B&B 4 Consciousness & Seizures Flashcards Preview

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Flashcards in B&B 4 Consciousness & Seizures Deck (174):
1

What 3 things are necessary for normal consciousness?

►LOC

►State of Consciousness

►Content of Consciousness

2

LOC

(Level of Consciousness)

►LOC
– A continuum
– asleep/minimal arousal to awake/aroused
– diffuse BRAINSTEM structures

3

State of Consciousness

►State of Consciousness
– Responsive to stimuli (verbal, pain, etc)
– multiple regions of THALAMUS

4

Content of Consciousness

►Content of Consciousness
– Perception, emotion, meaning, memories
– widespread regions of CEREBRAL CORTEX

5

Retricular formation

What is it?

• Numerous nuclei within the tegmentum of the brainstem

• capture all sensory info as it travels through brainstem

• Reticular = "diffuse," like a mesh, or net. It is a distributed network spread throughout brainstem gathering info from all modalities.

6

What Neurotransmitters are involved?

NE
Dopamine
Serotonin
Histamine
ACh

7

NE

• Produced in "locus ceruleus" in tegmentum of pons projecting to thalamus and forebrain

• Allows a focus on a specific task or sensory input

• Helps suppress less salient inputs

►Lesion in locus ceruleus = Low level of NE = low level of arousal

8

Dopamine

Dopaminergic neurons in the "ventral tegmental area" (VTA) project to prefrontal cortex and limbic structures

Promoting locomoter and exploratory behaviors toward positively rewarding stimuli (need to pee or hungry)

►Lesions in VTA affect attentive arousal – one becomes less attentive; indecisive.

9

Serotonin

Serotonin-releasing neurons in Raphe nuclei project to thalamus, cortex other NT systems in brainstem

In consciousness, serotonin regulates a quiet wakeful state:
• Mood, sense of well-being
• Sleep, lack of serotonin = insomnia
• Anxiety/Aggression controlled

10

Histamine

Histamine releasing neurons from tegmentum of midbrain project to thalamus and cortex
• stimulates wakefulness
• antihistamines induce drowsiness

11

Ach

ACh from the tegmentum of pons project to thalamus and cortex

• Increase thalamocorticol activation (more later) and arousal

12

What determines how responsive you are to your environment?

Thalamus → has many anatomically and functionally distinct nuclei
• Relay Nuclei
• Association Nuclei
• Intralaminar Nuclei
• Thalamic Reticular Nucleus (TRN)

13

What is the TRN?

Thalamic Reticular Nucleus

aka ....

"gatekeeper of consciousness"

►A thin mesh of neurons immediately outside of thalamus.

►Has dense reciprocal connecFons with:
– ARAS
– Other thalamic nuclei
– Cerebral CorFcal structures

►Is an interconnected network of GABAergic neurons.

►Coordinates the synchronous firing (40Hz) between cortex and thalamus necessary for consciousness

14

In order for you to walk, respond, or receive, ALL of these need to be talking back and forth

What are these?

Thalamus
Cortex
TRN
ARAS / NT Systems

15

What is required to establish significance and meaning of consciousness experience?

Cortex

• Synchronous and reciprocal connections with thalamus and other cortical areas.

• Prefrontal and parietal cortical areas important

16

Prefrontal Cortex

►Considered to have executive function over consciousness

►It is much more complex than other association areas in that it is involved in our ability to associated self with society and societies expectations
• to plan future actions
• to predict
• to be attentive
• to concentrate on a task
• to discriminate between the trivial and important
• to behave appropriately

►These executive functions are disrupted in frontal lobe disease

17

Where is the lesion?

►Groggy
...vs...
►Awake, but not responsive
...vs...
►Unable to make meaning of things in conscious realm (doesn't know name or place)

Groggy
→ Brainstem

Awake, but not responsive
→ Thalamus

Unable to make meaning of things in conscious realm (doesn't know name or place)
→ cortex

18

What is the carrying frequency of consciousness?

40 Hz

19

What is General Anesethesia?

Altered physiologic state characterized by the following components:

— Hypnosis (= loss of consciousness; “sleep”)
— Analgesia (pain relief - opioids)
— Amnesia (loss of memory - benzos)
— Immobility (in response to noxious stimulation)
— Inhibition of autonomic and sensory reflexes (block gag reflex etc)
— Muscle relaxation (±) → Sux, Rocuronium

20

What drugs did we use in Ambulatory Care during scopes?

Analgesia
- opioid pain relief: Fentanyl

Amnesia
- Midazolam (Versed) - Benzo: to not have memory of event`

21

Inhaled Anesthetics in OR

Sevoflurane
Desflurane
(both have very low blood-gas partition coefficients)

Chloroform was used a long time ago. Queen Victoria used it during labor. Not used any way due to hepato and cardiotoxicity.
Chloroform has a high blood-gas partition coefficient

22

What is Laughing Gas?

Nitrous Oxide

By itself it is not potent enough. But, has a very fast on/off and helps when used in combo with others of the drugs (desflurane, sevoflurane)

can cause nausea and vomiting though.

We do NOT use this much

23

The rate of uptake of an inhaled anesthetic is determined by ...

1) its solubility in the blood

2) partial pressure difference between alveoli and pulmonary venous blood

3) alveolar ventilation

24

What is FA / FI ?

Anesthetic concentration (FA) to the inspired anesthetic concentration (FI) over time

25

Modern agents are LESS soluble than gas.

We want LOW blood solubility!

Ultimately, we want the gas in the brain. We want equilibrium to be reached very quickly. OF the anesthetic is very soluble in the blood, then there is a larger, "pool" in the blood that makes it take longer for it get to the brain.

