Neurology Flashcards
1
Q
What is the central nervous system?
A
The brain and spinal cord
2
Q
What does the peripheral nervous system consist of?
A
12 pairs of cranial nerves, which connect the brain/brainstem and head and neck
31 pairs of spinal nerves
3
Q
What are the two divisions of the autonomic nervous system?
A
Sympathetic
Parasympathetic
4
Q
Where does sympathetic outflow come from?
A
The thoracic and lumbar cord
5
Q
Where does parasympathetic outflow come from?
A
The brainstem via cranial nerves and the sacral cord
6
Q
Where is the motor cortex?
A
At the precentral gyrus
7
Q
Where is the somatosensory cortex?
A
At the postcentral gyrus
8
Q
Where are the pyramids?
A
In the medulla
9
Q
What is the internal capsule?
A
A big white matter tract running between the deep brain structures
10
Q
What does the diencephalon consist of?
A
Thalamus
Hypothalamus
11
Q
What is the thalamus responsible for?
A
Motor control
Sensory relay
Visual processing
12
Q
What are the basal ganglia?
A
Caudate
Putamen
Globus pallidus
13
Q
Where does the spinal cord start and end?
A
Starts just below the medulla
Ends at L1-L2
14
Q
How many pairs of cervical nerves are there?
A
8
15
Q
How many pairs of thoracic nerves are there?
A
12
16
Q
How many pairs of lumbar nerves are there?
A
5
17
Q
How many pairs of sacral nerves are there?
A
5
18
Q
How many pairs of coccygeal nerves are there?
A
1
19
Q
From what level does the brachial plexus originate?
A
C5-8 and T1
20
Q
What do the spinal nerves contain?
A
Mixed somatic nerves comprised of motor fibres for skeletal muscles and sensory fibres (pain, temperature, touch, pressure, vibration, proprioception)
Joined by sympathetic fibres
21
Q
Where within the grey matter of the spinal cord do motor neurons terminate?
A
In the ventral grey horn
22
Q
Where within the grey matter of the spinal cord do sensory neurons terminate?
A
In the dorsal root ganglion
23
Q
What is a dermatome?
A
An area of skin supplied by a single spinal nerve
24
Q
What is a myotome?
A
Muscles supplied by a single spinal nerve
25
What do the ascending tracts within the cord (white matter) do?
Carry sensory information from the periphery to the CNS
26
What do the descending tracts within the cord (white matter) do?
Carry motor information from the CNS to the periphery
27
What are interneurons?
Neurons that allow reflexes by joining a sensory neuron directly to a motor neuron, bypassing the CNS.
28
What are the two main ascending tracts in the spinal cord?
1. Spinothalamic tract
| 2. Dorsal column pathway
29
What information is carried by the dorsal column?
Touch (particularly fine touch)
| Proprioception
30
What information is carried by the spinothalamic tract?
Pain and temperature
| Crude touch
31
Describe the path taken by the spinothalamic tract
Cell body is in the dorsal root ganglion
--> Projects to the dorsal grey horn and synapses with a second neuron.
--> Axons decussate via ventral white commissure
--> Ascend towards thalamus
--> Synapse with 3rd neuron in the thalamus
--> Axons project to somatosensory cortex
(Tract runs contralateral to the side of the body that it receives fibres from as decussation happens almost immediately)
32
Describe the path taken by the dorsal column pathway
Cell body is in the dorsal root ganglion
- -> axons ascend in the dorsal columns towards the cuneate/gracile fasciculus
- -> For upper limb, synapse with second neuron in cuneate fasciculus
- -> For lower limb, synapse with second neuron in gracile fasciculus
- -> Axons decussate in the medulla then ascend in the medial lemniscus
- -> Synapse with 3rd neuron in the thalamus
- -> Axons project to somatosensory cortex
33
What are the key descending tracts in the spinal cord?
Lateral and ventral corticospinal tracts
34
Do the corticospinal tract fibres decussate and where?
Ventral corticospinal tract does not decussate
| Lateral corticospinal tract fibres decussate at the pyramids
35
Describe the path taken by the corticospinal tracts
~85% of the fibres decussate at the pyramids to form the lateral CST
~15% of the fibres remain ipsilateral to form the ventral CST
--> upper motor neuron synapses with lower motor neuron in the ventral grey horn
--> axon leaves in the spinal nerve
36
Which cranial nerves arise from the brain and which arise from the brainstem?
I and II arise from the brain
| III-XII arise from the brainstem
37
What is the mnemonic for remembering which cranial nerves carry sensory/motor or both?
Some Say Money Matters But My Brother Says Big Brains Matter Most
38
Which cranial nerves also carry parasympathetic fibres?
III, VII, IX, X
| oculomotor, facial, glossopharyngeal, vagus
39
What does cranial nerve I do?
Olfactory
Sensory: smell
Axon bundles travel through cribriform plate --> olfactory bulb --> tracts --> temporal lobe
Connects with limbic system
40
What does cranial nerve II do?
Optic
Sensory: vision
Fibres travel from retina --> primary visual cortex (medial aspect of occipital lobe, calcarine sulcus)
Right and left visual cortices receive information from both eyes about opposite side of visual field
41
What does cranial nerve III do?
Oculomotor
Motor and parasympathetic
Motor to most of extraocular muscles (medial rectus, superior rectus, inferior rectus, inferior oblique, levator palpebrae superioris)
Parasympathetic: innervates sphincter to pupillae --> constriction in response to light
42
What does cranial nerve IV do?
Trochlear
| Motor - innervates superior oblique
43
What does cranial nerve V do?
Trigeminal
Sensory fibres: extensive distribution in the head, touch, pressure, pain, temperature, proprioception from TMJ and muscles of mastication
Motor fibres: Muscles of mastication
3 divisions: ophthalmic (S), maxillary (S), mandibular (S&M)
44
What does cranial nerve VI do?
Abducens
Motor
Innervates lateral rectus
45
What does cranial nerve VII do?
Facial
Sensory: taste anterior 2/3 of the tongue
Motor: muscles of facial expression
Parasympathetic: Lacrimal gland, submandibular and salivary glands
46
What does cranial nerve VIII do?
Vestibulocochlear
Sensory
Afferents from vestibular apparatus (balance) and cochlea (hearing)
47
What does cranial nerve IX do?
```
Glossopharyngeal
Sensory:
Taste - posterior 1/3 of the tongue
General sensation from pharynx, eustachian tube and posterior 1/3 of tongue
Motor:
One muscle of the pharynx
Parasympathetic: parotid gland
```
48
What does cranial nerve X do?
Vagus
Sensory: General sensation external auditory meatus, tympanic membrane, pharynx, larynx, oesophagus
Motor: Muscles of soft palate, pharynx and larynx
Parasympathetic: Thoracic and abdominal viscera
49
What does cranial nerve XI do?
Accessory - 2 parts
1. Cranial part (joins the vagus)
2. Spinal part
- Arises from ventral horn spinal cord C1-C5
- Travels up through foramen magnum
- Leaves again through jugular foramen
- Innervates sternocleidomastoid and trapezius
50
What does cranial nerve XII do?
Hypoglossal
| Motor: tongue muscles
51
Why do the forehead muscles still work in the case of an upper facial motor neuron lesion?
The upper part of the facial motor nerve receives input from both sides, but the lower part of the facial motor neuron receives input from only the lower side.
52
What are the two layers of the dura mater?
Periosteal (outer)
| Meningeal (inner)
53
What are the deeper pockets of the subarachnoid space called?
Cisterns
54
Where are the meningeal vessels?
In the extradural space
55
Where are the bridging veins?
In the subdural space
56
Where is the circle of Willis and its branches?
In the subarachnoid space
57
What is the cauda equina?
Lower spinal nerves at the bottom of the spinal cord below L1-2 level
58
Where is a lumbar puncture performed?
Below L2 level (L3-4 or L4-5)
59
From where do the left and right vertebral arteries arise?
From the subclavian arteries
60
What are the terminal branches of the internal carotid artery?
Anterior cerebral artery
| Middle cerebral artery
61
From where does the lateral surface of the brain receive its blood supply?
Mostly from the middle cerebral artery
62
What is Broca's area and where is it?
On the lateral surface of the cerebrum anterior to the middle cerebral artery.
Function: motor speech
63
What is Wernicke's area and where is it?
On the lateral surface of the cerebrum posterior to the middle cerebral artery.
Function: comprehension
64
From where does the medial surface of the brain receive its blood supply?
Mostly from the anterior cerebral artery
65
Where is the lower limb represented?
