Pathophysiology Flashcards
What can cause haemorrhagic stroke?
Ruptured Aneurysm
Head Trauma (Generally Subarachnoid or Intracerebral)
Dissection - carotid
What are the 2 types of stroke?
Haemorrhagic
Ischaemic
What are 3 forms of ischaemic stroke?
Cerebral Thrombosis
Cerebral Embolism - Thromboembolism, Fat Embolism, Air embolism
Lacunar stroke
What are some symptoms of stroke?
Weakness/Paralysis or numbness on contralateral side Vertigo/dizziness Headache Visual loss/blurred vision Faintness Confusion Speech problems Difficulty swallowing Cognitive problems Memory problems Consciousness alterations
What does FAST stand for in terms of stroke?
Facial weakness
Arm weakness
Speech problems
Time to call 999
What is the immediate stroke management plan?
FAST Scan – ischaemic or haemorrhagic Blood Tests Clot-Busting (4.5hr window) or haemorrhage evacuation Chest X-rays, ECG, Ultrasound
Which scans are best for each type of stroke?
CT – fast, easy to spot haemorrhage
DWI – best for ischaemic damage
Describe thrombolysis use in stroke management
Intravenous (IV) rtPA (Alteplase) within a 4.5hr window
Often stroke onset time unknown
If large clot burden, IV tPA poor response
Intra-arterial (IA) thrombolysis possible
Interventional neuroradioradiolgy - Endovascular thromboaspiration, Microcatheters can directly reach the thrombus
In which arteries might clot burdens be large?
Terminal carotid/proximal MCA and basilar
What are the 4 main types of CNS syndromes/infarct?
TACS (TACI) – Total Anterior Circulation Syndrome (ACA, MCA)
PACS (PACI) – Partial Anterior Circulation Syndrome
LACS (LACI) – Lacunar Syndrome
POCS (POCI) – Posterior Circulation Syndrome
What symptoms occur with Total Anterior Circulation Infarct?
Higher Dysfunctions Dysphasias Visuospatial problems Homonymous Hemianopia Motor/Sensory Deficits
What symptoms will lacunar infarcts produce?
Focal changes
Pure Motor or Sensory or Sensorimotor loss
Ataxic Hemiparesis
What symptoms occur with posterior circulation infarct?
Cranial nerve palsy & contralateral motor/sensory deficit
Bilateral motor or sensory deficit
Cerebellar signs
Eye Movement deficits/isolated homonymous hemianopia
What are cerebellar signs?
DANISH Dysdiadokinesia & dysmetria (overshoot) Ataxia Nystagmus Intention tremor Slurred speech Hypotonia
What are lacunar infarcts?
Small lesions – lake-like cavities, giving focal deficits
Common in brainstem regions and deep cerebral white matter
Occlusion of small vessels: Lenticulostriate, Thalamogeniculate
Brainstem perforating vessels
What are watershed infarcts?
Systemic hypotension causing infarct in areas of overlap of supply
Most common ACA-MCA infarct caused by occlusion of carotid artery
Man in a barrel- loss of trunk sensation/motor function and aphasia
MCA-PCA affects visual processing
Where are spinal watershed areas?
T4-T8 – watershed between radicular arteries (thoracic and great radicular artery)
L1 – watershed between Great radicular artery and ascending sacral arteries
What are main causes for adolescent strokes?
Hereditary CHD/AHD Congenital Abnormalities Trauma Infection Metabolic Neoplasia
What are transient ischaemic attacks?
Mini-Stroke, usually results from drop in perfusion, often: Carotid Artery Insufficiency, Vertebrobasilar Insufficiency
Symptoms same as Full Stroke
Amourosis fugax - loss of blood flow to retina
Severe symptoms for <30 mins
Full recovery within 24
Use it as a WARNING SIGN
How do you calculate the risk of stroke after a TIA?
ABCD2
A — Age: > 60 years, 1 point
B — BP: >140/90 mmHg, 1 point
C — Clinical features: unilateral weakness, 2 points; speech problems but no weakness, 1 point
D — Duration of symptoms: ≥ 60 mins, 2 points; 10–59 mins, 1 point
D — Diabetes: 1 point
Score ≥4, high risk of stroke
2 TIAs in close succession – high risk (even if ABCD2 <3)
1:10 TIAs with no treatment will have full stroke within 1 year
What assessment score is used for stroke risk in a patient with AF?
CHADVASC scale if patient has AF
What members of the MDT could be required in post stroke management?
Consultant physicians nurses physiotherapists occupational therapists speech and language therapists clinical psychologists rehabilitation assistants social workers
What are mortality rates post stroke?
20% mortality within first month
10% mortality within year
Rest recover but ~50% have disability
Recurrence rate 30-43%
What is post stroke pain?
