Intracranial Flashcards
(61 cards)
1
Q
Name 1 toxin that can cause peripheral vestibular disease and 1 that can cause central vestibular disease
A
- Peripheral: aminoglycosides, topical otic medications
- Central: metronidazole
2
Q
What are the definitions of:
- seizure
- reactive seizure
- epileptic seizure
- epilepsy
- cluster seizures
- status epilepticus
A
- Seizure = any sudden, short-lasting, transient neurological event caused by excessive electrical neuronal discharge
- Reactive seizure = seizure due to normal brain response to disturbance in function (metabolic / toxic)
- Epileptic seizure = excessive synchronous epileptic activity of neurons in the brain
- Epilepsy = at least 2 unprovoked epileptic seizures of any type occurring at least 24 hours apart, resulting from a disease in the brain
- Cluster seizures = 2 or more seizures in a 24-hour period
- Status epilepticus = seizure activity that lasts for more than 5 minutes, or occurrence of 2 or more seizures without recovery of consciousness in between
3
Q
What are the criteria for diagnosis of idiopathic epilepsy
A
All need to enter in definition of epilepsy = at least 2 unprovoked epileptic seizures > 24h apart
- Tier I:
- Age at seizure onset 6 months - 6 years
- Normal inter-ictal neurologic and physical exam
- Normal bloodwork / UA - Tier II:
- Normal fasting and post-prandial bile acids
- Normal brain MRI
- Normal CSF - Tier III:
- EEG abnormalities characteristic for seizure disorders
4
Q
When are brain MRI and CSF analysis recommended in dogs with epileptic seizure(s)
A
(Only once reactive seizures have been ruled out)
- Age at epileptic seizure onset <6 months or >6 years
- Interictal neurological abnormalities
- Status epilepticus or cluster seizures
- Presumptive diagnosis of idiopathic epilepsy and resistance with a single anti-epileptic drug at highest tolerable dose
5
Q
What is the pathophysiology of brain damage in status epilepticus
A
- Neuronal necrosis due to ATP depletion and lactate accumulation from increased metabolic rate
- Neuronal necrosis due to increased intracellular iCa from continuous stimulation
- Vasogenic cerebral edema due to increased cerebral blood flow from metabolic demand
- Cytotoxic cerebral edema due to failure of Na/K ATPase from ATP depletion
6
Q
What are the 2 phases of systemic effects of status epilepticus
A
- Phase I: increased catecholamines and cortisol -> tachycardia, hypertension, hyperglycemia, hyperthermia, ptyalism
Can cause arrhythmias, NCPE, rhabdomyolysis, acute tubular necrosis - Phase II (after ~ 30 min of seizures): failure of cerebral blood flow autoregulation and compensatory mechanisms -> systemic hypotension, hypoglycemia, hypoxia, acidosis, hyperkalemia, increased intracranial pressure, decreased cerebral blood flow
7
Q
When is initiation of anti-epileptic medication recommended for dogs with idiopathic epilepsy?
A
- Inter-ictal period < 6 months (2 or more seizures in 6 months)
- Status epilepticus or cluster seizures
- Severe post-ictal signs or lasting > 24h
- Increasing frequency or duration of epileptic seizures
- Anti-epileptics should always be started in case of seizure due to brain lesion or with history of TBI
8
Q
What is the therapeutic range of phenobarbital levels? When should levels be monitored?
