amygdala becomes active, the stress response follows.
• Projections from the amygdala to the PAG and diffuse modulatory systems result in anxiety.
• Projections to the hypothalamus maintain the state of anxiety and eventually lead to depression. (HPA activation and activation of SNS)

Question 142

how does the hippocampus regulate the HPA axis?

Answer 142

hippocampal activation suppresses CRH release

Question 143

describe how the hippocampus regulates the HPA axis, and why it can cause a more pronounced stress response?

Answer 143

• The HPA axis is also regulated by the hippocampus - the hippocampal activation suppresses CRH release.
• The hippocampus contains numerous glucocorticoid receptors that respond to the cortisol released from the adrenal gland in response to HPA system activation.
• Therefore, normal feedback involves inhibition of CRH release when circulating cortisol levels get too high.
• Continuous exposure to cortisol, such as during periods of chronic stress, can cause hippocampal neurons to become saturated/ wither/die.
• This degeneration of the hippocampus may set off a vicious cycle, in which the stress response becomes more pronounced, leading to even greater cortisol release and more hippocampal damage.
• Human brain imaging studies have shown a decrease in the volume of the hippocampus in some people suffering from anxiety disorder that is triggered by exposure to inescapable stress.

Question 144

in summary, what have anxiety disorders been related to?

Answer 144

both hyperactivity of the amygdala and diminished activity of the hippocampus

Question 145

psychotherapy for anxiety

• why works
• what happens
• what is the aim at neuro-biological level

Answer 145

• There is a strong learning component to fear; it can be an effective treatment for many anxiety disorders.
• The therapist gradually increases the exposure of the patient to the stimuli that produce anxiety, reinforcing the notion that the stimuli are not dangerous.
• At the neuro-biological level, the aim of the psychotherapy is to alter connections in the brain such that the real or imagined stimuli no longer evoke the stress response.

Question 146

what drugs are used to treat anxiety?

Answer 146

CBT:
- If you’ve been diagnosed with GAD, you’ll usually be advised to try psychological treatment before you’re prescribed medication

Selective serotonin reuptake inhibitors (SSRIs):

• First medication offered
• Antidepressant
• Works by increasing the level of serotonin in your brain
• E.g. sertraline, escitalopram, paroxetine
• Can be taken on a long-term basis but, as with all antidepressants, they can take several weeks to start working

Serotonin and noradrenaline uptake inhibitors (SNRIs):

• Second antidepressant to try if first doesn’t work
• Increases the amount of serotonin and noradrenaline in your brain
• E.g. venlafaxine, duloxetine

Pregabalin:

• Anticonvulsant
• Third option

Benzodiazepines:

• Type of sedative
• Short-term treatment during a particularly severe period of anxiety
• E.g. diazepam

Question 147

benzodiazepines

• how work
• what work on
• example
• what can cause anxiety disorder

Answer 147

• GABA is an important inhibitory neurotransmitter in the brain.
• GABA-A receptors are GABA-gated chloride channels that mediate fast IPSPs (An inhibitory postsynaptic potential).
• Too much inhibition results in a coma, and too little results in seizures.
• GABA binds to a binding pocket between the α and β subunits, causing Cl- ions to flow into the neuron, leading to a decreased chance of action potential (hyperpolarisation).
• In addition to its GABA binding site, the GABA-A receptor contains sites where chemicals can act to powerfully modulate channel function.
• Benzodiazepines bind to one of these sites (between α and ϒ sunbunits) and act to make GABA much more effective in opening the channel and producing inhibition.
• Diazepam is a highly effective treatment for acute anxiety.
• The anxiolytic effects of alcohol are also an obvious reason that anxiety disorders and alcohol abuse often go hand-in-hand.
• We may infer that the calming actions of benzodiazepines are due to the suppression of activity in the brain circuits used in the stress response.
• Benzodiazepine treatment might be required to restore normal function to these circuits.
• Alterations in the endogenous regulation of GABA receptors is a cause of the anxiety disorder.

Question 148

what are the side effects of benzodiazepines?

Answer 148

	Sedation
	Respiratory depression
	Tolerance
	Dependence – withdrawal symptoms including seizures
	Impaired cognition

Question 149

what is really important to remember about benzodiazepines?

