Neurological Diseases

Question 1

Evidence of Increased IOP

Answer 1

o Preop assessment of neurologic status: mental status, pupil size/reaction
o Signs, symptoms of raised ICP = vomiting, pupillary dilation, papilloedema

Question 2

Intracranial Space

Answer 2

3 components
o Brain tissue (80-85%)
o CSF (7-10%)
o Cerebral blood volume (5-8%)

ICP: pressure from all three components within non-distensible space

Question 3

Monroe-Kelly Hypothesis

Answer 3

for ICP to remain normal, volume increase in any one of the three components must be matched by a decrease in another

Question 4

Cushing’s Reflex/Triad

Answer 4

Rapidly increasing ICP indicated by arterial hypertension, bradycardia, respiratory irregularity (“vasopressor response”), frequently leads to cerebral herniation

o Sequalae of herniation includes brainstem compression, loss of consciousness, subsequent death

Question 5

Therapeutic Management for Increased ICP

Answer 5

Adequate sedation and analgesia

Improved cerebral venous drainage by elevating head (15-30 degrees angle)

Mannitol or hypertonic saline
–HSS: may improve cerebral hemodynamics, brain tissue oxygenation but used with caution as can cause hyperchloremic metabolic acidosis, subsequent renal impairment

Induction of anesthesia with thiopental , propofol or etomidate

Fast acting NMBA before intubation
–Avoid initiation of gag reflex, vomiting – increase ICP

Question 6

Effects of TBI On Brain Metabolic Activity

Answer 6

INCREASES

Euglycemic or hypoglycemic patient’s blood glucose concentrations may not allow for adequate substance delivery to compensate for hypermetabolic brain

Metabolic crisis: glucose <0.7mmol/L + increase in lactate to pyruvate ratio >40 in microdialyze fluid

Important to perform serial glucose monitoring during neuro anesthesia

Question 7

Hydrocephalus

Answer 7

active distension of ventricular system of brain that results from accumulation of abnormal amount of CSF from production within ventricles to point of absorption
 Avoid intracranial hypertension, maintenance of CPP
 Avoid increasing ICP
 Conservative fluid therapy

Question 8

Chiari-Like Malformation

Answer 8

–Increased ICP concerns + pain management

Question 9

Thoefner et al 2020 (VAA)

Answer 9

Pregabalin superior to placebo in reductions of clinical signs in dogs, dose range of 13 to 19 mg/kg PO BID encountered adverse effects acceptable to all but one owner
* AEs = increased appetite, ataxia

Question 10

Seizure Disorders

Answer 10

Associated with marked increases in CMRO2, CBF; potential risk for asphyxia in spontaneously breathing patients
o Six-fold increase in brain tissue lactate following 5s sz activity, subsequent loss of CBF autoregulation
o Hypoxia not predominant cause

Question 11

Anti Epileptic Drug Therapy MOA

Answer 11

o Reducing inward voltage gated positive currents (Na+, Ca2+)
o Increasing inhibitory neurotransmitter activity (GABA)
o Decreasing excitatory NT activity (glutamate, aspartate

Question 12

Phenobarbital

Answer 12

Increases seizure threshold, decreases electrical activity of seizure focus by potentiating effect of GABA on GABAA subunit

Also decreases influx of calcium into nerve cells, decreased release of neurotransmitter

CYP450 microsomal enzyme inducer - Avoid coadministration with chloramphenicol, ketoconazole due to inhibition of metabolism
* Also increases own metabolism

Usually first drug of choice for long term management of seizure disorders in dogs, cats

Question 13

Primidone

Answer 13

 Barbiturate derivative metabolized to phenobarb, PEMA; at least 85% of pharmacological activity derived from phenobarb
 Little advantage over phenobarb

Question 14

Valproic Acid

Answer 14

MOA unknown, fallen out of favor with use of zonisamide, gabapentin, Levetiracetam

Question 15

Levetiracetam - Keppra

Answer 15

 Mechanism of action incompletely understood
 Does not appear to affect membrane channels, GABA, membrane receptor activity or glutamate receptor neurotransmission
 Capable of suppressing seizure activity without affecting normal neuronal excitability

Question 16

Zonisamide

Answer 16

 Sulfonamide, unclear mechanism of action
 Does not affect GABA mediated mechanisms but may block voltage gated sodium, T type calcium channels which stabilize neuronal membrane, suppressed neuronal hyperactivity

Question 17

Felbamate

Answer 17

NMDA R antagonist

Question 18

Anesthetic Drugs that Increase sz activity

Answer 18

N2O in cats, sevo in children/high concentrations + hypocapnia

Enflurane: humans, rats - sustained EG, motor evidence of seizure activity induced by auditory stimuli and dogs anesthetized at >1 MAC of enflurane
 Activity became particularly evident during hypercapnia

