Neurological Diseases Flashcards
Evidence of Increased IOP
o Preop assessment of neurologic status: mental status, pupil size/reaction
o Signs, symptoms of raised ICP = vomiting, pupillary dilation, papilloedema
Intracranial Space
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
Monroe-Kelly Hypothesis
for ICP to remain normal, volume increase in any one of the three components must be matched by a decrease in another
Cushing’s Reflex/Triad
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
Therapeutic Management for Increased ICP
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
Effects of TBI On Brain Metabolic Activity
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
Hydrocephalus
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
Chiari-Like Malformation
–Increased ICP concerns + pain management
Thoefner et al 2020 (VAA)
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
Seizure Disorders
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
Anti Epileptic Drug Therapy MOA
o Reducing inward voltage gated positive currents (Na+, Ca2+)
o Increasing inhibitory neurotransmitter activity (GABA)
o Decreasing excitatory NT activity (glutamate, aspartate
Phenobarbital
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
Primidone
Barbiturate derivative metabolized to phenobarb, PEMA; at least 85% of pharmacological activity derived from phenobarb
Little advantage over phenobarb
Valproic Acid
MOA unknown, fallen out of favor with use of zonisamide, gabapentin, Levetiracetam
Levetiracetam - Keppra
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
Zonisamide
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
Felbamate
NMDA R antagonist
Anesthetic Drugs that Increase sz activity
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
Status Epilepticus
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
Acute Spinal Cord Injury
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
Stabilization for Acute Spinal Cord Injuries
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
Risks Assoc with Spinal Sx
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
Bruniges and Rioja 2019 (VAA):
Increasing anesthetic duration associated with increased risk of temperature > 39*Celsius but no other intraoperative complications
Pascal, Allison and Kaartinen 2020 (VAA):
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
Skelding, Valvede and Kilburn 2021 (VAA):
Both CRIs of ketamine + fentanyl, lidocaine + fentanyl provided adequate anesthetic conditions in dogs undergoing thoracolumbar hemilaminectomy
o Post operative analgesia adequate in both groups
Myelomalacia
- 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
Myelomalacia - Causes, Features
Embolization, thrombi, space occupying lesions, pronounced vasoconstriction following excessive hyperventilation decrease spinal perfusion pressure, spinal venous congestion
Myasthenia Gravis
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
Clinical Significance of MG
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
Clinical Signs of MG
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
Anesthetic Management of ME Patients
- High aspiration risks due to ME
- 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 - Minimize negative effects of sedation on resp function vs exacerbation of clinical signs/induction of MG crisis
- Muscle weakness - PPV required
Medical Management of MG
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
How does MG affect NMBA?
INCREASES sensitivity of non-depolarizing
DECREASES sensitivity to depolarizing
Dysautotonia
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
Peripheral Neuropathy
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)
Postoperative Cognitive Dysfunction
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
MOA POCD
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
Risk Factors for POCD
Age, pre-existing cerebral vascular and systemic vascular disease, systemic inflammation
Why Care About POCD
Potential consideration for working dogs (compromise ability to do job), geriatric animals with preoperative cognitive decline that have further decreases in QOL after anesthesia
Zboril et al 2020 (VAA)
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
Anesthetic Management of Myelography
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
Myelography
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
Ketamine: CMRO2/CBF
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
Etomidate: CMRO2/CBF
Potent VC - significant decrease in CBF
Decrease in CMRO2: initial mismatch CBF, CMRO2 – equilibrium after 10’ so CBF matches CMRO2
Propofol
decreases both CMRO2, CBF - agent of choice for intracranial dz patients
Preservation of autoregulation and central response to increased CO2
Alfaxalone, Barbiturates
decreases both CMRO2, CBF - effect = decrease ICP
Methohexital: seizures, CNS excitation
Inhalants
Decrease CMRO2 - least with halothane
Increase CBF - least with sevo, greatest with halothane
Des, en, +/- sevo (hypercapnia) = sz
N2O
Dramatic increases in ICP
