B&B Week 4 Flashcards
define consciousness
a state of awareness of self and environment, and awareness of the relationship between self and environment
what are the 3 neural correlates of consciousness?
- STATE of consciousness
- LEVEL of consciousness
- CONTENT of consciousness
what is responsible for “state” of consciousness?
refers to responsiveness to stimuli (i.e verbal, pain, etc)
multiple regions of the THALAMUS… thalamus and thalamic signalling–> the “gatekeeper” to the cortex
synchronized signalling between thalamus and cortex generates the STATE of consciousness
what is responsible for “level” of consciousness?
alertness–> drowsiness–> coma… its a continuum
diffuse BRAINSTEM structures–> projections from the brainstem reticular formation (RF) to the thalamus and cortex
projections between thalamus and cortex
what is responsible for “content” of consciousness?
sensations, emotions, memories and feelings that occur in our inner world –> perception, emotion, meaning, memories…
main player is the cortex which is accessed thru the thalamus …widespread regions of the CEREBRAL CORTEX
what are the 4 main neural players in consciousness?
- brainstem reticular formation
- thalamus
- thalamic reticular nucleus (TRN)
- cortex
where is the brainstem RF located?
in the tegmentum of the brainstem extending into the spinal cord
what are the 3 functional components of the brainstem RF?
- lateral zone–> processes afferent, sensory information
- medial zone–> processes efferent, motor information
- the sum of neurotransmitter systems that project to widespread areas of the CNS
what does the lateral zone of the brainstem RF do?
processes afferent, sensory information
what does the medial zone of the brainstem RF do?
processes efferent, motor information
what do the the sum of neurotransmitter systems that project to widespread areas of the CNS from the brainstem RF do?
influence the level of consciousness, wakefulness and sleep, as well as play a role in pain processing, motivation, emotion, reward, and addiction
together, the projections from the RF that ascend to the thalamus and cortex and play a role in modulation of consciousness are often referred to as the ascending reticular activating system (ARAS)
what is the ARAS? what is involved in it?
together, the projections from the RF that ascend to the thalamus and cortex and play a role in modulation of consciousness are often referred to as the ascending reticular activating system (ARAS)
- dopamine–> substantia nigra and ventral tegmental area
- noradrenaline–> locus ceruleus–> projects to thalamus and forebrain
- serotonin–> raphe nuclei–> projects to thalamus, cortex, basal ganglia, brainstem
- ACh–> tegmentum of pons–> projects to thalamus and cortex to strengthen output from thalamus to cortex
- histamine–> tegmentum of midbrain–> projects to thalamus and cortex for general arousal and alertness
what is the role of the thalamus in consciousness?
connects cortical areas with each other, integrating, modulating and gating the flow of info from one part of the cortex to the other
because it regulated information that will ultimately reach the cortex, it is called the “Gatekeeper” to the cortex
bidirectional communication between the cortex and nuclei of the thalamus provides an additional layer of information processing
contains specific inputs (drivers) and regulatory inputs (modulators)–> drivers contain info that must be forwarded to the cortex and modulators regulate whether or not it is forwarded
what is the role of the thalamic reticular formation (TRN) in consciousness?
the TRN is a sheet of neurons surrounding the thalamus
all neurons of the TRN are GABAergic and send their inhibitory projections into the thalamus, thereby negatively modulating the excitatory projections between the thalamus and the cortex (“gatekeeper of the gatekeeper”)
for conscious awareness, the connections between the TRN and the thalamus, and between the cortex and the TRN must be SYNCHRONIZED
consciousness means that the external and the internal experiences of an event are one, or are synchronized in time and space –> through this synchronization, the TRN creates consciousness or awareness of incoming sensory stimuli and cognitive processes
when neurotransmitter do the neurons in the TRN use?
GABA–> are all inhibitory
what is the role of the cortex in consciousness?
the cortex computes the CONTENT of consciousness where the thalamus DISPLAYS, and thus experiences, the results of those computations
different areas involved including the prefrontal (attention) and parietal areas (social) or cortex
what is the basic concept underlying unconsciousness (neurally)?
regardless of the cause, the basic concept underlying unconsciousness is that at least one of two areas must be damaged, either:
1. ascending reticular activating system (ARAS)
or
2. bilateral cerebral hemispheres or thalamo-cortical projections
what is a mnemonic for remembering the structural causes of unconsciousness?
TIPS
trauma/tumour/temperature
infection
psychogenic
subdural hematoma/subarachnoid hemorrhage/stroke/seizure
what are the structural causes of unconsciousness?
TIPS
trauma/tumour/temperature
infection
psychogenic
subdural hematoma/subarachnoid hemorrhage/stroke/seizure
how does trauma lead to unconsciousness?
head injury leads to loss of consciousness via several mechanisms
primary injury, produced at the moment of impact, includes COUP CONTUSION (at site of impact) and CONTRE-COUP CONTUSION (at the side opposite to that of impact) of the brain, which can lead to SUBDURAL or EPIDURAL hemorrhage
another mechanism of primary injury in head trauma is DIFFUSE AXONAL INJURY from the compressive, tensile and shear forces exerted on the brain–> shear injury predominates in white matter fibre tracts, disrupting a vast area of both cerebral hemispheres
secondary insults resulting from head trauma include intracranial hemorrhage (brain parenchyma, subdural or epidural space), raised ICP, hypoxia/ischemia, sepsis (usually due to lung or urinary infection that becomes systematic) and electrolyte disorders (SIADH, diabetes insipidus)
what happens when you have a lesion like a tumour, subdural hematoma, subarachnoid hemorrhage or stroke (unilateral, supratentorial, space occupying lesions)?
these types of lesions result in increased ICP, which leads to herniation syndromes
following munroe-kellie doctrine, the increased ICP leads to medial or UNCAL herniation through the tentorial notch beside the midbrain, distorting the midbrain ARAS, leading to decreased alertness
list the 5 mechanisms by which tumours can cause impaired consciousness
- mass effect from the tumour, edema or hemorrhage
- strategic location
- meningeal spread
- complication of therapy
- seizures
what are the most important factors concerning mass effects of tumours on consciousness?
speed of tumour growth and location
causes of rapid evolution of mass effect include:
- hemorrhage into a tumour
- cerebral edema
- necrosis of the tumour with swelling or rapid growth
tumours within or near centers for alterness (rostral brainstem, thalamus or, less likely, BOTH frontal lobes) can cause compression or distortion of these centers leading to decreased consciousness
how does tumour spread to meninges cause impaired consciousness?
can lead to obstruction of CSF circulation, hydrocephalus, and raised ICP
what might cause a seizure in a brain cancer patient?
may be due to brain or meningeal mets, chemo-related metabolic disturbance, infections, or, less commonly, a direct effect of a drug, all of which can lead to decreased consciousness
how does temperature affect consciousness?
hyperthermia–> in pyrexia (rectal temp greater than 41 degrees celcius), neurologic function is impaired due to several mechanisms
hypothermia–> in severe hypothermia (less than 25 degrees celcius) there is a LOSS OF CEREBROVASCULAR AUTOREGULATION and thus cerebral blood flow declines… furthermore, the combined effects of platelet dysfunction, increased fibrinolytic activity and release of a heparin-like substance produces a DIC-like syndrome
what are the mechanisms by which pyrexia (hyperthermia) impairs neurologic function?