Ketamine at low doses

Opioids : initiate generalized seizures +/- myoclonus after low to moderate doses, particularly when administered intrathecally to humans

Question 19

Status Epilepticus

Answer 19

Seizure with >5min continuous clinical +/- EEG activity or recurrent seizure activity without recovery btw

Increases in cerebral metabolism, CBF, catecholamine release, CO, arterial and CVP, HR

Must control quickly to avoid loss of CBF autoregulation, cerebral hypoxia, cerebral edema, intracranial hypertension

Reach for BZD, propofol, TP – avoid opioids

Question 20

Acute Spinal Cord Injury

Answer 20

Initial trauma caused by acute intervertebral disc herniation, vertebral injuries, penetrating injuries or by non traumatic injuries (FCE)

Often followed by second injury to spinal cord resulting from molecular, biochemical changes associated with the initial trauma
 Loss of spinal blood flow autoregulation
 Excessive release of aspartate, glutamate
 Intracellular calcium accumulation
 Inflammation

Question 21

Stabilization for Acute Spinal Cord Injuries

Answer 21

stabilization of patients cardiovascular, respiratory function to reduce spinal cord ischemia, hypoxia with subsequent progression of cord injury

Traditional tx: rapid expansion of IV vol via hypertonic or colloid solutions

Experimental/controversial = Methylprednisolone, polyethylene glycol, antioxidant therapy, calcium channel antagonists, amino steroids, opiate receptor antagonists, hyperbaric oxygen therapy, therapeutic hypothermia

Question 22

Risks Assoc with Spinal Sx

Answer 22

bleeding, infection, development of new neurologic deficits
o Respiratory muscle paralysis, blindness, positioning related injuries
o Ventral slot: recurrent laryngeal nerve injury caused by either direct pressure on the nerve during retraction +/- compression of submucosal branches by ETT

Question 23

Bruniges and Rioja 2019 (VAA):

Answer 23

Increasing anesthetic duration associated with increased risk of temperature > 39*Celsius but no other intraoperative complications

Question 24

Pascal, Allison and Kaartinen 2020 (VAA):

Answer 24

Medetomidine CRI (1 mcg/kg LD + 1.7mcg/kg/hr) decreased need for fentanyl CRI in otherwise healthy dogs undergoing thoracolumbar hemilaminectomy surgery during administration of ketamine CRI

Question 25

Skelding, Valvede and Kilburn 2021 (VAA):

Answer 25

Both CRIs of ketamine + fentanyl, lidocaine + fentanyl provided adequate anesthetic conditions in dogs undergoing thoracolumbar hemilaminectomy
o Post operative analgesia adequate in both groups

Question 26

Myelomalacia

Answer 26

• Ischemic or hemorrhagic necrosis of spinal cord as a sequel to acute spinal cord injury
• Reported in dogs, cattle, goats, horses

Have on radar if horse unable to stand in recovery

MOA: neuronal anoxia/hypoxia

Question 27

Myelomalacia - Causes, Features

Answer 27

Embolization, thrombi, space occupying lesions, pronounced vasoconstriction following excessive hyperventilation decrease spinal perfusion pressure, spinal venous congestion

Question 28

Myasthenia Gravis

Answer 28

Neuromuscular disease caused by deficiency of functional postsynaptic nAChR at NMJ

Congenital, acquired; dogs, cats
o Acquired form: Autoimmune disease characterized by autoantibodies directed against nAChR, assoc with thymic disease
o Congenital: not assoc with autoimmune response

Question 29

Clinical Significance of MG

Answer 29

Decrease number of nAChR causes decreased capacity of NM end plate to transmit nerve signal adequately leading to neuromuscular weakness, fatigue

Acute fulminating MG in dogs characterized by frequent regurgitation, aspiration of GI contents = subsequent aspiration ammonia

Also see rapid loss of muscle strength resulting in recumbency

Question 30

Clinical Signs of MG

Answer 30

bilateral facial weakness with decreased palpebral reflexes, marked SkM weakness in pelvic limbs, inability to retract claws, cervical ventroflexion, ME

Recumbency

EMG, nerve conduction velocity testing in dogs may not reveal abnormalities

Question 31

Anesthetic Management of ME Patients

Answer 31

1. High aspiration risks due to ME
2. Smaller number normal nAChR: increased resistance to succinylcholine (insufficient depolarization), increased sensitivity to non-depolarizing agents
   –Recommend initial dose reduction vecuronium, atracurium 1/5-1/6
3. Minimize negative effects of sedation on resp function vs exacerbation of clinical signs/induction of MG crisis
4. Muscle weakness - PPV required

Question 32

Medical Management of MG

Answer 32

o Daily dose of anticholinesterase medication = pyridostigmine
 MOA: increase ACh at NMJ
* Risk: cholinergic crisis from excess ACh at nicotinic, muscarinic R
 Preoperative use questioned: drug may interfere with metabolism of substrates of cholinesterase enzymes
 Humans: more severe disease + higher dose of pyridostigmine, more sensitive toward non depolarizing NMBAs

Question 33

How does MG affect NMBA?