26

What is MAC?

Minimal Alveolar Concentration

1 MAC = concentration of an inhaled anesthetic in the alveoli at 1 atm that prevents movement in response to a painful stimulus in 50% of patients

27

Factors that decrease MAC

• ↑age
• ↓Temp
• Pregnany
• Opioids
• Other Aenesthics (e.g. N2O) % CNS drugs

THEREFORE, these patients need less of drug (or we get an overdose effect)

28

Organ Effects of Inhaled Anesthetics

CNS:
Decrease in cerebral metabolic rate (CMRO2)
Cerebral vasodilatation - Increase in cerebral blood flow

CV
Decrease in arterial blood pressure
Ventricular arrhythmias (halothane)
N2O: mild sympathetic stimulation (but rarely used)

RESP
Respiratory depression
Decrease in airway resistance (bronchodilator)

RENAL
↓Renal Blood Flow & ↓GFR

MSK
Muscle relaxation

UTERUS
• Uterine relaxation (halothane and all other volatile agents)
• May lead to prolonged uterine atony & severe blood loss in parturients (women in labor)

29

What are the IV Anesethetics we covered?

Thipental
Propofol
Ketamine
Etomidate

30

Thiapental

= Barbiturate (derivative of barbituric acid)

No analgesic properties ... must use with opioid

Barbiturate

MOA: Facilitation of inhibitory neurotransmission via GABAa receptors

A/E: Resp depression, Hypotension (pearl harbor

NO LONGER USED

31

Thiapental

What is the problem with it's half-life?

The longer you give Thiopental, the longer the half-life

Propofol does NOT have this problem!

32

Propofol

= 2,6-diisopropylphenol

No analgesic properties ... must use with opioid

1990s answer to Thiapental
"pleasent dreams"

MOA: Facilitation of inhibitory neurotransmission via

A/E: Resp depression, apnea, sepsis due to egg lecithin breeding ground for bacteria (sterile technique!)

33

Ketamine

= Phencyclidine (PCP) derivative (psychomimetic drug, “Angel Dust”)

• Produces a state of “dissociative anesthesia”: patients appear conscious, yet unable to process or respond to sensory input (catatony, amnesia, analgesia)
• Produces little cardio-respiratory depression & maintains airway reflexes
• Has bronchodilator properties
• Can cause nightmares

MOA: Antagonist at NMDA (N-methyl-D-aspartate) receptors (type of glutamate receptor)

USED IN BATTLEFIELD

34

Etomidate

= Imidazole derivative

• Minimal effects on hemodynamics
— Useful for induction of unstable patients
• No analgesic properties
• Kinetics & mechanism of action similar to propofol
• Produces adrenal suppression

35

Pupillary Reflex

Pathway ...

►Afferent Component
CN2 → Optic tract → Pretectal Region → EW nucleus

►Efferent Component
CN 3 → ciliary ganglion → short ciliary nerves → constrictor muscle of iris

36

Corneal Reflex

Pathway ...

►Afferent Component
CN5v1 → chief sensory nucleus → spinal tract of V and spinal nucleus of V

►Efferent Component
→ facial motor nuclei → CN 7 → orbicularis oculi

Corneal reflexes depend on the integrity of pontine pathways between fifth and both seventh CNs

In conjunction with reflex EMs are important clinical tests of pontine function

37

Gag Reflex

Pathway ...

►Afferent Component
CN9 → tractus and nucleus solitaries

►Efferent Component
Nucleus ambiguous → CN X, striated muscles of pharynx

Reflex centre is in the medulla

38

What is the Apnea Test?

When ventilator is disconnected, hypercapnia should induce hyperventilation via respiratory centre in medulla

If medulla is damaged then there will be no reflexive hyperventilation

39

What is a structural cause of unconsciousness?

when function of both cerebral hemispheres or of the brainstem reticular activating system is compromised

40

Episodic loss of consciosness

What causes it?

seizures & syncope

Due to reduced supply of blood to cerebral hemispheres or brainstem from pan cerebral hypoperfusion caused by vasovagal reflexes, orthostatic hypotension, decreased cardiac output or from selective hypoperfusion of brainstem from vertebrobasilar ischemia

41

Confusional State / Coma

What are structural causes?

• hemorrhages
• large areas of ischemic infarction
• abscesses or tumors can expand over minutes or a few hours and cause brain tissue to herniated into the posterior fossa

42

Confusional State / Coma

What are non-structural causes?

• drugs (sedative hypnotics, ethanol, opiods)
• global cerebral ischemia
• hepatic encephalopathy
• hypercalcemia
• hyperosmolar states
• hyperthermia
• hypoglycaemia
• hyponatremia
• hypoxia
• hypothyroidism
• meningitis
• encephalitis
• seizure or prolonged postictal state
• subarachnoid hemorrhage
• thyrotoxicosis
• uremia
• Wernicke’s encephalopathy

43

What is the effect of alcohol on consciousness?

►CNS depressant → affects large number of membrane proteins that participate in signalling pathways

► Much attention has focused on alcohol’s effects on neurotransmission by glutamate and GABA (main excitatory and inhibitory neurotransmitters in CNS)

►Acute ethanol exposure enhances action of GABA at receptors

►Ethanol inhibits the ability of glutamate to open cation channel association with NMDA subtype of glutamate receptors which is implicated in many aspects of congitive function

44

Psychogenic Coma

• Diagnosis of exclusion made only on basis of compelling evidence
• May be manifestation of schizophrenia, somatoform disorders or malingering

What does Px exam show?

