1
Q
Restless legs syndrome is associated with what deficiency
A
Iron deficiency
2
Q
Characteristics of cateplexy
A
Cataplexy is a sudden muscle weakness that occurs while a person is awake. Strong emotions trigger cataplexy 1. The triggering experiences are usually positive, like laughter, witty conversations, and pleasant surprise. Episodes may also be triggered by anger, but rarely by stress, fear, or physical exertion
Associated with narcolepsy
3
Q
Definition of epilepsy
A
Epilepsy is a disease of the brain defined by any of the following
- At least two unprovoked seizures > 24 hours apart (recurrent unprovoked seizures)
- One or more seizures with a relatively high recurrence risk (≥ 60% over a decade - evidence for heightened risk from clinical, electroencephalographic or neuroimaging tests
- Diagnosis of an epilepsy syndrome/electro-clinical syndrome
4
Q
What is the most common iterictal EEG finding in adults with focal seizures?
A
Anterior temporal lobe spike discharge
5
Q
What do you have to be careful with in asian patients being started on carbamazepine and lamotrigine.
A
HLA B1502: normally of Chinese descent, prone to develop severe skin reactions like steven johnson syndrome.
6
Q
Which antiepileptics decrease the efficacy of hormonal supplements (OCP)
A
Topiramate (reduce efficacy of OCP) and lamotrigine
7
Q
What part of the brain is most commonly affected in focal seizures and what are the associated characteristics?
A
Temporal lobe
- Temporal lobe epilepsy is the most common type of focal epilepsy and the most common epilepsy syndrome presenting in adulthood.
○ Patients with this type of epilepsy typically experience complex partial seizures, which often begin with auras (an epigastric rising sensation or a feeling of deja vu).
○ These patients also may have simple partial or secondarily generalized seizures.
○ Mesial temporal sclerosis (neuronal loss and gliosis in the hippocampus) is a characteristic finding in patients with temporal lobe epilepsy - Frontal lobe epilepsy is the second most common type of focal epilepsy and is often characterized by nocturnal complex partial seizures that awaken patients from sleep because of chaotic movements.
○ Structural causes of focal epilepsy syndromes include brain tumors, vascular malformations, malformations of cortical development, chronic strokes, and head trauma.
An increasing number of genetic focal epilepsy syndromes are being recognized. Most of the time, however, the cause of focal epilepsy remains unknown
8
Q
Which anti-epileptics do you want to avoid in pregnancy?
A
Sodium valproate
Topiramate
9
Q
In herpes encephalitis, which HSV is more common?
A
HSV1 more common in encephalitis
10
Q
In HSV encephalitis, what would be found on neurological examination and imaging
Features of HSV encephalitis
A
- Frontotemporal signs: aphasia, personality change, focal/generalised seizures
- frontotemporal changes on MRI
- Patients with HSE typically present with a prodrome of headaches and fever, followed by:
- sudden focal neurological deficits, affecting medial temporal lobe leading to altered sense of smell, loss of vision, aphasia, memory loss, hemiparesis, ataxia, hyperreflexia
- Altered mental status, - seizures (focal or generalised)
- Characteristic clinical findings and brain imaging showing temporal lesions should raise suspicion for HSE.
- Lumbar puncture often reveals lymphocytic pleocytosis. The diagnosis is best confirmed with polymerase chain reaction (PCR) testing of cerebrospinal fluid.
- Because HSE has a rapidly progressive and potentially fatal course, treatment with acyclovir should begin as soon as the disease is suspected.
11
Q
Where would you find lesions on MRI for japanese encephalitis?
Characteristics of japanese encephalitis
A
Thalamic
- Transmitted via mosquito endemic in Asia and Western Pacific
- Range from asymptomatic to acute encephalitis (altered mental status + neurological deficits)
- Acute psychosis and flaccid paralysis
- Definitive: serology
12
Q
For polyiomyelitis, enterovirus and west nile encephalitis, what neurological signs do you expect to find>
A
Multifocal lower motor neuron, flaccid paralysis
13
Q
Characteristics of west nile encphalitis.
A
- Endemic in Africa, parts of Europe, South Asia, Australia, US and Middle Eaast
- Vectors: mosquitos
- Incubation Period: 2-14 days
- About 80% of human infections are apparently asymptomatic.
- Of those persons in whom symptoms develop, most have self-limited West Nile fever (WNF), characterized by the acute onset of fever, headache, fatigue, malaise, muscle pain, and weakness; gastrointestinal symptoms and a transient macular rash on the trunk and extremities are sometimes reported.
- Can cause acute flaccid paralysis - asymmetric weakness of lower extremities within 48 hours of symptom onset
- In neuroinvasive disease, can cause fever + either meningitis or encephalitis or flaccid paralysis
14
Q
Characteristics of MCA stroke
A
- Contralateral hemiparesis and sensory loss (excluding the forehead)
- Contralateral homonymous hemianopia without macular sparing
- Hemineglect if non-dominant (normally right)
- Aphasia if dominant (normally left)
Brocha’s: inferior frontal, expressive speech
Wernickes: superior temporal, receptive speech
Conduction Aphasia: lesion to supramarginal gyrus, supplied by the inferior division of MCA - Gaze deviates to side of the lesion
MCA stroke can causes CHANGes
• Contralateral paresis and sensory of the lower half of the face, arms and lower limbs
• Hemiparesis
• Aphasia (Dominant)
• Neglect (Non dominant)
• Gaze preference toward the side of the lesion
15
Q
Characteristics of ACA stroke
A
Contralateral weakness in the LL>UL Contralateral sensory loss in the LL>UL Executive dysfunction Urinary incontinence Dysarthria
16
Q
Signs of posterior circulation stroke
A
- Diplopia
- Dizziness
- Dysphagia
- Dysarthria
17
Q
Signs of left parietal stroke (dominant) - dominant parietal lobe
A
Gertsmann Syndrome (ALF)
- Agraphia
- Acalculia
- Left right disorientation
- Finger agnosia
Specifically affecting angular gyrus
By middle cerebral artery
18
Q
Signs of right parietal lobe stroke
A
Prosopagnosia (difficulty recognising familiar faces)
Disorientation to place
19
Q
Pure motor lacunar stroke
A
- Occlusion of the lenticulostriate artery affecting the posterior limb of the internal capsule
- Can also involve the striatum, corona radiata, basal pons, medial medulla
- Contralateral hemiparesis of the face, arm and leg (circumduction gait)
- In some cases dysarthria
- No sensory impairment
20
Q
Pure sensory lacunar stroke
A
- Affects the thalamus (most common) - deep perforating branches of PCA
- Contralateral numbness and paraesthesia of the face/arm/leg
21
Q
What are the characteristics of autoimmune encephalitis.