- IL-1 and other cytokines have a direct effect on the CNS
- brain concentration of EXTRACELLULAR GLUTAMATE is directly related to temperature–excessive amounts can lead to an encephalopathy and seizures
- systemic abnormalities from pyrexia (hypoglycemia, hypophosphatemia, electrolyte disturbances, uremia, other end organ damage) contribute to encephalopathy
- hemorrhages can occur in various organs (including the brain) at high temps due to endothelial damage and disseminated intravascular coagulation (DIC)–> common areas of brain hemorrhage include the cerebellar cortex, cerebral cortex, thalamus, striatum
- it has been proposed that activation of NMDA receptors plays a role in hyperthermia
what is pyrexia?
rectal temp greater than 41 degrees celcius
how does infection cause unconsciousness?
the mechanisms behind coma in CNS infections are complex and include disturbances of the microvasculature and larger cerebral arteries, and result in altered cerebral metabolism, altered cerebral blood flow, cerebral edema, increased ICP, focal cerebral lesions (including mass lesions with resulting tentorial or foramen magnum herniation) and hydrocephalus
how do psychogenic mechanisms cause unconsciousness?
unresponsiveness is a diagnosis of exclusion
the neuro exam shows REACTIVE PUPILS and NO REFLEX POSTURING to PAIN (i.e no decerebrate or decorticate posturing)
eyes remain in midgaze during the oculocephalic reflex, hence there is an ABSENT DOLL’S EYE response
ice water caloric testing will either INDUCE NYSTAGMUS or ROUSE the patient because of the discomfort produced
the EEG finding in psychogenic unresponsiveness reflects that of NORMAL WAKEFULNESS
what is decorticate posturing?
Decorticate posture is an abnormal posturing in which a person is stiff with bent arms, clenched fists, and legs held out straight. The arms are bent in toward the body and the wrists and fingers are bent and held on the chest.
This type of posturing is a sign of severe damage in the brain. People who have this condition should get medical attention right away.
what is decerebrate posture?
Decerebrate posture is an abnormal body posture that involves the arms and legs being held straight out, the toes being pointed downward, and the head and neck being arched backward. The muscles are tightened and held rigidly. This type of posturing usually means there has been severe damage to the brain.
what is the oculocephalic reflex and the doll’s eye response?
oculocephalic reflex:
ensure the C-spine is cleared.
the patient’s eyes are held open.
the head is briskly turned from side to side with the head held briefly at the end of each turn.
a positive response occurs when the eyes rotate to the opposite side to the direction of head rotation, thus indicating that the brainstem (CN3,6,8) is intact.
how does a subdural hematoma cause unconsciousness?
subdural hematomas are more common that epidural hematomas, occurring in approx 30% of severe head injuries
result most frequently from tearing of a bridging vein between the cerebral cortex and a draining venous sinus
with subdural hematomas, the force of impact is often transmitted to the brain itself
a subdural hematoma will appear on a CT scan as a crescent shaped blood collection between the brain and the dura
there is frequently an adjacent parenchymal contusion, and if large it may cause a midline shift, leading to uncal herniation and altered consciousness
how does subarachnoid hemorrhage lead to unconsciousness?
saccular and berry aneurysms of intracranial arteries lie unsupported in the subarachnoid space–> rupture of these thin walled vessels is the primary cause of subarachnoid hemorrhage
although the most common presenting symptom is an intense headache, accumulation of blood in the cranium can lead to a mass effect, leading to uncal herniation and altered consciousness
how does stroke cause unconsciousness?
the two classes of strokes are hemorrhagic (cause unconsciousness by similar mechanism to subarachnoid hemorrhage) and ischemic
ischemic strokes from thrombus or embolus blocking the vessel lumen account for 80% of strokes
ischemic strokes can cause altered consciousness if the involved vessel supplies the MIDBRAIN (i.e the vertebral-basilar system–> posterior cerebral artery)
infarcts of the internal carotid system are LESS likely unless there are bilateral infarcts of the anterior cerebral arteries
which are more common, ischemic or hemorrhagic stroke?
ischemic (80%)
how do seizures cause unconsciousness?
in generalized tonic-clonic seizures, the entire CNS is dominated by cycles of excitation and inhibition, thus all measures of consciousness are lost and a temporary coma results
in complex partial seizures, impaired consciousness usually reflects the spread of the seizure discharge throughout the LIMBIC system bilaterally
what is a mnemonic for remembering the metabolic causes of unconsciousness? what are the causes?
AEIOU
Alcohol electrolyte imbalance infection/insulin oxygen/opiates/other drugs uremia
how does alcohol cause unconsciousness?
alcohol is a CNS depressant that is through to potentiate the receptor function of the inhibitory amino acid GABA and inhibit the receptor function of the excitatory animo acid NMDA
alcohol also increases membrane fluidity and permeability, thus reducing the speed of synapses
it also acts on noradrenergic, dopaminergic, serotoninergic and opioid pathways
with high blood alcohol levels, stupor (0.4 blood alcohol) and coma (0.5 blood alcohol) can occur in acute alcohol intoxication
how does electrolyte imbalance cause unconsciousness?
confusion and coma can result from anything that causes HYPONATREMIA, or HYPERCALCEMIA
the (reversible) toxic effects of these abnormalities on the brain are not understood but may, in different cases, impair energy supplies, change ion fluxes across neural membranes, and cause neurotransmitter abnormalities
how can insulin (hypoglycemia) cause unconsciousness?
HYPOGLYCEMIA can cause neuronal death (and severe hypoglycemic reactions are commonly accompanied by seizures or by status epilepticus that can also contribute to cell death)
in hypoglycemic coma, extracellular CALCIUM concentration FALLS profoundly and intracellular calcium rises before energy stores are depleted
neuronal death is presumed to be calcium-mediated, with activation of free radicals and release of other autodestructive enzymes
how does hyperglycemia affect consciousness?
hyperglycemia can also cause decreased alertness
impairment of consciousness correlates with the degree and rapidity of the hyperosmolality, mainly due to cellular dehydration and volume loss
acetoacetate (not beta-hydroxybutarate) in high concentrations in diabetic ketoacidosis produces impaired consciousness and decreased cerebral oxygen use
how does hypoxia cause unconsciousness?
hypoxia results in cell death by a complex mechanism involving several components
hypoxia is most often accompanied by ischemia, which leads to cell death and glutamate release that stimulates NMDA receptors, thus stimulating calcium entry into cells
this increased intracellular calcium activates intracellular enzymes and genes, leading to cell damage and eventual cell death
upon dying, it releases its contents and perpetuates the cycle
how do opiates cause unconsciousness?
there are many types of opioid receptors to which these drugs can bind (Mu, kappa, delta, sigma and epsilon)
kappa receptors’ actions include analgesia, sedation, respiratory depression and miosis (since there is a high density of opioid receptors in the brain stem nuclei)
**almost any drug in sufficient quantity can cause coma
how does uremia cause unconsciousness?
unlike ammonia, urea itself does not produce CNS toxicity
therefore, a multifactorial cause for coma has been proposed including an increased permeability of the BBB to toxic substances such as organic acids and an increase in brain calcium or CSF phosphate content
what makes up intracranial volume?
80% brain
10% CSF
10% blood
what is the munroe-kelli doctrine?
(Vk is constant)
Vk equals Vbrain + Vcsf + Vblood
therefore, any ADDED volume within the skull displaces the other 3 normal constituents–> increase in pressure within the confined rigid skull (normally
what procedure is contraindicated in elevated ICP states?
lumbar puncture (risk of herniation)
how do you monitor ICP?
predominant methods are: extraventricular drains (ventriculostomy) fibre-optic pressure transducers
ventriculostomy relieves elevated ICP and hydrocephalus when CSF flow is obstructed
what is the major pathological result of closed head injuries?
increased ICP
what are the cellular effects of increased ICP?
mechanical compression on neurons, glia, and cerebral blood vessels
this causes neuronal dysfunction and eventual death, and decreased cerebral blood flow and ischemia
what are the neurologic effects of increased ICP?
general–> diffusely increased ICP will cause headache (morning headache or headache that is worse in valsalva maneuvers), nausea, vomiting, papilledema, Cushing’s response (HTN, bradycardia)
focal–> paralysis, aphasia, cranial nerve palsy, drowsiness, apnea (dependent on area being compressed)
what happens in a case of acute, severe elevated ICP?