• General physical exam reveals no abnormalities
• Neurologic exam generally reveals symmetrically decreased muscle tone, normal reflexes and a normal response to plantar stimulation
• Pupils are 2-3mm or occasionally larger and respond briskly to light
• Doll’s head testing may or may not be present since visual fixation can suppress this reflex
• Usually exhibits some voluntary muscle tone in the eyelids during passive eye opening
• Helpful diagnostic test is caloric testing of vestibular ocular reflex where brisk nystagmus is characteristic response in conscious patients but no nystagmus occurs in coma
• Normal EEG

45

In order to have nystagmus, you must have ...

intact cortical function

46

What is a Pseudo-coma?

Pt is not necessarily faking it, but it is likely the result of mental illness

47

Doll's Eye

Eye's stay focused straight up -- Brainstem intact

Eye's stay midgaze -- can see whites on either side -- Brainstem NOT intact

48

Caloric Test

Nystagus -- cortex gives us the nystagmus which is a corrective mechanism. Therefore, this is added info that cortex is intact!

Eyes's not moving (totally still) -- Brainstem is NOT intact

49

What is CBF?

Cerebral Blood Flow
• preserved via a variety of mechanisms
• Supply = two carotid arteries & two vertebral arteries

►CBF = CPP / CVR

CPP = cerebral perfusion pressure

CVR = cerebral vascular resistance

50

What is CPP?

Cerebral perfusion pressure

CPP = MAP - ICP

MAP = DP + 1/3PP
(mean arterial pressure)
(duh ... that's old concept!)

Normal ICP = 7–15 mm Hg

51

How is pressure in the brain auto regulated?

between 50-160 mmHg MAP the constant flow of blood to the brain is maintained via arteriole dilation and constriction

52

What is the affect of PCO2 on CBF?

cerebral vessels are very sensitive to changes in PCO2

Hypercapnia will cause vasodilation and increased CBF
(vice versa for hypocapnia)

53

What is the affect of PO2 on CBF?

Generally does not vary CBF unless PO2 falls below 50mmHg then CBF flow begins to rise exponentially due to nitric oxide and adenosine produced in response to hypoxia

54

How can we measure CBF?

►PET

►SPECT - via injection of dye that lights up areas of perfusion (used to help locate seizure activity in brain)

►Xenon CT

►CT / MRI perfusion scans

55

Monro-Kellie Doctrine

What is it?

Pressure-Volume relationship between ICP, volume of CSF, blood, and brain tissue

Cranial compartment is incompressible, and the volume inside the cranium is a fixed volume

Alteration in volume of any of the skull contents or addition of an extra content (e.g. tumour) will increase ICF

56

ICP

Normal Values?

What are dangerous values?

Normally ICP is ~ 10 mmHg
>20 is abnormal
>40 is lethal

57

ICP

How measured?
(3 ways)

►Intraventricular catheter
→ thin, flexible tube threaded into one of two lateral ventricles → has advantage of also therapeutic CSF removal but is more invasive

►Subarachnoid screw or bolt
→ placed just through the skull in space between arachnoid membrane and cerebral cortex

►Fibre optic transducers
→ placed through burr hole drilled through skull just over epidural covering ... not as invasive but cannot remove CSF if needed

►AVOID LUMBAR PUNCTURE → can worsen or lead to brain herniation

58

What are causes of increased ICP?

►Localized mass lesions
• Traumatic hematomas (extradural, subdural, intracerebral)
• Neoplasms (glioma, meningioma, metastasis)
• Abscess
• Focal edema secondary to trauma, infarction, tumor

►Disturbance of CSF circulation
• Obstructive hydrocephalus
• Communicating hydrocephalus

►Obstruction to major venous sinuses
• Depressed fractures overlying major venous sinuses
• Cerebral venous thrombosis

►Diffuse brain edema or swelling
• Encephalitis
• Meningitis
• Diffuse head injury
• subarachnoid hemorrhage
• Reye’s syndrome
• Lead encephalopathy
• Water intoxication
• Near drowning

►Idiopathic
• Benign intracranial hypertension

59

Cerebral Herniations

What are the types?

►Subfalcine herniation
• frontal lobe under falx
• displacement of part of one cerebral hemisphere, usually the cingulate gyrus, beneath the falx cerebri and into the other side

►Midline shift
• movement of one hemisphere toward the other

►Uncal (transtentorial) herniation
• occurs when the temporal lobe swells and presses medially disrupting ...
(1) CN3 → dilate "blown pupil"
(2) cerebral peduncle → contralateral plegia
(3) reticular activation centre of the brainstem → coma

►Tonsillar herniation
• brain is squeezed downwards through the foramen magnum compressing the tonsils of the cerebellum against the medulla of the brainstem → resp arrest → death.

60

ICP

Tx?
(ist vs 2nd tier)

►Ist TIER Tx
• general physiologic hemostasis
• CSF drainage
• head of bed elevation
• analgesia and sedation
• neuromuscular blockade
• diuretics (mannitol)
• hyperventilation

►2nd TIER Tx
• barbiturate coma (decrease metabolism coupled to decrease cerebral blood flow)
• optimized hyperventilation
• hypothermia
• decompressive craniectomy

61

What happens when MAP = ICP?

there is no more perfusion of the brain .... 4 min till brain death

62

Primary Brain Injury
...vs...
Secondary Brain Injury

Primary Brain Injury
• occurs at the time of the trauma
• permanent

Secondary Brain Injury
• occurs sometime after the trauma
• can often be prevented.