Answer 149

• Strict guidance on prescribing ≤ 4 weeks.
• SHORT TERM USE ONLY, other than in exceptional cases.
• risk of tolerance and dependence

Question 150

SSRIs for anxiety

• what line of therapy
• how work
• why work for anxiety
• examples
• compared to older drugs
• how long to start working
• addictive or not
• side effects

Answer 150

• These are the first line of treatments.
• SSRI (fluoxetine) is widely used in the treatment of mood disorders, especially anxiety disorders.
• Serotonin is released throughout the brain by a diffuse modulatory system originating in the raphe nuclei of the brain stem.
- blocks serotonin reuptake from synapse

• The actions of serotonin are mediated primarily by G-protein-coupled receptors and are terminated by reuptake, via serotonin transporter proteins, into the axon terminal.
• Thus, as the name implies, SSRIs act to prolong the actions of released serotonin at their receptors by inhibiting reuptake.
• The presence in some families of a rare mutation in the serotonin transporter gene was associated with a high incidence of OCD, further implicating serotonin in the origins of this disease.
• Therapeutic effects develop slowly, over a period of weeks, in response to regular daily dosing.
• This means that and immediate rise in extracellular serotonin caused by the SSRI is not responsible for the anxiolytic effect.
• Rather, the effect appears to be due to an adaptation of the nervous system to chronically elevated brain serotonin, via some structural or functional change that is not understood.
• One adaptive response to SSRIs is an increase in the glucocorticoid receptors in the hippocampus.
• SSRIs might act to dampen anxiety by enhancing the feedback regulation of the CRH neurons in the hypothalamus.
• Several SSRIs shown to be effective in GAD in RCTs e.g.
• escitalopram
• paroxetine
• sertraline
• Compared to older drugs e.g. tricyclic antidepressants:
• fewer side effects
• safer in overdose
• May take 1-3 weeks to start working
• Not addictive
• 50-70% likely to work – continue for at least 6 months if effective
• Side effects include
• GI disturbance (nausea, diarrhoea) – the most common, usually transient
• sexual dysfunction; dizziness; dry mouth; loss of appetite; sweating
• feeling agitated; insomnia
• Mild withdrawal effects occasionally, so tail off

Question 151

what is the glasgow coma scale (GCS)?

Answer 151

• The Glasgow Coma Scale or GCS is a neurological scale that aims to give a reliable, objective way of recording the conscious state of a person for initial as well as subsequent assessment.
• A patient is assessed against the criteria of the scale, and the resulting points give a patient score between 3 (indicating deep unconsciousness) and either 14 (original scale) or 15 (the more widely used modified or revised scale).
• eyes scored out of 4, verbal out of 5, motor out of 6

Question 152

what is memory? what is involved? what is difference between learning and memory?

Answer 152

• Memory – the mental capacity to store and later recall or recognise events that were previously experienced.
• Memory is an active mental system that receives, encodes, modifies and retrieves information.
• ‘Learning’ emphasises what is retained.
• ‘Memory’ emphasises what is forgotten.

Question 153

what are the three stages of memory?

Answer 153

(1) Perception; (2) Storage and (3) Retrieval

Question 154

short-term memory

• how long does it last
• capacity
• what is chunking
• how do we use acoustic code/engram
• what tends to be lost
• areas of activity

Answer 154

• Lasts seconds to minutes.
• Capacity of STM is limited to 7+/- 2 pieces of information (rule of 7).
• Chunking – we are able to combine ‘chunks’ of information to form a larger piece of information (e.g. telling a patient to take their medication: (1) name of drug, (2) how often to take it, (3) what to take it with, (4) what not to take it with etc – all these small chunks of information allow the patient to understand better the original command about taking their medication).
• Encoding: uses mainly an acoustic engram
 Engram – this is a coded bit of information which maps onto the neural network.
 We tend to use acoustic engrams. This means that to remember a piece of information, we repeat it to ourselves, such that we can hear ourselves repeating it.
• Acoustically similar material tends to be lost (e.g. “bat” / “cat”).
• Areas of activity include frontal and parietal lobes.

Question 155

long-term memory

• capacity
• semantic code
• what essential for consolidation (learning)

Answer 155

• Much greater (possibly unlimited) capacity.
- duration potentially unlimited
• Encoding: semantic code (memory for meaning) (words - but can be visual & auditory)
 Memory for ‘meaning’ is coded for differently than memory for ‘procedure’.
 On tests, things that mean similar things tend to get lost.
• Activity is spread throughout the brain but hippocampus is essential for consolidation (learning).
• Sleep is essential to consolidation, especially 7 days for emotional processing (amygdala involved).

Question 156

what are the different models of memory?

