Neurology Flashcards
1
Q
Define transient Ischaemic attack (TIA)
A
Transient / temporary neurological dysfunction secondary to ischaemia without infarction; within 24hrs
2
Q
Blood supply entering the brain with which arteries……
A
Internal carotid artery (ICA) - 90%
Vertebral (posterior) - 10%
3
Q
Main cause of TIA
A
Carotid thrombo-emboli
Increased emboli risk when Px has Afib - Remember CHA2DS2 VASc score is used as stroke risk in Afib Px.
4
Q
Risk factors for transient Ischaemic attack
A
HTN
Hypercholestraemia
T2DM
Afib
Obesity
IHD
Smoking
Ventricular septal defect
5
Q
Sx of TIA
A
Slurred speech
Facial weakness
Limb weakness
Amaurosis fugax - temporary painless vision loss; usually one eye.
6
Q
What signs are seen in TIA
A
Focal neurology: depending on which vessel is affected, have different signs
Anterior cerebral.A - Contralateral leg weakness
Middle cerebral.A - Contralateral body weakness + facial drooping forehead sparing + dysphasia
Posterior cerebral.A - Vision loss; contralateral hamonymous hemianopia
Vertebral.A - Cerebellar syndrome - D.A.N.I.S.H; +ve Ramberg test (sensory and motor ataxia)
Opthalmic/Retinal/Ciliary.A
Irregular pulse - if AFib is cause
Carotid bruit - suggests carotid artery stenosis
7
Q
How do you initially differentiate between TIA and Stroke
A
Can’t tell until after recovery:
TIA —> Sx resolve <24hrs with no infarct
Stroke —> Sx last ≥24hrs with infarction
8
Q
What investigation and Dx are needed for TIA
A
Clinical Dx; usually obvious if TIA/stroke is suspected
2 scoring systems that can be used:
FAST —> Face Arms Speech Time (public health campaign)
ABCD2 —> Age >60; BP >140/90; Clinical Sx unilateral weakness (2pt) / slurred speech (1pt); Duration Sx >1hr (2pt) / <1hr (1pt); DMT2 (1pt)
- refer to neurology ASAP (sig. increased risk of stroke)
9
Q
Treatment for TIA
A
Acutely —> Aspirin
Prophylaxis long term/2º prevention —> Clopidogrel (75mg) and Atorvastatin (80mg)
10
Q
Define stroke
A
AKA a Cerebrovascular accident.
Focal neurological defect lasting >24hrs with infarct
11
Q
What types of stroke are there
A
Ischaemic (85%)
Essentially prolonged TIA
Lacunar Ischaemic stroke
Haemorrhagic (15%)
Ruptured blood vessel
Intracerebral
Subarachnoid
Extradural/epidural not considered haemorrhagic strokes
12
Q
Causes of each type of stroke
A
Ischaemic stroke
Cardiac
Atherosclerosis; Carotid thrombo-emboli: thrombosis ± AFib embolisation, AFib, smoking, HTN, hyperlipidaemia
Vascular
Aortic dissection
haematological
Hypercoagubility; Antiphospholipid syndrome
Polycythaemia, sickle cell disease
Haemorrhagic stroke
Intracerebral
HTN, trauma
Subarachnoid
Berry aneurysm rupture, trauma
Intraventricular
* - bleeding within the ventricles; prematurity is a very strong risk factor in infants*
13
Q
Risk factors for stroke
A
TIA
HTN
Smoking
Obesity
T2DM
AFib
Hypercoagulability; polycythaemia, sickle cell
14
Q
Sx of a stroke
A
Focal neurology like TIA
+ For haemorrhagic stroke
Increased ICP —> Midline shifts; risk of tentorial herniation (the movement of brain tissue from one intracranial compartment to another.)
+ For lacunar strokes
V. Common type of Ischaemic stroke of lenticulostriate arteries (branches of MCA;supplying deep structures) —> ischaemia to basal ganglia, internal capsule, thalamus & pons
If a Px is on oral anticoagulants - suspect haemorrhagic stroke.