A
Dogs: 25-35 mg/L = ~100-150 umol/L
Cats: 15-45 mg/L = 65-190 umol/L
Levels should be measured 2 weeks after starting or any change in dose, 6 weeks after starting, and then every 6 months
9
Q
What is the definition of refractory status epilepticus and super-refractory status epilepticus
A
- Refractory SE: SE that does not respond to first-line anticonvulsant therapy
- Super-refractory SE: SE continuing or recurring more than 24 hours after initiation of treatment with anesthetic therapy
10
Q
What are the 4 stages of status epilepticus and their treatment recommendations
A
- Stage 1 = impending SE (5-10 min)
Can use first line treatments (benzodiazepines) - Stage 2 = established SE (10-30 min)
Responsiveness to benzo starting to decrease, add second-line (non-anesthetic agents) - Stage 3 = refractory SE (> 30 min)
Minimally responsive to 1st line and 2nd line treatments should use 3rd line (anesthetic agents) - Super-refractory SE (> 24h)
Likely minimally responsive to everything
11
Q
What are mechanisms of refractoriness in status epilepticus
A
- Internalization of GABA-A receptors (gamma subunits) + conversion to less benzodiazepine-sensitive ones
- In later stages, internalization of potassium-chloride transporter -> increased intracellular Cl
- Over-expression of NMDA receptors -> increased sensitivity to glutamate
- Over-expression of blood brain barrier drug transporters (eg. P-glycoprotein) -> drug efflux
12
Q
What are recommended first-line / second-line / third-line medications for status epilepticus management
A
- First-line: benzodiazepines
- IV or IN midazolam
- IV diazepam (2nd choice)
- (IM midazolam less recommended)
-> give up to 4 boluses within 60 min at > 2 min intervals +/- CRI if responded after more than 2 boluses (midazolam > diazepam) - Second-line:
- IV phenobarbital (IM or rectal less recommended)
- IV levetiracetam
- IV fosphenytoin if no response to first 2 - Third-line: anesthetic medications
- First step = IV ketamine bolus +/- CRI, IV dexmed bolus and CRI if no response
- Second step = propofol bolus and CRI
- Third step = anesthetic barbiturates (pentobarbital, thiopental)
- Fourth step = anesthetic inhalants
13
Q
If anesthetic medications are required to stop status epilepticus, for how long should they be continued
A
24-48h without seizure activity before discontinuation (but can try 12h)
14
Q
How should anti-epileptic drug CRIs be weaned
A
By 25-50% every 4-6h while no seizures ; increase to previous seizure-free dosage if seizures happen again
15
Q
What are the 3 steps in management of cluster seizures in hospital
A
- First step:
- IV midazolam or diazepam
- IN midazolam
- IM midazolam
- IV levetiracetam (IM or rectal less recommended) - Second step:
- Midazolam CRI (diazepam 2nd choice)
(Mostly for at home:)
- Oral long acting benzo (clorazepate, clonazepam)
- Additional doses of maintenance anti-epileptic drugs (pheno)
- Third step: anesthetic medications
- 1= IV ketamine bolus +/- CRI, IV dexmed bolus and CRI if no response
- 2 = propofol bolus and CRI
- 3 = anesthetic barbiturates (pentobarbital, thiopental)
- 4 = anesthetic inhalants
16
Q
What anti-seizure medications are recommended if no IV access is available
A
- IN midazolam
- or IM midazolam (2nd choice)
- or rectal diazepam (3rd choice)
17
Q
What benzodiazepine should be preferred for CRI
A
Midazolam
18
Q
What therapies can be attempted if everything fails at controlling status epilepticus
A
- Magnesium
- Hypothermia
- Neurostimulation
19
Q
How is the relation ship between intracranial volume and intracranial pressure
A
Exponential due to initial homeostatic mechanisms of the brain
20
Q
What are MAP and CPP goals for a patient with increased ICP
A
MAP > 80 mmHg (Doppler >100 mmHg)
CPP 50-90 mmHg, aim for 60 mmHg (if ICP measurement available)
21
Q
What are benefits of mannitol used for management of increased ICP? For how long does it last?
