Non-operative viva Flashcards
Explain how PET works
A radiolabelled tracer, such as Fluoride-18 is added to a ligand, such as Glucose. This is administered to the patient and the patient is placed into PET scanner which is a circumferential array of gamma cameras. As the tracer released positrons, these annihilate with electrons releasing gamma rays that are detected by the array. This is combined with a CT or MRI scan to provide spatial resolution. Based on the ligand, this is important for epilepsy and oncological investigations.
How should you structure your answers for this section?
Define > Classify > Amplify. e.g. neuroprotection is the stabilisation or correction of physiological parameters to prevent secondary brain injury. Common mechanisms include preventing excitotoxicity, improving cerebral perfusion, reducing the CMR02 and reducing ICP. These mechanisms work to reduce the metabolic requirements in the ischaemic penumbra, reduce the inflammatory response and improve oxygenation ang glucose supply to the brain thus reducing secondary injury to surrounding vulnerable cells.
What are the immediate management steps for a patient with a severe head injury?
The patient should be assessed in accordance with the ATLS algorithm by an experiences trauma team. The C-spine should be immobilized and the airway should be secure. If the GCS is less than 8 or the patient is combative then they should be intubated and ventilated with a cuffed ET tube. The ventilatory parameters should be optimised to ensure a pO2 = 13 KPa and pCO2 = 4.5-5 KPa. The haemodynamic parameters should achieve a MAP = 90 with a CPP = 60-70. Life-threatening injuries should be identified and treated. The patient should then have an assessment of their neurological status including GCS, pupils and any localizing or lateralizing signs.
How is CBF calculated?
CBF = CPP / CVR Normal = 50ml/100g/min (25 to WM and 75 to GM) Ischaemia = <20 ml/100g/min Cell death = <10 ml/100g/min
How is cerebrovascular resistance controlled?
- Metabolic-flow coupling 2. Pressure autoregulation - myogenic (likely impaired in head injury) 3. pO2 and pCO2 4. Neural control (sympathetics)
What is autoregulation?
The ability of the cerebral vasculature to maintain a constant CBF across a range of physiological MAPs through changes in the caliber of arterioles.
What is ICP?
The gold-standard is the pressure of CSF within the right frontal horn of the lateral ventricle. This is also measured from the parenchyma, the arachnoid or subdural spaces.
How do ICP monitors work?
Strain gauge Optical Pneumatic
What are the peaks of the ICP wave?
A - percussion - cardiac output B - Tidal - brain compliance C - Dichrotic - closure of the aortic valve In a non-complicant brain A=B=C whereas normally A>B>C.
What are Lundberg waves?
A = Sustained elevations in ICP>50 mmHg for >5 minutes.
B = Rise up to 25 mmHg for < 5 minutes
C = Physiological fluctuations in ICP seen every 10 seconds.
How does CBF change with pO2, pCO2, MAP?
CBF falls as pO2 increases and flattens off at 50 ml/100g/min
CBF rises as pCO2 rises. Optimal pCO2 is 4.5-5 KPa. Below this, it will induce ischaemia.
What temperature should be maintained in head injury?
Normothermia - based on the Eurotherm trial, where aggressive cooling below 35 deg resulted in poorer outcome.
How do you manage raised ICP in ITU?
I would go to assess the patient and ensure the HOB is 30 deg and that any tight-fitting collars were loosened to aid venous return.
I would ensure the patient is I&V and paralysed with physiological parameters were optimised, namely that the pO2 >13 kPa, pCO2 4.5-5 kPa, MAP >90 mmHg and if an ICP bolt is in situ then the optimal CPP can be measured utilising the pressure reactivity index.
I would ensure that the patient is normothermic, normoglycaemic and any metabolic derangements e.g. hypoNa have been corrected.
I would then institute hyperosmlar therapy using hypertonic saline 5% at 2-4ml/Kg/hour infusion until the serum osmo 320 or Na 150.
If ventricles are of an appropriate size I would also conder EVD insertion.
If these factors fail and the ICP remains refractory then I would undertake a decompressive hemicraniectomy as per the Rescue ICP trial.