Answer 156

1. Multi-store Model
2. Working Memory Theory
3. Levels of Processing Model
4. Constructivist Model

Question 157

describe the multi-store model

Answer 157

• Information is detected by the sense organs and enters the sensory memory.
• If this information is attended to, it enters the short-term memory (around 20 seconds).
• Information from the STM is transferred to the long-term memory only if that information is rehearsed.
• If rehearsal does not occur, then information is forgotten, lost from STM through the processes of displacement or decay.
• Sensory memory is an impression formed by the input of any of the senses.
• The STM is the only stage in which conscious processing takes place, material lasts in there as long as attention is held on the material.

Question 158

describe the model of working memory

Answer 158

• In this model instead of all information going into one single store, there are different systems for different types of information.
• Working memory consists of a central executive which controls and co-ordinates the operation of two subsystems: the phonological loop and the visuo-spatial sketchpad.

• Central Executive
 Drives the whole system and allocates data to the subsystems (visuo-spatial sketchpad and phonological loop).
 It also deals with cognitive tasks such as mental arithmetic and problem solving.

• Visuo-Spatial Sketchpad
 Stores and processes information in a visual or spatial form.
 The VSS is used for navigation.

• Phonological Loop
 It deals with spoken and written material. It can be used to remember a phone number.
 It consists of two parts:
1. Phonological Store – linked to speech perception. Hold information on speech-based form for 1-2 seconds.
2. Articulatory Control Process – linked to speech production. Used to rehearse and store verbal information from the phonological store.

• The phonological loop is assumed to be responsible for the manipulation of speech based information, whereas the visuo-spatial sketchpad is assumed to be responsible for manipulating visual images.
• The model proposes that every component of working memory has a limited capacity, and also that the components are relatively independent of each other.
• Episodic Buffer – this is dedicated to linking information across domains to form integrated units of visual, special, and verbal information and chronological ordering (e.g. memory of a story).

Question 159

describe the levels of processing model

Answer 159

• Instead of concentrating on the stores/structures involved, this theory concentrates on the processes involved in memory.
• Unlike the multi-store model it is a non-structured approach. The basic idea is that memory is really just what happens as a result of processing information.
• This model proposes that memory is just a by-product of the depth of processing of information and there is no clear distinction between short term memory and long term memory.
• This model compares superficial processing to deep processing.
• Depth is defined as “the meaningfulness extracted from the stimulus rather than in terms of the number of analyses performed upon it.”

Shallow/Superficial Processing
• This has two forms:
1. Structural processing – we encode only the physical qualities of something.
(e.g. the typeface of a word or how the letters look)
2. Phonemic processing – we encode the acoustic qualities of something.
• Shallow processing only involves maintenance rehearsal (repetition to help us hold something in the STM) and leads to fairly short-term retention of information.

Deep Processing
• Semantic processing – we encode the meaning of a word and relate it to similar words with similar meaning.
• Deep processing involves elaboration rehearsal which involves a more meaningful analysis (e.g. images, thinking, associations etc.) of information and leads to better recall. For example, giving words a meaning or linking them with previous knowledge.

Question 160

explain the following important concepts of LoP model

1. implicit memory
2. explicit memory
3. organisation
4. distinctiveness
5. effort
6. elaboration

Answer 160

1. Implicit memory – recollection of memory without conscious thought – non-conscious processing - (e.g tying shoe lace, driving a car).
2. Explicit memory – Conscious recollection of memory – conscious processing (in order to remember something you have to think about it). Attention is crucial.
3. Organisation – Mandler (1967) word cards sort experiment – instructed to sort into any number of piles using any system of categorization they liked. When asked to recall later, those who used more categories remembered more words. This study suggested that the organisation of memory is one of its central aspects (Mandler, 2011).
4. Distinctiveness – Eysenck and Eysenck (1980) speaking test – participants asked to say words in a distinctive way, e.g. spell the words out loud. Such participants recalled the words better than those who simply read the off a list.
5. Effort – Tyler et al. (1979) anagram study – some easy (FATHER) and some difficult (HREFAT). Participants recalled the difficult anagrams better, presumably because they put more effort into them.
6. Elaboration – Palmere et al. (1983) fictitious nation study – some short paragraphs and some with extra sentences elaborating African nation details. Recall was high for elaborated paragraphs.

Question 161

describe the constructivist model

Answer 161

• People who perform a memory task do not simply repeat what they have learned but actively reconstruct what they remember (schema).
• Memories stored in several interconnected units in network.
• Strength of unit increases as a function of learning.
• Strength of unit increases number of connections with other units.
• Challenges the MSM single system view.

Question 162

what are the different types of memory?

