Neuro (SACCM / Dobratz / seminal papers) Flashcards
1
Q
States of consciousness
A
- Normal
- Obtunded - state of decreased responsiveness / alertness, can be classified as mild, moderate or severe
- Stupor / semicoma - patient only responds to vigorous or painful stimuli
- Coma - patient does not respond to any stimuli. Spinal reflexes might be normal or exaggerated (in absence of other lesions), and CN can be present (depending on the location of the injury)
2
Q
Abnormalities in mentation indicates lesions where?
A
Cerebrum or ascending reticular activating system (ARAS) in the brain stem
- Ascending Reticular Activating System - AKA Reticular formation - a network of nuclei in the brainstem that function to activate the cerebral cortex and maintain consciousness.
3
Q
List metabolic causes of abnormal mentation (at least 10)
A
Hypoxia Ischemia Kernicterus (hyperbilirrubinemia) Endocrine diseases (hypothyroidism, HHS, Cushing's) Hepatic encephalopathy (liver failure) Uremic encephalopathy (renal failure) Hypoglycemia Electrolyte abnormalities (sodium / water, calcium, magnesium) AB disturbances (acidosis / alkalosis) Pain Sepsis Hypo/hypethermia CNS diseases (seizures, post ictal, meningitis / encephalitis)
4
Q
5 variables to assess in a patient with decreased mentation
A
Level of consciousness Motor activity Respiratory pattern Pupil size & responsiveness Oculocephalic reflex
5
Q
How will our patient be if he has a lesion at or caudal to the midbrain?
A
Decreased consciousness
Gait abnormalities - ataxia, paresis, plegia
Deficits ipsilateral to the lesion
6
Q
How will our patient be if the lesion is rostral to the midbrain?
A
Decreased mentation
Barely any gait abnormalities
No CP reactions on contralateral side
7
Q
Decerebrate rigidity
A
Extensor rigidity all 4 limbs
Opisthotonus
Stupor / coma
Lesion on midbrain and/or rostral pons
8
Q
Decerebellate rigidity
A
Extension rigidity in front limbs
Extension or flexion on hind limbs depending on where lesion is
Opisthotonus
Normal mentation and voluntary movements
Associated with acute cerebellar injury
9
Q
Respiratory patterns associated with intracranial disease
A
- Cheyenne-Stokes - alternating hyperventilation with apnea periods. Diffuse cerebral or thalamus lesions and metabolic encephalopathies.
- Central neurogenic hyperventilation - persistent hyperventilation that can lead to respiratory alkalosis. Midbrain lesions.
- Apneusis - breathing pauses during inspiration - pontine lesion.
- Irregular / ataxic breathing: irregular depth and frequency of breathing, normally leading to permanent apnea. Lower pons or medulla.
10
Q
Why is important to assess pupil size and reactivity in patients with abnormal mentation?
A
Pupil size is the result of balance between sympathetic and parasympathetic.
Parasympathetic is important as it is mediated through CN III that goes through midbrain - loss of PS innervation results in mydriasis).
11
Q
Pupillary abnormalities and lesion localization - unilateral mydriatic unresponsive pupil?
A
Loss of parasympathetic innervation to the eye. Compression or destruction of the ipsilateral midbrain or CN III - often associated with increased ICP and unilateral cerebral herniation. R/O atropine / tropicamide
12
Q
Pupillary abnormalities and lesion localization - bilateral miosis?
A
Metabolic encephalopathies
Diffuse midbrain compression with increased ICP - sometimes precedes bilateral, unresponsive mydriasis
13
Q
Pupillary abnormalities and lesion localization - bilateral mydriatic unresponsive pupils?
A
Fixed and dilated pupils.
Severe bilateral compression or destruction of midbrain / CN III, typically from bilateral cerebral herniation - grave prognosis
14
Q
Drugs that can cause mydriasis / miosis?
A
Bilateral miosis: opioids, benzodiazepines
Mydriasis: topical atropine, tropicamide
15
Q
Why it is important to assess the occulocephalic reflex (Dolls eye)?
A
Physiologic nystagmus or Doll´s eye is a combination of eye movements in response to vestibular input (turning head side to side).