A
- Decreases blood viscosity (plasma expansion) (immediate, within minutes) -> increased cerebral blood flow –> better O2 delivery –> cerebral vasoconstriction –> reduced cerebral volume and ICP
- Osmotic effect (15-30 min after administration) ->decreased water content of cerebral cells, decreased ICP
- Free radicals scavenging
Effect supposed to last 1.5-6 hours (begins within minutes, peaks at 15-20 min)
22
Q
Name 2 contra-indications of mannitol administration for management of increased ICP in a context of trauma
A
- Uncorrected hypovolemia
- Ongoing intracranial hemorrhage
23
Q
What are the 3 types of primary injury in TBI
A
- Concussion -> brief loss of consciousness, no histopathologic lesion
- Contusion -> brain parenchymal edema and hemorrhage (on site of impact = “coup” lesion or opposite site = “contre-coup” lesion) - unconsciousness for more than several minutes
- Laceration -> physical disruption of brain parenchyma with axial or extra-axial hematoma
24
Q
Explain the pathophysiology of secondary injury in TBI
A
- Intracranial mechanisms
- Increased ICP from hemorrhage, mass lesions, edema -> hypoperfusion -> neuronal death
- Release of excitatory neurotransmitters -> influx of Na and iCa in neurons -> neuronal swelling (Na) and necrosis (iCa)
- Excessive metabolic activity -> ATP depletion -> neuronal necrosis
- Hypoperfusion, acidosis, hemorrhage (source of iron) -> ROS production -> oxidative injury (lipid-rich environment) - Contributing systemic insults
- Hypotension
- Hypoxemia
- Systemic inflammation -> NO production, arachidonic acid cascade, coagulation cascade, disrupted blood-brain barrier
- Hyperglycemia / hypoglycemia
- Hypercapnia / hypocapnia
- Hyperthermia
- Electrolyte or acid-base imbalances
25
When should advanced imaging be considered for patients with TBI
- Presentation with moderate to severe neurological signs
- Lateralizing signs
- Failure to improve within the first couple of days
- Deterioration in neurological status
26
What could motivate the choice between mannitol of hypertonic saline for management of increased ICP
Both seem to have similar benefits on ICP decrease and increased cerebral blood flow due to decreased blood viscosity
- Mannitol must be avoided in hypovolemic and hyponatremic patients
- Hypertonic saline must be avoided in hypernatremic and overloaded patients
-> alternate based on volume and electrolytic status
- Hypertonic saline can also have immunomodulatory and vasoregulatory effects beneficial for patients with generalized trauma / shock
- HTS has a reduced likelihood of crossing BBB (higher reflection coefficient)
27
By how much should the head be elevated in management of increased ICP
15-30 degrees (using a slant board, not pillows to avoid compressing the jugulars)
28
What is the incidence of seizures in dogs following TBI
~7%
* 0% in cats
29
What are the different types of brain herniation
See picture
30
How long after initiating bromide therapy should levels be checked
6-12 weeks
31
What is a treatment for bromism
0.9% NaCl fluid therapy
32
What anti-epileptics are recommended in the 2015 ACVIM consensus on seizure management
- Phenobarbital (high recommendation)
- Imepitoin (high recommendation)
- Bromide (moderate recommendation)
- Levetiracetam (low recommendation)
- Zonisamide (low recommendation)
- Primidone = phenobarbital precursor (very low recommendation)
33
When should non-convulsive SE be suspected in veterinary patients?
In any animal with a prolonged period of altered consciousness (comatose or non-comatose types) after successful management of convulsive seizures, especially after the withdrawal of any general anesthetic or sedative drugs.
34
When is a benzodiazepine bolus considered effective?
If seizure cessa- tion occurs <5 minutes after administration and seizures do not relapse in <10 minutes after cessation.
35
Describe a tapering approach for anti-seizure medication in SE
1. If patient on anaesthetics, begin tapering after 24-48h of seizure free
2. Progressive sequential discontinua- tion of anesthetic drugs should be performed ideally over a 24 to 48-hour period (or 12h)
--> Simultaneous tapering of >1 anesthetic is not recommended.
3. Inhalation anesthetics can be discontinued first, followed by propofol or pentobarbital CRI, then ketamine CRI, and lastly, dexmedetomidine and BZD CRI
4. CRI can be decreased by 25%-50% every 4-6 hours before discontinuation
5. If there is no relapse of SE, then the next CRI drug can be tapered in the same manner
6. Non-anesthetic ASMs (eg, levetiracetam or phenobarbital) should be administered minimum until the animal is dis- charged from the hospital (in cases with reactive seizures) or over the long-term (in cases with an epilepsy diagnosis)
36
You have a patient on CRI medications for SE management. As you begin to taper therapy, the patient has a seizure. What is your approach.
CRI dosage should be increased back to the previous dosage that was sufficient to control seizures (where seizures re-occurred during dosage reduc- tion) or CRI should be re-introduced after a bolus (where sei- zures re-occurred after complete drug suspension)
37
Wha is the normal ICP in dogs
5-12 mmHg
38
What does the Monro-Kellie doctrine state?
What is another term for this characteristic of the brain?
Within the intact skull, volume remains constant (parenchyma + CSF + blood) --> an increase in one component must accompany a decrease in 1 or both of the other components to maintain a stable pressure
V intracranial = V brain + V csf + V blood + V mass lesion
* Intracranial compliance
39
What are the 3 mechanisms by which the pressure within the brain is maintained?