eventually the elevated pressure on focal areas of the brain will cause it to shift along the pathway of least resistance–> movement along pressure gradients so that parts of the brain HERNIATE into other compartments
list the 4 herniation syndromes we need to know
- subfalcine herniation
- midline shift
- tonsillar herniation
- uncal (transtentorial) herniation
what is a subfalcine brain herniation?
herniation of the FRONTAL lobe under the falx
what is a midline shift brain herniation?
movement of one hemisphere toward the other
what is a tonsillar brain herniation?
herniation of the cerebellar tonsils through the foramen magnum –> can compress the medulla and cause respiratory depression
what is an uncal brain herniation?
aka transtentorial brain herniation
herniation of the uncus (medial temporal lobe) through the tentorial hiatus and up against the brainstem
can compress CN III, the midbrain cerebral peduncle, and the PCA (leading to stroke)
MEDICAL EMERGENCY–> sign of imminent death
how do the presentations of increased ICP that occurs rapidly versus slowly differ?
increased ICP that occurs rapidly is generally an ACUTE emergency
increased ICP that occurs slowly will often have no neuro symptoms
what does the tentorium separate?
the cerebellum from the cerebrum
list the types of supretentorial herniation
- uncal
- central
- subfalcine
- transcalvarial
list the types of infratentorial herniation
upward (upward cerebellar or upward transtentorial
tonsillar (downward cerebellar)
there are 12 general steps to the examination of the unconscious patient… what are they?
- vitals (including HR, RR, BP, temp and O2 sat)
- glasgow coma scale
- general appearance
- pupils
- fundi
- spontaneous eye movement
- corneal “blink” reflex
- doll’s eye (oculocephalic) reflex
- oculovestibular (caloric) reflex
- gag reflex
- motor exam
- reflexes/plantar response
in terms of the examination of the unconscious patient, what are you looking for/at when you examine:
their glasgow coma scale rating
less than 8 indicates severe head injury (chart is on another question)
decorticate–> arm flexion to stimulation, indicates lesion above red nucleus
decerebrate–> extension to stimulation. indicates midbrain or rostral pons lesion (this is a worse sign)
what is the red nucleus?
The red nucleus or nucleus ruber is a structure in the rostral midbrain involved in motor coordination. It is pale pink in color; the color is believed to be due to iron, which is present in the red nucleus in at least two different forms: hemoglobin and ferritin.[1] It comprises a caudal magnocellular and a rostral parvocellular part. It is located in the tegmentum of the midbrain next to the substantia nigra. The red nucleus and substantia nigra are subcortical centers of the extrapyramidal motor system.
in terms of the examination of the unconscious patient:
what are the 4 N’s to look at on general appearance? what are you looking for specifically for each one?
Noggin–> trauma is seen via raccoon eyes, battle’s sign, or hemotympany
Neck–> immobilize in trauma, otherwise check for meningitis
Nose–> smell for alcohol, acetone, toxins)
Needle–> look for track marks
in terms of the examination of the unconscious patient, what are you looking for/at when you examine:
pupils
- size
- remember: PSNS constricts pupils, SNS dilates them
- pinpoint pupils–> SNS disruption below midbrain level
- unilateral dilation–> uncal herniation pressing on CN III
- bilateral dilation–> severe metabolic/toxic cause or bilateral CN III - symmetry
- asymmtery in coma indicates supratentorial tesion until ruled out
- otherwise–> eye trauma, aneurysm, cycloplegic drugs etc - reactivity
- unilateral non-reactive indicates uncal herniation
- bilateral non-reactive indicates the same things as bilateral dilation and some drugs
what do pinpoint pupils indicate on the exam of an unconscious patient?
SNS disruption below the midbrain level
what does unilateral pupil dilation indicate on the exam of an unconscious patient?
uncal herniation pressing on CN III
what does bilateral pupil dilation indicate on the exam of an unconscious patient?
severe metabolic/toxic cause or bilateral CN III
what does a unilaterally unresponsive pupil in an unconscious patient indicate?
uncal herniation
in terms of the examination of the unconscious patient, what are you looking for/at when you examine:
fundi
look for papilledema and cessation of venous pulsations in ICP; hemorrhages
in terms of the examination of the unconscious patient, what are you looking for/at when you examine:
spontaneous eye movements
look away from seizure focus, toward stroke
dysconjugate gaze indicates a brainstem problem
in terms of the examination of the unconscious patient, what are you looking for/at when you examine:
corneal “blink” reflex
sensation via CN V1, motor via CN III
in terms of the examination of the unconscious patient, what are you looking for/at when you examine:
dolls eye (oculocephalic) reflex
present if eyes move in orbit to remain fixed on ceiling, absent if eyes stay mid-gaze when turning the head to the side
indicates brainstem dysfunction/pseudocoma
in terms of the examination of the unconscious patient, what are you looking for/at when you examine:
oculovestibular (caloric) reflex
put ice water in ear and look at the direction that eye go
- nystagmus in both eyes with fast phase to side opposite water–> no coma, intact brainstem
- slow deviation to the side of water–> brainstem and MLF are intact
- ipsilateral eye only moves to cold water–> MLF lesion
- no eye movement–> brainstem dysfunction (structural or toxic)
in terms of the examination of the unconscious patient, what are you looking for/at when you examine:
gag reflex
sensation via CN IX, motor via CN X
in terms of the examination of the unconscious patient, what are you looking for/at when you examine:
motor exam
look at tone and symmetry
what are the 5 clinical levels of altered consciousness?
- lethargy
- stupor
- coma
- akinetic mutism
- locked-in syndrome
in the following level of altered consciousness, in what state are the
- eyes
- arousability of the patient
- content of consciousness of the patient?
lethargy
- eyes closed
- arousable
- mildly impaired content
in the following level of altered consciousness, in what state are the
- eyes
- arousability of the patient
- content of consciousness of the patient?
stupor
- eyes closed
- arousable with effort
- markedly impaired content
in the following level of altered consciousness, in what state are the
- eyes
- arousability of the patient
- content of consciousness of the patient?
coma
- eyes closed
- unarousable
- not applicable
in the following level of altered consciousness, in what state are the
- eyes
- arousability of the patient
- content of consciousness of the patient?
akinetic mutism
*presentation is secondary to frontal/basal forebrain dysfunction
- eyes open
- wakeful
- impaired
in the following level of altered consciousness, in what state are the
- eyes
- arousability of the patient
- content of consciousness of the patient?
locked-in syndrome
*presentation is secondary to basis pontis dysfunction
- eyes open
- wakeful
- normal
what is the glasgow coma scale? what are the 3 components and how are they ranked?
- eye opening
- spontaneous 4
- to speech 3
- to pain 2
- no response 1 - verbal response
- alert and oriented 5
- disoriented 4
- speaking but nonsensical 3
- moans 2
- no response 1 - motor response
- follows commands 6
- localizes pain 5
- withdraws to pain 4
- decorticate flexion 3
- decerebrate extension 2
- no response 1
mild–13-15
moderate–9-12
severe–3-8
define seizure
abnormal neurologic functioning caused by abnormally excessive activation of neurons, either in the cerebral cortex or in the deep limbic system
slides: the clinical manifestation of an abnormal and excessive excitation and synchronization of a population of cortical neurons
define epilepsy
recurrent unprovoked seizures due to genetically determined or acquired brain disorder
it is not an appropriate term to use for seizures that occur intermittently and predictably after a known insult, such as EtOH intoxication and withdrawal
slides: a tendency towards recurrent seizures
What is the etiology of epilepsy in infancy and childhood
prenatal or birth injury
inborn error error of metabolism
congenital malformation
What is the etiology of epilepsy in childhood and adolescence?
idiopathic
genetic syndrome
CNS infection
trauma
What is the etiology of epilepsy in adolescence and young adulthood?
head trauma
drug intoxication or withdrawal**this one is a cause of acute seizures and not necessarily epilepsy
What is the etiology of epilepsy in older adult?