(e.g.) minor concussion will cause little if any primary brain injury. If that unconscious patient later obstructs airway and is hypoxic then they could develop a lethal secondary brain injury because all of the brain dies from hypoxia

63

We cannot change the damage that occurs during Primary Injury. The damage that has occurred is done.

HOWEVER, we can prevent further damage. Therefore, our goal is to prevent secondary injury.

What are causes of secondary injury?

Secondary Brain Injury
• hypoxia
• hypotension
• infection
• seizure
• electrolyte abnormalities
• raised ICP causing brain herniations
• local hypoperfusion.

64

What is Cushing's Triad / Response?

Unique CV response to elevated ICP. This is the body's compensatory attempt to fix the problem:

⬆︎ BP - attempt to keep MAP > ICP (wide pulse pressure)
⬇︎HR - reflexive bradycardia
⬇︎ RR - Resp irregulatiries (if the medulla is hypo-perfused)

65

How does Hyperventilation help in the management of increased ICP?

Vessels get vaso-constrict in the presence of low CO2

►Hyperventiliate → decreases blood volume via vessels will get smaller due to low CO2 (but if we keep hyperventilating, the vessels will shrink so much that we will cause an infarct .. this would be secondary brain injury!)

CO2 should be at 40, the max we want to bring it down is to 30 (all the vessels get a bit smaller which multiples into relatively significant amount when added up among ALL the numerous vessels in the brain)

66

What is the cellular basis of seizure pathophysiology?

Glutamate, aspartate → inward Na, Ca currents → excitation

GABA → inward Cl, outward K currents → inhibition

67

What are the mechanisms of hyper excitable networks that contribute to seizures?

• Excitatory axonal sprouting
• Loss of inhibitory neurons
• Loss of excitatory neurons which would normally be driving inhibitory neurons

68

Classification of Seizures

General Overview
(as we discussed)

GENERALIZED SEIZURES
► Generalized tonic clonic seizures
– Tonic phase
– Clonic Phase
– Recovery
►Absence
►Other ...
tonic seizures, clonic seizures, myoclonic seizures

PARTIAL SEIZURES
►Simple Partial Seizures
►Complex partial seizures

69

Generalized tonic clonic seizures
(loss of consciousness usually without aura or other warning)

►Tonic Phase ...

– Initial manifestation are unconsciousness and tonic contractions of limb muscles for 10-30s producing first flexion and then extension particularly of the back and neck

– Tonic contraction may produce expiration induced vocalization and cyanosis and contraction of mastication muscles that may cause tongue trauma and patient falls to ground

70

Generalized tonic clonic seizures
(loss of consciousness usually without aura or other warning)

►Clonic Phase ...

– Follows tonic phase
– presents as symmetric limb jerking that persist for an additional 30-60s with ventilation resuming normal and cyanosis clears
– mouth may froth with saliva
– fall movements cease and muscles becomes flaccid; sphincters relax or detrusor muscle contraction may produce urinary incontinence

71

Generalized tonic clonic seizures
(loss of consciousness usually without aura or other warning)

►Recovery...

aka "Grand-mal"
– affects ENTIRE brain
– patient regains consciousness with postictal confusion and often headache
– full orientation commonly takes 10-30mins or even longer

72

Review ...

Classification of Seizures

General Overview
(as we discussed)

GENERALIZED SEIZURES
► Generalized tonic clonic seizures
– Tonic phase
– Clonic Phase
– Recovery
►Absence
►Other ...
tonic seizures, clonic seizures, myoclonic seizures

PARTIAL SEIZURES
►Simple Partial Seizures
►Complex partial seizures

73

Absence

– Genetically transmitted seizures
– Begin in childhood
– Rarely persist into adolescence
– Spells characterized by brief loss of consciousness without loss of postural tone
– Full orientation immediately follows cessation of the seizure
– Spells are characteristically inducible by hyperventilation
– EEG show a characteristic 3/s spike and wave pattern during seizures

74

►Other ...

(this is still within Generalized Seizures)

►Tonic seizures

►Clonic seizures

►Myoclonic seizures
– sudden, brief shock-like contractions that may be localized to a few muscles or one or more extremities or that may have a more generalized distribution

►Atonic
– seizures result from loss of postural tone leading to a drop attack

75

Review ...

Classification of Seizures

General Overview
(as we discussed)

GENERALIZED SEIZURES
► Generalized tonic clonic seizures
– Tonic phase
– Clonic Phase
– Recovery
►Absence
►Other ...
tonic seizures, clonic seizures, myoclonic seizures

PARTIAL SEIZURES
►Simple Partial Seizures
►Complex partial seizures

76

Simple Partial Seizures
(focal seizure WITHOUT loss of LOC)

?

MAY HAVE EITHER:
►Observable
– "Focal motor seizure" → single group of muscles
– "Autonomic Seizure" → (eg. ↑HR, diaphoresis, flushing, pallor, piloerection)

►Non-Observable
Subjective sensory or psychic phenomena only (visual halluciations or deja vu. "AURAS"


NOTE: Consciousness is preserved!

77

Complex partial seizures
("Focal dyscognitive)"
– involves loss of LOC

?

– Partial seizures in which consciousness, responsiveness or memory is impaired

– Seizure discharge usually arises from the temporal lobe or medial frontal lobe but can originate elsewhere

– Seizures generally persist for less than 30 min (average 1-3min)

– Motor manifestations are characterized by coordinated involuntary motor activity, termed automatis

78

How do we diagnose a seizure?

Clinical S&S

EEG

79

What is critical for treating seizures?

Must understand what is causing it?