1. Volume buffering
- First CSF is displaced extracranially
- Then blood volume becomes compromised --> ischemia
2. Autoregulation
- Pressure autoregulation
- Chemical autoregulation (PCO2, PO2)
3. Cushing response
- increase in MAP to overcome ICP and maintain CPP
40
Describe the impact of PCO2 of ICP and CBV
Decrease in PCO2 (hyperventilation) --> vasoconstriction --> decreased CBV --> decreased ICP --> tissue hypoxia
Increase in PCO2 (hypoventilation) --> vasodilation --> increased CBV --> increased ICP
41
What is the Cushing triad? Explain why each of these things occur
- Systemic hypertension --> sympathetic response to increased ICP: Decreased CBF associated with increased ICP leads to CO2 accumulation locally which is detected by the vasomotor centre and triggers sympathetic peripheral vasoconstriction to increase MAP
- Bradycardia --> baroreceptor response to increased MAP
- Irregular respiration (brainstem compression)
42
What can mimic a Cushing response during GA?
use of alpha2-agonists --> vasoconstriction and reflex bradycardia
43
What are the 2 major derangements that occur in intracranial hypertension to explain its clinical presentation?
- Decrease in CPP --> regional or global tissue ischemia
- Shifts in parenchyma --> mouvement of brain tissue or herniation
44
List 9 therapeutic considerations in patients with increased ICP
1. Maintain adequate CPP (50-90 mmHg)
- MAP > 80 mmHg
2. Decrease cerebral blood volume
- Head elevation, avoid neck compressions caution with PEEP
3. Control PaCO2
- 35-45 mmHg
4. Control PaO2
- > 60 mmHg
5. Reduce cerebral edema
- Hyperosmolar therapy
6. Control brain O2 demand
- Pain control. sedation, anticonvulsants, active cooling
7. Surgery
- Debulking mass, abscess drainage, depressed skull fractures...
8. CSF drainage
9. Supportive/nursing care
45
What is the fluid of choice for TBI and why?
Normal saline
--> smallest amount of free water --> least likely to contribute to cerebral edema
46
True or false: prophylactic anticonvulsant therapy has been shown to reduce development of delayed seizures after TBI in humans
False
47
Ture or false: hyperglycemia has been associated with worse outcome in dogs with TBI
False: hyperglycemia has been associated with more severe injury in TBI patients, but not an independent predictor of outcome
48
Which component of CBF is influenced by pressure autoregulation?
Cerebral vascular resistance
49
Name 3 locations where intracranial hematomas can occur
- Epidural
- Intraparenchymal
- Intraventricular
- Subarachnoid
- Subdural
50
In the secondary injury of TBI, how to influxes of Na+ and Ca2+ specifically lead to injury?
Na+ --> cytotoxic edema
Ca2+ --> activates destructive protease, lipases, endonucleases + mitochondrial dysfunction
51
List 4 Neurologic signs of increased ICP
- Altered mentation
- Decreased PLRs
- Decerebrate posture
- Loss of physiological nystagmus
52
Why is mannitol contraindicated in cases of intracranial hemorrhage?
Extravasation of mannitol could lead to worsening edema - unproven
53
What happens to CBF with loss of pressure autoregulation?
It becomes directly proportional to systemic BP
54
What GI pathology are patients with TBI at risk of?
GI ulceration
55
True or false: prophylactic hyperventilation is recommended in patients with TBI
False
56
Use a pressure - CBF to depict how MAP, PaCO2 and PaO2 impact CBF
See picture
57
What is the difference between cytotoxic edema and vasogenic edema?
Vasogenic edema is defined as extracellular accumulation of fluid resulting from disruption of the BBB and extravasations of serum proteins, while cytotoxic edema is characterized by cell swelling caused by intracellular accumulation of fluid.
58
What is the mechanism behind fixed mydriasis?
A dilated, unreactive pupil usually discloses compression of CN III due to midline shift and uncal herniation
59
What can bu used (calculated) to monitor mannitol therapy?
Osmolar gap
60
List 5 adverse effects of mannitol
1. Renal failure
- Osmotic nephrosis
2. Hyponatremia
- Natriuresis
3. Acidemia
4. Hyperkalemia
5. Hypochloremia
6. Hypotension with rapid administration
7. Cerebral perfusion and ICP rebound
61
How has the MGCS been associated with survival in dogs with TBI?
Dogs scoring 8 or lower at admission have 50% probability of survival at 48h