stroke
brain tumor
acute metabolic illness **cause of acute seizure not epilepsy
neurodegenerative
list seizure precipitants
- metabolic and electrolyte imbalance
- stimulantes (i.e cocaine)
- sedative or ethanol withdrawal
- sleep deprivations
- subtherapeutic or supratherapeutic AEDs
- hormonal variations
- fever or systemic infection
what is the pathophysiology of seizures?
seizures occur when the abnormal increased electrical activity of the initiating neurons activates adjacent neurons and propagates until the thalamus and other subcortical structures are similarly stimulated
when the ictal discharge extends below the cortex to deeper structures, the reticular activating system in the brainstem may be affected, altering consciousness
seizures are typically self limited–> at some point the hyperpolarization subsides and the burst of electrical discharge from the focus terminates
at the cellular level, why do seizures occur?
because of an imbalance between excitation and inhibition of neurons
excitations–> ionic: inwards Na+ and Ca2+ currents//neurotransmitters: glutamate and aspartate
inhibition–> ionic: inwards Cl- (GABAa), outwards K+ (GAGAb) currents//neurotransmitter: GABA
why do hyperexcitable networks occur?
as a result of:
- excitatory aconal sprouting
- loss of inhibitory neurons
- loss of excitatory neurons which would normally be driving inhibitory neurons (feed forward and feed back inhibition components)
how do you classify seizures?
they are either general or focal (partial)
generalizes seizures are abnormal neuronal activity in both cerebral hemispheres with loss of consciousness
focal/partial seizures are abnormal neuronal activity involving one cerebral hemisphere
list the types of generalized seizures
- absence (petit mal)
- tonic
- clonic
- tonic-clonic (grand mal)
- myoclonic
- atonic (drop attacks)
list the types of focal/partial seizures
- simple partial
- complex partial
- secondarily generalized
define absence/petit mal seizure
sudden onset and termination with impairment of consciousness only
define tonic seizures
tensing of skeletal muscles
define clonic seizures
cycles of muscle contraction and relaxation
define tonic-clonic/grand mal seizures
sequential occurrence of tonic and clonic phases, often preceded by an AURA
define myoclonic seizures
brief, involuntary twitching of a muscle or group of muscles
define simple partial seizure
consciousness is maintained
define complex partial seizure
impairment of consciousness
define secondarily generalized seizure
seizure that begins focally, and progressing to being generalized
what is status epilecticus?
defined as at least 30 minutes of persistent seizures or a series of recurrent seizures without intervening return to full consciousness
several authors have proposed shortening the time criterion from 30 min to 5 min
what are the two basic neural causes of seizures?
increased excitation, decreased inhibition or both
how does the body normally prevent hyperexcitable states?
normally there is feed back and feed forward inhibition to prevent these states
however, mechanisms that can generate abnormal hyperexcitable states are:
- excitatory aconal sprouting
- loss of inhibitory neurons
- loss of excitatory neurons which would normally be driving inhibitory neurons (feed forward and feed back inhibition components)
what is the foundation/idea behind anti-convulsant drugs (to treat seizures/epilepsy)?
decrease excitation or increase inhibition
list 3 anticonvulsant drugs whose MOA is to increase inhibition
- barbiturate
- benzodiazepines
- gabapentin
MOA of barbiturate?
increase inhibition
PROLONG GABA mediated Cl- channel openings
*some blockade of voltage gated Na+ channels
MOA of benzodiazepine?
increase inhibition
increase FREQUENCY of GABA mediated Cl- channel openings
MOA of gabapentin?
increase inhibition
increase neuronal GABA CONCENTRATION and enhance GABA mediated inhibition
list anticonvulsant drugs whose MOA is to decrease excitation
- phenytoin (dilentin)
- carbamazepine
- lamotrigine
- valproic acid
- ethosuximide
MOA of phenytoin (dilentin)?
decrease excitation
block voltage gated Na+ channels at high firing frequencies
what are some side effects of dilentin/phenytoin?
can cause hirsutism, gingival hypertrophy, facial coarseness, hair loss and weight gain
MOA of carbamazepine?
decrease excitation
Blocks voltage gated Na+ channels
MOA of lamotrigine?
decrease excitation
blocks voltage gated Na+ channels
MOA of valproic acid?
decrease excitation
blocks voltage gates Na+ channels
may enhance GABA transmission in specific circuits
good drug but TERATOGENIC so avoid use in women of child bearing age
what is a special consideration in the use of valproic acid?
good drug but TERATOGENIC so avoid use in women of child bearing age
MOA of ethosuximide?
decrease excitation
blocks low threshold, “transient” (T type) calcium channels in thalamic neurons
mainly used in CHILDREN
list 3 mixed action anticonvulsant drugs
- topiramate
- levetiracetam (keppra)
- oxcarbazepin (trileptal)
MOA of topiramate?
mixed action anticonvulsant
blocks voltage dependent Na+ channels at high firing frequencies
increases frequency at which GABA opens Cl- channels (at a different site than benzodiazepines)
antagonizes glutamate action at AMPA/kainite receptor subtype
MOA of levetiracetam?
aka keppra
mixed action anticonvulsant
reduces high voltage activated calcium currents
reverses inhibition of GABA and glycine gated currents
MOA of oxcarbazepin?
aka trileptal
mixed action anticonvulsant
blocks voltage gated Na+ channels at high firing frequencies
exerts effects on K+ channels
what is the main rehabilitation hospital for patients with brain injuries?
GF Strong
there are other smaller facilities with limited rehab, but GF Strong is the best facility for those with severe deficits whose prognosis is favorable
what are the admission criteria for rehabilitation programs through GF Strong?
above 18 years old
resident of BC
medically stable
primary diagnosis of acquired head injury (trauma, CVA, hemorrhage)
requires the services of an interdisciplinary team
what is the primary goal of head injury rehab?
to assist people to improve their independence and quality of life
treatment programs are designed to meet identified needs and functional goals of individual patients
what common functional problems are treated by head injury rehab programs?
- mobility–> inability to walk, difficulty with coordination and balance, weakness or loss of joint movement, difficulty completing an independent transfer
- self-care–> inability to control bladder and bowel, inability to self medicate, difficulty bathing, dressing, grooming or eating
- IADLs–> inability to manage household, finances, unable to drive or access public transit
- neurological–> inability to swallow, problems with memory, though processes, decision making, or reasoning, difficulty communicating with others, emotional problems
- recreational/vocational–> inability to participate in sports, need for job modification or skill retraining
what does the interdisciplinary team at GF strong consist of, for the rehab of head injured patients?
nurses
social worker
physio
OT
physician
speech and language pathologists
psychologist
recreation therapist
define general anaesthesia
altered physiologic state characterized by loss of consciousness, analgesia, amnesia and inhibition of autonomic and sensory reflexes
what are the pharmacokinetics of general anaesthesia?
anaesthesia is induced when critical concentration is reached int he brain (Pbr)
inhaled anaesthetic must travel down several concentration gradients:
delivered concentration–> inspired concentration–> alveolar concentration–> arterial concentration–> brain concentration
**the higher the blood/gas solubility, the higher the blood-gas partition coefficient, and the SLOWER the rate of induction
how are blood/gas solubility, the blood gas/ partition coefficient and rate of induction of anaesthesia related?
the higher the blood/gas solubility, the higher the blood-gas partition coefficient, and the SLOWER the rate of induction
i.e high blood solubility of an anaesthetic is a “Waste” because it is wanted in the BRAIN not the blood
what is the MOA of general anaesthetics?
- suppress excitable tissues by facilitating inhibition
- increased GABAa receptor-mediated transmission
- increased background “leak” K+ conductance - inhibits excitation
- decreased glutamate and ACh receptor mediated transmission
what is the MAC for general anaesthetics?
MAC is the minimum alveolar concentration
1 MAC is the concentration of an inhaled anaesthetic in the alveoli at 1 atm that prevents movement in response to a painful stimulus in 50% of patients (essentially is EC50)
how do inhaled anaesthetics affect the organs?
suppress all excitable tissues (CNS, PNS, cardiac, skeletal and smooth muscle)
what % of brain tumours are benign?