Medial surface of the cerebral hemisphere (anterior cerebral artery territory)
66
Where are the upper limb and face represented?
Lateral surface of the cerebral hemisphere (middle cerebral artery territory)
67
Which vessels supply the internal capsule, basal ganglia and hypothalamus?
Perforating vessels from the anterior and middle cerebral arteries
68
Which vessels supply the midbrain and hypothalamus?
Perforating vessels from the posterior cerebral artery
69
From where does the spinal cord receive its blood supply?
From paired posterior spinal arteries and one anterior spinal artery
Reinforced by supply from radicular vessels
70
What is the usual cause for extradural haemorrhage?
Trauma resulting in bleeding from the middle meningeal artery as a result of a skull fracture
71
How does extradural haemorrhage normally present?
Usually following head injury, although may be delayed
| Headache, drowsiness and neurological deterioration from brain compression
72
How does extradural haemorrhage appear on CT?
Acute bleed appears hyperdense on CT
Convex - does not conform to surface of the brain
Bleeding limited by suture lines
Possible midline shift due to compression of the brain
73
What is the usual cause of subdural haemorrhage?
Trauma, typically from a fall leading to bleeding from dural bridging veins
74
How does subdural haemorrhage usually present?
Bleeding is low pressure, so results in a gradual rise in intracranial pressure over several weeks or months, leading to gradual cognitive deterioration. Most likely in elderly, dementia patients, alcohol abusers and shaken babies.
75
How does subdural haemorrhage appear on CT scan?
Chronic bleed appears hypodense (dark)
Concave shape, conforms to the surface of the brain
Bleeding crosses suture lines
Midline shift may be present due to compression of the brain
76
What is the most common cause of subarachnoid haemorrhage?
Ruptured aneurysm on a cerebral artery
77
How does subarachnoid haemorrhage present?
Sudden onset severe 'thunderclap' headache
May have seizures
May be conscious/unconscious, may have reduced GCS
78
How does subarachnoid haemorrhage appear on imaging?
Acute bleed appears hyperdense on CT (bright white)
| Blood seen in fissures, cisterns and sometimes ventricles
79
What is the most common cause of intracerebral haemorrhage?
Aneurysm rupture
80
How does intracerebral haemorrhage usually present?
Depends on cause, size of bleed and brain region affected
| Can cause coma, confusion, weakness, seizures
81
How does intracerebral haemorrhage appear on CT?
Acute bleed --> hyperdense
Blood seen in the substance of the brain
Mass effect (e.g. midline shift) seen if large
82
What are the possible infective causes of meningitis?
Bacterial
Fungal
Viral
Parasitic
83
What are the possible non-infective causes of meningitis?
Paraneoplastic
Drug side effects
Autoimmune (e.g. vasculitis/SLE)
84
Name three routes of infection for meningitis
1. Contiguous spread e.g. from nasal carriage, otitis media, sinusitis
2. Haematogenous spread (i.e. bacteraemia)
3. Neurosurgical complications
85
Why is CNS infection so difficult for the body to clear?
The brain is protected by the blood-brain barrier, which prevents the immune system from attacking brain tissue. However, if pathogens manage to cross the barrier, they are then isolated from the immune system and can spread without resistance.
86
What is the classic triad or meningitis symptoms?
1. Fever
2. Headache
3. Neck stiffness
87
What other symptoms besides the classic triad can meningitis cause?
- Nausea and vomiting
- Photophobia
- Irritability
- Confusion
- Sleepiness
- Lethargy
- Purpuric rash
88
If a patient with suspected bacterial meningitis presents to the GP, what should they do?
Administer IM benzylpenicillin immediately and send the patient to hospital
89
What are the first management steps in the hospital for a patient with suspected meningitis?
1. Assess GCS (eye response, verbal response, motor response)
2. Blood cultures
3. Administer broad spectrum antibiotics - cefotaxime or ceftriaxone (assuming patient isn't allergic to penicillin). If patient has recently travelled, administer vancomycin too due to risk of penicillin resistance.
4. Steroids (IV dexamethasone) to reduce inflammation
5. Lumbar puncture to give definitive diagnosis
90
What are the contraindications for lumbar puncture?
- Raised ICP
- Petechial rash
- Abnormal clotting/patient on anticoagulants
- Suspicion of spinal abscess
91
Which patients should have a CT head before proceeding to lumbar puncture?
- Those aged 60+
- Immunocompromised
- History of CNS disease
- Seizure < 1 week
- GCS < 14
- Focal neurological signs
- Papilloedema/other signs of raised ICP
92
Which meningitis-causing organism appears on gram film as gram negative (pink) diplococci?
Neisseria meningitidis
93
Why is Neisseria meningitidis the most common cause of meningitis in children and young adults?
Due to high level of nasal colonisation
94
What meningitis-causing organism appears as gram positive (purple) diplococci?
Streptococcus pneumoniae
95
What meningitis-causing organism appears as gram positive bacilli?
Listeria spp
96
What meningitis-causing organism appears as gram positive individual cocci?
Group B streptococcus
97
Which meningitis-causing organisms appear as gram negative rods?
1. Haemophilus influenzae B
| 2. E coli
98
Which organisms cause chronic meningitis?
- Mycobacterium tuberculosis
- Syphilis
- Cryptococcal (fungus)
99
Which types of bacterial meningitis are more likely to affect neonates?
Group B strep
| E coli
100
Which types of bacterial meningitis are more likely to affect children?
Neisseria meningitidis
Streptococcus pneumoniae
Haemophilus influenzae B
101
Which types of bacterial meningitis are more likely to affect adults?
Neisseria meningitidis
| Streptococcus pneumoniae
102
Which types of bacterial meningitis are more likely to affect the elderly?
Neisseria meningitidis
Streptococcus pneumoniae
Listeria
103
What are the characteristics of CSF with bacterial infection?
Cloudy appearance
High white cell count
High protein
Low glucose
104
What are the characteristics of CSF with viral infection?
Clear appearance
High white cell count with lymphocytes
High protein
Normal glucose
105
Who needs to be notified in cases of meningitis?
All cases must be reported to Public Health immediately
For Neisseria meningitidis - identify close contacts and administer single dose of ciprofloxacin or rifampicin as a prophylactic measure.
106
What is encephalitis?
Inflammation of the cerebral cortex
107
What are the usual causes of encephalitis?
Viruses, particularly HSV and VZV
108
How does encephalitis usually present?
A flu-like illness that progresses to altered GCS with possible confusion, drowsiness and coma
Fever, seizures and memory loss may also be present
Possible meningeal irritation too --> meningoencephalitis
109
How is encephalitis managed?
MRI head
Lumbar puncture with viral PCR
Mostly supportive treatment with neuro rehabilitation
IV acyclovir if caused by HSV or VZV
110
Which organism found globally in soil produces spores that cause tetanus?
Clostridium tetani
111
What toxins are produced by Clostridium tetani and what do they do?
- Tetanolysin (destroys tissue)
| - Tetanospasmin (causes muscle contraction and spasms by binding to neurons and travelling retrogradely along axons)
112
How is symptomatic tetanus managed?
Muscle relaxants
Paracetamol
Immunoglobulin to mop up unbound toxins
Metronidazole
113
How is rabies managed?
Symptomatic rabies cannot be treated
Pre-exposure prophylaxis via vaccination in endemic areas
Post-exposure prophylaxis via vaccination and immunoglobulin therapy
114
What should all patients with CNS infections be tested for?
HIV
115
What are (usually) the three main branches coming off the aortic branch?
1. Brachiocephalic trunk
2. Left common carotid artery
3. Left subclavian artery
116
What does the brachiocephalic trunk divide into?
Right common carotid artery
| Right subclavian artery
117
What are the four segments of the internal carotid artery?
1. Cervical (in the neck - mobile)
2. Petrous (in the temporal bone - fixed)
3. Cavernous (in the cavernous sinus)
4. Supraclinoid (intradural)
118
Why were strokes a much more common consequence of road traffic collisions before the advent of seatbelts?
Because of the potential for dissection of the carotid artery at the point where it enters the skull base.
119
Which important vessel comes off of the cavernous internal carotid artery?
Ophthalmic artery
120
Why do some people have worse strokes than others?
Depends on collateral blood supply and how well it can compensate for routes being blocked.
121
What are the consequences of injuries to the cavernous sinus?
Pain
| Cranial nerve deficits
122
What surrounds the internal carotid artery in the cavernous sinus?
Sympathetic plexus
Venous blood supply
Cranial nerves: III, IV, V and VI
123
Why do the basal ganglia and internal capsule suffer irreversible damage very quickly?