Thalamic pain Occurs 1 week- 6 months after stroke
Can occur anywhere in spinothalamic system
Generally occlusion of thalamo geniculate arteries
Symptom (referred to contralateral side): Burning pain with sharp components, Hyperalgesia & Allodynia, Treat as for neuropathic pain (Amitriptyline)
What is vascular dementia?
Many vascular CNS events, including stroke
Multi-infarct dementia - from many small TIA
Single-infarct dementia - related to large stroke
Lacunar infarct – variable depending on size
Biswanger’s dementia – multiple lacunar infarcts caused by
arteriosclerosis of subcortical vessels
Multi-infarct dementia linked to step-wise progression in cognitive decline
Lifestyle changes/BP can prevent
Early detection vital
Early signs: vascular cognitive impairment, Slow thought, Difficulties planning, Speech impairment, Mood and behaviour changes, often mistaken for depression
Which patients are susceptible to sub dural haemorrhages?
Elderly and alcoholic
Due to neural shrinkage, bridging veins are under increased tension
What is a likely cause of a sub arachnoid haemorrhage?
Bleed here is from cerebral artery aneurysm
What can a meningioma lead to?
Can produce focal symptoms from cortical or cranial nerve compression
Raised ICP may cause multiple deficits, headache or loss of consciousness
What are the two layers of the dura mater?
Periosteal layer
Meningeal layer
Why can Periorbital infection spread from the orbit to the meninges?
Dura and subarachnoid space extend through the optic canal to the posterior of the orbit
Which artery runs past the pterion and is therefore at risk of rupture with a skull fracture?
Middle meningeal - extradural haemorrhage
What is a risk with an extradural haematoma?
Lucid period - patient will regain consciousness, seem fine and then suddenly collapse when pressure builds up
What innervates dura in the posterior cranial fossa?
And what clinical significance does this have?
Cervical spinal nerves
Compression of cervical nerves in neck can cause referred pain headache in occipital lobe
What carries sensory info from the meninges?
Trigeminal nerve (CN V) - Innervates a large amount of dura including the tenotoria CN V Also innervates face, sinuses and teeth – referred pain headaches possible
What feature allows rapid drainage of dural venous sinuses?
Valveless and endothelial lined
Where does the sigmoid sinus drain into?
Through jugular foramen
Into internal jugular vein
What drains the scalp?
Emissary veins through cranial bones to superior sagittal sinus
Where do periorbital veins drain?
Cavernous sinus. Form a route for orbital/nasal region infection spread
What is the Glasgow outcome score?
- Dead
- Vegetative state (sleep/wake cycle but not sentient)
- Severely Disabled (conscious but dependent)
- Moderately disabled (independent but disabled)
- Good recovery (may have minor sequelae)
What is diffuse axonal injury?
Trauma causes axon to twist and tear
Result is permanent death of the neuron
What are cardinal features of raised ICP?
Nausea
Papilloedema
Headache
What is the Monro-Kellie doctrine?
v.intracranial (constant) = v.brain + v.CSF+ v.blood + v.mass lesion
When should ICP be treated?
When above 20mmHg
What cranial perfusion pressure should be maintained?
Above 65mmHg
What is cerebral perfusion pressure?
CPP = MAP - ICP
What are Neurocritical care principles?
Free water (as dextrose solutions) NOT administered. Decrease plasma osmolality so increase water content of brain tissue Elevated blood sugar levels associated with worsening of neurologic injury after cerebral ischaemia. Ischaemic brain metabolises glucose to lactic acid, lowering tissue pH, exacerbating ischaemic injury Hypertonic solutions and osmotic diuretics (mannitol) - low molecular weight, osmotically active particles may leak into the cerebral interstitium, Mannitol - no effect in reducing brain water content
What Mental sequelae may exist in patients post head trauma?
personality disorders, memory disorders, reduced reasoning power, apathy, lack of drive, temper tantrums, family disruption
What is the most common neurological disorder?
Epilepsy
What are the main categories of epilepsy?
Partial and generalised
Which form of epilepsy has no loss of consciousness or post-ictal confusion and its symptoms depend on focal site?
Simple partial seizure
What symptoms might occur from a simple partial temporal seizure?
Aura-smell/taste, déjà vu, jamais vu, emotional changes, Oral automatisms, gestures eg dystonic or fidgetting
What symptoms might occur from a simple partial parietal seizure?
Sensory
Nausea, choking, sinking sensations
Illusions of body distortion
What symptoms might occur from a simple partial frontal seizure?
Brief, frequent, cluster, mainly motor, often bilateral eg kicking, cycling, violent, bizarre. Head version often from sleep
What symptoms might occur from a simple partial occipital seizure?
Visual hallucinations – simple or complex (shapes to scenes)
Vision may black out
Visuo-spatial distortions
Head turning, headache, nausea
What are complex partial seizures?