Metabolic and systemic causes respond poorly to anticonvulsants → need to treat underlying abnormality

80

Seizure Meds

Increasing inhibition drugs

►Barbiturates
– prolong GABA mediated Cl channel openings

►Benzodiazepines
– increase frequency of GABA mediated Cl channel openings

►Gabapentin
– increase neuronal GABA concentration
– enhance GABA mediated inhibition

81

Seizure Meds

Decreasing excitation drugs

►Phenytoin (dilentin), Carbamazepine, Lamotrigine
– block voltage-dependent Na channels at high firing frequencies
– Dilentin can cause hirsutism, gingival hypertrophy, facial coarseness, hair loss and weight gain

►Valproic acid
– blocks voltage-dependent Na channels; may enhance GABA transmission in specific circuits
– Good drug but teratogenic → avoid use in women of child bearing age

►Ethosuximide
– blocks low threshold, “transient” (T-type) calcium channels in thalamic neurons
– Mainly used in children

►Carbamazepine
– blocks voltage gated Na channel

82

Seizure Meds

Mixed action drugs

►Topiramate
– Blocks voltage-dependent Na channels at high firing frequencies
– Increases frequency at which GABA opens Cl channels (different site than benzos)
– Antagonizes glutamate action at AMPA/kainite receptor subtype

►Levetiracetam (keppra)
– Reduces high voltage-activated Ca currents
– Reverses inhibition of GABA and glycine gated currents

►Oxcarbazepin (Trileptal)
– Blocks voltage-dependent sodium channels at high firing frequencies o Exert effects on K channels

83

What happens if a patient fails to successfully manage seizure symptoms despite trying 2 or more different drugs?

Refer to neurosurgeon → consider temporal lobectomy
(last resort)

84

Define...
►Seizure
►Epilepsy

►Seizure:
– the clinical manifestation of an abnormal and excessive excitation and synchronization of a population of cortical neurons

85

Explain pathology and pathophysiology of closed head injuries.

Initial impact cause primary injury → long, delicate axons of neurons can shear

Subsequent neuronal damage due to sequelae of trauma due to hypoxia, hypotension, hydrocephalus, intracranial hypertension, and intracranial hematoma

86

Concussion
...vs...
Contusion

►Concussion
= temporary neuronal dysfunction following nonpenetrating head trauma; normal head CT

►Contusion
= bruise of brain occurring when force from trauma is sufficient to cause breakdown of small vessels and
extravasation of blood into the brain → appears bright on CT scan

87

What happens to axons during TBI?

Diffuse axonal injury

- caused by damage to axons throughout brain from rotational acceleration and then deceleration

88

What are ADLs?

What are IADLs?

ADLs ("death")
• dressing
• eating
• ambulation
• toileting
• hygiene

IADLs ("shaft")
• shopping
• housework
• accounting
• food prep
• transport/telephone

89

Brain Tumours

FACTS

• Half of all brain tumours are benign
• BUT ... they may recur and cause death

• Cure rate for most malignant brain tumours is significantly lower

90

Brain Tumous

Glioma Facts

40% of primary CNS tumours are gliomas

80% of malignant CNS tumours are gliomas

91

CNS Tumours RARELY actually metastasize

How do they cause their harm?

“malignant by position”

(i.e. depend on what vital structure it is in close proximity to)

92

Brain Tumours

Location (adults vs children)

►ADULTS
70% of CNS tumours are supratentorial
30% are infratentorial

►CHILDREN
30% are supratentorial
70% are infratentorial

("adults are supra, kids are infra")

93

Brain Tumours

How does pt present?

Seizures

Headache

Focal neurologic deficits

94

Brain Tumours

Risk Factors?

►Irradiation → meningiomas, gliomas, nerve sheath tumours
►Gliomas → men > women
►Meningiomas → women > men

95

Brain Tumours

Which have the BEST 5-yr survival rate?

Which have the WORST 5-yr survival rate?

BEST:
Oligodendroglioma: 60%
Ependymoma: 60%
Medulloblastoma: 60%
Pilocytic Astrocytoma: >80%
Meningioma: 70-90%

WORST:
Glioblastoma: 3-4%
Anaplastic Astrocytoma: 30%

96

So ... what is the worst brain tumour to have?

Glioblastoma
3-4% survival rate

97

What are prognostic features of brain tumours?

Patient
• age
• neurologic impairment
• Karnofsky score

Tumour
• type
• grade
• location

98

Tumour Types

Adults
...vs...
Children

ADULTS
• Glioblastoma
• Metastisis
• Malignant Astro
• Meningioma
• Pilocytic
• Schwannoma

CHILDREN
• Glioblastoma
• Medulloblastoma
• Astrocytoma
• Ependymoma
• Craniopharyngioma

99

Circumscribed Astryocytomas

Circumscribed = pilocytic astrocytoma
(WHO grade 1)

• Predominantly in children

• Usually cerebellum, optic tract, hypothalamus

• Potentially curable by complete excision

100

Diffuse Astryocytomas

►Diffuse
(WHO grade 2)
– shows nuclear pleomorphism and account for 40% of all primary CNS tumours and 78% of all malignant CNS tumours

►Anaplastic
(WHO grade 3)
– have evidence of mitoses

►Glioblastoma
(WHO grade 4)
– have evidence of capillary endothelial proliferation and necrosis

101

What gene has been shown to have an association with the prognosis of Glioblastoma?