Loss of occulocephalic reflex - lesion on midbrain and pons (medial longitudinal fasciculus) that coordinates CN III, IV and VI
Poor prognosis
16
Q
What characteristics should have an ideal coma scale?
A
a. Reliable (measures what it is supposed to measure)
b. Valid (yields the same results with repeated testing)
c. Linear (gives all components equal weight)
d. Easy to use
17
Q
What does involve the compensation for increased brain tissue volume?
A
Shifting CSF out of the skull
Decreased CSF production
Eventually, decreased cerebral blood flow.
18
Q
When are these compensatory mechanisms (for increased brain tissue volume) more effective?
A
When the increases in ICP are slow
19
Q
What happens when the capacity for compensation is exhausted?
A
A further small increase in intracranial VOLUME results in dramatic elevations of IC PRESSURE, with an immediate onset of clinical signs.
See PV curve
20
Q
How is TBI graded in human medicine and based on what?
A
a. Mild, moderate or severe
b. Glasgow Coma Scale
21
Q
What is the modified GCS?
A
a. A modification of the GCS used in humans, proposed for Veterinary Medicine.
b. Enables grading of the initial neurologic status and serial monitoring of the patient.
c. An almost linear correlation between mGCS and the short-term survival of dogs with head trauma has been evaluated.
22
Q
What are the categories assessed on the mGCS?
A
a. Level of consciousness, motor activity (gait and spinal reflexes) and brainstem reflexes (PLR and occulocephalic reflex).
b. Each of these 3 categories are assigned a score from 1 to 6 (lower worst)
23
Q
Can the motor activity be affected by the level of consciousness?
A
Yes
24
Q
What do we need to determine before extensive manipulation of the patient?
A
Whether spinal cord injury or severe orthopedic abnormalities are present.
25
How are the spinal reflexes normally in a patient with cerebral injury?
a. They are normal or often exaggerated, and present in all four limbs.
b. Severely affected comatose animals frequently lose muscle tone and reflex activity.
26
What indicates pupils that respond appropriately to light, even if miotic?
Adequate function of the rostral brainstem, optic chiasm, optic nerves and retinas.
27
If there is no ocular lesion, what can miosis indicate?
Lesion in the diencephalon, particularly in the hypothalamus as it is the origin of the sympathetic pathway
28
How can we assess the oculovestibular reflex?
a. With irrigation of the external auditory canal with ice-cold water
b. Absence of eye movements upon this irrigation of cold water is indicative of profound brainstem failure and is an accepted criterion of brain death in humans.
29
Do we have scales to assess long-term prognosis in veterinary medicine? And in humans?
a. No
| b. Yes, the Glasgow Outcome Scale (GOS)
30
25. Why cannot we apply the GOS to veterinary patients?
Because it is based on the ability of the patient to communicate and be self-sufficient.
31
What is another coma scale that has been introduced in human medicine?
a. FOUR score – Full Outline of UnResponsiveness
b. Includes much more important information than the GCS – measurement of brainstem reflexes, determination of eye opening, blinking and tracking; the presence of abnormal breath rhythms and a respiratory drive.
32
Do seizures occur more commonly in dogs or in cats?
Dogs
33
Define seizure
A clinical manifestation of a paroxysmal cerebral disorder, caused by a synchronous and excessive electrical neuronal discharge, originating from the cerebral cortex.
34
Define cluster seizures
Two or more seizures within a 24h period
35
Define epilepsy
Recurrent seizures of any type resulting from an intracranial cause.
36
What is status epilepticus (SE)?
Continuous seizures, or two or more discrete seizures between which there is incomplete recovery of consciousness, lasting at least 5 minutes.
37
How can we classify seizures?
a. Partial or generalized
b. Partial seizures originate from a focus in one cerebral hemisphere and usually manifest localized clinical sings. Usually have an acquired cause.
c. Generalized seizures are the most commonly recognized seizures in dogs and cats, the most common type is the tonic-clonic seizure.