They are supplied by perforating vessels, with no alternative circulation in case of a blockage.
124
Dissection of which arteries can occur simply by tipping the head back too vigorously?
Vertebral arteries
125
Which artery supplies the medulla and inferior cerebellum?
Posterior inferior cerebellar artery
126
The vertebral arteries unite to form a single basilar artery. Which arteries come off the basilar artery?
- Multiple perforating arteries to the brainstem
- Bilateral anterior inferior cerebellar arteries
- Bilateral superior cerebellar arteries
127
From where do the posterior cerebral arteries arise?
From the terminal bifurcation of the basilar artery
128
Which structures are supplied by perforating arteries from the posterior cerebral artery?
Thalamus
Geniculate bodies
Cerebral peduncles
Tectum
129
What are the three types of primary headache?
1. Migraine
2. Cluster
3. Tension type
130
Name some causes of secondary headache
```
Meningitis
Subarachnoid haemorrhage
Giant cell arteritis
Idiopathic intracranial hypertension
Medication overuse
```
131
Which aspects of a patient's history of headache would prompt investigation/referral?
1. Age >50
2. History of HIV/cancer/trauma/cerebral vein sinus thrombosis risk factors
3. Changing personality/cognitive dysfunction
4. Vomiting with no other obvious cause
132
Which characteristics of a patient's headache would prompt investigation/referral?
1. Jaw claudication or visual disturbance
2. Severe eye pain
3. Changing in frequency, characteristics or associated symptoms
4. Postural associations
5. Sudden onset/thunderclap
6. Triggered by exercise or valsalva
7. Focal neurological symptoms (e.g. limb weakness, aura)
133
What signs on examination of a patient with headache would prompt referral/investigation?
1. Fever
2. Altered consciousness
3. Neck stiffness
4. Other abnormal neurological examination
134
What are the 'red flags' for headache, which prompt urgent investigation?
1. New headache with history of cancer
2. Cluster headache
3. Seizure
4. Significantly altered consciousness, memory, confusion, coordination
5. Papilloedema
135
What are the 'orange flags' for headache, which prompt monitoring and a low threshold for investigation?
1. New headache where diagnostic pattern not emerged after 8 weeks
2. Exacerbated by exercise or valsalva
3. Headache associated with vomiting
4. Headache for some time that has changed significantly
5. New headache if >50 years
6. Headache that wakes patient from sleep
136
What are the 'yellow flags' for headache, which prompt management and possible follow-up?
1. Diagnosis of migraine or tension type headache
2. Weakness or motor loss
3. Memory loss
4. Personality change
137
What should be asked about when taking a history for headache?
- Types/number
- Time (onset/duration/frequency/pattern)
- Pain (severity, type, site, spread)
- Associated (nausea, vomiting, photophobia, phonophobia, cranial autonomic features e.g. red eye, watery eye, blocked nose)
- Triggers
- Response
- Between attacks (normal/persisting symptoms)
- Any change in attacks
138
What are the diagnostic criteria for migraine without aura?
5 attacks with the following features:
1. Lasting 4-72 hours
2: Two of the following: unilateral, pulsing, moderate-severe, aggravation by routine physical activity
3. During headache at least one of the following: nausea, vomiting, photophobia and phonophobia
Also, not attributed to another disorder
139
What is an 'aura' that can sometimes accompany migraine?
Usually occurs before headache, but can occur during
Most common - visual aura e.g. zig zags, flashing lights
Also sensory aura e.g. tingling on one side
Speech/language-related aura e.g. problems saying/understanding words
140
What are the diagnostic criteria for tension type headache?
>10 attacks occurring <1 day/month or <12 days a year and:
1. Lasts 30 minutes to 7 days
2. Two of the following: bilateral, non-pulsating, mild/moderate intensity, not aggravated by routine physical activity
3. No nausea/vomiting and no more than one of photophobia/phonophobia
Also, not attributed to any other disorder
141
Cluster headaches are less common than tension and migraine headaches. What are the diagnostic criteria?
At least five headache attacks with the following:
1. Severe or very severe unilateral orbital, supraorbital and/or temporal pain lasting 15-180 minutes if untreated
2. Headache is accompanied by ipsilateral cranial autonomic features and/or a sense of restlessness or agitation
3. Frequency varies from 1 every other day to 8 per day
Not attributed to another disorder
142
Classical trigeminal neuralgia is a common secondary cause of headache. What are the diagnostic criteria?
At least three attacks of facial pain with the following:
1. Severe or very severe unilateral orbital, supraorbital and/or temporal pain lasting 15-180 minutes if untreated.
2. Headache accompanied by ipsilateral cranial autonomic features and/or a sense of restlessness/agitation
3. Pain has at least three of the following four characteristics:
i) Recovering in paroxysmal attacks from a fraction of a second to 2 minutes
ii) Severe intensity
iii) Electric shock-like, shooting, stabbing
iv) Precipitated by innocuous stimuli to the affected side of the face
Also - no clinically evident neurological deficit
143
Which drugs can be used for acute treatment of migraine?
Normal treatment: Oral triptan with NSAID/paracetamol
| Consider anti-emetic
144
Which drugs should not be used to treat migraine?
Ergotamines (old drugs that were used in the past) and opiates
145
Which patients should not be prescribed triptans?
Those with heart disease
146
How do triptans work?
5-HT1 receptor agonists - cause vasoconstriction in the brain and inhibit the release of inflammatory peptides like CGRP and substance P.
147
Name some triptans
```
Rizatriptan
Zolmitriptan
Sumatriptan
Almotriptan
Eletriptan
Naratriptan
```
148
What drugs should be offered as a first line preventative treatment for migraine?
Topiramate or propranolol
149
What other treatments besides topiramate and propranolol may be helpful for prevention of migraine?
Acupuncture
Amitriptyline
Riboflavin vitamin B2 (400mg once a day)
Botox type A for prophylaxis of chronic migraine if all else fails
150
What is the most common cause of secondary headache?
Medication overuse
151
How is subarachnoid haemorrhage managed?
Resuscitation
Nimodipine
Early intervention to prevent further bleeding (radiological/surgical)
Monitor for complications
152
What are the features of headache caused by raised intracranial pressure?
- Worse on waking, coughing, sneezing, straining, lying down
- Nausea and vomiting
- Papilloedema
153
What are the risk factors for idiopathic intracranial hypertension?
Obesity
| Drugs e.g. tetracycline
154
What would CT scan and LP show in the case of idiopathic intracranial hypertension?
Both would be normal, but LP opening pressure would be high.
155
How is idiopathic intracranial hypertension managed?
- Lifestyle modification
- Monitor visual fields
- Drugs: acetazolamide/topiramate/diuretics
- May require repeated LPs, shunt, optic nerve sheath fenestration
156
What are the diagnostic criteria for giant cell arteritis?
3 of the following:
1. Age >50
2. New headache or new type of localised pain
3. Temporal artery abnormality: tenderness, decreased pulsation
4. ESR elevated >50
5. Abnormal temporal artery biopsy
157
What kind of visual disturbances are more likely to be associated with ophthalmology rather than neurology?
Monocular visual patterns
158
How can we differentiate between a surgical problem and a medical problem with CN III?
CN III (oculomotor) has parasympathetic fibres running along the outside, which are responsible for pupillary light reflex. If the pupil is affected, this could mean that something is compressing the nerve as the parasympathetic fibres are affected. If only motor function is impaired, there is no surgical problem and the patient can be managed as an outpatient.
159
What is the normal cause of medical problems with CN III?
Microvascular disease, usually as a result of diabetes. The only treatment is to optimise diabetic control.
160
What is internuclear ophthalmoplegia?
Asymmetric nystagmus, which results in double vision - caused by a lesion of the medial longitudinal fasciculus, which connects CN VI nucleus to CN III nucleus to move the eyes simultaneously.
161
What does internuclear ophthalmoplegia almost always signify in young people?
Multiple sclerosis
162
What is Horner's syndrome?
Miosis (constricted pupil), drooping eyelid and decreased sweating on one side of the face caused by damage to the sympathetic chain
163
What causes lateral medullary syndrome?
Acute ischaemic infarct of the lateral medulla.
164
What are the ipsilateral features of lateral medullary syndrome?
```
Horner's syndrome
Limb ataxia
Loss of pain and temperature sensation in the face
Reduced corneal reflex
Dysarthria
Dysphagia
```
165
What are the contralateral features of lateral medullary syndrome?
Loss of pain and temperature sensation
166
What is Brown-Sequard syndrome?