15
Q
What are the focal neurology signs *esp witnessed in a stroke/TIA *
A
Focal neurology = neurological defect; depending on which vessel is affected, presents with different signs
Anterior cerebral.A - Contralateral leg weakness
Middle cerebral.A - Contralateral body weakness + facial drooping forehead sparing + dysphasia
Posterior cerebral.A - Vision loss; contralateral hamonymous hemianopia
Vertebral.A - Cerebellar syndrome - D.A.N.I.S.H; +ve Ramberg test (sensory and motor ataxia)
Opthalmic/Retinal/Ciliary.A - Amaurosis fugax
16
Q
Name a specific sign in stroke
A
Pronator drift
Ask a Px to lift arms to ceiling; pronators takeover so the arm of the affected side will pronate and the palm of hand faces down.
17
Q
Investigation and Dx of stroke
A
G.Standard: Non-contrast CT head
Ischaemic stroke - usually normal
Haemorrhagic stroke - hyperdense blood
Could do MRI as alternative.
1st line: FBC, serum glucose, electrolytes, cardiac enzymes, PTT
± CT angiogram
18
Q
Tx for stroke
A
Ischaemic
When presented within 4.5hrs —> use CLOT BUSTER / fibrinolytic agent (Alteplase)
+ Aspirin
Haemorrhagic
Neurosurgery referral
IV Mannitol (for increased ICP)
2º prevention / prophylaxis for both: atorvastatin + Clopidogrel; could give Ramipril for haemorrhagic stroke.
19
Q
What does the DVLA say about strokes / TIAs
A
For cars/motorcycle:
Must not drive for 1month after TIA/strokes
For heavy vehicles:
Must not drive for 1 year
20
Q
What classification is used to categorise a stroke according to area affected
A
Bamford classification
21
Q
What does D.A.N.I.S.H acronym stand for and when is it used
A
Dysdiadochokinesis
Ataxia
Nystagmus
Intention tremor
Scanning dysarthria
Heel-shin test positivity
Used for cerebellar syndrome
22
Q
A 38-year-old female presents by ambulance with a severe occipital headache, which started suddenly 1 hour ago. She collapsed due to the pain. She has a history of hypertension.
What is the most likely Dx
A
Subarachnoid haemorrhage
23
Q
Describe the Pathophysiology of subarachnoid haemorrhages
A
Type of intracranial haemorrhage characterised by blood within the subarachnoid space where the cerebrospinal fluid is located (inbetween pia mater and arachnoid mater)
24
Q
What are the causes of a subarachnoid haemorrhage
A
Trauma
Atraumatic (i.e. spontaneous)
Ruptured berry (/ saccular) aneurysm
25
Describe what a berry aneurysm is and what it can cause
*Known as berry aneurysm as it looks like a berry off a vine.*
Arise at points of arterial bifurcation within the Circle of Willis; **most commonly** junction between the **anterior communicating** and **anterior cerebral arteries**
26
Risk factor for subarachnoid haemorrhages
Traumas
**Htn
Polycystic kidney disease**
FHx
Increased age
Marfan’s/EDS
27
Signs and Sx of subarachnoid haemorrhages
**_Occipital thunderclap headache_**
Sudden onset
“The worst headache of my life”: 0–>10 severity instantly
_Meningism_ (*photophobia + neck stiffness*)
*Kernig sign* - **when hip and knee are flexed, hard to extend knee again**
*Brudzinski sign* - **automatic knee flexion when neck is flexed** - *Severe neck stiffness causes a patient's hips and knees to flex when the neck is flexed*
_Reduced GCS_
_Nerve palsies (**CN3-6**)_
Cn3 - fixated eye pupils
Cn6 - non-specific sign of increased ICP
28
What type of headache might be experienced preceding a berry aneurysm rupture
Sentinel headache
*precedes the rupture by weeks ≈50% of cases* - throbbing occipital pain
29
What is the differential Dx of subarachnoid haemorrhage
Meningitis (*no thunderclap headache but w/ signs of infection*)
Migraine (*no meningism / thunderclap*)
30
What is GCS referring to…
_Out of /15_
Eyes /4
Verbal /5
Motor /6
15: normal
≤ 8: comatose
