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Flashcards in Neuro/Sp_senses Deck (164):
1

Damage to which cranial nerve causes MEDIAL strabismus?

CN VI

2

What are the 4 physiologic compartments of the cranial space?

Blood, CSF, intracellular fluid, extracellular fluid

3

Where is most CSF formed and where is it drained?

Formed by ultrafiltration from blood vessels of the choroid plexus lining the ventricles
Drains into the subarachnoid space, where it is absorbed

4

What forms the motor unit?

Lower motor neurons, neuromuscular junction, skeletal muscle fibers

5

What is the most common cranial nerve to be affected by a nerve sheath tumor?

The trigeminal nerve

6

What is neuropraxia?

The loss of nerve conduction without structural changes. Can occur from transient loss of blood supply and usually resolves over weeks to months.

7

What is axonotmesis?

Axonal damage without loss of supporting structures. It requires regeneration of the axons toward its specific muscle target before functional recovery.

8

How quickly does axonal regeneration occur?

1 mm per day

9

What is neurotmesis?

The complete severance of the nerve. This is typically seen with severe trauma.

10

How do patients with toxoplasmosis or neospora typically present?

They initially have flaccid paraparesis that may progress to a chronic state of extreme extensor tone. Once hind limb rigidity has developed, clinical improvement no longer occurs.

11

List 3 drugs that may result in neuropathies

Vincristine, thallium, organophosphates

12

How is masticatory myositis confirmed?

Either by muscle biopsy or through serum titers for antibodies against type IIM muscle fibers

13

Which breeds of dogs are over-represented in cases of acquired myasthenia gravis?

German shepherds, Labs, Akitas

14

What is the difference between localized, generalized, and fulminant myasthenia gravis?

Localized: Typically show facial, laryngeal, or pharyngeal dysfunction without appendicular muscle involvement

Generalized: Appendicular muscle weakness with out without signs of facial, pharyngeal, or laryngeal dysfunction

Fulminant: Sudden, rapid, progression of severe appendicular muscle weakness resulting in recumbency, frequent regurgitation, and facial, pharyngeal, and laryngeal dysfunction

15

In what percent of dogs with acquired myasthenia gravis will detectable levels of antibodies to acetylcholine receptors be found?

80-90%

16

In what percentage of dogs with myasthenia gravis will the disease be related to a thymoma?

15%

17

How long will it take to see complete resolution of signs in a dog with botulism?

2 to 3 weeks

18

How long after attachment of a tick will signs of tick paralysis be seen? And how quickly will signs resolve after the tick is removed?

3 to 5 days after attachment, signs will resolve within 24-72 hours after the tick is removed.

19

What nerves can be safely biopsied to diagnose a neuropathy?

Fascicular biopsies of the ulnar or peroneal nerves

20

What makes up a lower motor neuron?

Cell bodies found in the brainstem or spinal cord, and their motor axons within the cranial or spinal nerves respectively. They terminate on skeletal muscle fibers at the neuromuscular junction.

21

Equation for cerebral perfusion pressure?

CPP=MAP-ICP

22

What types of factors affect the volume of the blood in the brain?

Altered vascular tone or blood viscosity, impaired venous outflow (head-down posture, jugular vein compression, increased intrathoracic pressure)

23

What is the normal ICP int he dog?

5-12 mm hg

24

T/F: The upper limit of ICP in which tx for ICH should be instituted has not been defined in dogs, but is 20 mm Hg in humans

True

25

Name the three primary homeostatic mechanisms responsible for maintaining ICP in normal range

1. Volume buffering
2. Autoregulation
3. Cushing's response

26

Describe volume buffering and how it controls ICP

Monro-Kellie Doctrine: Increase in the volume of one component requires a compensatory decrease in one or more of the others if ICP is to remain unchanged

27

Describe autoregulatory mechanisms that control ICP

Pressure regulation: Prevents underperfusion or overperfusion of the brain; operates at perfusion pressures between 50-150 mm Hg; outside this range the CBF is linear with MAP
Chemical regulation: cerebral vascular resistance is influenced by PaCO2, PaO2, and cerebral metabolic rate of O2 consumption

28

T/F: Decrease in PaO2 causes vasodilation, causing increased CBF

True

29

T/F: Increased PaCO2 causes vasoconstriction

False- CO2 combines with water to form hydrogen ions, which stimulates cerebral vasodilation

30

Two broad categories of causes of ICH?