A rare neurological condition with hemiparaplegia on one side and hemianaesthesia on the other caused by an incomplete spinal cord lesion.
- Ipsilateral corticospinal tract dysfunction
- Ipsilateral dorsal column dysfunction
- Contralateral spinothalamic tract dysfunction
167
What is multiple sclerosis?
An inflammatory demyelinating disease affecting the CNS that causes progressive disability over time following an initial relapsing/remitting course.
168
What are the general features of active MS lesions?
- Demyelination with breakdown products
- Variable oligodendrocyte loss
- Hypercellular plaques
- Perivenous inflammatory filtrate (mainly macrophages and T-lymphocytes)
- Extensive blood-brain barrier disruption
- Older plaques may have central gliosis
169
What are the general features of inactive MS lesions?
- Demyelination without breakdown products
- Variable oligodendrocyte loss
- Hypocellular plaques
- Variable inflammatory infiltrate
- Moderate to minor blood-brain barrier disruption
- Plaques gliosed
170
What are the common sites of plaque formation in MS?
```
Cerebral hemispheres
Spinal cord
Optic nerves
Medulla and pons
Cerebellar white matter
```
171
What features of MS relate to the spinal cord?
```
Weakness
Paraplegia
Spasticity
Tingling
Numbness
Lhermitte's sign (electric shock going down back of neck to spine, then may radiate out of limbs)
Bladder dysfunction
Sexual dysfunction
```
172
What features of MS relate to the optic nerves?
Impaired vision
| Eye pain
173
What features of MS relate to the medulla and pons?
Dysarthria
Double vision
Vertigo
Nystagmus
174
What features of MS relate to the cerebellar white matter?
Dysarthria
Nystagmus
Intention tremor
Ataxia
175
What are the types of disease progression in MS?
1. Relapsing/remitting MS
2. Primary progressive MS (progression from onset)
3. Secondary progressive MS (initial relapsing/remitting followed by progression)
4. Progressive/relapsing MS (progression from onset with relapses)
176
What are the diagnostic criteria for MS?
1. Two or more CNS lesions disseminated in time and space (i.e. having an effect on more than one occasion and in more than one area of the CNS)
177
What investigations can be carried out for MS?
- Neurological examination
- MRI
- CSF
- Evoked potentials
178
What might be seen in CSF analysis in MS?
IgG oligoclonal bands in CSF that are not present in serum --> indicates immunoglobulin synthesis within the CSF
179
What is the main drug used to treat MS?
Interferon-beta (Betaferon)
180
What drugs can be used to treat mild to moderate spasticity associated with MS?
Oral medications e.g. baclofen, diazepam, dantrolene, clonidine, tizanidine
181
What can be used to treat severe spasticity associated with MS?
Invasive procedures such as intrathecal baclofen and functional neurosurgical procedures
182
What drugs can be used to treat tremor associated with MS?
```
Beta blockers (e.g. propranolol)
Low-dose barbiturates (e.g. phenobarbitone, primidone)
Gabapentin
Isoniazid
Carbamazepine
Clonazepam
```
183
What non-pharmacological treatments can be used to treat tremor associated with MS?
Orthotic devices - wrist bands containing small weights, computer-controlled mechanical damping devices
Thalamic surgery - stereotactic thalamotomy, thalamic electrostimulation
184
What treatments are available to treat erectile dysfunction in men with MS?
- Self-administered intracorporeal injection of papverine or prostaglandin E1
- Surgically implanted penile prostheses
- Oral yohimbine taken 1-2 hours before intercourse
185
What drugs can be used to treat pathological laughing and crying associated with MS?
- Low dose amitriptyline
- Levodopa
- Bromocriptine
186
What drugs can be used to treat anxiety associated with MS?
Alprozolam
| Diazepam
187
What exacerbates fatigue associated with MS?
Heat
188
What are the clinical indicators of poor prognosis MS?
- Male gender
- Late age at onset
- Early motor, cerebellar and sphincter symptoms
- Short inter-attack interval
- High number of early attacks
- Early residual disability
189
What treatment can be used to hasten recovery from an acute exacerbation of MS?
Oral/intravenous methylprednisolone
190
What is a functional neurological disorder?
Symptoms in the body, apparently caused by nervous system dysfunction, without being caused by physical neurological disease or disorder.
191
What is a dissociative/conversion disorder?
A partial/complete loss of normal integration between memories of the past, awareness of identity, immediate sensations and control of bodily movements.
192
What is somatisation?
Repeat presentation of physical symptoms in spite of repeated negative findings/reassurances from professionals
193
What is hypochondriasis?
Persistent preoccupation with the possibility of having one (or more) serious/progressive medical disorders
194
What are the four main symptom groups in terms of functional neurological disorders?
1. Sensory (brain normally 'gates' sensations by filtering out some stimuli, this can be disturbed in functional disorders)
2. Concentration/memory/fatigue
3. Motor (positive/negative - extra movements/failure of movements)
4. Seizures
195
How do functional seizures present, in comparison to epileptic seizures?
- Gradual onset
- Prolonged duration (>90s, but can be >20 minutes)
- Fluctuating severity
- Post-ictal emotional upset, but not confusion
- Hip thrusting/back arching, side to side movement
- Memory of event may be preserved
- Closed eyes
196
What other types of disorders are associated with functional neurological disorder?
- Other functional disorders (e.g. IBS/chronic pain)
| - Other comorbid neurological conditions (e.g. MS)
197
Name 4 types of dissociative/conversion disorders
1. Dissociative amnesia
2. Dissociative fugue
3. Dissociative stupor
4. Trance/possession disorders
198
La belle indifference is sometimes associated with functional neurological disorders. What is it?
A paradoxical absence of psychological distress despite apparently serious illness/symptoms
199
How do functional neurological disorders present on examination?
Examination findings inconsistent with physiology, e.g. sensory abnormalities that are non-dermatomal and therefore don't have a neurological cause, inconsistency between voluntary movements (impaired) and automatic movements (preserved) e.g. Hoover's sign
200
What is a stroke?
A clinical syndrome caused by cerebral infarction or haemorrhage, typified by rapidly developing signs of focal and global disturbance of cerebral functions lasting more than 24 hours or leading to death
201
What is a TIA?
A transient ischaemic attack - an acute loss of cerebral or ocular function with symptoms lasting <24h caused by inadequate cerebral or ocular blood supply as a result of low blood flow, ischaemia or embolism associated with disease of the blood vessels, heart or blood.
202
85% of strokes are ischaemic. What happens in ischaemic stroke?
A blood vessel in the brain gets blocked, usually from an atherosclerotic plaque embolus.
203
15% of strokes are haemorrhagic. What causes haemorrhagic stroke?
Bleeding from a blood vessel within the brain, usually as a result of high blood pressure.
204
What focal neurological deficits can be caused by stroke?
- Facial weakness
- Limb weakness
- Sensory loss
- Speech problems
- Visual defects
- Problems with perception/balance/coordination
205
Which neurological deficits might be caused by infarct in the middle cerebral artery territory?
- Facial weakness
- Weakness/sensory loss in upper limb
- Speech problems
206
Which neurological deficits might be caused by infarct in the anterior cerebral artery territory?
- Weakness/sensory loss in lower limb
207
Which neurological deficits might be caused by infarct in the posterior cerebral artery territory?
- Visual defects
| - Problems with perception
208
Which neurological deficits might be caused by infarct in the posterior circulation?
Disorders of balance and coordination
209
What are the differential diagnoses for stroke/TIA?
- Hypoglycaemia
- Labyrinthine disorders (e.g. labyrinthitis, vestibular neuronitis, BPPV, Meniere's disease)
- Migrainous aura
210
What scoring system is used to assess the risk of stroke within the next 7 days for a patient who has suffered a TIA?
ABCD2 score
211
How is ABCD2 score calculated?
A - Age (1 point if 60+)
B - BP (1 point if 140/90 or greater)
C - Clinical features (2 points for unilateral weakness, 1 point for speech disturbance without weakness)
D - Duration (2 points for 60 minutes or longer, 1 point for 10-59 minutes)
D- Diabetes (1 point)
212
What TIA patients are considered 'high risk'?
```
ABCD2 score 4 or more
or any of the following:
- Atrial fibrillation
- More than one TIA in a week
- TIA whilst on anticoagulant
```
213
How are low risk TIA patients managed?
- To see specialist within 7 days of symptom onset
- Start statin
- Start antiplatelets (clopidogrel/aspirin)
- No driving until specialist seen
214
How are high risk TIA patients managed?