≤ 3: unresponsive
31
Investigations and Dx of subarachnoid haemorrhages
_**Diagnostic** - non-contrast CT Head_
- ‘STAR shape’ on superior view
If positive: **CT Angiogram** - to see extent of rupture
If negative: **Lumbar puncture** - *wait ~12hrs; results are most sensitive >12hrs*
- Will see Xanthocheomia (yellowish CSF due to RBC haemolysis)
32
Treatment for subarachnoid haemorrhages
1st line:
Neurosurgery referral; endovascular coiling
+ **Nimodipine** (* CCB; decreased vasospasms + decreased BP*)
33
Define subdural haemorrhage
When blood accumulates between the dura mater and arachnoid mater (subdural space)
There’s bridging veins in that area; blood from the brain —> dural venous sinuses
Rupturing these veins (“in surgery is known as a very bad thing ;) *loveland jk* !”) and usually due to shearing injury (*met with pressure and separation of the 2 layers*)
34
Risk factors for subdural haemorrhages
Trauma
Child abuse - **shaken baby syndrome**
Increased age (*Cortical atrophy e.g. dementia*)
35
Signs and Sx of subdural haemorrhages
_Acute_ *sx incited within 3 days of an incident*
Reduced conciousness
Headaches & vomiting
Signs of increased ICP - **CUSHING TRIAD** + papilloedema
* - Widened pulse pressure, bradycardia, reduced respiration*
_chronic_
Start seeing focal neurological deficit (*CN3 palsy*)
36
Investigation and Dx of subdural haemorrhage
**Non contrast CT head:**
*Banana / crescent shaped haematoma; not confined to suture lines, midline shift*
- If acute = hyperdense (bright)
- if subacute = Isodense
- if chronic (late) = hypodense (darker than the brain image)
37
Tx for subdural haemorrhage
Surgery; Burr hole + craniotomy
To reduce ICP: IV mannitol
38
Complication of subdural haemorrhage
Brain stem herniation
+
Respiratory arrest
39
Define extradural haemorrhage
Haematoma found within the potential space and dura mater.
40
What is the most common cause of an extradural haemorrhage
Trauma
**Mainly leads to arterial bleeding - _middle meningeal artery_**
Due to damage of the pterion (thinnest part of the skull) / temporal region
41
Risk factors for extradural haemorrhages
Seen in 20-30y/o
*As age increases, risk decreases… as the dura is more firmly adhered to the skull*
Head trauma
42
Signs and Sx of extradural haemorrhages
_Acutely_
Initial loss of consciousness —> lucid intervals *of feeling okay* —> rapid deterioration because of ICP
Reduced GCS
Increased ICP signs; Cushing triad (*bradycardia, widened pulse pressure, irregular breathing*) + papilloedema
43
What causes the rapid deterioration in extradural haemorrhages…
**Increased ICP**
Blood clots become haemolysed and take up water (i.e. they’re osmotically active) so they **increase in volume**, increasing the pressure.
44
Complication of extradural haemorrhages
Death for respiratory arrest
*- herniation + coning of the brain = compressed respiratory centres
- due to untreated ICP*
45
Investigation and Dx of extradural haemorrhage
**Non-Contrast CT head**
*Lens shaped hyperdense bleed.
Confined to suture lines
Midline shift*
46
Tx for extradural haemorrhages
Urgent surgery
IV mannitol *to decrease ICP*
47
What types of headaches are there….
_1º headaches_
Migraines
Cluster
Tension
Trigeminal neuralgia
Drug overdose
_2º headaches_ *cause is more specific; coz of an underlying condition*
Giant cell artiritis
Infection
Head injury — subarachnoid haemorrhage
Carbon monoxide poisoning
48
Give an example of primary headaches
Tension
Cluster
Migraines
Trigeminal neuralgia
Drug-induced
49
Give an example of secondary headaches
Giant cell arteritis
Meningitis
Subarachnoid haemorrhages
Carbon monoxide poisoning
50
Give 6 questions you’d ask that are important when taking a history for a headache