Vascular (cerebral vasodilation from increased PaCO2, loss of vascular tone, venous outflow obstruction), non-vascular (increased brain water, masses, obstruction of CSF outflow)

31

Name and describe the states of consciousness

Normal- Normal demeanor and interaction with its environment
Obtunded- Decreased responsiveness or alertness, graded as mild/moderate/severe
Stupor/semicoma- Responds only to vigorous or painful stimuli
Coma- Patient does not respond consciously to any stimuli; cranial nerve reflexes may be present

32

Abnormalities in mentation indicate dysfunction in one of two which neuroanatomical locations?

Cerebrum
Reticular activating syndrome

33

What role does the RAS play in mentation?

distinct nuclei in the brainstem that function to activate the cerebral cortex and maintain consciousness; the most important ones are located in the midbrain, rostral pons, and thalamus

34

What are the main functions of the cerebrum?

Integration of sensory information, planning of motor activity, appropriate responses to information, emotion, memory

35

Name some common metabolic diseases that may cause altered mentation

hypoxia, ischemia, hypoglycemia, hepatic disease, renal failure, endocrine dysfunction, sepsis, hyperbilirubinemia, hyperthermia/hypothermia, pain, CNS disease, electrolyte or acid-base disturbances

36

Name some common drugs that may cause altered mentation

anticonvulsants, benzodiazepines, opiates, anesthetic drugs, atropine, abx, steroids, h2 receptor blockers, cardiac glycosides, antihypertensives, illicit drugs

37

Name structural lesions that cause altered mentation

neoplasia, infection, inflammation, trauma, vascular lesions, hydrocephalus, brain herniation

38

What are the 5 variables that evaluated in a patient with an altered mentation?

Level of consciousness
Motor activity
Respiratory patterns
Pupil size and reactivity
Oculocephalic movements

39

Name and describe 4 types of breathing patterns and their associated intracranial lesions

1. Cheyne-Stokes: hyperpnea alternating with periods of apnea; diffuse cerebral or hypothalamic disease, metabolic encephalopathy
2. Central neurogenic hyperventilation: persistent hyperventilation, may result in respiratory alkalosis; midbrain lesions
3. Apneusis: paused breathing at full inspiration; pontine lesion
4. Irregular/ataxic breathing: Irregular frequency and depth that proceeds apnea; lower pons/medulla lesion

40

Name and describe the pupillary abnormalities and lesion localizations

1. Unilateral mydriatic/unresponsive pupil: ipsilateral midbrain or CN III; increased ICP and unilateral cerebral herniation
2. Bilateral miosis: metabolic encephalopathies, diffuse midbrain compression; may precede mydriatic/unresponsive pupils
3. Bilateral/mydriatic/unresponsive: bilateral compression of midbrain or CN III; grave prognosis

41

Loss of oculocephalic reflex may indicate a lesion where?

Pons, midbrain (CN III, IV, VI)

42

If there is a lesion of CN III, IV, or VI innervating the extraocular eye muscles, you will get a loss of the oculocephalic reflex but should also see what?

persistent, nonpositional strabismus in the affected eye

43

T/F decerebrate rigidity occurs with lesions of the rostral pons and midbrain

True

44

T/F decerebellate rigidity may manifest as extensor rigidity of all four limbs?

False- that describes decerebrate rigidity

45

T/F decerebellate rigidity may manifest as extensor rigidity of the thoracic limbs and extension or flexion of the pelvic limbs

True

46

What are the three categories of the Modified Glasgow Coma Scale?

1. Level of consciousness
2. Motor activity
3. Brainstem reflexes

47

True or False: The level of consciousness is the most reliable empiric measure of impaired cerebral function after head injury

True

48

True or False: Pupils that respond to light, even if miotic, indicate adequate function of the rostral brainstem, optic chiasm, optic nerves, and retinas.

True

49

Injury to the cervical sympathetic pathway results in what findings in the ipsilateral pupil?

Constricted and fixed or sluggish to direct and contralateral light but normal consensual constriction in contralateral pupil.

May also see ptosis.

50

Injury to the oculomotor nerve results in what findings in the ipsilateral pupil?