Answer 162

Procedural Memory
• It is used to acquire, retain and employ perceptual cognitive and motor skills.
 How things are done
 Memories for actions, skills
 Acquired by practice & observation
 Little conscious recall of components

Declarative Memory
• Involves conscious effort of explicit information.
• Divided into 2 parts:
1. Semantic memory - involves meanings of words & concepts (e.g. E = mc2).
2. Episodic memory - involves autobiographical events in a person’s life.

Implicit Memory
• Non-conscious form of learning that emerges from experiences you are unaware of, that improve your performance on a task.

Explicit Memory
• Conscious process of remembering.
• Attention is crucial.

Question 163

what is definition of recall and recognition?

Answer 163

• Recall – reproducing information to which you were previously exposed.
 Faithful reproduction of previous learned ‘event’ – cue independent.
• Recognition – realising a stimulus is one you have seen or heard before.
 Connecting present stimuli with previous ‘event’ – cue dependent.

Question 164

describe Ebbinghau’s forgetting curve - what does it show?

Answer 164

• This curve shows that, initially, information is lost very quickly after it is learned.
• Factors such as how information was learned and how frequently it was rehearsed play a role in how quickly these memories are lost.
• The forgetting curve also shows that forgetting does not continue to decline until all of the information is lost. At a certain point, the amount of forgetting levels off.
 It indicates that information stored in long-term memory is surprisingly stable.

• fast decline in retention up to 2 days and then slows down dramatically before leveling of at 31 days ?

EBBINGHAUS’S FORGETTING CURVE

• Up to 5-7 days you get a very fast drop off in the information that’s remembered
• Then it plateaus, if you’ve remembered it for a week then you’ll likely to remember for a substantial more about of time

Question 165

what are the theories of forgetting?

Answer 165

1. Decay of trace/engram
    This deals with forgetting information from short-term memory.
    It proposes that STM naturally decays over time.
2. Interference
    This deals with forgetting information from long-term memory.
    It proposes a limitation to processing ability (e,g, lack of sleep).
3. Motivated forgetting
    A mental escape route.
    Repression inhibits conscious remembrance.
4. Superficial processing
    This proposes that information can be forgotten if it was only learned superficially (lack of context/ cues etc).

Question 166

what a rules about stroke and DVLA?

Answer 166

• After a stroke or TIA, the patient MUST STOP DRIVING IMMEDIATELY!
• This is temporary for most people.
• It is possible to return to driving as long as it is safe to do so and the correct procedures are followed.
• If you have a valid driving license, you are not allowed to drive for at least one month after a stroke or a TIA. After a month, the patient can start driving again if the doctor is happy with the recovery of the patient.
• If the patient has had a number of TIAs over a short period of time you will need to wait until you have not had any TIAs for three months before returning to driving.

Question 167

how does the location of a stroke impact on the effect it has on the person?

Answer 167

Right-brain stroke -> affects left side of body

• The right hemisphere of the brain controls the movement of the left side of the body
• A person with a right brain stroke may not be able to move the left side of the body (hemiplegia) or may be very weak in the left arm or leg (hemiparesis)
• Right half of brain controls judging distance, size, speed and position – this may cause a person with a right brain stroke to misjudge distances leading to falls – the person may not be able to control the hand to pick up an object
• Survivors often have problems making good decisions – patients often become impulsive
• They are often unaware of the changes that have happened to them – they believe they can do the same tasks as they did before the stroke
• May also have left-sided neglect – due to visual field changes, left-sided neglect causes the person to ‘forget’ or ‘ignore’ objects or people on the left side
• Some will also have issues with short-term memory

Left-brain stroke -> affects right side of body

• The left hemisphere of brain controls right side off body
• A person with left brain stroke may have hemiplegia in right side or hemiparesis in right arm or leg
• Left half of brain controls speech and language for most people
• Trouble speaking or understanding words said or written
• Slow, careful movement
• Trouble remembering on learning new things
• Not able to see things on right side
• Facial weakness, unclear speech or problems with swallowing