Altered consciousness, but may seem fully aware
Symptoms: automatisms (chewing, swallowing, repeated displacement
behaviour)
Prior to onset may experience senseof déjà vu/jamais vu, perceptual
changes, auras
Generally temporal lobe in origin, can progress to generalised
May have some post-ictal confusion
What is a Partial with Secondary Generalised seizure?
Simple partial seizure, patient conscious and aware progressing to generalised (Grand-Mal) when activity reaches thalamus
Temporal foci often associated with auras and hallucination
Frontal foci ‘motor seizures’, stiffness/jerking in limbs
Parietal foci ‘sensory seizures’, tingling/warmth on ipsi side
Occipital foci generally preceded by visual hallucinations light/colour
Which seizure type is characterised by tonic and clonic phases?
Generalised Tonic-Clonic (Grand-Mal)
What occurs in a tonic phase of a seizure?
whole body stiffness, breathing may stop (cyanosis), loss of bladder control
What is a post ictal period?
unconsciousness, muscle relaxation, slow regain of consciousness, confusion, sleepy, headaches and aching limbs, no recall of episode
What are the two forms of status epilepticus?
Convulsive - grand mal
Non convulsive - petit mal
Describe a convulsive status epilepticus seizure
Prolonged seizure state Whole brain involved Ictal period of > 5 mins Repeated seizures with no recovery between (>30 mins) Medical Emergency
What is a non convulsive status epilepticus seizure?
long-lasting, absence or focal-type seizures
What is an absence seizure?
Part of the generalised seizure spectrum
Rare in adults, generally starts between 6-12 yrs
Girls > Boys
Symptoms: seem to ‘switch-off’ but cannot be alerted or woken up
Responds well to anti-epileptics
What is NEAD?
Non-epileptic attack disorder, no physical reason or changes in brain activity, but has similar symptoms. Also known as psychogenic non-epileptic seizures. Bite tip of tongue, not sides as seen in grand mal
What is an EEG recording?
Activity patterns of populations of neurons by recording changes in
gross current flow
Levels of synchrony between neurons causes changes in patterns, if fire together give larger amplitude oscillations
Patterns of synchrony cause rhythms
What are the 5 rhythms seen on an EEG?
Alpha – 8-13Hz Mainly occipital, quiet, eyes shut, meditation
Beta >14Hz Parietal and frontal, activity and tension, sleep spindles
Gamma – 40Hz binding, learning and memory
Theta – 4-7Hz Parietal and temporal, alertness, L&M
Delta <3.5 Hz Cortical, deep sleep, coma
What 4 things can cause changes in neuronal excitability and lead to epileptic activity?
Reduction in GABA
Increase in Ach transmission
Increase in Na+ transmission
Decrease in K+ transmission
What are first line Treatments for Partial Seizures and Partial with Secondary Generalised seizures?
Carbamazepine Lamotrigine Oxcarbazepine Sodium valproate Levetiracetam
What are Second Line (adjuncts) treatments for partial seizures?
Clobazam, gabapentin, topiramate
What are first line treatments for grand mal seizures?
Sodium valproate
Lamotrigine
Carbamazepine
Oxcarbazepine
What are first line treatments for petit mal seizures?
Ethosuximide
Sodium Valproate
What treatments are given in an emergency situation for convulsive status epilepticus?
Commence i.v. Lorazepam (repeated after 10 mins)
After 25 mins: phenytoin sodium, fosphenytoin, or phenobarbital sodium
After 45 mins: Anaesthetize with thiopental, midazolam or non-barbiturate anaesthetic (propofol)
Buccal Midazolam/Rectal diazepam (if resus facilities not available)
What treatments are suitable for NEAD?
Remove any AEDs in use
Antidepressants
Psychotherapy
What is Antiepileptic Hypersensitivity Syndrome? And what do you do about it?
Starts 1-8 weeks from treatment initiation
Initial signs: Fever, rash, swollen lymph nodes
Severe signs: Blood, liver kidney and respiratory abnormailites, Vasculitis and organ failure
Withdraw drug immediately
Topical steroids and antihistamines for rash
Systemic corticosteroids?
Beware of rebound seizure activity
What are the generalised mechanisms of action of anti epileptic drugs?
Sodium Channel Blocker Calcium Channel Blocker GABA modulation GABA mimetics Most are dirty drugs so have multiple actions
How do Na channel blockers work as anti epileptic drugs?
Primarily targeted for voltage-dependent Na+ channels
Only block channels in inactivated state to reduce electrical activity by extending refractory period
Which antiepileptic drugs have Na channel blocker activity?
Phenytoin
Carbamazepine
Lamotrigine
Sodium Valproate
What are side effects of Na channel blocking AEDs?