Dilated and fixed to direct light
No consensual constriction from contralateral light but normal consensual constriction in contralateral pupil.
May also see ptosis and ventrolateral strabismus

51

Injury to the optic nerve results in what findings in the ipsilateral pupil?

Fixed to direct light
Absent consensual constriction in contralateral pupil
Normal consensual constriction from contralateral light
May also see spontaneous fluctuations in pupil size

52

Injury to the oculomotor and optic nerve results in what findings in the ipsilateral pupil?

Dilated and fixed to direct light
No consensual constriction from contralateral light and no consensual constriction in contralateral pupil
May also see ptosis and ventrolateral strabismus

53

Injury to the iris or ciliary body results in what findings in the ipsilateral pupil?

Dilated and fixed to direct light
No consensual constriction from contralateral light but normal consensual constriction in contralateral pupil
May also see signs of orbital injury, no strabisumus

54

What is the oculovestibular reflex?

It is eye movement with irrigation of external auditory ear canal with ice cold water.
When it is absent it is indicative of profound brain-stem failure and is an accepted criterion of brain death in humans.

55

What is the FOUR score?

It is the Full Outline of Unresponsiveness. It is a new coma scale in human medicine based on the bare minimum of tests necessary for assessing a patient with altered consciousness. It has four components: eye responses, motor responses, brainstem reflexes, and respiratory pattern.

56

Hepatic encephalopathy occurs most commonly because of what disease in dogs?

PSS

57

What are less common diseases (other than PSS) that can cause hepatic encephalopathy?

microvascular dysplasia, congenital urea cycle deficiencies, portal hypertension from chronic liver disease, hepatic lipidosis (most common in cats)

58

Which of the following is associated with HE?
A. CSF amino acid alterations
B. glutamate neurotoxicity
C. generation of reactive oxygen species
D. mitochondrial permeability transition
E. All of the above

E

59

Where is ammonia produced?

In the intestines as the end product of amino acid, purine and amine breakdown by bacteria, metabolism of glutamine by enterocytes, and breakdown of urea by bacterial urease

60

In the normal liver, what is ammonia converted into?

urea or glutamine

61

T/F: The permeability of the BBB increases during hepatic encephalopathy

T

62

What are the proposed mechanisms of decreased excitatory neurotransmission in HE?

down-regulation of NMDA receptors, blockage of Cl extrusion from the postsynaptic neuron

63

T/F the brain has a urea cycle

False- ammonia in the CNS is removed by transamination of glutamate into glutamine in astrocytes

64

How do glutamate and ammonia potentially cause neurotoxicity and seizures in HE?

Partly because of free radical formation secondary to overstimulation of NMDA receptors by ammonia and glutamate

65

What is the most important inhibitory neurotransmitter in the CNS?

GABA (gamma-aminobutyric acid)

66

Why are benzodiazepines contraindicated in patients with PSS?

there are increased levels of endogenous benzodiazepine receptor ligands in the portal blood and systemic circulation of some dogs with PSS

67

What two drugs experimentally have been shown to ameliorate CNS inflammation and brain edema in dogs with HE?

N-acetylcysteine and minocycline

68

What is often the only clinical signs associated with HE In cats?

ptyalism

69

What things can precipitate or worsen HE?

high protein meal, GI bleeding, systemic infection, medications (narcostics, anesthetics), electrolyte imbalances (hypokalemia), hypoglycemia, acidosis/alkalosis, constipation

70

T/F: samples for blood ammonia concentrations are effective when stored frozen if only for a short time?

false- must be run immediately

71

What are the general treatment goals for animals with HE?

reduce ammonia levels, decrease GABA, decrease endogenous benzodiazepines

72

T/F: a large meta-analysis of human trials showed probiotics reduce plasma ammonia levels but do not make a clinically relevant difference in outcome

true

73

T/F: animals with liver insufficiency commonly experience clinical or subclinical GI hemorrhage

true

74

What are the 3 primary homeostatic mechanisms responsible for maintaining ICP within a functional range for the brain?

Volume buffering, autoregulation, and the Cushing response

75

List 6 causes of added IC volume

Tumor, hemorrhage, CSF accumulation, vascular congestion, cerebral edema, decreased venous outflow

76

What are the 3 factors controlling chemical autoregulation of the brain?