Answer 33

INCREASES sensitivity of non-depolarizing

DECREASES sensitivity to depolarizing

Question 34

Dysautotonia

Answer 34

Rare, idiopathic condition characterized by degeneration of neurons and ANS ganglia

Clinical signs reflects severity of degeneration in both SNS, PSNS
 Dysuria with distended urinary bladder, mydriasis with absent PLR, 0 Estonia, decreased tear production, decreased anal tone, vomiting or regurgitation

Question 35

Peripheral Neuropathy

Answer 35

Associated with several other conditions including cancers, diabetes mellitus

Patients with diabetes more susceptible to peripheral nerve ischemia DT compression, stretching

During anesthesia, positioning/padding extremely important to prevent further injury
 May increase effects of depolarizing muscle relaxants because of neural damage, possibility of denervated induced upregulation (increased fetal nAChR)

Question 36

Postoperative Cognitive Dysfunction

Answer 36

Condition recognized clinically in humans, experimentally in animals

Acute or persistent deficits in attention, concentration, learning, memory following surgery and anesthesia not attributable to overt complication or insult arising from procedure

Greater risk in older patients
 Dogs >8yo , increases exponentially with age
 Affects up to 65% of human patients at hospital discharge

Question 37

MOA POCD

Answer 37

 Elevations of inflammatory markers peripherally, within CNS instrumental to development
 Potentially seen with inhalant anesthesia alone (no sx)
 Addition of lidocaine, vitamin C may attenuate loss of cognitive function after anesthesia

Question 38

Risk Factors for POCD

Answer 38

Age, pre-existing cerebral vascular and systemic vascular disease, systemic inflammation

Question 39

Why Care About POCD

Answer 39

Potential consideration for working dogs (compromise ability to do job), geriatric animals with preoperative cognitive decline that have further decreases in QOL after anesthesia

Question 40

Zboril et al 2020 (VAA)

Answer 40

No association between POCD and high concentrations of S100B, neuron-specific enclase (NSE) [markers of glial damage/astrocyte reaction; neuronal injury) in dogs <8yo

Serum concentrations of S100B elevated and aged dogs before anesthesia, might be related to chronic preoperative brain damage

Question 41

Anesthetic Management of Myelography

Answer 41

 Risk of post myelographic seizures (3-21% of dogs), avoid drugs with epileptic activity
 Remain under GA for 40-60’ can allow for dissipation contrast media from SAS
 tilting head up 30 degrees may help mitigate intracranial contrast accumulation, helps slow flow rate
 No ketamine, enflurane, sevo + hypocapnia, N2O
 Yes propofol, benzo, TP, iso

Question 42

Myelography

Answer 42

Injection of contrast media into cervical subarachnoid space

Serious effects: bradycardia, asystole, seizures, hyperthermia, exacerbation of preexisting CNS dysfunction, or hyperesthesia, vomiting, aseptic meningitis

GOOOD TECHNIQUE!!

Second generation nonionic media (iohexol, iopamidol) less neurotoxic vs earlier agents

Important to maintain hydration: premyelography dehydration shown to slow absorption of contrast media resulting in unnecessary neurotoxicity

Question 43

Ketamine: CMRO2/CBF

Answer 43

Increases, increases

Also increases ICP

Can attenuate with eucapnea, benzos

Epileptiform EEG - probably best to avoid in sz patients even though anti-sz activity at low doses

Question 44

Etomidate: CMRO2/CBF

Answer 44

Potent VC - significant decrease in CBF

Decrease in CMRO2: initial mismatch CBF, CMRO2 – equilibrium after 10’ so CBF matches CMRO2

Question 45

Propofol

Answer 45

decreases both CMRO2, CBF - agent of choice for intracranial dz patients

Preservation of autoregulation and central response to increased CO2

Question 46

Alfaxalone, Barbiturates

Answer 46

decreases both CMRO2, CBF - effect = decrease ICP

Methohexital: seizures, CNS excitation

Question 47

Inhalants

Answer 47

Decrease CMRO2 - least with halothane
Increase CBF - least with sevo, greatest with halothane

Des, en, +/- sevo (hypercapnia) = sz

Question 48

N2O

Answer 48

Dramatic increases in ICP