A
- Subacute onset (<3 months) of memory deficits, seizures and altered mental status
- Antibodies target either intracellular or cell-surface antigens
- INTRACELLULAR antibodies (eg: anti-Hu, anti-Ma, anti-Ri, anti-yo) tend to occur in older people, associated with PARANEOPLASTIC syndromes, have T cell mechanisms and poor response to treatment.
Treat the cancer - EXTRACELLULAR antibodies (eg: NMDA, GABA, VGKC) tend to occur in younger individuals, less likely to be paraneoplastic, B cell response, responsive to immunomodulatory therapy and good response
Responds to PLEX
22
Q
What is the associated syndrome and cancer associated with anti-Hu
A
- Associated with small cell lung cancer
- Limbic encephalitis
- Peripheral neuropathy/neuronpathy
23
Q
What is the associated syndrome and cancer associated with anti-yo
A
- Associated with breast and ovarian cancer
- Paraneoplastic cerebellar degeneration
24
Q
What is the associated syndrome and cancer associated with anti-Ri
A
- Associated with breast, small cell lung cancer
- Ataxia, opsoclonus myoclonus, brain stem encephalitis/rhomboencephalitis
Opsoclonus/myoclonus: Symptoms include rapid, multi-directional eye movements (opsoclonus), quick, involuntary muscle jerks (myoclonus), uncoordinated movement ( ataxia ), irritability, and sleep disturbance
25
What is the associated syndrome and cancer associated with anti-Ma/Ta
- Testicular, lung, breast cancer
| - Limbic encephaliits, rhomboencephalitis
26
What is the associated syndrome and cancer associated with CV2/CRMP5
- SCLC, thymoma
- Limbic encephalitis, progress cerebellar degeneration, chorea, uveitis, optic neuritis, retinopathy, sensorimotor neuropathy
27
What is the associated syndrome and cancer associated with amphiphysin.
- Stiff person syndrome
- Paraneoplastic encephalomyelitis
- limbic encephalitis
- Breast and sclc
28
Characteristics of anti-NMDAR encephalitis
- Associated with IgG antibodies against the GluN1 subunit of NMDAR
- Associated with ovarian teratoma
- Young individuals < 45yo
- F:M = 4:1
- Older men and older women more likely to have carcinoma
29
Clinical features of anti-nmdar encephalitis
- Multistage disease
- 1st phase: prodromal, observed in >50% (fever, headache, upper respiratory tract infection, vomiting, diarrhoea)
- 2nd Phase: prominent early behaviour and psychiatric disturbances (eg: disorientation, inattention, speech difficulties like pressured speech, mutism), seizures, movement disorders especially orofacial lingual dyskinesias
- 3rd phase: autonomic dysfunction including central hypoventilation, htn, cardiac arrythmias, decreased LOC
- Disease course is prolonged and up to several months
30
Ix of anti-NMDAR encephalitis
- CSF: lymphocytic pleocytosis, elevated protein and oligoclonal bands (in later stages) and anti- NMDAR ab (more sensitive and specific when found in CSF, 99% sensitive in CSF)
- MRI Brain: temporal lobe limbic changes
- EEG: seizurs and encephalopathy
- Underlying malignancy - pelvic US, malignancy screen
31
Treatment of anti-NMDAR encephalitis
- First line:
Removal of disease associated tumours
IV methylpred or IVIG or plasma exchange.
- 2nd line: rituxumab and cyclophosphamide
- Some case studies show use of proteasome inhibitor bortezomib (Velcade) or IL6 (tocilizumab)
32
What is catatonia?
Catatonia is a group of symptoms that usually involve a lack of movement and communication, and also can include agitation, confusion, and restlessness.
Treat with benzos, eg: lorazepam, diazepam
33
What are voltage gated potassium channel (VGKC) complex antibodies
- LGI-1 antibodies (more common): limbic encephalitis often with hyponatremia and patients have typical faciobrachial dystonic seizures. Cognitive and memory changes.
Good response to treatment but overall poor recovery of cognition and memory
- Casper 2: limbic encephalitis, Morvan's syndrome (neuromyotonia, insomnia, autonomic disturbance)
- neuromyotonia (NMT), pain, hyperhydrosis, weight loss, severe insomnia and hallucinations
Associated with thymoma, NSCLC
34
What makes up the limbic system ad function?
- Amygdala, hippocampus, cingulate gyrus.
- The limbic system is the part of the brain involved in our behavioural and emotional responses, especially when it comes to behaviours we need for survival: feeding, reproduction and caring for our young, and fight or flight responses
35
What is morvan's syndrome characterised by?
- neuromyotonia,
- insomnia,
- autonomic disturbance: hypertension, tachycardia , increased body temperature
neuromyotonia (NMT), pain, hyperhydrosis, weight loss, severe insomnia and hallucinations
- Associated with anti-Casper 2 antibodies
- Can be associated with thymoma
36
What is neuromyotonia?
- Acquired neuromyotonia is an inflammatory disorder characterized by abnormal nerve impulses from the peripheral nerves that result in continuous muscle fiber activity.
- Affected individuals often experience progressive muscle stiffness and cramping especially in the hands and feet, increased sweating (hyperhidrosis), and delayed muscle relaxation. Symptoms may persist even during sleep or under general anesthesia.
37
Characteristics of Anti-LG1 antibody limbic encephalitis
- Male predominance
Clinical features:
• Seizures (faciobrachial dystonic seizures, focal seiures)
• Memory loss, altered mood and personality
• TCS later after cognitive symptoms
• REM sleep dysfunction
• Myoclonus like movements (FBDS)
- Epileptic prodrome to LGI1/VGKC complex Ab LE
- Tonic dystonic movements of face/arm/leg
- Very brief (few sec) 50-100 times/day
- Misdiagnosed as myoclonus
- Poor response to AED
5-10% have underlying malignancy - thymoma, breast or renal cell carcinoma
38
What MRI finding is seen in anti-LGI1 antibody limbic encephalitis?