- To see specialist within 24 hours of symptom onset
- Start statin
- Start antiplatelets (clopidogrel/aspirin)
- No driving until specialist seen
215
Briefly describe what happens at the neuromuscular junction
- Motor neuron depolarisation causes an action potential to travel down the nerve fibre to the neuromuscular junction
- Depolarisation of the axon terminal causes an influx of calcium, which triggers fusion of the synaptic vesicles and release of neurotransmitter (ACh)
- ACh diffuses across the synaptic cleft and binds to AChR on the postsynaptic membrane
- Local depolarisation of sarcolemma
- Voltage gated sodium channels open
- Depolarisation of the sarcolemma travels down T-tubules and causes release of calcium from sarcoplasmic reticulum
- Release of calcium from SR triggers contraction
216
What three things does efficient neuromuscular junction transmission require?
1. Clustering of AChR
2. Release of ACh from the presynaptic vesicle
3. Removal of ACh from the neuromuscular junction
217
Myaesthenia gravis is an autoimmune condition. Patients with this condition normally produce antibodies to one of which two proteins?
1. AChR
| 2. MuSK (muscle specific kinase protein)
218
Seronegative myaesthenia gravis patients often have a low affinity antibody against what?
Clustered AChR
219
How does myaesthenia gravis typically present?
Usually present first with extraocular weakness, then develop limb and bulbar weakness (leading to dysarthria, nasal speech, swallowing difficulties, weak chewing)
220
Fatigability is a hallmark symptom of myaesthenia gravis. What is it?
Worsening weakness after prolonged and sustained muscle contraction.
221
How does myaesthenia gravis affect tendon reflex and sensation?
It doesn't. They are normal.
222
Describe two tests for myaesthenia gravis
1. Ice pack test - apply to ptotic eye for 2-5 minutes. Positive test if >2mm improvement in ptosis
2. Cogan's lid twitch - ask patient to look down, then straight ahead again. Lid will overshoot before returning to resting position.
223
What are the 5 subgroups of myaesthenia gravis?
1. Ocular myaesthenia gravis
2. Early onset AChR myaesthenia gravis <40
3. Late onset AChR myaesthenia gravis >40
4. MuSK myaesthenia gravis
5. Seronegative myaesthenia gravis
224
What feature is seen in most patients with early onset AChR myaesthenia gravis and may be present mildly in patients with ocular or seronegative myaesthenia gravis?
Thymus hyperplasia
225
What feature is seen in patients with late onset AChR myaesthenia gravis?
Thymus atrophy
226
What investigations should be carried out for myaesthenia gravis?
```
Antibody tests (AChR and MuSK)
EMG
CT chest (some patients have thymoma)
```
227
Myaesthenic crisis is a medical emergency. What are the features?
Respiratory failure (quiet breathing, reduced chest expansion, tachycardia)
Impaired swallow
Severe limb weakness
228
What is the best investigation to perform for suspected myaesthenic crisis?
FVC - if <1L or <15ml/kg, ITU admission required
229
What factors can exacerbate myaesthenia gravis?
1. Infection
2. Stress
3. Withdrawal of cholinesterase inhibitors when symptoms not fully controlled
4. Rapid introduction/increase of steroids
5. Electrolyte imbalance (hypokalaemia, hypophosphataemia)
6. Anaemia
7. Medications, e.g. some antibiotics, penicillamine, succinylcholine, quinidine, procainamide, beta blockers, CCBs, lithlium, chlorpromazine, phenytoin, cisplatin, Botox.
230
What drugs can be used to manage myaesthenia gravis?
1. ACh esterase inhibitors e.g. pyridostigmine
2. Steroids - prednisolone
3. Steroid-sparing agents - azathioprine, ciclosporin, methotrexate, mycophenolate mofetil
231
What non-pharmacological treatment options are available for myaesthenia gravis?
1. Plasma exchange
2. IV immunoglobulin
3. Consider thymectomy if onset <65 years
232
Lambert-Eaton Myaesthenic Syndrome (LEMS) is an autoimmune disorder. These patients produce antibodies to which proteins?
Voltage-gated calcium channels at the pre-synaptic membrane
233
What other disorders are associated with LEMS?
Cancer (50-60%)
Type 1 diabetes
Thyroid disease
234
What MSK symptoms are associated with LEMS?
Proximal muscle weakness, particularly in the lower limbs
| Diminished/absent reflexes
235
What autonomic features are associated with LEMS?
Dry mouth
Sphincter problems
Postural hypotension
Erectile dysfunction
236
What does EMG usually show in LEMS patients?
Reduction in compound muscle action potential with subsequent increase of more than 100% with repetitive stimulation
237
What are the red flags for LEMS?
Rapid progression
Early distal muscle involvement
Dysarthria (motor speech disorder)
Erectile dysfunction
238
What drug can be used to treat LEMS and how does it work?
3,4 diamino pyridine - blocks K channels in the nerve terminal
239
What causes congenital myaesthenic syndrome?
Mutations in the genes that encode NMJ proteins
240
What condition is caused by autoantibodies to voltage-gated potassium channels in the nerve terminal?
Neuromyotonia
241
What are the features of neuromyotonia?
Hyperexcitability leading to:
1. Cramps
2. Fasciculations
3. Hyperhidrosis
4. Myokymia (unilateral lid twitch)
5. Fatigue
6. Exercise intolerance
7. Stiffness
242
Name some differential diagnoses for epilepsy
- Postural syncope
- Cardiogenic syncope
- Migraine
- Hypoglycaemia
- Benign paroxysmal positional vertigo
- Dystonia
- TIA
- Parasomnia
- Non-epileptic seizure
- Hyperventilation
- Cataplexy
243
Transient loss of consciousness can be caused by primary or secondary disturbances of brain function. What are the primary disturbances?
Epilepsy
| Non-epileptic seizures
244
What secondary disturbances of brain function can lead to transient loss of consciousness?
Cardiac problems
| Low blood pressure
245
What is the definition of an epileptic seizure?
A paroxysmal event in which changes of behaviour, sensation or cognitive processes are caused by excessive, hypersynchronous neuronal discharges in the brain.
246
What is shown on an EEG during an epileptic seizure?
Large spikes due to summation of potentials from excessive, hypersynchronous neuronal discharges.
247
What are the main characteristics of epileptic seizures?
- Duration 30-120 seconds
- 'Positive' ictal symptoms (e.g. excess movement, feeling, hearing, seeing)
- 'Negative' postictal symptoms (e.g. lack of movement)
- Stereotypical seizures (usually the same for that person)
- May occur from sleep
- May be associated with other brain dysfunction e.g. injury, tumour, stroke, abnormal development, scarring
- Typical seizure phenomena e.g. lateral tongue bite, deja vu
248
What is the most common type of epilepsy?
Temporal lobe epilepsy
249
How does a tonic-clonic seizure present?
A tonic phase with rigid movements followed by a clonic phase with larger movements, then a postictal 'negative' phase.
250
A patient is not responding to commands, but making autonomous movements such as repetitive swallowing and lip smacking. What kind of seizure is this?
A partial temporal lobe epileptic seizure
251
A patient is conscious but seems to lose control of their limbs on one side. What kind of seizure is this?
A partial seizure involving the prefrontal cortex
252
What is the definition of syncope?
A paroxysmal event in which changes in behaviour, sensation and cognitive processes are caused by an insufficient blood or oxygen supply to the brain.
253
What are the main characteristics of syncope?
- Situational (e.g. hot, dehydrated)
- Typically from standing (though may occur from sitting)
- Rarely from sleep
- Presyncopal symptoms e.g. nausea, lightheadedness
- Duration 5-30 seconds
- Recovery within 30 seconds
- Can involve shaking
254
What are the main characteristics of non-epileptic seizures?
- Situational (usually a scenario that leads up to them)
- Duration 1-20 minutes
- Dramatic motor phenomena or prolonged atonia
- Eyes closed
- Ictal crying and speaking
- Surprisingly rapid or slow postictal recovery
- History of psychiatric illness/other somatoform disorders
- Often starts with tremor rather than tonic-clonic movements, amplitude of movements changes but not frequency
255
What is focal epilepsy?
Epilepsy associated with a focal brain abnormality, patients can have secondary generalised seizures or partial seizures with or without loss of consciousness.
256
What is the first line treatment for focal epilepsy?
Carbamazepine
| Lamotrigine (women of childbearing age)
257
What is genetic generalised epilepsy?
A type of epilepsy with no associated brain abnormality that usually manifests before the age of 30.
Seizure types include:
- Absence seizures
- Myoclonic seizures
- Primary generalised tonic-clonic seizures
258
What is the first line treatment for generalised epilepsy?