Tx of glioblastoma via epigenetic silencing of MGMT DNA repair gene compromises DNA repair of tumour cells and has been associated with longer survival

In other words ... having MGMT turned OFF results in better outcome

MGMT = O6-methylguanine-DNA methyltransferase

102

Oligodendroglial tumors

►Oligodendroglioma
(WHO grade 2)

►Anaplastic (malignant) oligodendroglioma
(WHO grade 3)

Has “fried egg”and “chicken-wire vasculature” appearance

LOH 1p / 19q
– Lost of heterozygosity
– good response to tx
– better prognosis

103

Mixed Gliomas

►Mixed oligoastrocytoma
– WHO grade 2

►Anaplastic (malignant) oligoastrocytoma
– WHO grade 3

104

Ependymal Tumors

►Ependymoma
(WHO grade III)

►Anaplastic ependymoma
(WHO grade II)

►Myxopapillary ependymoma

►Subependymoma
(WHO grade I)

105

Neuronal

Low grade
– ganglioglioma
– gangliocytoma

Neuroblastic
– medulloblastoma
– cerebral neuroblastoma

106

Cranial & Spinal Nerves

►Schewannoma

►Neurofibroma

►Maliganant peripheral nerve sheath tumour (MPNST)

107

Sellar Region

Pituitary adenoma → secrete different endocrine
hormones

108

Lymphoma

►Primary CNS lymphoma
– rare
– usually in elderly or immunocompromised
– Need to differentiate it from toxoplasmosis and PML
– first treat for toxo ... if no response then biopsy
– Very poor prognosis (3 month survivial)

109

Metasteses

• Most common sites = lung, brest, skin, kidney

• Prostate, ovary and Hodgkin’s disease very rarely spread to brain

• 90% supratentorial

110

What does bleeding look like on CT?

Epidural
Subdural
Subarachnoid

►Epidural – lens
(meningeal artery)

►Subdural – crescent
(venous)
Acute: bright white
Chronic: could look the same as normal tissue (grey) or even be quite dark

►Subarachnoid – follows contours of brain
(Arterial Aneurysm)

111

Which bieed can be present despite a totally normal physical exam?

Chronic Subdural Bleed

112

"Worst headache of my life!"

No Hx of Trauma

What must we consider?

►Non-traumatic (spontaneous) subarachnoid haemorrhage
– generally caused by the rupture of an arterial aneurysm
– “worst headache of my life”

113

Unconscious pt in ER

What does our exam look like

►Vitals (HR, RR, BP, LOC)
►History
►4Ns: Noggin, Neck, Nose, Needle
►Eyes
– Pupils: size, symmetry, reactivity
– Fundi
– Corneal Reflexes
– Oculocephalic Reflex (Doll’s eyes)
– Oculovestibular Reflex (Calorics)

►Other Findings
– Gag Reflex
– Motor System
– Reflexes

114

Corneal Reflex

aka :blink reflex"
– involuntary blinking of the eyelids elicited by stimulation of the cornea
– caused by touching, foreign body, bright light, or any peripheral stimulus including loud sound
– Stimulation should elicit both a direct and consensual response (response of the opposite eye)

115

Oculocephalic Reflex

aka "Doll’s eyes"
(can only do in non-Cspine!)

►Eye's stay focused straight up
→ Brainstem intact

►Eye's stay midgaze (can see whites on either side)
→ Brainstem NOT intact

116

Oculovestibular Reflex

aka "Caloric Test"

Adding cold water to one side creates an imbalance in the L&R vestibulocular reflex

Eyes deviate slowly to cold water side, no nystagmus → brainstem is intact, but pt is unconscious (no cortex input)

Nystagmus → cortex gives us the nystagmus which is a corrective mechanism. Therefore, brainstem & cortex intact

Eyess not moving (totally still) -- Brainstem is NOT intact

COWS (indicates direction of nystagmus): cold­ opposite, warm­ same side

117

What does COWS indicate?

COWS
– indicates direction of the fast movement during the nystagmus that occurs:

►Cold water added to L ear results in:
– Fast component to R (opposite)
– Slow component to L (same side)

►Warm water added to L ear results in:
– Drives reflex in opposite direction (allows other side to increase)
– Fast component to L (same side)
– Slow component to R (opposite)

118

When we put COLD water in the LEFT ear, what happens?

Mechanism?

Afferent signal (SSA) from L ear travels to CN 8 nuclei in floor of 4th ventricle

THEN, goes to contrateral CN 6 in pons
then, 2 destinations:
(1) Lat Rectus
(2) contralateral CN3 via MLF

causes "jerk" fast movement to R (opposite side)

119

Which nerves are involved in corneal reflex?

CN 5 (aff)
CN 7 (eff)

►Afferent Component
CN5v1 → chief sensory nucleus → spinal tract of V and spinal nucleus of V

►Efferent Component
→ facial motor nuclei → CN 7 → orbicularis oculi

120

HR 100
RR 20
BP 120/80
Temps 39.5

What is going on?
Ddx?

►Infection
sepsis

►Thyroid Storm

►Toxic Ingestion

121

HR 40
RR 12
BP 90/60
Temps 28

What is going on?
Ddx?

Hypothermia

122

HR 130
RR 30
BP 90/60
Temps 36.5

What is going on?
Ddx?

Bleeding Out

123

HR 100
RR 40
BP 130/80
Temps 36.9

What is going on?
Ddx?

Hypoxia
Acidosis

124

HR 60
RR 20
BP 240/120
Temps 36.8

What is going on?
Ddx?

►Hypertensive Encephalopathy
– hypertensive crisis
– transient migratory neurologic symptoms that are associated with the malignant hypertensive state in a hypertensive emergency.

►Bleeding from brain → could be Cushing's Triad
↓HR - reflexive bradycardia
↑BP - attempt to keep MAP > ICP
↓RR - Resp irregulatiries (if the medulla is hypo-perfused)

►Stroke

125

HR 110
RR 24
BP 120/70
Temps 37.3

What is going on?
Ddx?