50%
can benign brain tumours be dangerous?
yes you can get recurrence and based on location they can cause death (ie “malignant by position”)–> this is different from benign tumours elsewhere in the body
how does the cure rate for malignant brain tumours compare to tumours elsewhere in the body?
its lower
what is the lifetime risk for a brain tumour?
1/200
what types of brain tumours have the best prognosis? which ones have the worst?
well-circumscribed tumours often have a good prognosis, but it depends on location
diffuse tumours have no cure and a poor prognosis–> excision may somewhat prolong life but complete excision is impossible
what is the etiology of brain tumours?
etiology of most is unknown
irradiation can cause meningiomas, gliomas and nerve sheath tumours
immunosuppression can cause primary CNS lymphoma
list some risk factors for brain tumours
- sex
- gliomas are 60% male, meningiomas are 70% female - association between breast cancer and meningiomas (hormone receptors)
- genetic factors play a role
- occupation may be a risk factor
- no convincing data for diet or trauma to be risk factors
- cell phone use may be of concern
list clinical features of brain tumours
- epilepsy
- headache
- raised ICP
- focal neurological deficit
- short history (CNS tumours are generally aggressive)
- primary tumours of the CNS rarely metastasize
- in adults, brain tumours are 70% supratentorial and 30% infratentorial; in kids its the opposite
list prognostic features for brain cancer for both the patient and the tumour
patient: age, neurological impairment, Karnofsky score
tumour: type, grade, location
list the 4 types of gliomas
- astrocytomas
- oligodendrogliomas
- ependymal cell tumours
- mixed gliomas
how are gliomas classified by the WHO?
grade I–> circumscribed, localized
grade II, III and IV–> diffuse and infiltrative (based on presence of nuclear pleomorphisms, mitoses, capillary endothelial proliferation and necrosis)
name a circumscribed, grade I astrocytoma
pilocytic astrocytoma
name a grade II, grade III and grade IV astrocytoma
II: diffuse astrocytoma
III: anaplastic astrocytoma
IV: glioblastoma
what is MGMT and how does it relate to gliomas?
MGMT is a DNA repair protein responsible for the major mechanism of chemo-resistance in gliomas
silencing this gene by alkylating agents has been associated with longer survival
are oligodendrogliomas well circumscribed or diffuse?
diffuse tumours
name two oligodendrogliomas
- oligodendroglioma (II)
2. anaplastic (malignant) oligodenroglioma (III)
where would you find an ependymal cell tumour in an adult? in a kid?
adults–infratentorial
kids–supratentorial
where do ependymal cell tumours often occur?
around the ventricles in the brain
name two histological features associated with ependymal cell tumours
perivascular pseudorosettes
true ependymal rosettes
name 4 ependymal cell tumours
- ependymoma (II)-> relatively well circumscribed but have small infiltrating projections that make them very difficult to excise
- anaplastic epenymoma (III)
- myxopapillary ependymoma
- subependymoma (I)
are mixed gliomas diffuse or well circumscribed?
diffuse
name two mixed gliomas
mixed oligoastrocytoma (II)
anaplastic oligoastrocytoma (III)
what are PNETs?
Primitive Neuro-Ectodermal Tumours
if there is a PNET in the cerebellum, what is it called?
medulloblastoma
- most common posterior fossa tumour in kids (often in the vermis)
- tendency to “seed” through the CSF
- small blue cell tumour
- 5 year survival 5–70%
- amplification of MYCN gene indicated poor prognosis
if there is a PNET in the cerebrum, what is it called?
neuroblastoma
if there is a PNET in the retina, what is it called?
retinoblastoma
if there is a PNET in the pineal gland, what is it called?
pineoblastoma
name 3 tumours of cranial and spinal nerves
- schwannoma
- neurofibroma
- malignant peripheral nerve sheath tumour (MPNST)
how many types of neurofibromatosis (causing neurofibromas) are there?
2–> neurofibromatosis types 1 and 2
what is another name for neurofibromatosis type 1?
von Reckinghausen’s disease
what is the mutation associated with neurofibromatosis type 1?
17q11
how is neurofibromatosis type 1 inherited?
autosomal dominant
what is the pathophysiology of neurofibromatosis type 1?
associated with defect in neurofibromimin (encoded by a tumour suppressor gene)
tumours in NF1: neurofibroma, optic gliomas, astrocytomas, meningioma and schwannoma (but not bilateral vestibular schwannoma)
what is the mutation associated with neurofibromatosis type 2?
22q12
what is the pathophysiology of neurofibromatosis type 2?
inactivation of schwannomin (merlin)
tumours in NF2: bilateral acoustic schwannoma, neurofibroma, astrocytoma, meningioma, ependymoma
what % of cranial tumours are meningiomas?
15%
are males or females more likely to get a meningioma?
females
where are meningiomas usually located?
90% intracranial
9% spinal
1% other
describe meningiomas
generally slow growing and well circumscribed
tend to spread into the skull not the brain
characteristic WHORLS and PSAMMOMA bodies
what % of meningiomas are benign? atypical? malignant?
benign –85%
atypical –10%
malignant –5%
what does recurrence of meningiomas depend on?
grade, completeness of surgical excision, presence or absence of brain invasion
rank the pituitary adenomas from most common to least common
- prolactin
- GH
- ACTH
- null cell
- mixed
- FSH/LH
- TSH
how common are primary CNS lymphomas?
rare
occur most often in the elderly or the immuno compromised
describe primary CNS lymphomas
can be solitary or multifocal
differential diagnosis: toxoplasmosis vs. PML vs. lymphoma (treat for toxo first, if no response then biopsy)
how do primary CNS lymphomas respond to steroids?
sensitive to steroids at first, but will always regress then recur
what type of lymphoma do primary CNS lymphomas tend to be?
B cell
what is the prognosis for primary CNS lymphomas?
very poor
how common are metastatic tumours to the CNS? where do these mets usually spread to in the brain?
just as common as other types of brain tumours
usually spread to parts of the brain with the greatest blood flow–> superficial areas and cerebral hemispheres (supretentorial)
what are the most common primary tumours that spread to brain?
lung
breast
skin (melanoma)
GI
name CN IX
glossopharyngeal
where does CN IX/glossopharyngeal nerve exit the brainstem?
posterolateral area of the medulla
what modalities are included in CN IX/glossopharyngeal?
GSA GVA SVA SVE/BE GVE
what is the function of the GSA modality of CN IX/glossopharyngeal nerve?
general sensation from posterior 1/3 of tongue, tonsil, skin of external ear, internal surface of tympanic membrane, pharynx
what is the function of the GVA modality of CN IX/glossopharyngeal nerve?
chemo/baroreceptors in the CAROTID BODY
visceral afferent info from the tongue and pharynx–> GAG reflex
what is the function of the SVA modality of CN IX/glossopharyngeal nerve?
taste from posterior 1/3 of tongue
what is the function of the SVE/BE modality of CN IX/glossopharyngeal nerve?
motor to stylopharyngeus muscle
what is the function of the GVE modality of CN IX/glossopharyngeal nerve?
PNS to parotid gland
name CN X
vagus
where does CN X/vagus nerve exit the brainstem?
posterolateral area of the medulla
what modalities does CN X/vagus nerve carry?
GSA
GVA
SVA
SVE
GVE
what is the function of the GSA modality of CN X/vagus nerve?
sensory from posterior meninges, external acoustic meatus, skin posterior to ears
what is the function of the GVA modality of CN X/vagus nerve?
sensory from larynx, trachea, esophagus, thoracic and abdominal viscera, stretch receptors in AORTIC ARCH, chemoreceptors in AORTIC BODIES
what is the function of the SVA modality of CN X/vagus nerve?
special sensory from taste buds in epiglottis
what is the function of the SVE modality of CN X/vagus nerve?
motor to pharyngeal muscles and intrinsic muscle of larynx
what is the function of the GVE modality of CN X/vagus nerve?