38
How can we subclassify partial seizures?
a. Simple or complex partial seizures.
b. Simple partial seizures: there is no alteration in consciousness, and the clinical signs during the seizure are limited to isolated muscle groups (e.g., tonus or clonus of a limb). Additional clinical sings (e.g. autonomic signs) may be present during a simple partial seizure.
c. Complex partial seizures are accompanied by an alteration in consciousness. There might be involuntary or compulsive actions such as chewing, licking and defensive or aggressive behavior. They are AKA as psychomotor seizures.
d. Both types of partial seizures may spread throughout the brain, causing generalized seizures.
39
What is kindling?
The process by repeated stimulation of the cerebral cortex by a subconvulsive electrical stimulus causes generalized seizures.
40
What is a mirror focus?
When abnormal electrical activity may be recorded over the contralateral cerebral cortex following establishment of a focal seizure focus.
41
Why does SE happen?
Because there is a failure of the normal brain homeostasis mechanisms that work to stop seizures => persistent neuronal excitation, inadequate neuronal inhibition or both.
42
How long can it take for SE to cause brain injury?
a. About 45min – that is in experimental animals – most likely occurs in clinical patients after a much shorter time.
b. SE might cause neuronal necrosis, particularly in brain regions with high metabolic rates.
43
What is the pathophysiology of SE?
a. In early SE, an increase in blood flow may be protective for the brain
b. In late SE, cerebral blood flow decreases simultaneously as blood pressure decreases and cerebral metabolic rate (e.g. glucose and oxygen use) increases. This leads to ATP depletion and lactate accumulation which contribute to neuronal necrosis.
c. SE may be associated with systemic problems, including hypoxemia, hyperthermia, aspiration pneumonia, systemic lactic acidosis, hyperkalemia, hypoglycemia, shock, cardiac arrhythmias, neurogenic pulmonary edema and AKI.
44
How can we classify the etiology of seizures?
a. Intracranial vs extracranial
b. Intracranial: progressive vs non-progressive
c. Extracranial: outside the body (toxins) and inside the body (e.g. liver disease) causes.
45
Mention some causes of progressive intracranial disease
a. Inflammation (GME), neoplasia, nutritional alterations (thiamine deficiency), infection, anomalous entities (hydrocephalus) and trauma.
b. Most animals with progressive IC disease are clinically abnormal between seizures and usually have progression of clinical signs.
46
Nonprogressive causes of seizures
Inherited epilepsy, infectious, trauma.
47
What do we need to have as a part of a good diagnostic plan for seizures?
History (important to ask specific seizure history – age at onset, frequency and description of seizures, behavior between seizures and temporal associations), signalment, PE, neurological examination, blood work +/- imaging (CT/MRI), EEG
48
When is EEG particularly useful?
In patients undergoing treatment for status epilepticus because the external manifestations of seizures may be abolished by drugs.
49
Does CSF helps provide a definitive diagnosis?
Most of the times is supportive of the diagnosis, however, occasionally provides diagnostic information with some infections (e.g. Cryptococcus neoformans) and some neoplasms (e.g. lymphoma)
50
What are the goals of anticonvulsant therapy?
Reduce the severity, frequency and duration of seizures to a level that it is acceptable to the owner, without intolerable or unacceptable adverse effects on the animal.
51
What is the base for a good treatment plan?
a. Treat the underlying disease
| b. Select the appropriate anticonvulsant drug
52
What should be the treatment for SE?
a. Immediate emergency evaluation and treatment (airways, breathing, cardiovascular function, body temperature, glucose concentration and blood pressure)
b. Pharmacologic treatment
c. Mannitol should be considered as cerebral edema occurs often in patients that present in SE.
53
What are the first line drugs for treatment of SE in dogs and cats?
Diazepam and midazolam
54
Which drugs are commonly used as maintenance anticonvulsant?
Phenobarbital and levetiracetam.
55
Why can propofol be used to control seizures?
a. Because it is a rapid-acting, lipid-soluble general anesthetic agent.
b. It is a third line drug for the management of SE in dogs and cats.
c. The anticonvulsant effect is likely because of its GABA agonist activity.
d. Its use is controversial because seizures are associated with its use in humans.
56
Successful maintenance anticonvulsant therapy depends on what?
On maintenance of plasma concentrations of appropriate anticonvulsant drugs within a therapeutic range defined for the species in which the drug is to be administered.