**Time**; Onset / Duration / Frequency / Pattern
**Triggers**; any factors aggravating / alleviating the headaches
**Type of pain**; Severity / Site / Does pain spread? / Is it impacting QoL?
**Associated Sx**; Photophobia, Phonophobia, V&N
**Response**; to medication
**Sx in between attacks**
51
Give red flags for more serious conditions (raised ICP/intracranial haemorrhage) when presenting with a headache
Rapid/new onset headache
Fever + neck stiffness
Seizures
Papilloedema
Significantly altered consciousness / confusion
52
Describe the pain of a migraine
**Unilateral
Throbbing
Moderate—>Severe
Worsened on exercise**
±
Photophobia / phonophobia
N &/ V
53
Types of migraine
**Episodic** with Aura *(20%)* / without Aura *(80%)*
**Chronic**
May also have:
**Silent migraines**
*migraines with aura but without headache*
**Hemiplegic migraines**
*Migraine mimicking a stroke; typical Sx of migraine + hemiplagia (unilateral weakness of limbs)*
54
What do Px with migraine + aura complain of …
Visual disturbance / phenomena; ZIGZAG lines
*Sparks in vision
Blurring vision
Lines across vision
Loss of different visual fields*
55
What triggers are there for migraine
**_CHOCOLATE_**
**C . H**ocolate
**O**ral contraceptives
**C**heese
Alcoh**O . L**
**A**nxiety
**T**ravel
**E**xercise
56
How long does migraine last
**Prodrome** (stage before the headache); *mood ∆*
± Aura (part of the attack, minutes before the headache)
Throbbing headache
**4 - 72hrs**
57
With a women complaining of migraines and is on oral contraceptive… what would you do as her dr
Stop O.C.
Offer alternatives; as it acts as a trigger, increases stroke risk, decreases Triptan efficacy
58
Investigation and Dx of migraine
Dx: clinical; unless a different pathway is suggested
The clinical Sx (*Should meet this requirement*):
_≥2 of…_
Unilateral pain
Throbbing
Moderate —> severe
Motion-sickness
+
_≥1 of…_
N &/ V
Photophobia / Phonophobia
*with normal neuro exam*
59
Tx for migraines
_Acute_
Oral Triptan (**Sumotriptan**)
Or
**Aspirin** 900mg
_Prophylaxis_
**Beta-blocker** (propanolol); if asthmatic give Topiromate (anti-convulsant)
**Amitryptiline** (**T**ri**C**yclic **A**ntidepressant)
_Avoid Opiates_
_Consider Anti-emetics_; Metoclopramide (if N &/V)
60
What drug class is Triptan
5-HT receptor agonist (serotonin receptor agonists)
61
MoA of Triptans and what condition can they be used in
Smooth muscle in arteries to cause **vasoconstriction**
Peripheral pain receptors to **inhibit activation of pain receptors**
**Reduce neuronal activity** in the central nervous system
- Headaches; migraines / cluster headaches
62
What are the pharmacological and non-pharmacological prophylaxis for migraines
_Pharmacological_
Propanolol (B. Blocker) / topiromate (anti-convulsant)
Amitryptiline
_Non-Pharmacological_
Acupuncture
Vit B supplement (riboflavin)
63
Wheat is the most common type of 1º headache
Tension headaches
64
Describe the pain of a tension headache
**Bilateral
Generalised pain; _pressing/tight_
Mild —> moderate
Not exercise induced**
*Pain in Frontalis, temporalis and occipitalis muscles*
*Rubber band, tight around head*
65
What is the duration of a tension headache
30 mins —> 7days
66
Excluding the generalised pain in tension headaches, are there any other sx
No
No motion sickness
No aura
No photophobia / phonophobia
67
Tx for tension headache
Analgesia:
Aspirin or paracetamol
*Avoid opiates - dependence*
68
Describe the pain of a cluster headache
**Unilateral
Pain around an eye / temporal area
Severe —> very severe
Headache is accompanied by _cranial autonomic features_**