What is the BBB?
This is a physiological barrier between the systemic circulation and the brain parenchyma. It is formed by endothelial tight junctions within capillaries. The BBB is absent at the circumventricular organs: posterior pituitary, lamina terminalis (organum vasculosum), tuber cenereum (median eminance), pinal gland, subforniceal organ and area postrema. **It is present at the subcommissural organ**
What are the types of cerebral oedema?
Cytotoxic e.g. stroke
Vasogenic e.g. tumour / infection
Interstitial e.g. hydrocephalus
Osmotic e.g. hypoNa
Is decompressive hemicraniectomy more efficacious in children?
A single RCT from 2001 showed decompressive craniectomy resulted in a favourable outcome in 54% compared to 14% in the medical group.
In RescueICP ages ranged from 10-65 years whilst in DECRA it ranged from 15-60 years.
How are seizures classified?
The ILAE 2017 operational classification of seizures is Focal, Generalised and Unknown. Focal seizures are divided into motor and non-motor and also into aware or impaired awareness (dialeptic). Generalised seizures are Motor or non-motor (absence). Unknown seizures are motor, non-motor or unclassified.
What are the different types of motor seizures?
GTCC
Tonic
Clonic
Atonic
Myoclonic
Epileptic spasms
Hyperkinetic
What is the definition of a generalised seizure?
Bilateral hemispheric symmetrical and synchronous onset with loss of consciousness from the start (40% of all seizures). Classified as motor or non-motor.
What are clonic seizures?
Bilateral synchronous semirhythmic jerking with elbow flexion and knee extension
What are tonic seizures?
Sustained increase in tone. Characteristic cry or grunt.
What are absence seizures?
Impaired consciousness with no motor involvement and no post-ictal confusion. EEG shows 3 Hz spike and wave.
Tx = Ethosuxamide
What are myoclonic seizures?
Shock-like body jerks with generalised EEG changes. “Messy breakfast” - worse in the morning.
Tx = valproate
What are atonic seizures?
Sudden loss of tone that causes falls.
What are psychomotor seizures?
Alteration of awareness with automatisms and aura (usually epigastric rising sensation)
What is the characteristic feature of a seizure arising in the uncus?
Olfactory hallucinations - cacosmia = perception of a bad odour
What is the role of the hippocampus?
Spatial memory (dominant), verbal memory (non-dominant) and learning concepts
What are the common semiological features of a mesial temporal lobe seizure?
Behavioural arrest, staring, oral automatisms, posturing of the contralateral arm. Seizures last a few minutes and post-ictal confusion, amnesia and aphasia (if dominant side).
What are the characteristic EEG features in mesial temporal lobe epilepsy?
Rhythmic theta (4-8 Hz) maximal in basal temporal electrodes
What is Lennox-Gastaut syndrome?
Atonic seizures resulting in drop attacks
Medically refractory
Valproate reduces seizure frequency by 50%
Corpus callosotomy is the treatment of choice
What factors lower seizure threshold?
Sleep deprivation
Hyperventilation
Photic stimulation
Infections / Drugs / Metabolic disturbances
Trauma / Stroke
What is Todd’s paresis?
Post-ictal weakness due to involvement of the motor cortex in the functional deficit zone
What are the classes of antiepileptic medications?
Barbiturates - phenobarbital
Benzodiazepines - lorazepam / diazepam
GABA analogues - gabapentin
Voltage-gated sodium channel blockage - phenytoin / carbamazepine
Synaptic vesicle protein (SV2A) blockage - levetiracetam
Which antiepileptic drugs interfere with platelet function?
Valproate and Phenytoin
What is the drug of choice for GTCS?
Valproate
Phenytoin
Levetiracetam
What is the drug of choice for focal seizures?
Carbamazepine
Phenytoin
Levetiracetam
(Valproate is second line)
What is the action of sodium valproate?
Voltage-gated sodium channel blocker
Calcium channel ‘T current’ blocker
What are the pharmacokinetics of phenytoin?