Valproate (most effective)
| Lamotrigine can be given to women of childbearing age
259
What are the three potential targets for epilepsy medication?
1. Presynaptic neuron
2. Inhibitory interneuron
3. Postsynaptic neuron
260
How do carbamazepine and lamotrigine work?
Blocking voltage-gated sodium channels in the presynaptic neuron, stopping the Na+ influx that drives action potentials.
261
How do pregabalin and gabapentin work?
Blocking voltage-gated calcium channels in the presynaptic neuron, preventing exocytosis of the neurotransmitter
262
SV2A (synaptic vesicle glycoprotein 2A) is required for release of neurotransmitter from vesicles. Which drug inhibits this protein?
Levetiracetam
263
How does retigabine work?
Increases the activity of the voltage-gated K+ channel at the presynapse, allowing more K+ to escape and decreasing neuronal excitability
264
What is the target of benzodiazepines, barbiturates, felbamate and topiramate at the presynaptic neuron?
GABA(A) receptor
265
Which drug increases GABA levels by inhibiting GABA transaminase in the inhibitory interneurons?
Vigabatrin
266
Which drug increases GABA levels by inhibiting the GABA transporter?
Tiagabine
267
Name 3 drugs that inhibit glutamate receptors at the postsynaptic neuron to reduce excitability
1. Perampanel
2. Felbamate
3. Topiramate
268
What non-pharmacological treatments can be used for epilepsy?
Resective surgery
| Vagal nerve stimulator
269
What are the three main types of clinical presentation for brain tumours?
1. Focal deficits (depending on location and anatomical specialisation)
2. Epilepsy/seizure disorder
3. Raised intracranial pressure
270
What is a glioma?
A metastatic tumour of the glial tissue
271
Why can't diffuse gliomas be cured surgically?
They infiltrate diffusely into the brain tissue, meaning that it is impossible to remove all of the tumour cells, so the tumour recurs from the infiltrating cells left behind.
272
How are primary CNS tumours classified?
WHO classification based on a mixture of histopathological and molecular features (if molecular testing available - otherwise just based on histology "NOS")
Assigned a grade 1-4 based on 'biological potential' where 1 is essentially benign and 2-4 become more aggressive.
273
How is the WHO grading scheme applied to astrocytomas?
Grade 1 - pilocytic astrocytoma - good prognosis
Grade 2 - diffuse astrocytoma - nuclear atypia (>5 years)
Grade 3 - diffuse astrocytoma - mitotic activity (2-5 years)
Grade 4 - diffuse astrocytoma - necrosis and proliferation (<1 year)
274
What are the three types of adult diffuse glioma?
1. Astrocytoma IDH mutant (grade 2-4)
2. Oligodendroglioma IDH mutant and 1p/19q deleted (grade 2-3)
3. Glioblastoma multiforme IDH wild-type (grade 4)
275
What mutation is present in most low grade diffuse gliomas and some higher grade gliomas?
Isocitrate dehydrogenase 1 (IDH1)
276
What molecular feature is considered a defining feature of oligodendrogliomas?
Codeletion of 1p19q
277
Grade 2-4 astrocytomas may have which molecular features?
Always IDH mutation
May also have ATRX and p53 mutations
NOT 1p19q codeleted
278
Glioblastoma Multiforme IDH wild-type is a diffuse astrocytic grade 4 tumour. What would be seen on histology of this tumour?
Mitoses, necrosis and vascular proliferation
279
Pilocytic astrocytoma is a grade 1 tumour predominantly seen in children. Where is it found and what defining feature is often seen on histology?
Usually found in cerebellum, but can also appear at optic nerves or hypothalamic/midline structures.
Rosenthal fibres often seen on histology.
280
What is a medulloblastoma?
A primitive tumour of the cerebellum, usually seen in childhood, high malignant potential (therefore grade 4) but may respond well to surgery and chemo.
281
Mutations in which genes may be seen in medulloblastoma?
SHH, Wnt, N-MYC, C-MYC
282
From where do meningiomas arise?
From the dura mater
283
What are the most common primary cancers that end up in the brain?
- Lung (45%)
- Breast
- Melanoma
- GI tract
- Kidney
284
Why should you never perform a lumbar puncture without doing a CT scan first if there is a suspicion of raised intracranial pressure?
Raised intracranial pressure can lead to herniation of brain tissue. Removal of CSF can exacerbate the pressure gradient and increase the chance of a fatal hernia developing.
285
What are the four types of herniation that can develop in the brain?
1. Lateral tentorial (uncal) hernia
2. Tonsillar herniation
3. Subfalcine cingulate gyrus herniation
4. Central diencephalic herniation
286
Why might a lateral tentorial hernia cause pupillary dilatation?
From compression of CNIII (oculomotor)
287
Besides CNIII, what other structures can become compressed as a result of a lateral tentorial hernia?
- Posterior cerebral artery
- Contralateral cerebral peduncle (motor fibres) --> hemiparesis ipsilateral to the lesion
- Brainstem
288
Why might a mass lesion in the brain cause localised hydrocephalus despite a decreased volume in CSF?
Due to obstruction of CSF flow
289
What is encephalopathy?
Reduced level of consciousness/diffuse disease of brain substance (usually non-infective but multiple aetiologies)
290
What two signs can indicate meningeal irritation?
1. Kernig's sign (unable to straighten leg >135 degrees without pain)
2. Brudzinki's sign (severe neck stiffness causes hips and knees to flex when neck is flexed)
291
What are the signs of papilloedema as seen on fundoscopy?
1. Venous engorgement
2. Optic disc blurring
3. Haemorrhage near optic disc
4. Loss of venous pulsation haemorrhages
292
What does bilateral papilloedema indicate?
Raised intracranial pressure
293
What are the risks of lumbar puncture?
- Headache
- Infection
- Damage to spinal cord/haematoma
- Cerebral herniation and death
294
What investigations should be performed on CSF?
- Opening pressure
- Protein and glucose
- Microscopy, culture and sensitivity
- Viral and bacterial PCR
(Take blood simultaneously to compare CSF and serum glucose levels)
295
What will the CSF results of an acute bacterial infection show?
- Raised opening pressure
- Cloudy CSF
- Neutrophils
- High protein
- Low CSF:plasma glucose ratio
296
What will the CSF results of a viral infection show?
- Raised opening pressure
- Clear CSF
- Lymphocytes
- Normal/high protein
- Normal CSF:plasma glucose ratio
297
What does bloodstained CSF indicate?
Subarachnoid haemorrhage
298
What are the features of HSV encephalitis?
Fever, headache, lethargy, behavioural change.
| May progress to focal signs, seizure, coma.
299
How is HSV encephalitis treated?
10mg/kg aciclovir IV tds
300
How does CJD present?
Neurodegenerative changes - behavioural changes, cognitive decline, eventual coma, death
301
What is progressive multifocal leukoencephalopathy?
Progressive inflammation of white matter, caused by JC (John Cunningham) virus (present in 90% of population)
302
Which patients are at risk of progressive multifocal leukoencephalopathy?
Immunocompromised, e.g. AIDS, transplant patients
303
What are the features of progressive multifocal leukoencephalopathy?
Motorsensory changes, personality changes, speech and visual disturbances
304
How is progressive multifocal leukoencephalopathy treated?
Assisting reversal of immune system, e.g. stop natazilumab, start HAART for HIV
305
What is the most common cause of dementia?
Alzheimer's disease
306
What are the three main histopathological features of Alzheimer's disease?
Amyloid-beta plaques
Neurofibrillary tangles with Tau protein
Lewy bodies
307
Why do amyloid-beta plaques form?
Amyloid-beta peptide misfolds and becomes sticky.
308
How does Tau cause neurofibrillary tangles?
Tau normally stabilises microtubules, but a misfolded version results in tangle formation.
309
Individuals with trisomy 21 are more likely to develop Alzheimer's. Why is it thought that this happens?
APP (amyloid precursor protein) gene is on chromosome 21 - it is thought that this could result in these individuals producing more amyloid-beta and somehow developing Alzheimer's more readily as a result.
310
What other pathological features are found in the brain of a person with Alzheimer's disease besides plaques and tangles?