Question 168

overview of treatment for stroke

Answer 168

First few hours after stroke: (while the tissue can be saved)
1. TPA (‘the clot buster medicine’) – dissolves the blood clot
2. Thrombectomy – minimally invasive procedure – for removing larger clots
After, treatment is targeted at reducing the chance of another stroke:
- Daily aspirin – reduces changes of clotting
- Blood thinners – for people with abnormal health rhythms (e.g. atrial fibrillation)
Recovery:
- Can be slow
- May work with: speech therapists, physical therapists, occupational therapists
- Depression – common after stroke
Treating ischaemic strokes:
- Thrombolysis – alteplase – ‘clot-busting’
- Thrombectomy – involves inserting a catheter into an artery, often in the groin – small device is passed through the catheter into the artery in the brain
- Antiplatelets – aspirin
- Anticoagulants – e.g. warfarin
- Antihypertensives – thiazide diuretics, ACE inhibitors, calcium channel blockers, beta-blockers, alpha-blockers
- Statins – reduce level of cholesterol in your blood by blocking an enzyme in liver that produces cholesterol
- Carotid endarterectomy
Treating haemorrhagic strokes:
- Antihypertensives
- Treatment to reverse effects anticoagulants if they were taken before stroke
- Surgery – craniotomy – remove any blood from brain and repair any burst blood vessels
- Surgery for hydrocephalus – complication of haemorrhagic strokes where damage resulting from stroke causes CSF to build up in ventricles of brain

Question 169

what is central facial palsy?

Answer 169

• Central facial palsy is a symptom or finding characterised by paralysis or paresis of the lower half of one side of the face
• It usually results from damage to upper motor neurons of the facial nerve

Central facial palsy manifests with impairment of the lower contralateral mimic musculature. In contrast, peripheral facial palsy leads to impairment of the ipsilateral mimic muscles and also affects the eyelids and forehead.

Question 170

how is blood supplied to the brain?

Answer 170

• The internal carotid arteries (from common carotid artery) (anterior blood supply)
• Vertebral arteries (from subclavian artery) (posterior blood supply)

Question 171

what’s the importance of the circle of Willis? however, what’s the issue with this?

Answer 171

• Ring of arteries at base of brain – forms an anastomose
• Provides a ‘safety mechanism’ – if one of the arteries gets blocked the ‘circle’ will still provide the brain with blood
• However, actual significance of this is dependent on size of communicating arteries (which should allow collateral flow):
• highly variable between individuals in elderly population
• anastomoses are not sufficient due to narrowing of large vessels and communicating arteries because of vascular disease

Question 172

what is the course of the middle cerebral artery?

Answer 172

passes through lateral sulcus & travels along lateral surface of frontal and parietal lobes

Question 173

what does occlusion of the middle cerebral artery lead to?

Answer 173

• contralateral paralysis (mostly in lower face and in arm)
• general somatosensory deficits
• speech defects (aphasia) if dominant hemisphere affected

Question 174

describe the course and branches of the basilar artery

Answer 174

• Runs forward in midline on ventral surface of pons
• Numerous branches – anterior inferior cerebellar, pontine, superior cerebellar
• Divides at rostral end of midbrain – posterior cerebral arteries

Question 175

what does occlusion of the basilar artery lead to?

Answer 175

coma - followed by death due to respiratory failure

Question 176

describe the course and the branches of the posterior cerebral artery

Answer 176

• Curve around midbrain and reach medial surface of cerebral hemisphere
• Important branches – cortical branches supply visual cortex, posterior choroidal, posterior communicating

Question 177

what are the arterial territories? (lateral aspect and medial aspect)

Answer 177

ARTERIAL TERRITORIES: LATERAL ASPECT

• Anterior cerebral artery – anterior section going back 2/3
• Middle cerebral artery – lateral side
• Posterior cerebral artery – posterior 1/3 and sides

ARTERIAL TERRITORIES: MEDIAL ASPECT

• Anterior cerebral artery – all of the middle and anterior
• Middle cerebral artery – none
• Posterior cerebral artery – occipital lobe (visual cortex)

Question 178

what are the different symptoms of stroke depending on location - what do the different areas of the brain do?

Answer 178

• Frontal lobe – judgement, foresight, and voluntary movement
• Frontal lobe (lower) – smell
• Motor cortex – movement
• Central sulcus
• Sensory cortex – pain, heat, and other sensations
• Parietal lobe – comprehension of language
• Temporal lobe (anterior) – intellectual and emotional functions
• Temporal lobe (posterior) – hearing
• Brainstem – swallowing, breathing, heartbeat, wakefulness centre and other involuntary functions
• Cerebellum – coordination
• Broca’s area – speech
• Wernicke’s area – speech comprehension
• Occipital lobe – primary visual cortex

Question 179

what is mortality of haemorrhagic stroke?

Answer 179

mortality hasn’t changed for 40 years – mortality still about 40% after 1 month

Question 180

what causes cell death and the inflammatory response?

Answer 180

• Energy failure
• Cells depolarise because they lose their membrane potential
• Glutamate is released
• Which causes cell death (triggers microglial cells to respond to it)
• Then produce an inflammatory response

Question 181

what happens in first minutes and what causes secondary damage?