1st order (eliminiation proportional to concentration) then zero-order (elimination at constant rate i.e. elimination saturated). Half-life 24 hours. Aim for therapeutic levels 10-20 mcg/ml. Serum binding is affected by urea and albumin levels i.e. in hypoalbuminaemia the active phenytoin level is higher than expected (because 90% is protein bound). The correction is calculated by the Sheiner-Tozer equation.
How does NG feed affect phenytoin levels?
Absorption is decreased by 70% when given with NG feeds. The feed should be held for 2 hours before and 1 hour after.
What are the cardiac effects of phenytoin?
Hypotension
Arrhythmias - bradycardia
(Should be given as slow IV with cardiac monitoring and BP check at a max rate of 50 mg/min). Note the loading dose is 18 mg/kg and maintenance is 300-500 mg per day i.e. 100 mg TDS.
What are the advantages of fosphenytoin?
Fosphenytoin is a prodrug that is converted to phenytoin
Less venous irritation
Can be given IM
Fewer arrhythmias and can be given 2x as fast as phenytoin, therefore.
What are the side effects of phenytoin?
Purple glove syndrome in the elderly
Diffuse maculopapular rash
Cognitive slowing
SLE-like syndrome
Megaloblastic anaemia
Cerebellar degeneration
Gingival hypertrophy
Neonatal haemorrhage
TEN / Steven-Johnsons
Osteoporosis / rickets
Teratogenic
What factors require phenytoin dose adjustment?
Albumin and Ureamia
(Renal failure without uraemia does not need adjustment)
Scheiner-Tozer equation
What effect does carbamazepine have on hepatic enzymes?
Auto-induction - induces the hepatic enzymes to increase metabolism of itself and other drugs
What are the common signs of carbamazepine toxicity?
Diplopia
Ataxia
Drowsiness
Marrow suppression - Leucocytopenia
SIADH
Steven-Johnsons syndrome
What is the benefit of oxcarbazepine over carbamazepine?
No need for monitoring
No Cytochrome P450 induction so minimal drug interactions
BD dosing
Linear kinetics
Fewer side effects
What is the main concern with valproate in women of childbearing age?
Causes neural tube defects
What is the drug of choice for absence seizures?
Ethosuximide
How do you manage an adult with a new-onset seizure?
History / examination
Bloods to rule out infectious or metabolic causes
EEG +/- sleep deprivation EEG
MRI
What is the incidence of seizures within the first 7 days of a severe head injury?
30%
What is the risk of post-traumatic seizures following a penetrating head injury?
50%
What is the role of seizure prophylaxis following head injury?
In severe head injury, phenytoin reduces the risk of seizures by 73% for the first week but does not affect long term seizure rates. (Ref Temkin et al NEJM 1990 Double-blinded RCT)
What features are suggestive of non-epileptic seizures?
Arching of the back
Asychronous movements
Forced eye closure
Bilateral shaking with preserved awareness
Weeping
What is the definition of status epilepticus?
Seizure >5 minutes or persistent activity after 1st and 2nd line AEDs
What % of seizures that persist >5 mins will continue >1 hour?
60%
What is the management of status epilepticus?
ABCs
Bloods incl glucose, electrolytes & AED levels
Lorzepam / midazolam / diazepam > phenytoin / levetiracetam / valproate > I&V midazolam or propofol > If continues to sz despite above then phenobarbital
CT head
** If low glucose give thiamine first before dextrose to prevent wernicke’s encephalopathy
How does Carbamazepine work?
Blocks voltage-gated Na channels. Risk of drowsiness, diplopia, ataxia, marrow suppression, stevens johns syndrome and hepatitis.
How does Valproate work?
Voltage gated Na channels
GABA action
T-type Ca channels
Side effects are teratogenicity, thrombocytopaenia, hepatotoxicity and high ammonia
How does Gabapentin work?
Voltage-gated Ca channel blockade
GABA-B receptor blockade
How does ethosuxamide work?
T-type Ca currents in the thalamus. Used for absence seizures!
How does perampanel work?
AMPA antagonist
How does phenytoin work?
Voltage-gated Na channel blockade
What the management of seizures in pregnancy?
Monotherapy with the lowest possible dose of carbamazepine (focal) and lamotrigine or Keppra (generalised).