- Damaged mitochondria
| - Inflammation of the brain more likely
311
Name some of the presenting features of Alzheimer's disease
- Memory loss
- Poor judgement (--> bad decision)
- Loss of spontaneity and sense of initiative
- Taking longer to complete normal tasks
- Repeating questions
- Trouble handling money and paying bills
- Wandering and getting lost
- Losing things/misplacing them in odd places
- Mood/personality changes
- Increasing anxiety and/or aggression
- Problems recognising family and friends
- Hallucinations, delusions, paranoia
- Impulsive behaviour e.g. undressing at inappropriate times/places, vulgar language
312
Name some of the severe clinical features of Alzheimer's disease
- Inability to communicate
- Weight loss
- Seizures
- Skin infections
- Difficulty swallowing
- Groaning, moaning or grunting
- Increased sleeping
- Loss of bowel and bladder control
313
How long after diagnosis do Alzheimer's patient normally die?
8-10 years
314
What sorts of things are tested when assessing a patient with suspected Alzheimer's?
1. Semantic history, e.g. "Name as many animals as you can"
2. Immediate and delayed recall
3. Phonemic fluency e.g. "How many words beginning with C can you think of?"
315
What kind of neuroimaging is used to diagnose Alzheimer's (although not definitively)?
Usually structural MRI
| Sometimes might use CT head
316
What features might be seen on neuroimaging in Alzheimer's disease?
Atrophy, particularly of the hippocampus
317
What drugs are given to treat mild to moderate Alzheimer's?
Cholinesterase inhibitors, e.g.
donepezil
rivastigmine
galantamine
318
What drug is sometimes given to treat moderate to severe Alzheimer's?
Memantine - NMDA (glutamate) receptor antagonist
319
Name some risk factors for Alzheimer's disease
- Genetics
- Head injury
- Obesity
- Smoking
- Physical inactivity
- Poor cognitive reserve
- Hypertension
- Stroke
- Diabetes
- Hypercholesterolaemia
320
Bipolar patients seem to have a lower incidence of Alzheimer's. Why?
Lithium appears to affect the accumulation of Tau.
321
Where do upper motor neurons go?
From the motor cortex to the medulla
322
Where do lower motor neurons go?
From the motor cortex to the spinal cord
323
Which motor neurons supply the oropharyngeal muscles?
Bulbar (upper) motor neurons
324
Which motor neurons supply the limb muscles?
Somatic (lower) motor neurons
325
Where in the spinal cord does the lower motor neuron (and the afferent sensory fibre) synapse?
In the anterior horn
326
What is primary lateral sclerosis?
Degeneration of upper motor neurons only
327
What is primary muscular atrophy?
Wasting of the muscles caused by degeneration of lower motor neurons only.
328
Amyotrophic lateral sclerosis makes up 90% of motor neuron disease cases. What is it?
A mixture of both upper and lower motor neuron degeneration.
329
How are the three different presentations of motor neuron disease?
1. Limb onset (75%)
2. Bulbar onset (affecting speech and swallow) (25%)
3. Respiratory onset (<1%)
330
What are the upper motor neuron symptoms that occur in the limb?
```
Pyramidal weakness (preferentially spares antigravity muscles - ones that help maintain upright posture)
Spasticity (abnormal muscle tightness due to prolonged contraction)
```
331
What are the lower motor neuron symptoms that occur in the limb?
Wasting
Weakness
Fasciculations
332
What are the red flags for motor neuron disease?
1. Relentless progressive disability
2. Presence of both upper and lower motor neuron pathology (e.g. wasting and stiffness)
3. Weakness in the absence of sensory symptoms (MND only affects motor pathways)
333
What are the bulbar features of motor neuron disease?
Dysarthria (slurred/quiet speech, particularly when tired)
Dysphagia
Excessive saliva
Choking sensation especially when lying flat
Tongue fasciculations
334
What are the limb features of motor neuron disease?
```
Focal weakness
Falls/trips (due to foot drop)
Loss of dexterity
Muscle wasting
Muscle twitching/fasciculations
Cramps
No sensory features
```
335
What are the respiratory features of motor neuron disease?
```
Hard to explain respiratory symptoms
Shortness of breath on exertion
Excessive daytime sleepiness
Fatigue
Early morning headache
Orthopnoea (SOB when lying down)
```
336
What are the cognitive features associated with motor neuron disease?
```
Behavioural change
Emotional liability (not related to dementia)
Fronto-temporal dementia
```
337
What factors are NOT supportive of motor neuron diagnosis?
- Bladder/bowel involvement (Olaf's nucleus unaffected)
- Prominent sensory symptoms
- Double vision/ptosis (oculomotor system unaffected)
- Improving symptoms
338
Give some examples of things that contribute to the development of motor neuron disease.
Smoking
Somatic mutation
Genetic predisposition
Chemical exposure
339
What three types of genes are implicated in motor neuron disease?
1. Genes involved in protein homeostasis
2. Genes involved in altered RNA-binding proteins
3. Genes involves in cytoskeletal proteins
340
Which drug is used in motor neuron disease and can prolong a patient's life for about 3 months?
Riluzole (inhibits glutamate release)
341
What non-pharmacological treatment is often used to improve quality of life and prolong survival in patients with motor neuron disease?
Non-invasive ventilation
342
What is spinomuscular atrophy?
A genetic condition found in children - mutation in SMM1 gene results in breathing difficulties and difficulties using arms and walking etc.
343
What treatments are available for spinomuscular atrophy?
1. Gene therapy using a viral vector to insert functioning SMM1 (very expensive, only useful for young children who aren't immune to the viral vector yet)
2. Antisense oligonucleotides
344
Brainstem death occurs when the reticular activating system is affected. What are the criteria for brainstem death that must be met for organ donation to proceed?
1. Pupils fixed and dilated
2. Corneal reflex absent
3. Caloric vestibular reflex absent
4. Cough reflex absent
5. Gag reflex absent
6. No response to pain
7. No independent respiratory activity
345
What are the 4 types of sensory fibres?
```
Large diameter:
1. A-alpha (proprioception)
2. A-beta (light touch, pressure, vibration)
Small diameter:
3. A-delta (cold) - myelinated
4. C-fibres (heat) - unmyelinated
```
346
Name three common mononeuropathies
1. Carpal tunnel syndrome
2. Ulnar neuropathy
3. Peroneal neuropathy
347
What neuropathological features occur if the A-alpha fibres are affected?
Loss of proprioception, e.g. balance problems
348
What neuropathological features occur if the A-beta fibres are affected?
Loss of light touch, vibration, pressure sensations
349
Which sensory fibres are most at risk of damage?
C-fibres due to lack of protective myelination
350
What is usually the first symptom of small fibre damage?
Burning pain sensation
351
What feature is characteristic of sensory ataxia?
Worsening of ataxia when eyes closed/in the dark
352
What are the three main types of clinical presentation in peripheral neuropathy?
1. Symmetrical sensorimotor (distal limbs affected on both sides)
2. Asymmetrical sensory (proximal, unilateral)
3. Asymmetrical sensorimotor (distal limbs, asymmetrical distribution)
353
Symmetrical sensorimotor neuropathy is the most common type of peripheral neuropathy. How does it normally present?
- Longer fibres affected first --> symptoms start distally, especially in toes
- Initially sensory, so tingling, numbness and pain occur first
- Motor symptoms appear later
354
Asymmetrical sensory neuropathy involves patchy distribution of sensory symptoms as the dorsal root ganglia are affected. Which two diseases are associated with it?
Sjogren's disease
| Coeliac disease
355
How can nerve conduction studies differentiate between demyelinating and axonal conditions?
Demyelination results in slow conduction velocities
| Axonal problems result in reduced amplitudes of potentials
356
What disease is present in 50% of patients with axonal neuropathy?
Diabetes
357
Aside from nerve conduction studies, what other neurophysiological test can be used in diagnosing peripheral neuropathies?
Quantitative sensory testing
358
What is chronic idiopathic axonal polyneuropathy?
- Chronic (develops over at least 6 months)
- Idiopathic (no identifiable aetiology)
- Axonal (Axons affected, usually length-dependent)
359
What is the umbrella term used for all hereditary chronic neuropathies?
Charcot Marie Tooth disease
360
What is Guillain-Barre syndrome?
An acute polyneuropathy, usually demyelinating (although there are also axonal motor and axonal sensorimotor versions)
361
What are the clinical features of Guillain-Barre syndrome?
- Rapid ascending paralysis and sensory deficits (hours to days)
- Often preceding infection
362
How should Guillain-Barre syndrome be treated?
- Immediate intravenous immunoglobulin infusion or plasma exchange
- Monitor respiratory function
- ITU admission
- Refractory GBS may require further IVIG doses
363
What is the definition of a stroke?
A sudden onset of focal neurological signs, of presumed vascular origin, lasting longer than 24 hours
364
What is the definition of a transient ischaemic attack?