Answer 181

First minutes:
-	Energy failure 
-	Excitotoxicity 
-	Depolarisation 
-	Necrosis 
Secondary damage: (hours to days)
-	Inflammation 
-	Programmed cell death

Question 182

describe the acute phase of the immune response in stroke

Answer 182

• Immediately after stroke, you see an increase in molecules produced by damaged cells – DAMPs (damage associated molecular patterns)
• Macrophages will recognise things that shouldn’t be there and then try clean-up some of the mess
• Microglial cells then produce inflammatory cytokines, proteases in order to kill pathogen that they think is there – this can be damaging to neurone cells
• It’s a knock-on-effect, the neurone dies which activates the microglia which then produces substances that damage neurones
• Over time, there’s an infiltration of lymphocytes into the brain – they may play some role in resolving the inflammation

Question 183

what’s a cytokine that causes brain cells to die after stroke? how can it be targeted?

Answer 183

INTERLEUKIN-1 (IL-1)
IL-1B = cytokine – released in hypothalamus of the brain – causes increase temperature – causing hyperthermia – get during fever
- It also causes brain cells to die after stroke

• IL-1 receptor antagonist (I1RA) = drug that blocks it – naturally occurring compound – body produces it
• Rheumatoid arthritis
• Neonatal-onset multisystem inflammatory diseases
• Now in phase 3 clinical trial for haemorrhagic stroke
• Already safe and effective for ischaemic stroke
• This drug blocks the early immune response after stroke

Question 184

give an overview of the pathophysiology of stroke

Answer 184

Arterial occlusion -> ischaemia (deprived of oxygen and nutrients (glucose))
 Energy failure (don’t have ATP production) -> Ca2+/Na+ influx
 Glutamate release -> glutamate receptors -> Ca2+/Na+ influx
If you don’t have ATP, the pump will fail and so you have passive transport of ions inside and outside the neurones -> neurones become electrically inactive

Question 185

what does and doesn’t the BBB allow through it?

Answer 185

• Oxygen, glucose and other nutrients – passive diffusion into the brain
• It doesn’t allow the passage of micro-molecules or immune cells

Question 186

what is the neurovascular unit?

Answer 186

Conceptual model by which close interaction of brain cells (astrocytes, microglia and neurones) with the brain endothelium and the extracellular matrix contributes to the maintenance of brain homeostasis and functions
Components of the NVU are:
- Astrocytes (star-shaped glial cells), microglia, neurones
- Endothelial cells and pericytes
- Extracellular matrix

Question 187

neurogenesis

• what is happening
• where is it happening
• how does it bring about repair

Answer 187

VISUALISING NEUROGENESIS
- Nucleotides (e.g. thymidine) are incorporated into DNA strands during replication
- 3H-thymidine incorporates into dividing cells
NEUROGENESIS IN THE ADULT BRAIN
Where neurogenesis takes place:
- Sub-granular zone (SGZ) of Dentate Gyrus – hippocampus level
- Sub-ventricular zone (SVZ) – adjacent to lateral ventricle
Process:
- Neural stem cells (located in these specific regions in the brain)
- Upon stimulation, they develop into neural precursor cells
- These can undergo cell death or differentiate into different cell types
NEUROGENESIS IN THE SUBGRANULAR ZONE
- Newly formed cells migrate from the outer sub-granular zone to inner granule cell layer in the hippocampal dentate gyrus
- Neural stem cells in sub-granular zone
- They proliferate
- They then migrate
- Then they integrate and differentiate into neurons and make connections with fibres from entorhinal cortex (area of brain located in the medial temporal lobe and functioning as a hub in a widespread network for memory, navigation and the perception of time – it’s the main interface between the hippocampus and the neocortex)
- This is one of the main mechanisms by which neurogenesis contributes to memory – the hippocampus is believed to be one of the main centres for memory in the brain

NEUROGENESIS IN THE SUBVENTRICULAR ZONE

• In normal brain, neural progenitors migrate from SVZ to olfactory bulb via Rostral Migratory Stream (RMS)
• Following injury, neural progenitors from SVZ leave RMS and migrate laterally towards the damaged area

NEUROGENESIS IN BRAIN INJURY AND REPAIR

1. Injured brain area secretes many factors like growth factors, cytokines, chemokines and mitogens – endogenous signals from injured neurones (DAMPs)
2. These factors diffuse to SVZ and induce progenitor migration to try to neuronal network to part of brain that has been subjected to ischaemia
3. Newly formed cells migrate from subventricular zone to damaged area
4. The increased proliferation and migration of neural progenitors continues for months after injury to the brain

Question 188

what factors are involved in angiogenesis after brain injury?