57
What are the first line of anticonvulsant drugs recommended for chronic seizure disorders in dogs? And in cats?
a. Phenobarbital and bromide
| b. Phenobarbital.
58
What are the stages of spinal cord injury following trauma?
a. Initial primary tissue damage from direct mechanical disruption
b. Secondary damage via biochemical and vascular events
c. When cellular membrane integrity is disrupted, a complex cascade of biochemical reactions is initiated, including the release of excitotoxic amino acids, free fatty acids, oxygen free radicals and vasoactive agents.
d. NDMA receptors are activated and voltage-sensitive calcium and sodium channels open. These membrane changes result in increased intracellular calcium and sodium, decreased intracellular potassium and increased extracellular potassium.
e. In addition to changes in ionic concentrations, a decrease in blood flow occurs as a result of direct, mechanical compression and/or loss of autoregulation, vasospasm, and hemorrhage, leading to spinal cord ischemia.
f. Ischemia results in cytotoxic edema, axonal degeneration, demyelination, abnormal impulse transmission, conduction block and cellular death.
59
What is a diagnostic test we should do on a patient that has been HBC, fall from a height or suffered severe bite wounds, before performing a full neurological exam?
Radiographs of the entire spinal column
60
In which regions do we divide the spinal cord for neurolocalization purposes?
Five: C1-C5, C6-T2, T3-L3, L4-S1 and S1-S3
61
Which spinal cord segments are located in the vertebral body with the same vertebral number in the dog? What happens with the other spinal cord segments?
a. C1, C2, T13, L1 and L2
b. More caudally along the spine, the spinal cord segments lie in the spinal canal cranial to the vertebrae with the same number.
62
Why is this important when we are evaluating a patient?
Is particularly important when evaluating the lower lumbar spine, where for example in dogs, spinal cord segments L7, S1, S2, S3 and Cd1 may be present within the fifth lumbar vertebral body.
63
What is spinal ataxia characterized by
Incoordination and wobbly gait (increased stride length, dragging or scuffing the toes, walking on the dorsum of the paw or crossing over of the limbs).
64
What are the spinal cord segments S1 to S3 responsible for?
Give rise to the lower motor neurons (LMNs) and sensory fibers that contribute to the sciatic, pelvic, pudendal and perineal nerves and also connect the caudal spinal cord segments to the spinal cord.
65
What are general signs of LMN dysfunction? And signs of S1-S3 injury?
a. Flaccidity diminished segmental reflexes and rapidly progressing muscle atrophy (1-2 weeks).
b. Paresis/paralysis of the sciatic nerve, anal sphincter and bladder
66
What does the spinal cord segments L4-S1 include?
Lumbar intumescence and give rise to the spinal nerves that contribute to the femoral, obturator, sciatic, pelvic and pudendal nerves.
67
What will a lesion of L4-S1 show?
Dysfunction of the pelvic limbs, tail and anus with normal thoracic limb function.
68
Where does the UMN system originates? And where does it end?
a. It originates in the cerebral cortex and brainstem, is confined to the CNS and terminates on the LMN.
b. The UMN results in movement and muscle tone through its actions on the LMN.
c. Urinary incontinence may be accompanied by a large bladder because of either LMN paralysis or increased urethral sphincter tone (a UMN sign).
d. The more caudal the lesion, the more evidence of LMN involvement.
69
What will be the signs of T3-L3 lesions?
a. UMN signs caudal to the level of the lesion
b. Paresis or paralysis, spasticity, exaggerated segmental reflexes, crossed extensor reflex and diminished to absent postural reactions (only on pelvic limbs).
c. Urinary retention, a moderate-size firm bladder and fecal incontinence (despite normal anal tone) may occur.
70
Explain the Schiff-Sherrington phenomenon
a. T3-L3 lesion that results in increased tone to the thoracic limbs.
b. Results from a lack of ascending inhibitory input to the thoracic limbs originating from the border cells located in the lower thoracic and lumbar spinal cord.
c. Border cells are responsible for tonic inhibition of extensor muscle alpha-motor neurons in the cervical intumescence. Increased thoracic limb tone caused by the Schiff-Sherrington phenomenon is not accompanied by proprioceptive deficits or deficits in voluntary motor function.