*Classified as Trigeminal Autonomic Cephalgia (TAC) - thought to happen because of hypersensitivity of trigeminal autonomic reflex arc (vascular dilation + nerve stimulation) & increased histamine release from mast cells — adding to the Sx*
69
How long do cluster headaches last
15 min —> 3hrs
70
What is the most disabling 1º headache
Cluster headaches
71
Risk factors of cluster headaches
Male
Smoking
Genetics
72
Signs and Sx of cluster headaches
Crescendo unilateral peri-orbital excruciating pain - AKA **suicide headaches**
**With ipsilateral autonomic features**
*Ptosis (droopy eye);
miosis (constricted unilateral pupil);
lacrimation (watery blood shot eyes);
rhinorrhoea (runny nose)*
73
Investigation and Dx of cluster headaches
Clinical Dx; ≥ 5 similar attacks confirms Dx
*But remember these headaches come in clusters and so they may experience Sx for like a week — month but then not experience them for years before the next cluster.*
74
Tx of cluster headache
_Acute_
Triptans; Sumatriptan
High flow O2 (can be given at home)
_Prophylaxis_
Verapamil (CCB)
75
Describe the pain of Trigeminal neuralgia
**Unilateral electric shock** pain
Across the face (V1, 2, 3) - *mainly V3 is affected*
Very severe
76
What are the branches of trigeminal nerve
**Cranial nerve 5**
V1 —> Opthalmic
V2 —> Maxillary
V3 —> Mandibular
77
What is the duration of pain for trigeminal neuralgia
A few seconds
(Secs —> 2mins)
78
Name some triggers of trigeminal neuralgia
Eating *(spicy foods / citrus fruit)*
Cold weather
Brushing teeth
Talking
79
Name 3 risk factors for trigeminal neuralgia
**Multiple sclerosis**
Increased age
Female
80
Investigations and Dx of trigeminal neuralgia
Clinical; ≥ 3 attacks of the Sx
81
Tx for trigeminal neuralgia
Carbamazepine (anti-convulsant)
*Surgery if all else fails*
82
Define giant cell arteritis
Systemic vasculitis affecting large arteries; esp. temporal arteries
83
Key complication of giant cell arteritis
Vision loss (amaurosis fugax )
*HIgh dose **steroid** used to prevent development/progression of the vision loss*
84
Which condition does giant cell arteritis have a strong link with
Polymyalgia rheumatica
85
What are the sx of giant cell arteritis
Severe Unilateral scalp tenderness and headache around temple and forehead
Jaw claudication
Blurred / double vision (*curtains over field of view*)
86
Investigation and Dx of giant cell arteritis
**_Temporal artery biopsy_** (*do a big sample to capture as many skip lesions*):
*Granulomatous non-caseating inflammation of intima+media; with skip lesions — multinucleated giant cells*
**Raised ESR / CRP**
**Normacytic normochromic anaemia**
87
Tx of giant cell arteritis
Corticosteroids (prednisolone)
Any signs of amaurosis fugax —> high dose methylprednisolone STAT
88
Define epilepsy
_Neurological disorder_ characterised by **recurrent seizures**.
Seizure = paroxysmal alteration of neurological function leading to **hypersynchronous discharge of neurons** within the brain
(*I.E. sudden uncontrollable burst of electrical activity*)
89
What types of seizures are there?
**_Generalised seizures:_**
Motor seizures;
**_Tonic-clonic seizures_**; *Typical epileptic seizure*
_Tonic_ - *stiffening of arms, leg / trunk*
_Clonic_ - *Jerking of arms/legs on 1 or both sides of body*
Non-Motor seizures;
**_Absence seizures_**
**_Focal seizures_**
**Simple**
**Complex**
*_Myoclonic_ - Some or all of body **twitches** lasting < 1sec.
_Atonic_ - Sudden loss of muscle strength (floppy). Can cause person to **drop** to the ground. - THESE CAN BE GENERALISED / FOCAL*
90
Define tonic-clonic seizures
AKA ‘Grand male’
Typically, tonic comes before clonic!