Increased FLAIR signal in medial temporal lobe bilaterally.
39
Treatment for anti LGI-1 antibody LE?
- IV methylpred, IVIG, plasma exchange
40
Characteristics of anti-caspar2 antibodies.
- Caspar2 is a cell adhesion molecule that glusters VgKCs at the juxtaparanodes of myelinated axons in both peripheral and the CNS
- Less frequent than LGI-1 LE
- Clinical features: peripheral nerve hyperexcitability (neuromyotonia), sensory neuropathy and pain, cognitive impairment, seizures, dysautonomia
- Associated with thymoma
- Associated with co-existing myasthenia gravia
- Morvan syndrome: neuromytonia, autonomic disturbance, insomnia, mainly men
41
Treatment for anti-caspar 2 LE
1st line: IV methylpred, IVIG, plasma exchange
| - 2nd line: rituxumab, cyclophosphamide
42
Characteristics of anti-GABAbR encephalitis
- 60yo, M:F = 1:1
- 50-60% associated with lung cancer (SCLC)
- Causes limbic encephalitis with prominent seizures and status epilepticus.
- Onset:
60% seizures often very severe and difficult to control
40% cognition/behaviour
10-15% resembles rapidly progressive dementia.
43
Broca's and Wernicke's Aphasia
- Broca's Aphasia, non fluent, expressive speech, dominant frontal lobe (BEF)
- Wernicke's Aphasia, fluent, conductive speech, temporal (WCT)
- Conductive aphasia: mixture between 2, able to comprehend with elements of fluent aphasia and poor repetition. Arcuate fasciculus.
44
Absolute contraindications for tpa
-Intracranial haemorrhage on CT
-Clinical presentation suggests subarachnoid haemorrhage
- Neurosurgery, head trauma or stroke in the past 3 months
-Uncontrolled hypertension (>185/110)
- History of intracranial haemorrhage
-Known intracranial ateriovenous malformation, neoplasm or aneurysm
-Active internal bleeding
-Suspected/confirmed endocarditis
- Known bleeding diathesis
-Platelet count <100,000
Received heparin within 48 hours and elevated aPTT
Current use of oral anticoagulation and INR > 1.7
Current use of direct thrombin inhibitors or direct factor Xa inhibitors
Abnormal blood glucose (<50mg/dL)
45
Treatment for stroke
Thrombolysis <4.5 hours of symptom onset
Endovascular clot retrieval - large vessel occlusion within 6 hours
Can do thrombectomy up to 24 hours
46
Indication for carotid endarterectomy
- The strongest evidence for carotid endarterectomy is within 2 weeks of an event (TIA or stroke, including retinal ischaemia) in the relevant territory, < 3 months at latest
- Carotid stenosis of 70-99% if asymptomatic
- Considered if stenosis 50-69% and symptomatic
- All patents should be treated with intensive vascular secondary prevention therapy.
If unfavourable anatomy - stenting
47
Reversal agents for dabigatran, rivaroxaban, apixaban
Idarucizumab (Praxbind) - Dabigatran (direct thrombin inhibitor) reversal
Andexanet alfa - direct factor Xa inhibitor for apixaban and rivaroxaban
48
Patent PFO
- In patients <60 years of age with embolic stroke and no other clear aetiology, percutaneous PFO closure reduces the risk of stroke recurrence.
- Transthoracic echocardiogram with Saline Bubble Study (and effective Valsalva) usually sufficient to make the diagnosis
49
Where is the area affected for the following conditions
- Wernicke and Korsakoff syndrome
- Hemiballism
- Huntington chorea
- Parkinsons disease
- Kluver bucy syndrome - hypersexuality, hyperorality, hyperphagia, visual agnosia
- Wernicke and Korsakoff syndrome: medial thalamus and mammillary bodies of the hypothalamus
- Hemiballism: subthalamic nucleus of the basal ganglia
- Huntington chorea: stratium (caudate nucleus) of the basal ganglia
- Parkinsons disease: substantia nigra of the basal ganglia
- Kluver bucy syndrome - hypersexuality, hyperorality, hyperphagia, visual agnosia: amygdala
Hemiballismus – sudden flailing movements of contralateral limbs – lesion STN
Chorea – dancelike – jerky, purposeless movements of limbs, face & tongue, eg. Huntington’s
chorea (genetic – autosomal dominant) - results from degeneration of D2 GABA cells in striatum
(which are part of the indirect pathway).
Athetosis – slow writhing movements trunk and proximal limbs with varying degrees of spasticity,
eg. cerebral palsy. Commonly combined with chorea – known as choreoathetosis.