PaCO2, PaO2, and the cerebral metabolic rate of oxygen consumption

77

List 3 mechanisms of vascular ICH

Cerebral vasodilation secondary to increased PaCO2, distention of cerebral vessels resulting from loss of vascular tone, or venous outflow obstruction

78

List 3 nonvascular mechanisms of ICH

Increased brain water (interstitial edema or intracellular swelling), masses, or obstruction of CSF outflow

79

What ophthalmic exam finding is a reliable sign of ICH?

Papilledema

80

Where are the mechanisms responsible for consciousness located?

Rostral brainstem, ascending reticular activation system, and diffusely throughout the cerebrum

81

What neurologically is responsible for pupillary constriction?

Midbrain and efferent parasympathetic fibers of CN III

82

Mydriasis indicates a lesion where?

Midbrain or CN III

83

Conjugate oculovestibular movements require integrity of what pathways?

Cranial cervical spinal cord and medulla oblongata rostrally to the nuclei of CN III, IV, and VI, via the medial longitudinal fasiculus

84

Absent corneal reflex indicates damage to what part of the CNS?

Afferent trigeminal nerve (CN V), efferent facial nerve (CN VII) or their reflex connections within the pons and medulla oblongata are damaged

85

What is Cheyne-Stokes respiration and it's presence implies a lesion where?

Hyperpnea regularly alternating with apnea; lesion is deep in the cerebral hemispheres or in the Rostral brainstem

86

List 4 viral causes of central vestibular disease

FIP, FIV, FeLV, rabies, pseudorabies, borna disease virus, distemper

87

What are 3 protozoal causes of central vestibular disease?

Toxo, neospora, and encephalitozoonosis

88

What are 3 parasitic causes of peripheral vestibular disease?

Angiostrongylus vasorum, cuterebra larval myiasis, dirofilaria immitis

89

List 5 fungal causes of central vestibular disease

Cryptococcus, blasto, histo, coccidiomycosis, aspergillosis, phaeohyphomycosis

90

T/F An intact tympanum rules out otitis media

FALSE

91

T/F Otitis media cannot be reliably diagnosed on the basis of a ruptured tympanum

True

92

List 3 drugs that can cause peripheral vestibular disease

Aminoglycosides, furosemide, chlorhexidine, or aural administration of 10% fipronil solution

93

List 2 toxic causes of central vestibular disease

Lead, metronidazole

94

List 2 neoplasticism causes of peripheral vestibular disease

SCC, fibrosarcoma, osteosarcoma, ceruminous gland or sebaceous gland adenocarcinoma

95

List 3 neoplastic causes of central vestibular disease

Meningioma, lymphoma, oligodendroglioma, medulloblastoma, extension of middle ear neoplasia, metastasis

96

What are 3 disease processes that can cause either peripheral or central vestibular disease?

Hypothyroidism, cuterebral larval migrans, cryptococcosis, bacterial infection

97

What cranial nerve deficit (other than VIII) can be associated with peripheral vestibular disease?

VII - can result in facial paresis, paralysis, or more rarely, spasm

98

With horizontal nystagmus in peripheral vestibular disease, the fast phase is towards or away from the lesion?

Away from the side of the lesion

99

Are paresis and/or proprioceptive deficits commonly ipsilateral or contralateral to the side of the lesion with central disease?

Commonly ipsilateral

100

T/F spinal cord segments C1, C2, T12, and L3 are the only spinal cord segments located within the vertebral body with the same vertebral number in the dog

F, C1, C2, T12, T13, L1, and L2 are the only segments to which this applies

101

What spinal cord segments might one expect to find in the 5 lumbar vertebral body?

L7, S1-3, Cd 1

102

Define spinal ataxia

Incoordination, a wobbly gait with increased stride length, dragging or scuffing of toes, walking on the dorsum of the paw, or crossing over of limbs

103

What are the segmental reflexes?

Extensor Carpi radialis, triceps, biceps, quadriceps, cranial tibial and gastrocnemius

104

What is the definition of a neurological grade 3?

Non ambulatory paresis

105

List 6 biochemical events that occur when the cellular membrane is disrupted in spinal cord injury

Release of excitotoxic amino acids, free fatty acids, oxygen free radicals, and vasoactive agents. NMDA receptors are activated and voltage sensitive Ca and Na channels open.

106

List 6 consequences of spinal cord ischemia

Cytotoxic edema, axonal degeneration, demyelination, abnormal impulse transmission, conduction block, and cellular death.