*Generalised seizures involve both hemispheres of the brain at onset*
- No aura
- Tonic phase; **muscle tensing**/Rigidity, so fall to the floor
- Clonic phase; **muscle jerking**
You see… **Upgazing open eyes, incontinence, _tongue-biting_**
91
Define an absence seizure
*Generalised seizures involve both hemispheres of the brain at onset*
Manifests in childhood; moments of blankly staring into space (secs—>mins) then carrying on from where they left / repeated movements like lip-smacking
92
What’s seen on an EEG of an absent seizure
3Hz spike
93
What can cause seizures
Remember **V.I.T.A.M.I.N…D.E**
Vascular
Infection
Trauma
Autoimmune conditions (SLE)
Metabolic (hypocalcaemia)
**Idiopathic** —> EPILEPSY
Neoplasm
Dementia / Drugs
Eclampsia
94
Define epilepsy relative to its seizures
Epilepsy = idiopathic cause of seizures
≥2 episodes more than 24hrs apart
95
Risk factor for epilepsy
Inherited
**Family Hx**
Metabolic disorders
Acquired
Dementia
Ischaemic stroke
96
What’s the difference between epileptic and non-epileptic seizures
Eyes **open**
Synchronous movement
Can **occur in sleep**
For epileptic seizures
97
Pathophysiology of an epileptic seizure
Imbalance between excitation (**glutamate**) and inhibition (**GABA**) within the neurons of the brain…
Balance shifts towards the excitatory neurotransmitter (glutamate) by stimulation + inhibition of GABA
98
Describe what a seizure period is
_Pre-ictal_
*Aura / deja vu / triggers*
_Ictal_
*Seizure*
_Post-ictal_
*headache / confusion / reduced GCS / amnesia
TODD’s paralysis; if motor cortex affected (frontal lobe), may have temporary paralysis / muscle weakness*
99
Define a focal seizure
Features are confined to a specific region; depending on which lobe of the brain is affected will depend on the Sx experienced
- Could progress to 2º generalised seizures
**Simple focal**; Px is *Awake and Aware*, just got uncontrolled muscle jerking
**Complex focal**; Px is *Unaware / has impaired consciousness* during the seizure.
100
What is jacksonian march
If jerking activity starts in specific muscle group and spreads to surrounding muscle groups as more neurones are affected its referred to as a JACKSONIAN MARCH.
Usually from more **distal areas towards the face**
101
What sx are seen if temporal region of brain is affected in epilepsy
**Temporal lobe i.e., Memory, understanding speech, emotion**
• Aura (80%); Deja-vu, auditory hallucinations, funny smells, fear
• Automatisms e.g., lip smacking
102
What sx are seen if frontal region of brain is affected in epilepsy
**Frontal lobe i.e., Motor, thought processing**
• Motor features e.g., posturing, peddling movements of leg
• **JACKSONIAN MARCH** – seizures march up/down the motor homunculus
• Post-Ictal Todd’s palsy
• Starts distally in a limb & works its way upwards to the face
103
What sx are seen if parietal region of brain is affected in epilepsy
Parietal lobe i.e., Sensation
• Sensory disturbances e.g. tingling/numbness
104
What sx are seen if occipital region of brain is affected in epilepsy
Occipital lobe i.e., Vision
• Visual phenomena e.g. spots, lines, flashes
105
Most common lobe saffected in epilepsy
Temporal
106
What investigation and Dx are the for epilepsy
Blood glucose, FBC Electrolyte panel, Tox screen, CSF lumbar puncture analysis- *rule out other potential causes*
MRI/CT head
**Electroencephalogram** (EEG)- not diagnostic but can help support diagnosis and may help determine type of epileptic syndrome
107
Tx of epilepsy
_Generalised:_
*Tonic-clonic*
1st line:**Sodium valproate**
2nd line: **Lamotrigine**
*Absence*
1st line:**Sodium valproate**
2nd line:**Ethosuximide**
_Focal:_
1st line: **Lamotrigine**
2nd line: **Carbamazapine**
108
Complication of generalised seizures
Status epilepticus
-It is a medical emergency. It is defined as seizures lasting more than 5 minutes or more than 3 seizures in one hour.