A sudden onset of focal neurological signs, of presumed vascular origin, lasting less than 24 hours
365
What is the difference between a haemorrhagic stroke and an ischaemic stroke?
A haemorrhagic stroke involves bleeding in to the brain
| An ischaemic stroke involves an interruption to the blood supply
366
How do ischaemic and haemorrhagic strokes show up on CT scans?
An ischaemic stroke will show up as a dark area
| A haemorrhagic stroke will show up as a bright white area
367
What are the symptoms of stroke/TIA in the carotid territory?
- Face/arm/leg weakness
- Dysphasia
- Amaurosis fugax
368
What are the symptoms of stroke/TIA in the posterior circulation?
- Dysarthria
- Dysphagia
- Diplopia
- Dizziness
- Ataxia
- Diplegia
369
What is a lacunar infarction?
Occlusion of the deep penetrating arteries, which affects a small volume of subcortical white matter.
370
What are the lacunar syndromes?
- Pure motor hemiparesis
- Ataxic hemiparesis
- 'Clumsy hand' and dysarthria
- Pure hemisensory
- Mixed sensorimotor
371
When a patient presents with a stroke, a CT scan is done immediately. Why is a follow-up MRI also performed?
- CT cannot usually diagnose an infarct in the acute phase
- MRI more sensitive for picking up abnormalities such as demyelination, mass lesions, microhaemorrhages and lacunar/posterior circulation infarcts.
- Comparison of ADC (apparent diffusion coefficient) and DWI
372
What should normally be administered to a stroke/TIA patient immediately to break down an acute clot?
IV tissue plasminogen activator e.g. alteplase 0.9mg/kg
373
Who should not be given alteplase?
- Patients with hypertension due to increased risk of haemorrhage
- Recent major surgery (within past 3 monhts)
- Brain malignancy
374
What is another acute management option for stroke/TIA besides thrombolysis?
Mechanical thrombectomy
375
What medication should a stroke/TIA patient take in the long term?
```
Antiplatelet:
Aspirin 300mg for 2 weeks
Clopidogrel lifelong
Hypertension medication (standard management)
Statin
Anticoagulant if evidence of AF
```
376
How should high risk TIAs be managed?
- Antiplatelet therapy - 300mg aspirin for 2 weeks, switch to clopidogrel
- MRI
- Carotid dopplers to check for stenosis of internal carotid
- 24/72 hour ECG to check for episodes of AF
377
Which patients with carotid stenosis should be referred to the vascular team?
Those with >50% stenosis
378
How is severe stenosis of the carotid artery treated?
Two options:
1. Carotid endarterectomy (pull the clot out - need to get the whole clot otherwise bits can break off and cause a stroke)
2. Carotid stenting
379
What is the main cause of brain haemorrhage?
Hypertension
380
What are the other causes of brain haemorrhage besides hypertension?
- Trauma
- Anti-coagulation
- Tumour
- AVM
381
What are the five steps for managing a haemorrhagic stroke?
1. ABCDE - monitoring with regular neuro-observations
2. Blood pressure management
3. Bleeding tendency? E.g. coagulopathy/low platelets/medication
4. Check for underlying malformation (further imaging) e.g. tumour,
aneurysm, AVM)
5. Neurosurgical intervention
382
What can happen following a seizure that is sometimes misdiagnosed as a stroke?
Todd's paresis (post ictal weakness)
383
What are the two broad categories of head injury?
- Blunt/non-missile
| - Penetrating/missile
384
What focal injuries can be caused as a result of blunt trauma to the head?
1. Scalp: contusions, lacerations
2. Skull: fractures
3. Meninges: haemorrhage, infection
4. Brain: contusions, lacerations, haemorrhage, infection
385
What is a contusion?
A bruise
386
What injuries can be caused as a result of diffuse brain lesions?
1. Diffuse axonal injury
2. Diffuse vascular injury
3. Hypoxic ischaemic change
4. Swelling
387
What sort of fractures are caused by flat surfaces?
Linear fractures
388
Extradural haematoma is usually associated with what?
A skull fracture
389
Extradural haematomas are found in 15% of fatal head injuries. How can they cause death?
- Brain displacement
- Raised ICP
- Herniation
390
What is the usual cause of subdural haematoma?
Tears in bridging veins (the ones that go from the surface of the brain to the inner surface of the dura mater)
391
What can a chronic subdural haematoma be mistaken for in elderly patients?
Dementia - can cause progressive cognitive decline
392
What is the usual cause of subarachnoid haematoma?
Burst aneurysm
393
How do superficial and deep cerebral and cerebellar haemorrhages appear on imaging?
Superficial haemorrhages are more likely due to severe contusion and appear as one large bleed.
Deep haemorrhages are related to diffuse axonal injury and present as many small bleeds.
394
What is the major cause of CNS infection?
Skull fracture
395
What is a 'contrecoup' lesion?
A lesion that appears away from the site of impact, usually the inferior surface of the frontal lobe
396
Contrecoup lesions are more common in which type of head injuries?
People who have been hit on the back of the head
397
What three things cause brain swelling in trauma patients?
1. Congestive brain swelling due to vasodilation and increased cerebral blood volume
2. Vasogenic oedema caused by extravasation of oedema fluid from damaged blood vessels
3. Cytotoxic oedema due to increased water content of neurons and glia
398
Which areas of the brain are particularly vulnerable to hypoxia-ischaemia following head trauma?
Hippocampus
| Purkinje cells of cerebellum
399
Chronic traumatic encephalopathy is a long term condition that can result from head injury. What are the features?
- Personality change e.g. irritability, impulsivity, aggression
- Memory loss --> dementia
- Gait problems
- Speech problems
- Parkinsonism
400
Chronic traumatic encephalopathy is associated with pathology in which protein in 85% of cases?
TDP-43
401
What would you expect to see on imaging for chronic traumatic encephalopathy?
- Atrophy of neocortex, hippocampus, diencephalon and mamillary bodies
- Neurofibrillary and astrocytic tangles
- Thin corpus callosum
- Wide lateral ventricles
- Tau deposits, particularly around blood vessels
402
Name 2 'hardware problem' neurodegenerative movement disorders
1. Parkinson's disease
| 2. Huntington's disease
403
Name 3 movement disorders due to 'circuit problem' with no cell loss or structural changes
1. Essential tremor
2. Dystonia
3. Tourette
404
What are the three cardinal features of Parkinson's?
1. Bradykinesia/akinesia
2. Tremor (at rest)
3. Rigidity
405
What sort of problems can bradykinesia associated with Parkinson's cause?
- Problems with doing up buttons, using a keyboard
- Writing smaller
- Deterioration in walking e.g. small steps, dragging one foot
- Decreasing amplitude/accuracy of repetitive movements e.g. foot tapping
406
Describe the tremor associated with Parkinson's disease
- Present at rest
- May be unilateral
- Often asymmetrical
407
What symptoms are associated with rigidity due to Parkinson's disease?
- Pain (not well localised, usually a dull ache)
| - Difficulty turning in bed
408
What pathological features are present in a brain affected with Parkinson's?
- Loss of substantia nigra in the mesencephalon
| - Presence of Lewy bodies (microscopic)
409
What three types of drugs are available for treatment of Parkinson's disease?
1. MAO-B inhibitors
2. Dopamine agonists
3. L-Dopa
410
Which of the Parkinson's drugs is the most powerful?
L-Dopa
411
What motor complications can occur in late stage Parkinson's?
- Medication doesn't work as well as previously
- Hyperkinetic, choreiform movements when drugs work
- Fixed, painful dystonic posturing when drugs don't work
- Unpredictable loss of mobility (freezing)
412
MAO-B inhibitors are the least powerful of the Parkinson's drugs, but they help some patients. Name two.
1. Rasagiline
| 2. Selegiline
413
Dopamine agonists reduce the risk of dyskinesias in the short-medium term in Parkinson's. Name two.
Ropinirole
Pramipexole
Rotigotine (patches)
414
Which Parkinson's patients should be started on dopamine agonists as a first line treatment?
Patients under 60
415
Which Parkinson's patients should be started on L-Dopa as a first line treatment?
Patients over 60
416
What non-motor problems are associated with Parkinson's disease due to disturbances in the dopamine system?
- Depression and other psychiatric problems
- Dementia
- Autonomic problems e.g. constipation, urinary frequency
417
What is essential tremor?
Tremor usually on action, not at rest with gradual worsening and no increased tone
418
What drugs can be used in the treatment of essential tremor?
1. Beta blockers (but not in asthma/diabetes)
2. Primidone (barbiturate)
3. Gabapentin (anticonvulsant)