107

What is the neurological description of a grade 4 spinal lesion?

Paralysis, deep pain positive

108

The sacral spinal cord segments give rise to the LMNs and sensory fibers of what nerves?

Sciatic, pelvic, pudendal, and perineal nerves

109

What deficits are expected with sciatic nerve dysfunction?

Shuffling in pelvic limbs, plantigrade posture, failure to replace a knuckled paw, and cranial tibial, gastroc, and withdrawal reflexes may be decreased

110

Where would you expect sensory deficits with damage to the spinal segments of S1-S3?

Perineum, tail, lateral and caudal skin of the distal pelvic limbs

111

Spinal cord segments contribute to what 5 peripheral nerves?

Femoral, obturator, sciatic, pelvic, and pudendal nerves

112

What pelvic limb nerve is responsible for weight bearing?

Femoral

113

What is responsible for the increased thoracic tone noted with Schiff-Sherrington posture?

Lack of ascending inhibitory input to the thoracic limbs originating from the border cells located in the lower thoracic and lumbar spinal cord

114

What are the border cells of the spinal cord responsible for?

Tonic inhibition of extensor muscle alpha motor neurons in the cervical intumescence

115

T/F Schiff-Sherrington posture is associated with a poor prognosis for regain of pelvic limb function

False- no effect

116

The cervical intumescence gives rise to what 7 peripheral nerves?

Subscapular, suprascapular, musculocutaneous, axillary, radial, median, and ulnar nerves

117

Why can Horners be seen with damage at C6-T2?

Damage to the sympathetic fibers that leave the spinal cord at this level

118

What is meant by a neuro scale of 2?

Ambulatory paresis

119

A 2 engine gait is associated with dysfunction of what spinal cord segments?

C6-T2

120

What are 2 potential lesions that may be missed if an imaging modality other than MRI is used to image the spine?

Intramedullary lesions or non compressive nuclear pulposus extrusions

121

Why are IV fluids indicated for all acute spinal cord injuries?

Presumed compromise of spinal cord vasculature that inhibits normal autoregulation of arteriolar blood flow so blood flow to damaged spinal cord is dependent on MAP so CV stability should be optimized

122

What are commonly seen complications associated with long term cervical splint treatment?

Soiled bandage with eating/drinking, frequent pyoderma, and pressure necrosis along the ventral mandible

123

What landmarks should be used for bandage material to hold a cervical splint in place?

Just caudal to the ears and extending beyond the caudal aspect of both scapulae

124

Internal spinal fracture fixation should be attempted when?

If the fracture incorporates the articular facets, the vertebral body, or both

125

What comprises the ventral buttress?

Vertebral body, dorsal and ventral longitudinal ligaments, and intervertebral disks

126

What mortality rate has been reported with surgical cervical fracture repair?

40%

127

Small dogs with cervical spinal fractures should be splinted where?

Along the ventral cervical region; large dogs often need dorsal, ventral, or even circumfrential splinting

128

What are 3 indications for surgical decompression of IVDD?

Grade 3 or greater deficits, recurrent episodes, or episodes unresponsive to medical treatment

129

T/F In animals with cervical spinal fracture that are not deteriorating, external support and rest are the treatments of choice vs in similar fractures of the thoracic and lumbar vertebrae surgery is recommended

TRUE

130

What is the expected success rate with A-A subluxations for medical vs surgical management?

Splint 62.5% have good outcome (but 25% relapse) vs 61-91% good outcomes with surgery

131

T/F There is significant variability in expected prognosis with surgical decompression of a cranial cervical vs caudal cervical disk compression?

True- long term resolution of 66% with C2-3, C3-4 with surgery vs only 21% of patients with lower cervical IVDH had long term resolution of signs with surgery

132

List Ddx for a young, painful dog with acute onset of spinal signs

Trauma, IVDD type 1, +/- neoplasia, anomalous, or infectious/inflammatory disease

133

What is the equation for cerebral perfusion pressure?

CPP= MAP-ICP

134

What is the definition of intracranial pressure?

The pressure exerted by the tissues and fluids against the cranial vault

135

What are the components of ICP?