50
Lacunar syndromes - location and clinical features of pure motor and pure sensory stroke
Pure Motor
- Posterior limb of the internal capsule caused by occlusion of the lenticulostriate artery
- Contralateral hemiparesis of the face, arm and leg
Pure Sensory Stroke
- Thalamus
- Contralateral numbness/parathesia of the face/arm/leg
51
Features of lateral medullary syndrome (Wallenberg)
PICA (posterior inferior cerebellar artery)
Nucleus ambiguus (CNIX, X, XI): ipsilateral bulbar palsy (dysphagia, hiccups, decreased gag reflex)
Vestibular nuclei: ipsilateral nystagmus and vertigo
Lateral spinothalamic: contralateral decrease in pain and temperature
Spinal trigeminal: ipsilateral loss of pain and temp in face
Inferior cerebellar peduncle: ipsilateral limb ataxia and dysmetria
Sympathetic: ipsilateral horner syndrome
52
Medial medullary syndrome
Paramedian branches of anterior spinal artery and/or vertebral arteries
Hypoglossa: ipsilateraly tongue palsal
Corticospinal: contralateral heiparesis
Medial lemniscus: contralateral decrease in proprioception
53
Definition of encephalitis
Major
- Altered mental state, personality change > 24 hours with no other cause found
Minor (3 or more for confirmed, 2 for possible)
- Documented fever >38 within 72 hours before or after presentation
- Generalised or focal seizures and no prior seizure disorder
- New focal neurological findings
- Abnormal CSF
- Abnormal MRI with brain parenchyma changes
- Abnormal EEG
54
Characteristics of limbic encephalitis
- Subacute psychiatric manifestations - psychosis, hallucinations, behavioural changes
- Poor short term memory
- Temporal lobe seizures
- MRI changes in unilateral or bilateral temporal lobes
Limbic structures: hippocampus, amygdala, hypothalamus
55
Characteristics of rhomboencephalitis
Decreased conscious state
| Cranial nerve signs and brainstem signs
56
Diagnosis and treatment for HSV encephalitis
- LP: lymphocyte pleocytosis, elevated protein, HSV PCR positive
- MRI: T2 hyperintensity in medial and inferior temporal lobe extending up to insular cortex
Oedema, necrosis, haemorrhage and breakdown of BBB
- EEG: focal slowing, periodic epileptiform discharges
TX
IV acyclovir
57
Features of listeria encephalitis
- Most common cause of rhomboencephalitis
- Increased incidence in pregnancy, elderly, immunocompromised
- Decreased conscious state, cranial nerve abnormalities, meningitis
-BLOOD CULTURES - most important and positive in 60-70%, low sensitivity in LP
- LP: pleocytosis, listeria culture (low sensitivity), PCR
MRI: brainstem enhancement, abscess
IV benpen, ampicillin
58
Immune related adverse effects of immune checkpoint inhibitors
CTLA4 - ipilimumab
PD1 - nivolumab, pembrolizumab
PD ligand 1 - atezolizumab, avelumab
Can cause
- Myaesthenia gravis
- Neuropathy
- Myositis
- Encephalitis
TX
- remove checkpoint inhibitor
- For severe disease - IV steroids, IVIG
59
Characteristics of PRES (posterior reversible encephalopathy syndrome)
- Clinical and radiological syndrome of encephalopathy and posterior circulation oedema
RF
- HYPERTENSION
- Pre-eclampsia/eclampsia
- Renal failure
- Immunosuppressive drugs
- Autoimmune conditions; SLE, vasculitis
- Infection/sepsis
Symptoms
- Acute mental status changes: mild agitation to coma
- Headaches
- Visual disturbances
- Seizures - most common symptom
Signs
- HTN!!
- Altered consciousness
- Bilateral optic disc swelling with haemorrhage
- Visual changes
- Increased reflexes and up going plantars
- Brain MRI reveals areas of white matter edema in posterior brain regions (occipital and parietal cortex).
```
Tx:
- Aggressive blood pressure control
- Seizure management
- Treatment of any other potential causes
Reduce or cease immunosuppression
Treat renal failure
```
60
What does contrast enhancement on MRI indicate?
Indicates inflammation and damage to BBB
61
Brainstem at cranial nerve nucleus = LMN or UMN
| Anterior Horn Cell = LMN or UMN
Brainstem at cranial nerve nucleus = UMN
| Anterior Horn Cell = LMN
62
What is pyramidal vs extrapyramidal weakness
Pyramidal: UMN,
UL: weakness of extensors
LL: weakness of flexors
Extrapyramidal: parkinson's, basal ganglia
63
How does a hyperacute/acute UMN lesion present
Due to spinal shock, UMN initially presents with flaccid paralysis, hyporeflexia, decreased tone
64
Function of the frontal lobe
- Primary Motor Cortex (precentral gyrus): where the UMN are found
- Personality
- Primitive Reflexes:
○ Babinski
○ Grasp
○ Palmar omental
○ Snout/pout
These reflexes gets inhibited as you age, but with time in dementia, there is disinhibition of these reflexes - lead to frontal release signs
- Dysphasia Expressive (dominant) - brocha's area
- Anosmia
- Optic nerve compression
Foster-Kennedy Syndrome is characterized by unilateral visual loss with a compressive optic atrophy in one eye and contralateral papilledema caused by increased intracranial pressure.
- Gait apraxia
65
Function of the parietal lobe
- Parietal sensory cortex (postcentral gyrus)
- Gertsmann Syndrome (dominant parietal - left): dominant angular gyrus
Acalculia, agraphia, L/R disorientation, finger agnosia
- Neglect (non-dominant parietal - right)
- Construction and dressing apraxia
- Sensory inattention
- Astereognosis (tactile agnosia)
- Lower quandrantopia
Inferior homonymous quadrantanopia
66
Function of the temporal lobe
- Primary auditory cortex
- Receptive dysphasia - wernicke's
- Memory loss (where hippocampus lies)
- Upper quandrantopia
superior homonymous quadrantanopia
- prosopagnosia (difficulty recognising faces)
67
Function of occipital lobe
- Homonoymous hemianopia
- Anton's syndrome - cortical blindness with confabulation due to bilateral occipital lobe lesion
- Alexia (can't read)
Anton Syndrome - cortical blindness due to affecting bilateral posterior cerebral arteries affecting bilateral occipital lobes, bilateral visual loss, unawareness or denial of blindness
68
How do the motor fibres travel from the brain to the spine?
Primary motor cortex (precentral gyrus frontal) --> corona radiata --> interna capsule --> crus cerebi (midbrain) --> basis pontis (pons) --> pyramids (medulla) --> corticospinal tract
Posterior limb and genu carry corticospinal tract and some sensory fibres - motor fibre
Note: anterior limb is thalamus to frontal lobe, sensory
69
Locked in syndrome
Occurs due to bilateral ventral pontine stroke
proximal and mid portions of the basilar artery (pons) can result in patients being 'locked in'
- Paralysis of voluntary muscles - quadriplegia due to corticospinal tract effected
- Bulbar palsy - dysarthria, dysphagia
- Horizontal gaze palsy - can only look up and blink
- Preserved consciousness
70
Tip of basilar artery occlusion
"Top-of-the-basilar" syndrome involves occlusion in the rostral part of the basilar artery, resulting in ischemia affecting the upper brainstem and the thalamus. Clinical manifestations include behavioural changes, hallucinations, somnolence, visual changes, and oculomotor disturbances.
Can progress very quickly
eg: sudden dysarthria, then diplopia, then hemiparesis then sudden drop in GCS
Pontine warning syndrome is a basilar artery atherosclerotic disease characterized by motor and speech disturbances that occur in a waxing and waning manner. These patients typically experience recurrent on-and-off attacks of hemiparesis and dysarthria. This syndrome is indicative of an imminent basilar artery branch occlusion with infarction of the supplied region.