Proper seizure control is the primary goal. The risk of maternal and fetal hypoxia/acidosis with seizures outweighs the risk of teratogenicity from AEDs.
Give 5 mg/day (normal dose is 400 mcg) of folic acid prior to conception and continue the intake until at least the end of the first trimester.
What is the equation for osmolality?
= 2x ([Na] + [K]) + urea + glucose in mmol/l
What is the [Na] in normal saline?
0.9% which means 9g per litre
Define SIADH
Hypotonic hyponatraemia with serum osmo <275 (dilute) and inappropriately concentrated urine with urine osmo >100.
What is the difference between CSW and SIADH?
CSW has extracellular fluid depletion due to renal sodium loss. Renal [Na] >20.
What is the classification of the severity of hypoNa?
Mild <135, Moderate <130 and Severe <125
What is the cause of a low Na in a dry patient i.e. Na <135 and serum osmo >295?
Hyperglycaemia or mannitol administration
What is the cause of a low Na in a hypotonic patient i.e Na <135 and serum osma <275?
If urine osmo dilute (urine osmo <100) then psychogenic polydipsia or low Na intake. If urine osmo conc (urine osmo >100) then check volume status. If dry and urine Na >20 then CSW / diuretics / Addison’s disease. If dry and urine Na <20 then extrarenal losses of Na such as GI tract or burns etc. If euvolemic then SIADH If hypervolaemic and urine Na >20 then renal failure or hypothyroidism. If hypervolaemic and urine Na <20 then CHF and cirrhosis.
What is the treatment for SIADH?
Fluid restriction
What is the treatment for CSW?
Volume replacement and Na replacement
Fludrocortisone can be used for low Na if refractory
What is the incidence of SIADH and CSW in SAH?
SIADH 35% and CSW 20%
What are the causes of isotonic hyponatraemia?
Osmo 275-295: pseudohyponatraemia due to hyperlipidaemia or hyperparaproteinaemia;
What are the causes of hypertonic hyponatraemia?
Osmo >295: Hyperglycaemia / mannitol administration
What are the causes of hypotonic hyponatraemia?
Osmo <275: Urine osmo <100 - psychogenic polydipsia Urine osmo >100 - depends on fluid status Hypervolaemic: Renal failure if urine Na >20 and CHF / cirrhosis if urine Na <10 Euvolaemic: SIADH Hypovolaemic: CSW / Addisons if urine Na >20 and GI tract or skin losses if urine Na <10
What are the causes of SIADH?
Malignancy Infection (meningitis / encephalitis / TB) Pulmonary disorders Endocrine disturbances (adrenal insufficiency / hypothyroidism) Drugs
What are the diagnostic criteria for SIADH?
Serum osmo <275 (hypotonic) Urine osmo >100 (inappropriately conc urine) Clinically euvolaemic Urinary Na >40 Normal thyroid and adrenal function No diuretic use
What is the most rapid recommended correction of Na?
8 mmol/24 hours
What urine osmo is suggestive of SIADH?
>100 mOsm/kg
What is the definitive test for SIADH?
Water load test: Give a water load of 20ml/Kg (max 1.5L). Urine output should be 2/3 of the water load at 4 hours, otherwise the patient has SIADH.
What is the contraindication to the water load test?
Na<125 or symptomatic hyponatraemia
How would you treat a patient with acute (<48 hours) and severe hypoNa (Na<125)?
ICU transfer 3% saline (1-2 ml/h/kg body weight) with 20mg Frusemide Check Na every 2 hours and adjust 3% saline infusion rate Replace K Max correction 8mEq/24 hours
How would you treat a patient with chronic (>48 hours) and severe hypoNa (Na<125)?
Fluid restriction based on the solute ratio For refractory cases consider demeclocycline (partial antagonist to ADH in the renal tubules) or conivaptan (vasopressin receptor antagonist)
How can CSW be differentiated from SIADH?
CVP, volume status and serum K (raised in CSW but not SIADH). Haematocrit is raised as patient is dry.
What is the treatment of CSW?