PNS to smooth muscles and glands of pharynx, larynx and thoracic/abdominal viscera
cardiac muscle
name CN XI
accessory
where does CN XI/accessory nerve exit the brainstem?
posterolateral area of the medulla
what modalities are carried by CN XI/accessory nerve and what do they do?
SVE–> sternocleidomastoid and trapezius
what brain system is the neuroanatomical structure primarily responsible for arousal? where is it located? how does it manage arousal?
the ascending reticular activating system (ARAS)
located in the paramedian tegmental zone of the brainstem
input of somatic and sensory stimuli to the cerebral cortex is controlled by the ascending RAS and functions to initiate arousal from sleep
can a coma result from only one affected cerebral hemisphere?
no usually both need to be affected
what is necessary for arousal?
a completely intact brainstem–> if the ARAS is impaired, the cerebral cortex cannot be aroused and depressed consciousness or coma results
what structures, essential to arousal/consciousness, are particularly vulnerable to toxins, metabolic derangements or mechanical injury?
insults to the cerebral cortex or brainstem can each independently cause depressed consciousness or coma
list systemic/metabolic etiology of altered mental status/coma
see page 99 of the BB review notes!!!
- hypoxia
- severe anemia or pulm disease
- enviro/toxin like cyanide or near drowning - disorders of glucose
- hypoglycemia (i.e in chronic alcohol abuse, or excessive use of insulin)
- hyperglycemia (i.e diabetic ketoacidosis, non-ketotic hyperosmolar coma) - decreased cerebral blood flow
- hypovolemic shock
- cardiac problems (i.e arrhythmias, MI, congestive heart failure, pericaridal effusion)
- infectious (septic shock, bacterial meningitis)
- vascular/hematologic (i.e hypertensive encephalopathy, pseudotumour cerebri, hyperviscosity like in sickel cell, hyperventilation, DIC) - metabolic cofactor deficiency
- thiamine deficiency (wernicke-korsakoff)
- folic acid (from chronic alcholol abuse)
- niacin deficiency - electrolyte/pH disturbance
- acidosis, alkalosis
- hyper or hyponatremia
- hyper or hypocalcemia
- hypophosphatemia
- hyper or hypomagnesemia - endocrine disorders
-myxedema coma
-hypopituitarism
-addisons disease
-cushings
-pheochromocytoma
hyper or hypoparathyroidism - endogenous toxins
- hyperammonemia (liver failure)
- uremia (renal disease)
- carbon dioxide narcosis
- porphyria - exogenous toxins
- alcohols
- acid poisons (salicylates, paraldehyde)
- antidepressant meds (lithium, TCAs, SSRIs, MAOIs)
- stimulants (meth/amphetamines, cocaine)
- narcotics/opiates (morphine, heroin, codeine, oxycodone, meperidine, methadone, fentanyl etc)
- barbituates, benzodiazepines, rohypnol, bromide
- hallucinogens
- herbs/plants (aconite, jimson weed, morning glory)
- volatile substances (hydrocarbonds, nitrites, anaesthetic agents)
- ketamine
- penicillin
- anticonvulsants
- steroids
- heavy metals
- cimetidine
- organophosphates - disorders of temperature regulation/environmental temp
- hypothermia
- heat stroke
- malignant hyperthermia
- high altitude cerebral edema
- dysbarism - primary glial or neuronal disorders
- adrenoleukodystrophy
- creutzfeldt-jakob disease
- progressive multifocal leukoencephalopathy
- gliomatosis cerebri
- central pontine myelinosis - other disorders of unknown etiology
- seizures
- postictal states
what are the dural reflections? what do they do?
the dural reflections are places where the inner dural layer is reflected as sheet-like protrusions into the cranial cavity.
these dural reflections compartmentalize the brain
the FALX CEREBRI separates the hemispheres
the TENTORIUM CEREBELLI separates the cerebrum from the cerebellum and brainstem
why do herniations occur in the brain?
when intracranial volume and ICP increase beyond the compensatory capacities of the CNS (i.e shifting of CSF into spinal cord), cerebral herniations occur along the path of least resistance (i.e the U shaped free edge of the tentorium cerebelli)
what is the pathyphysiology of an uncal herniation and how does this explain the symptoms associated with such a herniation?
occurs when the uncus of the ipsilateral temporal lobe hernaites and is compressed against the tentoruim
CN III is compressed leading to–> sluggish papillary reflex, impaired extraocular movements, pupillary dilation
ipsilateral peduncle compresses against the tentorium leading to–> contralateral hemiparesis and thus bilateral DECEREBRATE posturing (decorticate is not always present)
may also compress the PCA leading to PCA ischemic stroke
babinski’s sign is positive
if there is progressive herniation, you can proceed to brainstem compression and failure–> CV arrest–> death
what is Kernohan’s phenomenon?
related to uncal herniations
usually, you get a situation where the ipsilateral peduncle compresses against the tentorium leading to–> CONTRALATERAL hemiparesis and thus bilateral DECEREBRATE posturing (decorticate is not always present)
however, in kernohan’s phenomenon, you can get CONTRALATERAL peduncle compression against the opposite edge of the tentorium, leading to IPSILATERAL hemiparesis
what is cerebellotonsillar herniation?
cerebellar tonsils herniate through the foramen magnum
large central vertex mass (frontal or occipital pole) that forces brainstem displacement–> impingement of the MEDULLA–> SUDDEN respiratory and/or CV arrest
compression of the corticospinal tracts can cause FLACCID QUADRIPLEGIA
in what situations would you order at CT for a patient after a witnessed traumatic loss of consciousness?
(canadian head CT rule)–>after a witness traumatic loss of consciousness, CT is only required for patients with any ONE of the following:
- glasgow coma scale score lower than 15 at two hours after injury
- suspected open or depressed skull fracture
- two or more episodes of vomiting
- 65 years or older
- amnesia before impact of more than 30 min
- dangerous mechanism
1-4 are “high risk for neurosurgical intervention”
5, 6 are “medium risk for brain injury detection by CT”
name 4 specific types of closed head injury
- concussion
- brain contusion
- diffuse axonal injury
- intracranial hematoma
what is a concussion?
any head injury that temporarily affects normal brain function
most concussions are mild and do not cause loss of consciousness but this is not always the case
what are some immediate symptoms that might indicate concussion?
people suffering from a concussion can exhibit a number of immediate symptoms, including:
- headache
- dizziness
- nausea
- ringing in ears
- slurred speech
- vomiting
may also be confused, unable to concentrate, or have difficulty balancing
in some cases, sx do not surface until hours or days after the incident –> secondary sx include mood swings, sensitivity to light and noise, and changes in sleep patterns
what is a brain contusion?
brain contusions are bruises of the brain tissue that occur as a result of brain trauma
in some cases, brain contusions lead to hemorrhages which are absorbed into brain tissue
if blood is absorbed into the CSF it can cause permanent neuro damage
are LOCALIZED–> distinguishes contusions from concussions which are more diffuse
how do contusions and concussions differ?
contusions are localized whereas concussions are more diffuse
in what % of brain injuries would you expect to find a brain contusion?