Answer 188

• cytokines
• chemokines
• integrins ECM
• growth factors

Vascular endothelial growth factors (VEGF)
 VEGFR1 (in some endothelia) -> embryonic vascular development
 VEGFR2 (in all endothelia) -> angiogenesis in repair

Angiopoetin-1 and -2 (Ang1) -> tie-2 -> angiogenic during inflammation

ECM -> integrins -> embryonic vascular development

Question 189

how doe extracellular matrx mediators lead to angiogensis?

Answer 189

Normal blood vessels -> injury, BBB leakage -> VEGF, Ang-1, endothelial activation and proliferation -> ECM deposition, EC proliferation to new vessels, involvement of integrins (invovled in adhesion of cells) -> vessel stabilisation, pericyte and astrocyte attachment

Question 190

explain what glial scarring is

Answer 190

• Neurogenesis and angiogenesis can take a long time to take place in effected region
• Alongside this, glial cell formation takes place
• Formed maybe by astrocytes
• They form a physical barrier between the injured part of the brain and the healthier part of the brain
• Protecting the healthy part of brain from the injured part

Question 191

describe the dual role of inflammation

Answer 191

Post-ischaemic inflammation -> activation of glial cells:
	Neuronal death 
	Alterations in synaptic transmission 
	Changes in synaptic plasticity 
	Neurogenesis

Question 192

how do microglia contribute to CNS renewal?

Answer 192

CNS injury
 Primary activation of resting microglia -> M1 microglia (acute phase)
 Delayed activation of resting microglia -> M2 microglia (recovery phase)

Acute phase – neurotoxic microglia -> neurotoxicity, tissue injury
Recovery phase – phagocytic microglia -> immune suppression, tissue repair (express lot of anti-inflammatory mediators and neurotrophic factors)

Resting microglia go around the brain checking that there’s no problems (basically the brain macrophage)

Question 193

give a summary of the repair mechanisms

Answer 193

Perivascular astrocytes and microglia:
- Astrogliosis/microgliosis in the glial scar
Angiogenesis:
- Endothelial cells proliferation and migration
Neurogenesis:
- Neural stem cells proliferation and migration

Question 194

what is dysarthria?

Answer 194

when muscles used for speech are weak or you have difficulty controlling them

Question 195

why do check peripheral pulses with potential stroke patients?

Answer 195

Peripheral pulses – atherosclerosis in peripheries – intermittent claudication (pain caused by too little blood flow, usually during exercise)

Question 196

what do you have to exclude with potential stroke patients?

Answer 196

hypoglycaemia - if BM < 3.5 treat urgently and reassess

Question 197

what’s used to measure stroke severity?

Answer 197

NIH stroke scale

- the higher the score, the more severe the stroke

Question 198

thrombolysis

• using what
• when beneficial
• complications

Answer 198

• Alteplase (tPA) iv. bolus, plus 1-hour infusion
• Only when haemorrhage has been excluded by brain scan
• Time is Brain: ideally within 180 minutes of onset
• Generally, only beneficial after 4.5 hours of symptom onset – often difficult to know when onset was
• The quicker we treat, the better the outcome
• Complications: haemorrhage (infarct turns into haemorrhage – very often fatal (3-5% have haemorrhage?)), anaphylaxis (angio-oedema 6-7%, serious in 1%)

Question 199

thrombectomy

• what happens
• when beneficial
• how compare to thombolysis

Answer 199

• Good evidence for thrombectomy with stent retrievers
• Benefits time dependent: certainly within 6 hours from symptoms onset
• If penumbra still present, can be beneficial up to 24 hours
• Stent retriever is passed through the clot and opened up, then pulled back out, bringing the clot with it
• Much more beneficial than intravenous thrombolysis

Question 200

what is significant stenosis?

Answer 200

> 50%

Question 201

what is the serial position effect?

Answer 201

Items that appear early and later in the list are generally remembered better – primary and recency effects

Question 202

what are schemas?

Answer 202

organised knowledge and expectations about familiar events or objects

Question 203

what is sensory memory?