Tx:
A-E approach
Give **Benzodiazepine** IV lorazepam; repeated after 10 minutes if seizure continues
109
Define syncope
Insufficient blood / oxygen supply to the brain causing paroxysmal changes (periodic marked changes) in behaviour, sensation and cognitive processes
110
Give 5 signs that transient loss of conciousness is due to syncope
Situational
5 - 30 secs
Pallor
Nausea
Sweating
Dehydration
111
Which seizure is likely to last longer: epileptic / non-epileptic seizure
Non-epileptic *lasts around 1-20 mins
Whereas epileptic lasts around 30-120 secs*
112
A Px complains of having black-outs. They tell you before the black out they felt nauseous and were sweating. They tell you that their friends all said they looked pale. Is this a blood circulation problem or a disturbance of brain function
Likely to be a blood circulation issue e.g. **syncope**
113
How does carbamezapine work as an anti-epileptic drug
**Inhibits pre-synaptic Na+ channels** and so prevents axonal firing
114
What’s the major side effect of sodium valproate
Teratogenic
115
What is dopamine produced from
Tyrosine —> L-DOPA —> Dopamine
116
Define Parkinson’s disease
**Loss/degeneration of dopaminergic neurones in the substantia niagra, pars compacta**
*Pars compacta is a sub-portion of substantia niagra*
- 2nd most common neurodegenerative disorder
- **Idiopathic**
117
Where is substantia niagra found and where does the substantia niagra project to
_Found_ on either side of the _midbrain_ and part of the basal ganglia
Project to the _Striatum_ *(which consists of Caudate + Putamen)*
**The _Pars compacta_ sends messages to the _striatum_ via neuron rich neurotransmitter dopamine.**
**- Forming nigrostriatal pathway; helps stimulate cerebral cortex to initiate movement by signalling striatum to stop firing to pars reticulata to then stop movement inhibition**
*The other region of substantia niagra (pars reticulata) receives signals from the striatum which are then relayed to the thalamus using neurons rich in neurotransmitter GABA; which send signals to cortex to inhibit movement*
118
Pathophysiology of Parkinson’s
**The _Pars compacta_ sends messages to the _striatum_ via neuron rich neurotransmitter dopamine.**
**- Forming nigrostriatal pathway; helps stimulate cerebral cortex to initiate movement by signalling striatum to stop firing to pars reticulata to then _stop movement inhibition_**
*The other region of substantia niagra (pars reticulata) receives signals from the striatum which are then relayed to the thalamus using neurons rich in neurotransmitter GABA; which send signals to cortex to inhibit movement*
Degeneration of substantia niagra pars compacta means reduced signalling so harder to initiate movement.
119
Risk factor for Parkinson’s
FHx
Increased age (*since its progressive*)
Males
120
Aetiology of Parkinson’s
Idiopathic
May be genetic; Mutation in PINK1 / Parkin / ∂-synuclein
Rare: Parkinsonians Sx may be caused by recreational drugs (MPPP)
121
Signs and symptoms of Parkinson’s
**Cardinal Sx:
TRIAD; _Tremor, Rigidity, Bradykinesia_
+ Postural instability**
Tremor; **Pill-rolling resting** tremor
Rigidity; **Cogwheel** rigidity = tension in arms/legs when passively moved gives movement in small increments (*jerk movement*)
Bradykinesia; **Shuffling gait** as a result of Bradykinesia and **Hypomimia** - reduced facial expressions
+ Amnosia
122
Would you describe the Parkinson’s Sx as symmetrical or asymmetrical
One side is always worse than the other
- **Sx are asymptomatic / unilateral**
123
Investigation and Dx of Parkinson’s
**Clinical**
(Bradykinesia + ≥1 cardinal sign)
124
Give a differential Dx for Parkinson’s
_Lewy body dementia (associated with Parkinson’s)_
Parkinson’s Sx then dementia = Parkinson dementia
Parkinson’s Sx after dementia = Lewy body dementia with Parkinsonism
125
Tx of Parkinson’s
Doesn’t stop neurodegeneration; helps with Sx
Main aim is to _increase dopamine signalling_ in the brain
*Dopamine doesn’t cross the Blood-Brain Barrier… its precursor Levadopa does; converted in the brain to dopamine by **decarboxylase inhibitor**; carbidopa - given as combination with L-Dopa; Co-careldopa* - but theres also peripheral dopa decarboxylase which converts dopamine —> epinephrine… *we dont want this* so use decarboxylase inhibitors as that’ll stop dopamine breakdown and wont pass the BBB either.