20-30%
what are some symptoms of a brain contusion?
may feel weak and numb, lose coordination and struggle with memory or cognitive problems
what is diffuse axonal injury?
one of the most debilitating traumatic brain injuries
frequently caused by high speed transportation accidents; sometimes associated with shaken baby syndrome
causes PERMANENT damage to nerves in the brain
may cause brain swelling and increased ICP
unlike more minor closed head injuries, severe diffuse axonal injuries lead to VEGETATIVE STATES or COMAS in 90% of patients
what is an intracranial hematoma?
occurs when the brain is forced against the inside of the skull, resulting in a pool of blood outside the blood vessels of the brain or in between the skull and brain –> the brain is not designed to drain this much fluid!!
as a result, intracranial hematomas can compress brain tissue, requiring immediate medical attention
blood that collects in the brain, or in between the brain and skull, may lead to unconsciousness, seizures and/or lethargy
what are the 3 types of intracranial hematoma?
intraparenchymal
subdural
epidural
what is a subdural hematoma?
occurs when a vein ruptures between the brain and the dura matter
what is an epidural hematoma?
caused by a rupture of a blood vessel between dura and skull
what is an intraparenchymal hematoma?
occurs when blood collects within brain tissue
list some potential complications that can arise from closed head injuries
a traumatic brain injury can put a patient at risk of developing a variety of complications, including increased ICP and swelling of brain
- seizures
- nerve damage
- cognitive disabilities
- communication difficulties
- personality changes
- changes in sensory perception
- post concussion syndrome
- coma
most patients suffering from mild closed head injuries report headaches, dizziness, and short term memory loss
a severe closed head injury can lead to death or cause a patient to remain in a permanent vegetative state
what should be done immediately in the case of a head injured patient in order to give them the best chances for rehab?
- initially should receive a loading dose, then week long maintenance, of PHENYTOIN (dilantin) to decrease chance of seizures
- supportive tx of fever and hyperglycemia (which both increase neuronal death)
- head trauma patients who are asymptomatic/only have headache, dizziness, or scalp lacerations/who did not lose consciousness–> have a low risk for intracranial injury and may be discharged home without a CT
- patients with a hx of altered or lost consciousness, amnesia, progressive headache, skull or facial fracture, vomiting, or seizure have a moderate risk for intracranial injury and should undergo prompt head CT
- patients with depressed consciousness, focal neuro deficits, penetrating injury, depressed skull fracture or changing neurologic exam have high risk of intracranial injury and need immediate CT and observation
what are the long term tools for rehabilitation of the head injured patient?
- physio
- OT–> improve ADLs and IADLs
- social work
- psychology
- vocational counselor
- chemical dependency team
- recreation therapist
what neurotransmitter is associated with the Raphe nuclei in the brainstem?
serotonin (they are serotoninergic)
what neurotransmitter is associated with the ventral tegmental area?
it is dopaminergic
what neurotransmitter is associated with the locus ceruleus?
it is noradrenergic
what is the locus ceruleus?
The locus coeruleus is a nucleus in the pons (part of the brainstem) involved with physiological responses to stress and panic
what modalities does the reticular formation process?
the reticular formation in the brainstem receives and modifies afferent input from ALL sensory modalities
in what part of the reticular formation would you find ARAS?
lateral zone
what are the neuromodulators and what do they do?
the neurotransmitter systems associated with ARAS, use neurotransmitters which are referred to/considered NEUROMODULATORS: norepinephrine dopamine serotonin histamine ACh
each of these gives a QUALITY to the consciousness continuum and the conscious experience
**need to recognize these 5 neurotransmitters as being important for consciousness continuum (dont need to know detailed mechanisms)
where does the lateral zone of the reticular formation receive input from?
sensory info from spinoreticular tract afferents from spinal cord
where does the lateral zone of the reticular formation send information to? what is the information that goes to each?
- hypothalamus–> influences autonomic output
- thalamus–> influence cortical output
- aminergic and cholinergic nuclei–> to influence level of consciousness
- medial zone of reticular formation–> to influence output to spinal cord thru the medial zone
what response/reaction is norepinephrine responsible for?
fight or flight
where is norepinephrine manufactured?
locus ceruleus in the tegmentum of the pons projecting to thalamus and forebrain
what does the locus ceruleus influence? (via norepinephrine)
arousal
attention
sleep/wake state
(also cognitive function, mood, pain)
norepinephrine allows a FOCUS on a specific task or sensory input–> helps suppress less salient inputs
what happens if there is a lesion in the locus ceruleus?
low level of norepinephrine leading to low level of arousal
which neuromodulator allows for focus on a specific task or sensory input, by suppressing less salient inputs?
norepinephrine produced in the locus ceruleus
what would happen if you gave someone dopamine exogenously while they were asleep?
they would wake up and start looking around i.e “why am i awake, what do i NEED?” (because dopamine promotes exploratory behaviors towards positively rewarding stimuli)
where are the dopaminergic neurons and where do they project to?
dopaminergic neuros in the ventral tegmental area (VTA) project to prefrontal cortex and limbic structures
what are the dopaminergic neurons from the VTA responsible for?
BEHAVIOURAL arousal and waking
promote locomotor and exploratory behaviors toward positively rewarding stimuli (i.e food)
geared towards REWARD and MOTIVATION
what happens when you get a lesion in the VTA?
dopaminergic neurons are affected
this affects ATTENTIVE AROUSAL–> one becomes less attentive and more indecisive
where are the serotonin releasng neurons found? where do they project?
the RAPHE nuclei –> project to the thalamus, cortex, other NT systems in brainstem
what does serotonin (from the raphe nuclei) do when you are conscious?
in consciousness, serotonin regulates a QUIET, WAKEFUL state–>
sense of wellbeing, anxiety and aggression is controlled while u are awake
allows you to be productive when you are in the wakeful state plus influences the SLEEP WAKE continuum
- mood
- aggression
- sleep/wake
what happens if you lack serotonin/lesion in raphe nuclei?
insomnia
where would you find histamine releasing neurons and where fo they project?
histamine releasing neurons from the tegmentum of the MIDBRAIN project to the thalamus and cortex
what does histamine do in the brain?
stimulates WAKEFULNESS
if you block histamine you lower your state of arousal–> thus with antihistamines you get drowsy
where would you find ACh releasing neurons in the brainstem? where do they project to?
ACh is released from the tegmentum of the PONS–> fibres project to the thalamus and the cortex
what does the ACh released from the tegmentum of the pons do?
increases THALAMOCORTICAL activation and arousal
turning on next target of consciousness info stream–> signals the thalamus which them signals the cortex
(thalamus acts as gatekeeper of into to cortex)
what brain structure most correlates with STATE of consciousness?
thalamus –> determines how responsive you are to the environment
what is the thalamic reticular nucleus? (TRN)
REMEMBER THE TRN!!
it is a grouping of neurons that covers the outside of the thalamus–> it is a reticular meshwork (like a fishnet stocking) –> an interconnected mesh of neurons
has dense reciprocal relationships with ARAS, other thalamic nuclei and cerebral cortical structures
it is one of the “other” nuclei associated with the thalamus (along with the intralaminar nuclei)… there are also relay nuclei and association nuclei in the thalamus
what type of neurons are those found in the thalamic reticular nucleus? (TRN)
it is an interconnected network of GABAergic neurons–> thus it is an interconnected network of dense INHIBITION
why is the thalamic reticular nucleus (TRN) important?
it is the GATEKEEPER OF CONSCIOUSNESS
it coordinates the synchronous firing (40 hz) between the cortex and the thalamus that is necessary for consciousness
what is the “consciousness channel”?
the “consciousness channel” is a 40 hz channel between ARAS and the thalamus, and the thalamus and the cortex
neurons “speak” to each other on a 40 hz frequency, which is the channel encoding consciousness
other information (i.e how much skin is being touched) is processed simultaneously but on a different frequency–> the actual consciousness of the touch is processed on 40 hz
why is the cortex important for consciousness?
required to establish SIGNIFICANCE and MEANING of conscious experience
synchronous and reciprocal communication with the thalamus and other cortical areas
which parts of the cortex are most important for consciousness?
prefrontal and parietal cortical areas are important –> these areas decide what sensory information is important and they decide what to do about what you feel
both of these areas need to be fully functional and intact for the consciousness experience
what does the parietal cortical area do relating to consciousness?
attention
awareness of self
awareness of extrapersonal space
what does the prefrontal cortical area do in relation to consciousness?
directing and maintaining attention
morality
problem solving
adjusting behaviour to social norms
planning
working memory
deliberate decisions
**executive function over consciousness
**involved in our ability to associate self with society and societies expectations
what are some important questions to ask in a patient presenting with seizures?