71
What does C6-T2 segments involve?
Cervical intumescence - gives rise to spinal nerves that make up the subscapular, suprascapular, musculocutaneous, axillary, radial, median and ulnar nerves.
72
Which type of signs will a lesion in C6-T2 cause?
UMN signs to the pelvic limbs (spastic paresis/paralysis, exaggerated segmental reflexes and diminished to absent postural reactions) and LMN to the thoracic limbs (short-strided gait, flaccidity, diminished segmental reflexes, diminished to absent postural reactions and rapidly progressing muscle atrophy).
73
Why does a patient with C6-T2 injury can develop Horner’s syndrome?
It results from damage to the sympathetic fibers that leave the spinal cord at this level.
74
What is a two-engine gait?
A characteristic gait with lesions of C6-T2 spinal cord segments, where the pelvic limbs may show spinal ataxia and the thoracic limbs a short-strided gait.
75
What are the signs a patient will have with C1-C5 lesion?
a. UMN to all 4 limbs.
b. Respiration may be shallow or absent because of the loss of phrenic and intercostal nerve function.
c. Spinal ataxia of all limbs is seen, characterized by a long-strided or floating thoracic and pelvic limb gait.
76
What is spinal shock?
a. Profound depression of segmental reflexes caudal to a lesion, despite reflex arcs remaining physically intact.
b. These signs are often transient, with evidence of areflexia lasting from 12-24h after injury. That is why it is important to perform serial neurologic examinations after a spinal cord injury to ensure accurate neurolocalization.
77
How accurate are spinal column radiographs to diagnose intervertebral disk herniation?
Inaccurate
78
Name some differentials for spinal cord injury
Trauma (spinal fracture, luxation or subluxation; bruise; compression by intervertebral disk), vascular disease (hemorrhage, fibrocartilaginous emboli, infarct), neoplasia, malformations (compression from atlantoaxial subluxation or caudal cervical spondylomyelopathy; arachnoid cyst; syrinx) and, less commonly, infectious (toxoplasma, Rocky Mountain spotted fever, neosporosis, ehrlichiosis, feline infectious peritonitis, fungal, bacterial), inflammatory (granulomatous meningomyelitis) and degenerative disease (degenerative myelopathy).
79
Name some differentials for spinal cord injury
Trauma (spinal fracture, luxation or subluxation; bruise; compression by intervertebral disk), vascular disease (hemorrhage, fibrocartilaginous emboli, infarct), neoplasia, malformations (compression from atlantoaxial subluxation or caudal cervical spondylomyelopathy; arachnoid cyst; syrinx) and, less commonly, infectious (toxoplasma, Rocky Mountain spotted fever, neosporosis, ehrlichiosis, feline infectious peritonitis, fungal, bacterial), inflammatory (granulomatous meningomyelitis) and degenerative disease (degenerative myelopathy).
80
How is the sensitivity for detection of disk herniation on myelography vs CT?
a. Myelography 84% and CT 82%
| b. CT may be more accurate in chronically affected dogs and in dogs >5kg.
81
Why is fluid therapy indicated in all acute spinal cord injuries?
a. Because of presumed compromise of spinal cord vasculature that inhibits the normal autoregulation of arteriolar blood flow.
b. As a result, blood flow to the damaged spinal cord is dependent on mean arterial blood pressure, so cardiovascular stability therefore must be optimized.
82
What is the treatment of choice in animals with atlantoaxial subluxation?
Surgical fixation
83
Which patients may be candidates for conservative treatment in displaced or unstable cervical spinal fractures? Why is that?
a. Patients in which the neurological status is not deteriorating -> external support and strict rest.
b. High incidence of mortality (approximately 40%) associated with surgical intervention for cervical fractures.
84
Why is surgery stabilization recommended for displaced or unstable fractures of the thoracic or lumbar vertebrae?
Because splinting the thoracic or lumbar vertebrae column is more challenging.
85
Why sacrococcygeal injuries can be more devastating in cats than in dogs?
Because of the extension of the spinal cord more caudally (to the level of the sacrum) compared with dogs.
86
What are factors that affect prognosis for spinal cord injury?