71
Cortical vs subcortical
Cortical: language, neglect, visual changes, aphasia
Subcortical
- Internal capsule, thalamus, basal ganglia
- motor weakness, sensory loss
72
What are the 4 nuclei of the thalamus
- Terminal for all sensory nerves
- Arterial supply from PCA
Anterior nuclei: language and memory function (frontal)
Lateral: motor and sensory fx (parietal)
Medial: maintaining arousal and memory (brainstem)
Posterior: visual (occipital)
Lesion of thalamus will not cause cortical signs
73
If there is face involvement where is the lesion?
Above the spinal cord
74
Lesion of vermis of cerebellum
Truncal ataxia , eg: rombery
Nystagmus (flocculonodular lobe) and effects limbs
Cerebellar hemisphere lesions cause IPSILATERAL deficits
75
What does the brain stem contain?
Midbrain
Pons
Medulla
```
Contains the cranial nerve nuclei
Motor tracts
Medial longitudinal fasciculus
Medial lemniscus
Spinothalamic tract
Spinocerebellar
Sympathetic tract
Sensory nucleus of CNV
```
Brainstem signs = midbrain/pons/medulla signs
- Cranial nerve signs
- Split signs (face vs limbs)
76
Sympathetic pathway
- Hypothalamus --> Brainstem --> C8-T1 is where they synapse --> brachial plexux over the lung apex --> common carotid artery --> superior cervical ganglion where it synapses again -->
- Goes to the external carotid it supplies the facial sweat glands
- Goes to the internal carotid which supplies nerve to pupil dilator and nerve to tarsal muscle
Horner's Syndrome
- Miosis (constriction of pupil)
- Partial ptosis
- Anhidrosis
Internal Carotid Dissection
- Miosis
- Partial ptosis
- No anhidrosis
Remember the three areas where they synapse
- Hypothamus --> C8-T1 --> Superior Cervical Ganglion --> splits into internal and external carotid
Eg: case where someone has wasting of the hands and a horner's syndrome and also scar of the lung
The lesion is between the C8-T1 to superior cervical ganglion
77
IF YOU HAVE MULTIPLE CRANIAL NERVE PALSIES AND NO LONG TRACT SIGNS, THEN THE LESION IS LIKELY OUTSIDE OF THE BRAINSTEM
IF YOU HAVE MULTIPLE CRANIAL NERVE PALSIES AND NO LONG TRACT SIGNS, THEN THE LESION IS LIKELY OUTSIDE OF THE BRAINSTEM
78
Lacunar syndromes
1. Pure Motor: posterior limb of IC or anterior portion of pons (basis pontis)
2. Ataxic Hemiparesis
- Posterior limb of IC, basis pontis, corona radiata
- Combination of cerebellar and motor symmptoms
- Usually affects the legs > arms
3. Dysarthria/clumsy hand: basis pontis
4. Pure sensory: thalamic infarct
5. Mixed sensorimotor
Thalamus and posterior limb of IC
79
Features of cerebral amyloid angiopathy
Syndrome of
- Haemorrhage in LOBAR distribution
- ELDERLY PATIENT and associated COGNITIVE IMPAIRMENT
- MRI Brain: multiple lobar microhaemorrhages
- Higher risk of ischaemic stroke + TIAs
- Cortical microhaemorrhages
- White matter disease and cortical infarcts
- Dementia
- Genetic association with APOE E4 and E2 allele
- Amyloid deposition in leptomeningeal and cortical vessels of cerebellar and cerebral lobes.
Tx
Avoid anticoagulation, antiplatelet, thrombosis
HTN control
80
Features of cerebral venous sinus thrombosis
- Increased risk with hormonal therapy and post partum
- More common in women
- RF
Obesity
Thrombophilia including OCP
Local infections
Chronic inflammatory disease
Malignancy
Pathophysiology
- Thrombosis leads to increased capillary and venular pressure
- Local venous pressure rises and decreased perfusion leads to ischaemia and cytotoxic oedema
- Venous and capillary rupture leads to haemorrhage
- Sinus obstruction leads to poor csf absorption.
Presentation
- Isolated intracranial HTN - headache, visual changes, papilloedema
- Focal neurological abnormalities
- Seizures
- Encephalopathy
Mx
Anticoagulation even in the event of haemorrhage
- Clexane, if not then heparin
- Afterwards, for NOAC
- Even if they bleed, you need to continue clexane/heparin
- They are bleeding because of oedema so you want to break down the clot that is causing the congestion
For those who progress - endovascular thrombectomy or thrombolysis
Hemicraniectomy
Raised intracranial htn - acetazolamide or surgicial intervention if severe.
81
Characteristics of VZV encephalitis
VZV vasculitis: internal carotid or smaller vessel necrosis and thrombosis causing strokes
- Varicella cerebellitis: meningism and ataxia, mild CSF lymphocytosis
- Varicella meningoencephalitis: seizure, impaired consciousness
82
KELCH-11
Cerebellar syndrome in men related to testicular seminoma
83
What are the viral disease belonging to the Flaviviridae family (mosquito borne diseases).
- West Nile virus (most widely distributed arbovirus, endemic in africa, parts of europe, south asia, australia, US, middle east
- Dengue virus
- Zika virus
- Yellow fever virus
- Japanese encephalitis
- Murray valley encephalitis: Australia, PNG, indonesia
84
Weber Syndrome
Medial Midbrain Syndrome
Branches of PCA
ipsilateral III palsy
contralateral weakness/hemiparesis
85
What cause alexia without agraphia
Alexia - unable to read
Agraphia - unable to write
Alexia (inability to read), without agraphia (inability to write) occurs because of an infarction of the left posterior cerebral artery (callosal branch) which perfuses the splenium of the corpus callosum and left visual (occipital) cortex
Lesion of LEFT OCCIPTAL LOBE + CORPUS CALLOSUM (SPLENIUM)
- Right homonymous hemianopia
- Alexia without agraphia
86
Features of anti-GAD
Anti-GAD antibody associated with breast, colorectal and small cell lung carcinoma
stiff person's syndrome or diffuse hypertonia
87
AICA
Retinal/ophthalmic artery
Basilar artery
- Anterior inferior cerebellar artery (lateral pontine syndrome):
Contralateral: contralateral hemiplegia (corticospinal tract) and loss of pain and temperature
(spinothalamic tract)
Ipsilateral: ipsilateral limb ataxia (spinocerebella), facial paralysis (facial nerve), hearing loss (vestibulocochlear nerve), vertigo, nystagmus
Affect
- Corticospinal tract
- Spinothalamic tract
- Facial nerve, vestibulocochlear nerve
- Cerebellar tracts
- Retinal/ophthalmic artery: Amaurosis fugax
- Basilar artery: 'Locked-in' syndrome
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Cause of palatal myoclonus
Palatal myoclonus is a specific feature of hypertrophic olivary degeneration. This is caused by a lesion in the triangle of Guillain and Mollaret (triangle linking the inferior olivary nucleus (medulla), red nucleus (midbrain) and the contralateral dentate nucleus (cerebellum)). An MRI brain is the gold standard imaging for this lesion.