**L-Dopa** + decarboxylase inhibitor **(carbidopa)** = **Co-careldopa**
Could also give:
Dopamine agonist - Bromocriptine / Cabergoline
**Can also give enzyme inhibitors to stop dopamine breakdown in different pathways**
COMT inhibitors - Entacapone
MAO inhibitors - Selegiline
126
You ask a Px who you suspect might have PD to walk up and down the corridor so that you can assess their gait. What features would be suggestive of PD
Stooped posture
Assymetrical arm swing
Small steps
Shuffling
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Histological findings in Parkinson’s disease
Lewy bodies
Loss of dopaminergic neurones in substantia niagra
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Give an example of a dopamine agonist
Bromocriptine
Cabergoline
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Give an example of a COMT inhibitor
Entacapone
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Give an example of a MAO inhibitor
Selegiline
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Give side effects of levodopa
Dyskinesia (involuntary movement)
Has an “on/off” effect i.e. there’ll be well controlled periods w/ sudden declines
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Define huntington’s chorea
Autosomal dominant genetic disorder trinucleotide repeat that causes progressive deterioration of the nervous system
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What mutation is found in Huntington’s chorea
**Trinucleotide repeat disorder**; genetic mutation in **HTT gene** on **chromosome 4**
134
What triplet code is repeated in Huntington’s disease
CAG triplet repeats
≥36 times
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Define anticipation
Genetic anticipation is a feature seen in trinucleotide repeats.
As generation earlier age onset
The more repeats, the increased severity of disease
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Pathophysiology of Huntington’s
The trinucleotide repeat (of CAG) leads to mutated HTT proteins formation but they also affect the DNA replication itself.
These can aggregate in neuronal cells of the basal ganglia (caudate nucleus; striatum) causing neuronal cell death.
Neurotransmitter affected = GABA (lack of) + excessive nigrostriatal pathway
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What features and signs are seen in Huntington’s
_Early onset_
Irritability
Depression
Personality change
_Later onset_
Chorea (*fidgety*)
Athetosis (*slow involuntary movement*)
Psychiatric problems
Dementia
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Investigation and Dx of huntingtons
Clinical; FHx of earlier + severe huntingtons
Genetic test to count CAG repeats
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Tx for Huntingtons
Extensive counselling
_Medication_
Dopamine antagonist for chorea; **Tetrabenazine**
Could also give:
Antipsychotics; Olanzapine
Benzodiazepines; Diazepam
140
Define multiple sclerosis
Chronic autoimmune, cell-mediated **demyelinating disease** of the CNS.
141
Epidaemiology of multiple sclerosis
Females
20-40y/o
Rare in the tropics
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Risk factors for multiple sclerosis
Other autoimmune conditions
Female
20-40y/o
EBV
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Describe the aetiology of multiple sclerosis
Environmental
Genetic predisposition
Idiopathic
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Pathophysiology of multiple sclerosis
Genetic susceptibility + environmental trigger —> T-Cell activation —> B-cells and macrophage activation —> Inflammation, demyelination and axon destruction
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Where would the plaques be seen histologically
Around blood vessels; perivenular
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Does myelin regenerate in someone with multiple sclerosis
Yes but its much thinner which causes inefficient nerve conduction
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Give 3 main features of MS plaque
Inflammation
Demyelination
Axon loss
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What types of multiple sclerosis is thee
_Relapsing - remitting_
Sx; the Px has random attacks over a number of years and inbetween the attacks theres no progression
_1º progressive_
Gradual deterioration without recovery
_2º progressive_
Relapsing-remitting —> 1º progressive
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Signs and Sx of multiple sclerosis
_Symptoms:_
Paraesthesia
Blurred vision
**Uhtoff’s phenomenon** - worsening Sx following a rise in temperature (hot shower)
_Signs:_
**Optic neuritis** (inflamed optic nerve + **can’t see red** properly) —> 1st presenting Sx