Age, size, breed, etiology, onset of clinical signs, severity of clinical sings, location of disease and type of therapy.
87
Do animals with spinal trauma have a good prognosis?
Yes, recover rate of 82% if the animal does not suffer from pulmonary complications.
88
What are the main complications of cervical spondylomyelopathy post op?
a. Vertebral instability and subluxation
| b. Hypoventilation
89
What is the prognosis for T3-L3 injuries that has lost the deep pain for more than 12-24h?
Poor to grave.
90
Where can C. tetani spores be found?
In moist soil but also indoors
91
What kind of bacteria is C. tetani?
Spore-forming, gram positive, anaerobic
Spores are resistant to boiling water and autoclaving at 120C for 20 minutes
Not all strands produce the toxins
92
What causes relative resistance of dogs and cats to tetanus compared to humans and horses?
C. tetani is unable to penetrate and bind to the nervous tissue
93
Examples for how infections can occur?
Contaminated wounds, parturition, teething, surgery
94
Which two toxins are excreted in anaerobic conditions such as necrotic tissue and what are the effects?
Tetanospasmin and tetanolysin
Spasmin: Muscle contraction
Lysin: Local tissue destruction to facilitate spread of the infection
95
How does tetanospasmin induce tetanus?
It acts presynaptically to prevent release of neurotransmitter
96
Transport of tetanospasmin?
Mostly intra-axonally but can also get into blood stream
Transport occurs first in motor nerves, and later also in sensory and autonomic nerves
Transport speed 75-250 mm per day
97
How is neurotransmitter release in inhibitory neurons prevented by tetanospasmin?
It inactivates synaptobrevin, which is a molecule (“docking protein”) that is needed to export NT from their vesicles into the synaptic cleft. Additionally, tetanospasmin can crosslink the vesicles to the cytoskeleton so that NT release is impossible
98
Neurons with which NT are primarily affected by tetanospasmin?
GABA, glycine
99
Other than muscle spasm, which other signs can be seen (if hypothalamus and medulla are affected)?
Autonomic disinhibition with catecholamine excess
100
Why does recovery of tetanus take long?
Neuronal binding of the toxin is irreversible. Recovery occurs via re-growth of axons.
101
Tetanus - onset of clinical signs?
5-12 days but can be as long as 3 weeks
102
Which part of the body is most commonly affected in dogs?
Eyes / face
103
What sign do cats sometimes show with tetanus?
Carpal flexion as opposed to extension as seen in dogs
104
Name a few signs of tetanus
Muscle rigidity, trismus, elevated tail, sardonic grin, sawhorse stance, stiff gait, respiratory distress, dysphagia, salivation, elevation of third eyelid with enophthalmos, opisthotonos, seizure-like activity due to contraction of opposing muscle groups
Bronchospasm is possible
105
Tetanus mortality rate
8-50%, higher with autonomic signs?
106
Autonomic signs of tetanus?
Bradycardia, tachycardia, hypertension, vasoconstriction, pyrexia, dysuria, urinary retention, constipation, gaseous distension
Humans: Autonomic storm
Autonomic signs occurred in 37% of dogs in one study
107
Tetanus neuro exam?
Reflexes usually exaggerated, withdrawal reduced
108
Tetanus canine severity classification?
Class I: Facial signs only
Class II: Generalized rigidity, dysphagia (with or without class I signs)
Class III: Recumbency, seizures???? Or seizure like activity, in addition to class I or II signs
Class IV: Additionally abnormal HR, RR or BP
109
Differential diagnosis for tetanus?
Immune-mediated polymyositis, strychnine toxicity, hypocalcemia, spinal injury, meningoencephalitis, TMJ ankylosis/luxation, severe ear disease or retrobulbar abscess can also lead to lock jaw.
110
Tetanus definitive diagnosis?