Olivary nucleus is located in medulla
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Different types of aphasia
- Expressive dysphasia: Speech is non-fluent and halting, brocha's area (inferior frontal)
- Receptive dysphasia: causes fluid but incomprehensible speech, loss of comprehension, wernicke's area (superior temporal)
- Global dysphasia: problems with fluency, understanding and repetition and suggests widespread intracerebral damage.
- Conduction dysphasia: speech fluent, but repetition poor. Comprehension is relatively intact.
This causes fluid speech with relatively preserved comprehension but poor repetition. It is caused by damage to the ARCUATE FASCICULUS, typically as a consequence of a stroke affecting the parietal lobe. (connects frontal, temporal, parietal)
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Areas of the hypothalamus and its function
- Anterior Hypothalamus: heat dissipation to cool down the body (parasympathetic)
- Posterior Hypothalamus: responsible for heat generation to maintain core body temperature.
- Suprachiasmatic nucleus: regulates the circardian rhythm
"suprachiasmatic nucleus (SCN) - Sun Censing Nucleus)"
- Ventromedial Area: Satiety stimulated by leptin. Often invaded by craniopharyngiomas. This area of the hypothalamus controls the satiety center and it is removed during surgery, the patient can have uninhibited hunger leading to significant weight gain.
- Lateral Nucleus: hunger, stimulated by ghrelin, inhibited by leptin.
" Injury to the Lateral nucleus makes you Lean (due to the absence of hunger), and injury to the VentroMedial nucleus makes you Very Massive (due to the absence of satiety)."
- Paraventricular and supraoptic nucleus: regulate water balance, synthesis of ADH, oxytocin which are transported to the posterior pituitary for storage and release.
"Functions of hypothalamic nuclei (Supraoptic nucleus releases, ADH release, Paraventricular nucleus release, OXytocin): SAD POX"
- Mamillary Body: memory
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Visual field defects
- left homonymous hemianopia means visual field defect to the left, i.e. Lesion of right optic tract
- homonymous quadrantanopias: PITS (Parietal-Inferior, Temporal-Superior)
- incongruous defects = optic tract lesion;
- congruous defects = optic radiation lesion or occipital cortex
- A congruous defect simply means complete or symmetrical visual field loss and conversely an incongruous defect is incomplete or asymmetric.
Homonymous hemianopia
• incongruous defects: lesion of optic tract
• congruous defects: lesion of optic radiation or occipital cortex
• macula sparing: lesion of occipital cortex
Homonymous quadrantanopias*
• superior: lesion of the inferior optic radiations in the temporal lobe (Meyer's loop)
• inferior: lesion of the superior optic radiations in the parietal lobe
• mnemonic = PITS (Parietal-Inferior, Temporal-Superior)
Bitemporal hemianopia
• lesion of optic chiasm
• upper quadrant defect > lower quadrant defect = inferior chiasmal compression, commonly a pituitary tumour
• lower quadrant defect > upper quadrant defect = superior chiasmal compression, commonly a craniopharyngioma
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Treatment for brain abscess
IV ceftriaxone + metronidazole
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Wernicke-Korsakoff
- Occurs due to thiamine deficiency - vitamin B1
COAT RACK
Wernicke:
- Confusion
- Ophthalmoplegia
- Ataxia
- Thought impairment (memory impairment)
Korsakoff
- Retrograde amnesia (unable to remember past memories)
- Anterograde amnesia (trouble making new memories but remembers past)
- Confabulation
- Kan't be bothered - anhedonia
Can have nystagmus
MRI may show mammillary body involvement
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What is a chiari malformation?
Chiari 1 malformation is a condition characterised by herniation of the cerebellar tonsils through the foramen magnum. It causes symptoms by compressing the brainstem, cerebellum and by disturbing the flow of cerebrospinal fluid (CSF). Disturbed CSF flow either causes hydrocephalus (uncommon) or syringomyelia (common; ~50%).
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Function of superior and inferior colliculus
Midbrain
Superior Colliculus: vision, oculomotor nucleus
Inferior Colliculus: hearing
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For ischaemic stroke when should AC be commenced?
Anticoagulation should be commenced 14 days after an ischaemic stroke. Earlier anticoagulation may exacerbate any secondary haemorrhage.
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Cauda equina syndrome
Cauda equina syndrome results from compression of the cauda equina and classically includes leg weakness, saddle anaesthesia and sphincter disturbance.
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A 68-year-old man has been brought to the emergency department after his family noticed a progressive deterioration in his breathing. He has a past medical history of COPD and is managed with inhalers.
On examination, he has no wheeze but is making minimal respiratory effort. He has wasting of the small muscles of his hands, fasciculations of the left bicep and calf muscles, increased tone of the upper limbs, hyporeflexia of the biceps and reduced power in upper and lower limbs.
An arterial blood gas (ABG) on room air demonstrates a mild type 2 respiratory failure. A chest x-ray demonstrates bilateral diaphragmatic palsy.
What is the best treatment for prolongation of life in this patient?