Answer 203

(Sensory Information Store (SIS))

• Lasts about 0.1 to 0.5 of a second (for most)
• Holds quite an accurate and complete representation
• Encoding is sense-specific – different sensory memory stores for different sensory modalities (sight, hearing, smell, taste, touch)

Question 204

describe the organisation of memory (semantic associations)

Answer 204

• One of memory’s central aspects
• Important to the Levels of Processing Model
• Memories stored in several interconnected units in network
• Strength of unit increases as a function of learning
• Strength of unit increases number of connections with other units (one idea linking with another idea)
• E.g. if you say the word bird, words such as fish will be partially activated/primed in the brain – if a concept is partially activated, it will spring to mind more easily

Question 205

what is prospective memory?

Answer 205

remembering to do things

Question 206

what’s the idea of interference? what are the two ways?

Answer 206

Idea that new material interferes with memory at some point before retrieval

• Retroactive interference – new material is introduced after the encoding of material to be learnt
• Proactive interference – new material is introduced before the encoding of material to be learnt

Question 207

what are different ways of improving your memory?

Answer 207

The SQ3R method:

• Survey
• Question
• Read
• Recite
• Review

The Method of Loci

• Simonides
• Memorising by forming associations
• Mentally locate information in a place that’s meaningful to you – makes much more likely to remember
• Establish lot of locations in a place that’s familiar to you

Question 208

describe the arousal-performance curve

Answer 208

• Increasing arousal increases performance
• Until impaired performance because of strong anxiety due to too strong arousal
• Memory poorest at end of consultation when highly anxious

Question 209

what’s the Yerkes-Dodson law?

Answer 209

How anxiety affects performance: (increasing anxiety)

• Increasing attention and interest
• Optimal arousal and optimal performance
• Impaired performance because of strong anxiety

Question 210

which neurotransmitter is associated with axiety? which with depression?

Answer 210

GABA – anxiety
Serotonin – depression
But both are linked

Question 211

GABA

• what is it
• how synthesised
• agonist at which receptors
• describe receptor
• drug treatments

Answer 211

• Inhibitory neurotransmitter – present in 30% of brain synapses
• Y-aminobutyric acid (GABA) is the main inhibitory neurotransmitter in the mammalian CNS
• Synthesised by decarboxylation of the amino acid glutamic acid
• Major role in regulating neuronal excitability and muscle tone
• GABA is the endogenous agonist at two main receptors:
• GABAa receptor: multiple ligand binding sites
• GABAb receptor: baclofen is a GABA analogue which acts as a selective agonist at GABAb receptors – used clinically as a muscle relaxant

GABAa RECEPTOR
- A transmembrane, ligand-gated ion channel receptor
- Consists of five subunits (i.e. ‘pentameric’) arranged around a central chloride channel
Etc.
- Activating subunits opens the chloride channel

• Benzodiazepines (e.g. diazepam) bind at a separate site between the alpha and gamma subunits
• this potentiates the action of GABA and increases Cl- influx
• i.e. diazepam is a positive allosteric modulator (POM) at the GABAa receptor
• GABAa receptors lacking a gamma subunit are insensitive to benzodiazepines

Question 212

what is the NICE guidance steeped care approach for GAD?

Answer 212

Step 1: recognition and diagnosis of GAD
Step 2: offer treatment in primary care
- Benzodiazepines should not usually be used >2 weeks – risk of tolerance and dependence
- Longer-term care: interventions with positive evidence base:
a) Psychological therapy (e.g. CBT)
b) Pharmacological therapy (an SSRI licensed for GAD)
c) Self-help (online self-education)
- Shared decision-making

Step 3: non-response: review and offer alternative treatment
Step 4: review and offer referral to secondary care
- If 2 interventions has been provided and the person still has significant symptoms, then referral to specialist mental health services should be offered
Step 5: care in specialist mental health services
- Thorough, holistic reassessment

Question 213

how does pregablin work?

Answer 213

Binds to the alpha-2-delta subunit of the voltage-dependent calcium channel in CNS – this decreases the release of neurotransmitters including glutamate, noradrenaline and substance P

Question 214

why are benzodiazepines used for outbursts of anxiety?

Answer 214

symptoms of anxiety reduce within 30 to 60 minutes

Question 215

benzodiazepines

• how do they differ
• what efficacy related to
• what act on

Answer 215

• Differ mainly in half life
  e. g. diazepam (Valium) 30 hours vs. triazolam 2 hours
• Efficacy related to potentiation of GABA transmission
• Benzodiazepines act at GABAa receptor

Question 216

beta blockers

• what are they
• why may be used with anxiety
• contraindicated with what

Answer 216

• Antagonist at adrenergic B receptors in heart muscle, smooth muscle, and other tissues of the sympathetic nervous system
• Effective in treating physical but not psychological symptoms of anxiety – tremor, palpitations
• Contraindicated in asthma