Measurement of tetanospasmin antibodies. Need to send in sample of a healthy animal for control as well
Culture of C. tetani from wound is usually not rewarding (it requires few organisms to produce enough toxin, so there may be no growth, additionally, it is difficult to grow C. tetani)
111
Tetanus treatment
a. Antitoxin to neutralize the unbound toxin (equine or human)
Likelihood for adverse events is higher with human antitoxin
No objective data that confirms that it is effective, however it appears to be used commonly
Dose: 100-1000 U/kg (max 20,000 U) IV, IM or SQ – do not repeat dose to decrease risk for hypersensitivity and the antitoxin levels persist for 2 weeks!!
b. Wound debridement
Irrigation with H2O2 increases oxygen tension in the wound, which inhibits growth of C. tetani, but it may be detrimental to wound healing.
c. Antibiotics: (Penicllin G), metronidazole (most recommended), clindamycin and tetracycline, doxycycline
d. Control of rigidity:
Quiet, dark environment to avoid stimulation
Sedation with benzos
Phenobarbital
Acepromacine to reduce hyperexcitability
Propofol/pentobarbital
MgSO4 – supraphysiologic 100 mg/kg/day (monitor for side effects by measuring Mg q 4-6 h, monitor patella tendon reflex, BP, continuous ECG, pulse ox)
112
What are some proposed effects of Mg in tetanus treatment?
Acts as a non-specific Ca channel blocker less Ca available for muscle contraction/
At the NMJ, Mg decreases Ca entry (Ca is needed to release acetylcholine)
Decreases sensitivity of the acetylcholine receptors on the post synaptic membrane
Decreases catecholamine release from the adrenal gland and peripheral nerve terminals
Reduces catecholamine sensitivity
113
What could be a novel treatment for tetanus?
Botox
114
How long does recovery from tetanus usually take?
5-12 days
Presence of autonomic disturbance is a poor prognostic indicator
Survival: 100% in class I and II, 58% in class III and IV in one study
Full recovery of all signs may take up to 5 months, and some animals may not fully recover even if they survive
115
Which 3 CNS areas receive input from the vestibular nerve?
Cortex, cerebellum, spinal cord
| The projection to the cerebral cortex includes extensions to extraocular muscles
116
What is the pathway of the vestibular apparatus?
Input comes from the vestibular receptors in the membranous labyrinth (which is in the bony labyrinth in the petrous temporal bone – inner ear) these axons from the vestibulocochlear nerve which leaves the petrous temporal bone via the internal acoustic meatus, alongside the facial nerve
The VC nerve then enters the medulla. The cell body for this first neuron lies in the vestibular ganglion
The cell body for the second neuron lies in the vestibular nucleus in the medulla oblongata. Te axons then travel in the medial longitudinal fasciulus, giving off side branches to CN III, IV and VI, as well as the vomiting center
Vestibulospinal tract: Connections from the vestibular nuclei to the spinal cord (extensor motor neurons) throughout the entire length of the cord
The vestibular nuclei also project to the cerebellum (ipsilateral flocculonodular lobe cortex, fastigious nuclie). This pathway goes both ways
117
Signs of unilateral vestibular disease?
Head tilt to the affected side
Ataxia
Nystagmus with fast phase away from the lesion
118
With vestibular disease, to which side is the head tilt?
- Peripheral: toward the side of the lesion
- Central: either toward or away from the lesion, ”paradoxical”; that is if the lesion is not in the vestibular nuclei but the cerebellum)
119
What is typical for bilateral vestibular disease?
Side-to-side head movements
120
What is positional nystagmus?
If nystagmus is induced or changes direction when head position is changed
121
Which types of nystagmus are associated with central VD?
Horizontal (although not confirming), positional nystagmus (also not 100%)
Animals with bilateral VD do not have nystagmus
122
What is characteristic of vestibular ataxia?
Wide-based stance; may lean or drift in the direction of the lesion
123
What other signs can be associated with peripheral VD?
Horner’s, facial nerve paresis/paralysis, facial nerve spasm.
124
What signs can be seen with central vestibular disease?
Proprioceptive deficits (ipsilateral), hemiparesis, tetraparesis, altered mental state, dysfunction of other cranial nerves, decerebellate posturing (tis can be intermittent!!!)
125
What blood test that is not part of a minimum database should be performed in dogs with vestibular disease?
Thyroid pannel
126
What are advanced test to diagnose the nature of vestibular disease?
CT, MRI, CSF sampling, myringotomy with cytology/fluid analysis/culture
127
What is a common cause of peripheral VD in cats?