```
Long-term oxygen therapy (LTOT)
Non-invasive ventilation (NIV)
Pulmonary rehabilitation
Pyridostigmine
Riluzole
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Motor neuron disease - treatment: NIV is better than riluzole
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MND
Motor neuron disease is a neurological condition of unknown cause which can present with both upper and lower motor neuron signs. It rarely presents before 40 years and various patterns of disease are recognised including amyotrophic lateral sclerosis, primary lateral sclerosis, progressive muscular atrophy and progressive bulbar palsy. In some patients however, there is a combination of clinical patterns
Amyotrophic lateral sclerosis (50% of patients)
typically LMN signs in arms and UMN signs in legs
in familial cases the gene responsible lies on chromosome 21 and codes for superoxide dismutase
Primary lateral sclerosis
UMN signs only
Progressive muscular atrophy
LMN signs only
affects distal muscles before proximal
carries best prognosis
Progressive bulbar palsy
palsy of the tongue, muscles of chewing/swallowing and facial muscles due to loss of function of brainstem motor nuclei
carries worst prognosis
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Features of CADASIL
Cerebral Autosomal Dominant Arteriopathy with Subcortical Infarcts and Leukoencephalopathy (CADASIL)
- rare cause of multi-infarct dementia
- patients often present with migraine
- This is a genetic condition due to a mutation in the NOCTH3 gene on chromosome 19
- It usually presents with the onset of migraines in middle age, followed by recurrent TIAs and strokes, and resulting in neuro-cognitive decline, psychiatric problems and dementia.
- MRI often shows multiple widespread hyper-intense lesions in the white matter, basal ganglia, thalamus and pons.
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Supply of facial nerve
| Causes of bilateral facial nerve palsy
Supply - 'face, ear, taste, tear'
face: muscles of facial expression
ear: nerve to stapedius
taste: supplies anterior two-thirds of tongue
tear: parasympathetic fibres to lacrimal glands, also salivary glands
Causes of bilateral facial nerve palsy
sarcoidosis
Guillain-Barre syndrome
Lyme disease
bilateral acoustic neuromas (as in neurofibromatosis type 2)
as Bell's palsy is relatively common it accounts for up to 25% of cases f bilateral palsy, but this represents only 1% of total Bell's palsy cases
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What is narcolepsy associated with?
Narcolepsy is associated with low orexin (hypocretin) levels
It is characterised by daytime somnolence and dysregulation of sleep. 70% also have cataplexy - a condition in which sudden emotions can trigger collapsing episodes. It is theorised this is due to the destruction of neurons that produce orexin (hypocretin), which promotes wakefulnes
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Where is melatonin produced
Melatonin is a hormone released by the pineal gland that leads to the feeling of sleepiness.
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Features of 3rd Nerve Palsy
| Causes of 3rd Nerve Palsy
- Downward and outward deviation of eye (down and out) due to unopposed actions of the lateral rectus and superior oblique muscles.
- Weakness of the levator palpebrae superioris muscle results in ptosis
- Mydriasis due to impairment of parasympathetic function
- Horizontal diplopia that worsens when turning the gaze away from the affected side
CAUSES
- diabetes mellitus
- vasculitis e.g. temporal arteritis, SLE
- false localizing sign* due to uncal herniation through tentorium if raised ICP
- posterior communicating artery aneurysm
○ pupil dilated
○ often associated pain
- cavernous sinus thrombosis
- Weber's syndrome (medial midbrain): ipsilateral third nerve palsy with contralateral hemiplegia -caused by midbrain strokes
- other possible causes: amyloid, multiple sclerosis
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Cavernous sinus thrombosis
Cavernous sinus thrombosis
- other causes of cavernous sinus syndrome: local infection (e.g. sinusitis), neoplasia, trauma
- periorbital oedema
- ophthalmoplegia: 6th nerve damage typically occurs before 3rd & 4th
- trigeminal nerve involvement may lead to hyperaesthesia of upper face and eye pain
central retinal vein thrombosis
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Medications that cause tinnitus
Aspirin/NSAIDs
Aminoglycosides
Loop diuretics
Quinine
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Causes of Miosis
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Causes of miosis (small pupil)
Horner's syndrome
Argyll-Robertson pupil
senile miosis
pontine haemorrhage
congenital
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Drugs causes
opiates
parasympathomimetics: pilocarpine
organophosphate toxicity
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Vestibular schwannoma
Vestibular schwannomas (sometimes referred to as acoustic neuromas) account for approximately 5% of intracranial tumours and 90% of cerebellopontine angle tumours.
The classical history of vestibular schwannoma includes a combination of vertigo, hearing loss, tinnitus and an absent corneal reflex. Features can be predicted by the affected cranial nerves:
- cranial nerve VIII: vertigo, unilateral sensorineural hearing loss, unilateral tinnitus
- cranial nerve V: absent corneal reflex
- cranial nerve VII: facial palsy
Bilateral vestibular schwannomas are seen in neurofibromatosis type 2.
Patients with a suspected vestibular schwannoma should be referred urgently to ENT. It should be noted though that the tumours are often slow growing, benign and often observed initially.
MRI of the cerebellopontine angle is the investigation of choice. Audiometry is also important as only 5% of patients will have a normal audiogram.
Management is with either surgery, radiotherapy or observation.
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Each of the following are causes of peripheral neuropathy. Which one is associated with predominately sensory loss?
```
Diphtheria
Hereditary sensorimotor neuropathies
Porphyria
Lead poisoning
Uraemia
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Uraemia
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Cause of amaurosis fugax - transient monocular vision loss
amaurosis fugax - transient monocular vision loss
Occurs due to transient occlusion of the CENTRAL RETINAL ARTERY
Anterior circulation --> internal carotid artery --> ophthalmic --> supply optic nerve and central retinal artery
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Weakness of which muscle differentiates Bell's palsy from a cortical stroke?
A. Frontalis
B. Orbicularis oris
C. Levator palpabrae superior
D. Zygomaticus
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Frontalis
- Stroke: UMN, spares the forehead, lower facial droop due to dual cortibulbar innervation of the forehead
- Bell's Palsy: LMN, facial droop
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Where is CSF made?
- In the choroid plexus which lines the lateral ventricle and the roof of 3rd/4th ventricle
- CSF exits via the foramen of Magendie + Luschka to enter subarachnoid space --> CSF then reabsorbed by arachnoid granulations in dural venous sinus system
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Horner's Syndrome
- Ptosis
- Miosis (constricted)
- Anhydriosis
Causes: stroke, ICA dissection, pancoast apical tumour
CT carotid angiogram
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In horner's syndrome, ptosis of the eye results from weakness in which of the following muscles?