Atmospheric pressure- weight of the atmosphere on the brain
Hydrostatic pressure- orientation of the neuraxis relative to gravity
Filling pressure- volume of fluid within cranial vault

136

Name benefits of intracranial pressure monitoring

1. Allows assessment of actual ICP and trends in ICP
2. Optimization of cerebral perfusion pressure guided therapy
3. Earlier interventions are possible
4. Reduces indiscriminate tx of ICH
5. Assessment of the effects of ICH tx
6. Allows assessment in anesthetized or comatose animals
7. Provides assessment of brain death

137

What is the equation for cerebral perfusion pressure?

CPP= MAP-ICP

138

What is the definition of intracranial pressure?

The pressure exerted by the tissues and fluids against the cranial vault

139

What are the components of ICP?

Atmospheric pressure- weight of the atmosphere on the brain
Hydrostatic pressure- orientation of the neuraxis relative to gravity
Filling pressure- volume of fluid within cranial vault

140

Name benefits of intracranial pressure monitoring

1. Allows assessment of actual ICP and trends in ICP
2. Optimization of cerebral perfusion pressure guided therapy
3. Earlier interventions are possible
4. Reduces indiscriminate tx of ICH
5. Assessment of the effects of ICH tx
6. Allows assessment in anesthetized or comatose animals
7. Provides assessment of brain death

141

What is the equation for cerebral perfusion pressure?

CPP= MAP-ICP

142

What is the definition of intracranial pressure?

The pressure exerted by the tissues and fluids against the cranial vault

143

What are the components of ICP?

Atmospheric pressure- weight of the atmosphere on the brain
Hydrostatic pressure- orientation of the neuraxis relative to gravity
Filling pressure- volume of fluid within cranial vault

144

What type of catheter has been used in small animals for ICP monitoring during brain surgery?

fiberoptic ICP monitoring systems (transducer tipped catheters)

145

What are the downsides to ICP in the classic location of the cisterna magna in animals?

Patient needs general anesthesia, ICP may not accurately reflect more compartmentalized elevations in ICP, risk of brain herniation, doesn't allow for ongoing measurements

146

What are some pros to using external pressure transducers to measure ICP?

Accurate, can be recalibrated after insertion, minimal zero drift, cheaper

147

T/F: The fluctuations seen with placement of an epidural or subdural placement of a fluid filled catheter are generally reliable for measurement of ICP?

true

148

What is normal ICP in the dog and cat?

5-12 mm Hg above atmospheric pressure

149

Cons to using internal pressure transducer?

Cannot be rezeroed after insertion, some zero drift, expensive

150

What is the gold standard for ICP monitoring in people?

Ventriculostomy catheters- most accurate, can be used to withdraw CSF for tx of ICH, easy and reliable to palpate

151

Why are ventriculostomy catheters more difficult to place in dogs and cats than in people?

Marked variation in skull size, variation in size/shape/location of lateral ventricles of the brain, more musculature overlying cranial vault

152

Which type of ICP monitoring systems can be used in awake dogs for 2-5 days post op?

Catheter tip ICP sensors

153

Describe a subarachnoid bolt monitoring system for ICP

Screw secured to calvaria through a burr hold over a cerebral convexity

154

What is normal ICP in the dog and cat?

5-12 mm Hg above atmospheric pressure

155

What is responsible for the CSF fluid pulse pressure wave?

contraction of the LV of the heart causing distension of the arterioles

156

What are the ICP respiratory waves?

slower pressure oscillations that fall with inspiration and rise with expiration

157

What are some physiologic phenomena that can increase ICP?

Coughing, sneezing, straining, low head position, jugular compression, suctioning back of throat, regurgitation

158

What is responsible for the CSF fluid pulse pressure wave?

contraction of the LV of the heart causing distension of the arterioles

159

What are the ICP respiratory waves?

slower pressure oscillations that fall with inspiration and rise with expiration

160

What are some physiologic phenomena that can increase ICP?

Coughing, sneezing, straining, low head position, jugular compression, suctioning back of throat, regurgitation

161

At what ICP is treatment generally recommended?

15-20 mm Hg

162

What are some other guidelines for instituting tx for ICH?

ICP 15-20 mm Hg that are slowly increasing, ICP

163

Name complications of ICP monitoring

infection, hemorrhage, device malfunction, obstruction, malpositioning

164

In what groups of animals is ICP monitoring likely to be more useful?

1. Research animals
2. Anesthetized, comatose, or post op brain surgery
3. Severe, progressive neurologic deficits that may respond to treatment with time
4. Severe TBI