Nasopharyngeal polyps
128
In dogs and cats, what is the most common underlying cause of HE?
PSS
129
What are other causes of hepatic encephalopathy?
Hepatic AV malformations, hepatic MV dysplasia, congenital urea cycle deficiency, hepatic lipidosis, …
130
What is an Eck-fistula?
An end-to-side portocaval shunt vessel
131
What metabolites are implicated in hepatic encephalopathy?
Ammonia, mercaptans, free fatty acids, phenols, bile salts
132
Where/how is ammonia produced and what happens with it in the normal animal?
Gut: Bacteria produce urea from amino acid, purine, amine and urea breakdown
Enterocytes: metabolism of glutamine
Normally, ammonia is transported to the liver where it is metabolized into urea or glutamine
133
What effects does ammonia have on the brain?
- Down-regulation of excitatory neurotransmitters (for example by downregulation of NMDA receptors)
- Inhibition of chloride flux, thus decreasing inhibitory NT as well
134
How is ammonia processed in the brain?
- Transamination of glutamate to glutamine in astrocytes -->> CSF glutamine concentrations are elevated in HE.
- After production of glutamine, the glutamine is exchanged across the BBB for tryptophan -> increased levels of tryptophan and its metabolites (such as serotonin and quinolinate) in the CNS.
- Glutamine is transported from astrocytes into neurons, where is is metabolized back to glutamate -> stimulation of NMDA receptors (both ammonia and glutamate can do that) -> seizures, neurotoxicity via free radical formation
135
What function/effect does serotonin have?
Inhibitory
136
What effect does quinolinate have?
Excitatory
137
What is the role of GABA in HE?
- Unclear, but likely there is an increase in endogenous GABA ligands (benzos and neurosteroids)
- Also, elevated ammonia and manganese levels induce expression of peripheral type benzodiazepine receptors (PTBR) in astrocytes -> increased mitochondrial cholesterol uptake and production of neurosteroids which may then act on GABA receptors
138
What is the role of amino acids in HE?
HE leads to a change in the ratio for BCAA to aromatic AA (decreased BCAAs such as valine, leucine, isoleucine compared to aromatic AA such as phenylalanine, tyrosine, tryptophan) these AA are transported across the BBB and induce formation of false neurotransmitters, reduction of NE and dopamine production
139
Clinical signs of HE
Lethargy, depression, disorientation, personality change, stupor, pacing, hypersalivation, coma, seizures, head pressing, star gazing, blindness (“amaurotic” blindness -> transient????)
Usually, signs of depression dominate over signs of excitation.
PU/PD, GI signs, urinary signs.
In cats, salivation is often the only clinical sign.
Signs can be precipitated by protein rich meals, GI bleedings, medications, infection, e-lyte imbalances, hypoglycemia, acid base disturbances, constipation.
140
What is the cause of PU/PD in HE?
Decreased urea production -> medullary washout.
Increased cortisol levels due to HE, with subsequent partial nephrogenic DI
141
Diagnosis hepatic encephalopathy?
Ammonia levels and bile acid levels (pre- and postprandial)
Rectal portal scintigraphy
Liver histopathology
CT?
142
Treatment of HE induced seizures?
Benzos are controversial
Can use mannitol (or Keppra I would say)
Maintenance anti-seizure: KBromide, pheno
143
How can acid base an e-lyte abnormalities aggravate HE?
Alkalosis support ammonia diffusion into the CNS and hypokalemia supports ammonia production in the kidneys.
Careful with older blood products as ammonia is a storage lesion!!!!!
144
Other treatments for HE
- Lactulose PO or as enema to produce 2-4 soft stools per day.
- Antibiotics.
- Diet: low protein (13-17% of dry matter in dogs, 30-35% in cats; high content of BCAA; needs to contain enough arginine for cats because it is essential AA for urea cycle).
- GI protectants to reduce likelihood of GI bleeding, which can increase protein load.
145
How does lactulose ameliorate HE?
Increased GI passage -> less time to absorb ammonia.
Decreased colinic pH -> turns ammonia into NH4 form, which cannot be absorbed via the GI tract plus Nh activates ammonia translocation from the blood into the GI tract!!!