Hypoglycemia
CO poisoning

126

Severe head trauma will result in what GCS?

<8

127

What are the 4Ns i the examination of the unconscious patient?

►Noggin
– Evidence of trauma?
– Raccoon eyes
– Battle’s sign (behind ears)

►Neck
– C-spine needed?
– If not, check for meningismus / neck stiffness → Infection? Subarachnoid Hemorrhage?

►Nose
– Odours- alcohol, acetone, fetor hepaticus, toxins

►Needle
– Track marks

128

Pupils ... balance between parasympathetic & Sympathetic

What controls each?

►Parasympathetic
• Edinger-Westphal nucleus in rostral midbrain
• CN3

►Sympathetic
• Hypothalamus → Medulla → upper thoracic spinal segments → Dilator Muscle

129

Pinpoint Pupils bilaterally

Ddx?

►Pinpoint pontine pupils
– midbrain parasympathetic flow intact
– damage to sympathetic flow caudally → classically in Pons (infarct or hemorrhage) → pupils constrict bilaterally

►Opioid OD

130

Huge dilated pupils

Bilateral
...vs...
Unialteral

Ddx?

►Bilateral
●Structural → bilateral midbrain/CN3
●Non-structural
– SEVERE toxic/metabolic damage (pupillary reflex resistant to most mild metabolic insults)
– selected toxins

►Unilateral
• transtentorial / uncal herniation

131

Unconscious patient presents with asymmetric pupils

What MUST we consider?

expanding supratentorial herniation

(must rule this out)

132

Pupils: Small to midrange, equal, reactive

Cause?

most likely toxic/metabolic cause

133

Pupils: pinpoint pupils

Cause?

either pontine insult
...or...
opioid OD

134

Pupils: unilateral dilated pupil

Cause?

supratentorial mass lesion until excluded

135

Pupils: bilateral dilated non-reactive pupils

Cause?

bilateral structural midbrain
...or...
severe metabolic

136

Pupils: bilateral midrange non-reactive

Cause?

severe metabolic
...or...
barbiturate OD

137

Pupils: bilateral dilated reactive

Cause?

mild / moderate toxic / metabolic
...or...
structural

138

►Epileptic seizure

...vs...

►Epilepsy

►Epileptic seizure:
• a transient occurrence of signs and/or symptoms due to abnormal excessive or synchronous neuronal activity in the brain.
• requires the occurance of at least 2 unprovoked seizures (low blood sugar, head injury do NOT count!)

►Epilepsy:
• a disorder of the brain characterized by an enduring predisposition to generate epileptic seizures.

139

Status Epilepticus

Tx?
(order of progression...)

►DAMPENS FIRE
• Lorazepam IV (Ativan)
• Midazolam IM (Versed)

►PUTS OUT FIRE
• Phenytoin (Dilantin)

►STILL CONVULSING...?
• Valproic Acid
• Phenobarbitol
• ICU Intubate: Midazolam

140

What are indications for Epilepsy Surgery?

Drug resistant focal epilepsy
– mesio-temporal sclerosis (Jared)
– lesional epilepsies
GOAL: Cure

Drug resistant drop attacks
— corpus collusm is sectioned to impede
seizure frequency
GOAL: palliation (improvement, not curative)

141

Lennox–Gastaut Syndrome
(LGS)

What is it?

aka " Lennox syndrome"

• difficult-to-treat form of childhood-onset epilepsy that most often appears between age 2-6
• frequent seizures and different seizure types
• often accompanied by developmental delay
• psychological and behavioral problems.

142

What are driving rules for those with seizures?

Remember:
seizure is an event
Epilepsy is a DIAGNOSIS

Not allowed to drive for 3 months following first unprovoked seizure

Patients diagnosed with epilepsy:
►6 months seizure free
►5 years seizure free for those operating heavy machinery

143

• R pupil 6 mm, sluggishly reactive
• L pupil 3 mm, reactive

What will motor exam show?

L motor weakness

EXPLANATION:
This is a blown pupil, highly suggestive of Transtentorial / Uncal Herniation → occurs when the temporal lobe swells and presses medially disrupting ...
(1) CN3 → dilate "blown pupil"
(2) cerebral peduncle → contralateral plegia
(3) reticular activation centre of the brainstem → coma

144

Generalized
...vs...
Focal Seizure–

►Generalized Seizure
– originate within or rapidly evolve to involve networks within both cerebral hemispheres


►Focal Seizure
– originate within networks limited to ONE cerebral hemisphere.
– May be discretely localized or more widely distributed within that hemisphere; and may later spread to become bilateral (hence secondary generalized)

145

Seizure History Taking

►Description:
– any prodrome / aura
– seizure onset (focal features vs generalized from onset)
– seizure evolution (focal, generalized, automatisms)
►Duration of seizure
►Tongue Biting / Incontinence
►Post Icteral Confusion? For how long?
►Seizure Triggers (sleep deprivation, stress, alcohol)
►Any recollection of events?

146

What are automatisms?

– set of brief unconscious behaviors
– last for several seconds to minutes or sometimes longer, a time during which the subject is unaware of his/her actions

147

What are examples of Automatisms?

simple gestures, such as finger rubbing, lip smacking, chewing, or swallowing, or more complex actions, such as sleepwalking

Others may include speech, which may or may not be coherent or sensible

The subject may or may not remain conscious otherwise throughout the episode. Those who remain conscious may be fully aware of their other actions at the time, but unaware of their automatism.