CNS effects, cognitive impairment, visual impairment Peripheral neuropathy Skin problems Gum hyperplasia Anaemia and other blood disorders Osteomalacia Teratogenicity
In what ways can AEDs affect GABA activity?
Enhance activation of GABA-A mediated channels Action at co-agonist sites Inhibition of GABA breakdown Inhibition of GABA uptake GABA mimetics
How do benzodiazepines work as AEDs?
Act on GABAA receptor (γ subunit) to increase activity as co agonist
Reduces neuronal transmission by enhancing inhibition
What is Flumazenil?
Benzo antagonist
Included in coma cocktails
What are barbiturates?
Work in same way as benzos but on the β-subunit of the GABAA receptor to increase activity
Reduces neuronal transmission by enhancing inhibition
Commonly used as anaesthetics/anxiolytics
What are Side Effects of BDZs and Barbs?
Short-term use only (< 12 weeks) Tolerance and dependency can develop Impaired motor coordination (↓muscle tone) Impaired cognitive performance Sedation Disturbed sleep patterns (↓SWS) Retrograde amnesia Withdrawal on termination
What is Tiagabine?
Act to inhibit GABA transporter so prevent its reuptake
What is Vigabatrin?
Act to inhibit GABA transaminase so prevent GABA breakdown
Which AEDs block calcium channels?
Ethosuximide (T-type Ca2+ blocker)
Gabapentin
What are some future AED targets?
Glutamate Antagonists
Gap Junction inhibitors
Steroids
Broad spectrum drugs (e.g. Topiramate,Levetiracetam)
Which AED can be used to treat trigeminal neuralgia?
Carbamazepine
What AED and antidepressant combo can be used to treat neuropathic pain?
Gabapentin and Amitriptyline
What arteries make up the circle of Willis?
Anterior cerebral artery (ACA) Anterior communicating artery (AComm) Middle cerebral artery (MCA) Posterior cerebral artery (PCA) Posterior communicating artery (PComm) Basilar artery (BA)
Explain why a haemorrhage into the pons could cause a sudden and profound unconsciousness
Damage to reticular formation
Explain why performing a lumbar puncture in a patient with raised ICP might be disastrous
Coning
What are the signs of decerebrate rigidity?
Extension of arms and legs and medial rotation of arms
Describe herniation syndrome
Supratentorial swelling; uncus forced through opening in tentorium cerebelli; pressure on midbrain; rise in pressure in posterior fossa; coning of medulla and cerebellar tonsils in foramen magnum
What type of disorder is MS?
An autoimmune demyelinating disorder
In the CNS which cells are responsible for the production of the myelin sheathing around axons?
Oligodendrocytes
Diagnosis of MS is supported by lumbar puncture and CSF analysis. What is a common feature of CSF from MS patients?
The presence of oligoclonal bands is supportive of a diagnosis of MS. Oligoclonal bands indicate that a CNS immune response has been triggered; between 2 and 5 bands present suggests the presence of immunoglobulins (IgG)
One of the characteristic feature of early MS is optic neuritis. What is optic neuritis and why is the optic nerve susceptible to degeneration in MS?
Optic neuritis: inflammation of optic pathways visible on fundoscopy
Optic nerve and tracts are actually developmental extensions of CNS, myelin coating is provided by oligodendroglial cells. When function is disrupted it can trigger inflammatory responses which results in optic neuritis
Besides the relapsing remitting type, what other forms of MS exist?
Primary progressive Secondary progressive Relapsing progressive Benign Spinal fomr Neuromyelitis optica (Devic disease) Marburg variant
How does benign MS differ from relapsing-remitting MS?
Benign MS marked by episodes of neurological deficit that return to normal in between. Relapsing remitting, early stages are characterised by a return to normal following episodes but as the disease progresses there is incomplete recovery and a gradual decline in function. Late in the disease this becomes more progressive in nature. No such decline is seen in benign MS
Which therapeutic drugs are available for MS?
Symptomatic only: muscle relaxants (baclofen, benzodiazepines); short term use of steroids (e.g. methylprednisolone) for reducing inflammatory responses during relapses and analgesics for pain
Interferon-beta and glatiramer are licenced for the treatment of relapsing-remitting MS
What dietary supplement(s) are suggested to be beneficial to MS patients?
healthy, balanced diet
Linoleic acid found in seed oils, nuts and seeds, certain supplements, including evening primrose oil
Vitamin D
42 yo man admitted to ED suffering paralysis of lower limbs, severe pain in legs and dysphagia. Symptoms came on over 3 days, started out as tingling sensation in legs, weakness and unsteadiness. Two weeks prior - minor cold and tickly throat. Which demyelinating disorder could account for all of the patient’s symptoms?
Guillain barré syndrome
What are two main treatments available for Guillain-barré syndrome?
IV immunoglobulin (IVIg) plasma exchange (plasmapheresis)