0.9% or 3% saline; salt can also be administered orally. Other treatments include fludrocortisone, hydrocortisone
What is the action of ADH?
Water absorption from the collecting ducts through Aquaporin channels
Interpret this UL SSEP
Top trace is over central sulcus (C3) - N19 - primary sensory cortex (+ so downward deflection) and P22 is motor cortex (- so upward deflection)
Middle trace is placed over the cervical region and shows activity at the root entry zone.
Bottom trace is with electrode placed over the brachial plexus (Erb’s point) and shows the stimulation passing through the brachial plexus
Interpret this LL SSEP
L5-T12 shows activity in the lumbar plexus (positive deflection P22)
Cv7 (cervical electrode) shows activity in the dorsal columns - N27
Cz - shows P40 activity at the sensory cortex
Comment on these NCS results
DML between 4.5-6.5 with SNAPs present = Moderate CTS on the Canterbury scale
How is cordotomy performed?
Mostly performed percutaneously at C1/2 using CT guidance. Palliative procedure in patients with <6 months prognosis.
A radiofrequency needle is inserted into the anterior lateral cord and an ablation is performed within the lateral spinothalamic tract. There is a somatotopy to the tract with C = anterior and S = posterior.
What are the side effects of VIM stimulation?
Paraesthesia (too posterior - stimulation of lemniscal fibres entering the ventralis caudalis nucleus)
Dysequilibrium (due to ZI stim)
Dysarthria (too medial - stimulation of the medial Vim) or too lateral if also associated with muscle contractions - stimulation of the internal capsule)
Ataxia (too ventral and medial - stimulation fo the brachium conjunctivum)
High voltages needed for tremor suppression (too anterior due to stimulation of the ventralis oralis posterior)
Phosphenes (too deep - optic tract stimulation)
What side effects are expected with the following electrode locations for Vim stimulation?
a - electrode is too anterior and within the VOP - requires high voltages to induce tremor suppression
b - electrode is too short within the Vim - will likely not to result in any tremor suppression.
c - electrode too posteroir and within the ventralis caudalis nucleus - will likely results in paraesthesias due to leminiscal fibre stimulation
What side effects are expected with the following electrode locations for Vim stimulation?
a - medial location within the Vim. Likely to result in dyarthria.
b - deep location stimulating the ZI and brachium conjunctivum. Likely to cause ataxia.
c - lateral location so within the internal capsule. Likely to cause dysarthria and facial pulling movements/dystonia.
Label the adjacent structures to the STN (axial and coronal images shown)
Superior = ventralis oralis anterior / ZI (stim results in tremor suppression)
Inferior = Substantia nigra (stim results in akinesia)
Medial and deep = midbrain / CN3 nuclus (double vision and gaze deviation)
Anterior or Lateral = internal capsule (dysarthria and muscle contraction)
Posterior = (perspiration and mydriasis)
What are the side effects of incorrectly placed DBS electrodes?
Based on the target:
STN / VIM / GPi
What is the direct pathway in PD?
In normal circumstances the direct pathway causes movement and the indirect pathway prevents movement.
Direct pathway - motor cortex stimulates the striatum (Caudate + putamen). The striatal GABA release inhibits the GPi. The GPi release of GABA on the thalamus is reduced so excitign the motor cortex and allowing movement. The STN excites the SNc. DA neurons from the SNc then release DA on the D1 striatal neurons and increases the GABA release on the GPi. There is negative feedback between the SNc and STN.
*The DA from the SNc on the D1 in the striatum amplifies the DIRECT pathway
What is the indirect pathway in PD?
Indirect pathway inhibits motor movement.
Motor cortex stimulates the striatum. The striatum GABA inhibits the GPe. The GPe release of GABA on the STN is therefore reduced so the STN activation of the GPi increases. The GPi inhibition of the thalamus increases which then inhibits the motor cortex. This prevents movement. The STN activity also stimulates the SNc. The SNc then releases DA on the striatum and activates the DIRECT pathway i.e. negative feedback loop.
What are Onodi cells?
Posterior extension of the ethmoidal air sinus to the sphenoid sinus. Risks damage to the optic nerve.