148

What is the goal of the Hx taking for seizure?

Goal is to determine whether the episode was truly a seizure or a seizure mimic

Seizure mimics (other causes of transient neurological dysfunction)
– TIA
– migraine auras
– Syncope
– Non-epileptic (psychogenic) seizures

149

Risk Factors for Seizures

– Family Hx of Seizures / epilepsy
– Personal Hx of febrile seizures
– Personal Hx of CNS infection (meningitis, encephalitis)
– Head trauma with post-concussive Sx or loss of LOC
– Perinatal hypoxia / head trauma
– Structural brain lesions
– Childhood exposure to herbicides or insecticides
– Personal Hx of development delay

NOTE: Maternal smoking during pregnancy is NOT a r/f

150

Triggers for Seizures
– Sleep deprivation
– Alcohol / substance use or withdrawl
– Stress
– Infection
– Hypoglycemia
– Hyponatremia
– Perimenstrual Period
– Head Injury

NOT triggers for Seizures
– Elevated barometric pressure
– Hypokalemia (low K+)

151

EEG

What is it?

What does it do for us?

Electroencephalography
– most useful test for diagnosing epilepsy, classifying seizures as partial or generalized, and may identify specific epilepsy syndromes in same cases.

– Early EEG after first seizure can be a helpful predictor of seizure recurrence.

– The first interictal EEG is normal in 50% of patients with epilepsy. With additional routine EEGs, the yield increases to ~90%. There is little value to repeating EEG more than 4 times.

152

Lumbar Puncture

What are indications?

Suspicion of infectious or inflammatory process.

(fever, altered LOC ... not relevant for seizure)

153

What is the effect of anti-epileptic drugs (AED) on:
• long-term risk of epilepsy
• frequnecy & severity of seizures

AED therapy does NOT alter the long-term risk of epilepsy, but will reduce the frequency and severity of seizures

154

Generalized Epilepsy Syndromes

Rx?

►Valproic Acid
– first-line agent
– broad spectrum agent
– teratogenic, do NOT use women of child-bearing age

For women of child-bearing age:
►Lamotrigine (Lamictal)
►Topiramate (Topamax)
►Levetiracetam (Keppra)

155

Partial (focal) Seizures

Rx?

Carbamezapine
– first-line (but lots of others ...)

156

Phenytoin
Valproic Acid

What do we need to be aware of when using these?

Monitor CBC & Liver enzymes

These are older meds that can cause liver and BM toxicity

157

During a seizure, as convulsions subside, what should be done to the patient?

Roll into recovery position

158

Mesial Temporal Sclerosis

(MTS)

●Characterized by neuronal loss (atrophy) and gliosis (scarring) in the hippocampus, especially in the CA1 & CA2 regions.

●Most common pathological finding in patients with temporal lobe resection for drug-resistant temporal lobe seizures.

●Up to 80% of pateints with mesial temporal lobe epilepsy and MTS have a prior history of febrile seizures

159

How is MTS identified?

Coronal T2-weighted MRI sequences, which show:
– decreased hippocampal volume
– increased T2 signal
– loss of internal architecture (poor grey / white matter differentiation)

160

Circuit of Papez

What is it?

● Involved in formation of new memories
● Part of Hippocampal formation

NOTE: Hippocampus is located in mesial temporary lobe, forming the floor of the temporal horn of the lateral ventricle

161

Status Epilepticus

What is the most common cause ...
●in children
●in adults?

CHIDLREN:
febrile seizures

ADULTS:
– acute stroke
– hypoxia
– metabolic causes
– change in medication or change in anti-convulsant

162

Status Epilepticus (SE)

What is the first line in-hospital tx?

Lorazepam (Ativan)

2-4 mg IV

163

What if we can't get an IV line !?!?

IM Midazolam

RAMPART TRIA:
Established IM midazolam (Versed) as an effective first-line Tx if IV access is not available

164

Lorazepam has a short half-life, therefore, all pts in status epilepticus should also be given a second anti-epileptic drug to prevent recurrent seizures.

What drug?

Phenytoin (Dilantin
20mg / kg IV

165

Status Epilepticus

What is the mortality rate?

What is the prognosis?

Mortality:
– Rate for adults with a first episode is 20%
– depends on, and is often due to, the underlying cause of status

Prognosis:
– 20-50% of survivors will have significant functional disability

166

Status Epilepticus

What are negative prognostic factors?

– older age
– longer seizure duration
– subtle SE after generalized convulsive SE
– Female sex
– Presence of comorbities

167

Benzos & Barbs act on ....

GABA type A- chloride

168

A man with known brain malignancy has a huge, full body seizure.

What do we call this?

Secondary Generalized Seizure

169

An alcoholic has been without for 20 hours. Has a big bad seizure with urinary incontinence.

What do we call this?

Tonic-Clonic

170

A young woman is witnessed to have an episode of unresposiveness, during which she smacks her lips, and stares off.

What do we call this?

Complex Partial
(she LOST consciousness / awareness)

171

Pilocytic astrocytoma

Characteristics

– May be cystic
– Vascular neogenesis is not a prognostic factor
– Usually has good prognosis

172

Meningiomas

Characteristics

• Adults > Children
• Women > Men
• May have receptors for Estrogen
• Most are benign

Calcification does NOT have prognostic significance

173

Metabolic coma
...vs...
Coma caused by supratentorial & subtentorial mass

HOW TO DIFFERENTIATE?

Pupils remain PERL in metabolic coma.

Pupils may be messed up when masses are involved

174

What is the Cushing response/reflex?

• increase systolic BP
• Decrease HR
• Erratic respiration