Superior Tarsal Muscle
Muscles of Eye Opening
- Levator Palpebrae Superioris: oculomotor nerve
- Superior Tarsal Muscle: sympathetic fibres
As Levator >Superior Tarsal, CNIII palsy will lead to worse ptsosis
Eyes Closure
- Orbicularis oculi supplied temporal and zygomatic branches of facial nerve
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What nerves are involved in the CORNEAL REFLEX
CNV and CN VII
Reflex Arc
- Sensory (afferent) : CNV1 (ophthalmic)
- Motor (efferent): CNVII
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Feature of the accommodation reflex
Accommodation Reflex
- Miosis: contraction of iris sphincter muscle
- Convergence: contraction of both medial rectus muscles → eyes look inward
- Accommodation: preganglionic parasympathetic fibers from Edinger-Westphal nucleus travel with the oculomotor nerve → ciliary muscle contraction → increased lens convexity
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Pupillary Light Reflex
- Afferent
- Efferent
AFFERENT: OPTIC
- Retinal photoreceptors → ipsilateral optic nerve → nuclei of bilateral pretectal areas (nasal fibers of the optic nerve cross to the contralateral side at the optic chiasma)
EFFERENT: OCULOMOTOR
- The efferent pathway transmits neural impulses to the iris sphincter muscles:
- Nuclei of pretectal area → bilateral Edinger Westphal nuclei (parasympathetic preganglionic nucleus of the oculomotor nerve) → bilateral oculomotor nerves (synapse at the ciliary ganglion) → bilateral iris sphincter muscles → bilateral pupillary constriction.
Shining a light into one eye causes constriction of the ipsilateral pupil (direct pupillary reflex) as well as that of the contralateral pupil (indirect or consensual pupillary reflex).
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Which cranial nerves contain parasympathetic fibres?
3, 7, 9, 10
CNIII: ciliary ganglion to eye
CNVII:
pterygopalatine to nasal mucosa + lacrimal glands
submandibular ganglion to submandibular + sublingual glands
CNIX:
- Otic ganglion to parotid gland
CNX: all viscera of the thorax + abdomen
Craniosacral outflow (S2-4) provides parasympathetic outflow to rest of body
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A mass lesion of the cerebellopontine angle is most likely to impair function of which nerves?
CN V, VII, VIII
Normally occurs due to vestibular schwannoma + meningioma
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NOACs vs Warfarin for non valvular AF risks
- Reduced relative risk of ischaemic + haemorrhagic stroke 19%
- Reduced relative risk of haemorrhagic stroke 51%
- Increase in gastrointestinal bleed 25%
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What is the medication against dabigatran?
Idarucizumab
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When is the risk of recurrent ischaemic stroke the highest
In the first 2 weeks
| Following a minor non-cardioembolic stroke/TIA, DAPT for up to 30 days
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What are the risk factors for recurrence after TIA/Stroke
```
Strongest RF for recurrence
- Multiple infarctions on imaging
- Large artery atherosclerosis
- ABCD2 6-7
Age > 60
BP >140/90
Clinical features of TIA
Diabetes
Duration of symyptoms
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What antihypertensives should be used in the prevention fo stroke?
- All antihypertensives good EXCEPT beta blockers (increase the risk of ischaemic stroke unless you have ischaemic heart disease)
- Used CCB
125
What is indication for evolocumab?
- Reduces cardiovascular death, MI, stroke by 20% in patients with cardiovascular disease
- Benefit on top of intense statin therapy
- Used in familial homozygous hypercholesterolemia
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Summary of brain haemorrhage
- Hypertensive Haemorrhages
- Amyloid Angiopathy
- AVM
- SAH
Hypertensive Haemorrhages
- typically in small penetrating artery distribution, including BRAINSTEM
Amyloid Angiopathy
- Typically LOBAR
- Multiple MICROHAEMORRHAGES
AVM
- Can be anywhere
- Contrast may show a "leash" of draining veins
SAH
- Basal cisterns secondary to berry aneurysm
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Aim for BP in intracerebral haemorrhage
BP lowering < 140mmHg for the first 7 days
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Benefits of acute stroke unit
- Improves post stroke outcome
- Aim temp < 37.5, BSL < 11
- Swallow assessment
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Medical management of TIA
All TIAs must go home in a CAB
- Cholesterol lowering - aim LDL < 1.8
Statin +/- ezetimibe
```
- Antithrombotic
DAPT in first 3-4 weeks
1st line: aspirin
2nd line: clopidogrel or aspirin + dipyramidole
AC if AF
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Mediterranean diet involved in stroke reduction
- Blood pressure lowering
Aim BP <140/90
BB increase risk of stroke recurrence but indicated if concurrent IHD
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Carotid stenosis in stroke management
- Cerebral DSA (digital subtraction angiography) is gold standard
- MRA/CTA/Doppler can also be used
TX:
- Symptomatic extracranial carotid arteries with 70-99% stenosis need revascularisation.
- Stenting for the young < 65yo
- Otherwise favour CEA - carotid endarterectomy
- Extracranial dissection: risk of ischaemic stroke
- Intradural dissection: risk of fatal bleed/SAH
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Contraceptive pill and vascular risk
- Doubling of risk with estrogen-containing preparations (regardless of route)
Still negligible risk unless older, smoker or prior event
- No increased risk with progesterone only preparations
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Ventricles and their connections
- Lateral ventricle
- Foramen of Monro: connects lateral to 3rd ventricle
- Cerebral Aqueduct: connects 3rd to 4th ventricle
- Foramen of Magendie and Luschka: 4th ventricle to subarachnoid space
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Vessels of the circle of willis
- Anterior cerebral artery
- Anterior communicating artery.
- Internal carotid artery
- Posterior cerebral artery
- Posterior communicating artery
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What are the 2 parts of the substantia nigra
divided into two parts - the pars compacta and pars reticulata.
Parkinson's disease is characterized by the loss of dopaminergic neurons in the substantia nigra pars compacta.
Most of the neurons that project out of the pars reticulata are inhibitory GABAergic neurons (i.e., these neurons release GABA, which is an inhibitory neurotransmitter).
The pars compacta serves mainly as a projection to the basal ganglia circuit, supplying the striatum with dopamine. The pars reticulata conveys signals from the basal ganglia to numerous other brain structures