- are they seizures?
- if so, are they generalized or focal from onset?
- if focal, where do they originate from?
- what is the cause of the seizure?
- are antiseizure meds indicated?
- how is patient quality of life affected?
- can anything be offered beyond meds?
what signs might indicate previous undiagnosed seizures in a patient on history?
- childhood staring spells, episodes of amnesia
- isolated aura
- bizarre nocturnal behavior
- myoclonic jerks
what is the DDx for seizures?
- syncope–> neural or cardiogenic
- psychiatric–> panic attacks, fugue state, psychogenic non-epileptic events
- other neuro conditions–> migraine, paroxysmal movement disorder, sleep disorder, TIA, transient global amnesia (TGA), encephalopathy
what is syncope?
loss of consciousness and postural tone caused by cerebral hypoperfusion with spontaneous recovery
can have:
1. neurally mediated–> vasovagal, reflex-mediated, autonomic, valsalva, carotid sinus syndrome, reflex anoxic)
- cardiogenic–> arrhythmias, cardiac structural anormalities
what are some clues that a “seizure” is more likely psychogenic?
- precipitated by stress
- suggestible and distractible
- occur in wakefulness in the presence of a witness
- asynchronous asymmetrical movements–> pelvic thrusting, back arching, side to side head
- eyes closed with tightening upon attempted passive eye opening
- consciousness retained or fluctuating during “convulsion”
- crying
- intractable to anti-epileptic meds
- no post ictal confusion
- belle indifference (inappropriate lack of emotion usually regarding the event)
what is the DDx for paroxysmal neurologic symptoms?
seizure
TIA
migraine
what is the major test done for the investigation of seizures?
EEG
identify epileptiform activity (best sensitivity if done within 24 hours)
exclude non-convulsive seizures (in context of unexplained prolonged altered mental status)
what is the status epilepticus treatment algorithm?
- lorazepam or midazolam
- -after 0-30 min– - phenytoin with cardiac and resp monitoring
- -after 30-60 min– - either valproic acid //or phenobarbitol //or ICU/intubate with bolus of midazolam or propofol, thiopental or pentobarbital infusions
(considered refractory status after step 2)
which anti seizure med that we have to know is the only one that cant be used for both partial and generalized seizures?
lacosamide (vimpat)–only partial seizures
what is the definition of drug resistant epilepsy?
failure of adequate trials of TWO tolerated appropriately chosen and used AED schedules (whether as monotherapy or in combo) to achieve sustained seizure freedom
what are the indications for epilepsy surgery?
- drug resistant focal epilepsy–> goal is CURE with cessation of debilitating seizures
- drug resistant drop attacks and GTCs (i.e lennox gastaut syndrome)–> goal is PALLIATION with cessation of GTCs and drop attacks
is “seizure” a diagnosis?
no its a symptom of underlying brain dysfunction –> epilepsy is a clinical diagnosis
what are the three main determinants of cerebral blood flow? (CBF)
vessel radius (r)
pressure gradient (delta P)
blood viscosity (n)
in what range of mean arterial pressures is a constant flow of blood to the brain maintained? how is this achieved?
between 50-160 mmHg mean arterial pressure–> via pressure autoregulation
pre-capillary arterioles dilate or constrict
this is myogenic–> via stretch sensitive Ca2+ channels
how does Pco2 affect cerebral blood flow?
cerebral blood vessels are very sensitive to changes in Pco2
HYPERcarbia (hypoventilation) causes VASODILATION and INCREASED CBF
HYPOcarbia (hyperventilation) causes VASOCONSTRICTION and DECREASED CBF
these changes are mediated by extra-cellular H+ concentration
how does Po2 affect cerebral blood flow?
CBF doesn’t vary much with changes in Po2 above 50mmHg
when Po2 falls below 50 mmHg, cerebral blood flow begins to rise exponentially
NO and adenosine (both vasodilators) are produced in response to cerebral hypoxia
what cell type links cerebral blood flow and metabolism?
astrocytes
they send processes both to synapses and blood vessels, and communicate with other astrocytes through gap junctions
in what type of seizures would you use phenytoin/dilantin?
partial seizures
secondarily generalized seizures
side effects of valproic acid?
weight gain
menstrual irregularities
transient hair loss
tremor (rare)
what anticonvulsant should be avoided in women of child bearing age? what is a good alternative?
valproid acid–>teratogen
alternative is lamotrigine
what is a side effect of AED levetiracetim (keppra)?
potential behavior changes in some people who take this drug
i.e anxiety, agitation, mood swings, depression, suicidal ideation
list AEDs that have shown efficacy for primary generalized epilepsy
- ethnosuximide
- valproic acid
- lamotrigine (keppra)
- levetiracetam
- dilantin (phenytoin)
what is the meyer-overton rule of general anaesthetics?
an agent’s MAC inversely correlates with its lipid solubility–> the more lipid soluble an anaesthetic agent is, the more potent it is
how do inhaled anaesthetics affect the CNS?
decrease in cerebral metabolic rate–> greatest with isoflurane
cerebral vasodilation–> increase in cerebral blood flow (N2O inly has a modest effect)
how do inhaled anaesthetics affect the cardiovascular system?
decrease in arterial blood pressure as a result of reduction in cardiac output (i.e with halothane) and/or reduction in total peripheral vascular resistance (i.e isoflurane)
ventricular arrhythmias (halothane) –> “sensitization” of the myocardium to circulating catecholamines
N2O causes mild sympathetic stimulation
how do inhaled anaesthetics affect the respiratory system?
respiratory depression–> increase in rate and decrease in depth of breathing (decreased tidal volume), net effect is a reduction in alveolar ventilation and elevation of Pco2, decrease in respiratory response to elevation in Pco2
decrease in airway resistance–> advantage for patients with asthma
how do inhaled anaesthetics affect the kidneys?
reduction in renal blood flow leading to decreased in GFR and urinary output
how do inhaled anaesthetics affect the skeletal muscle?
muscle relaxation
potentiation of the effects of nondepolarizing muscle relaxants (greatest with isoflurane)
how do inhaled anaesthetics affect the uterus?
uterine relaxation (halothane and all other volatile agents)
may lead to prolonged uterine atony and severe blood loss in parturients
list some characteristics about inhaled anaesthetics that make them so popular with anaesthesiologists
- ability to induce and maintain anaesthesia regardless of age or body habitus of the patient
- presence of clinical signs that give an indication of depth of anaesthesia
- ability to increase or decrease depth of anaesthesia at will
- a predictable pattern of recovery from anaesthesia
- provision of all of the components of the state of general anaesthesia in many patients without the use of adjuvants
- knowledge of the concentration of the drug at the site of action
- ability to deliver a broad range of oxygen concentrations
what is an important difference between inhaled and IV anaesthetics?
the dose of an IV agent cannot be manipulated by the anaesthesiologist once injected
thus, their specific pharmanokinetic properties must be known
name 4 IV general anaesthetics
thiopental
propofol
ketamine
etomidate
what type of drug is thiopental?
IV general anaesthetic
barbituate (derivative of barbituric acid)
what is the clinical use of thiopental?
rapid induction of hypnosis (NO ANALGESIA PROPERTIES)
MOA of thiopental?
facilitation of inhibitory neurotransmission via GABAa receptors
pharmacokinetics of thiopental?
rapid induction in one “arm-brain circulation time” (less than 20 sec
the brain concentration falls rapidly as a result of redistribution and thus the patient normally wakes up approx 5 min after a single bolus IV injection
when tissues are saturated, i.e as a result of continuous infusion or repeated doses, elimination and not redistribution determines the time of emergence
half life is 11 hours
adverse effects of thiopental?
hypotension–> exaggerated in the presence of hypovolemia; dose reductions necessary in the elderly
respiratory depression
histamine release
arterial occlusion is possible
clinical use of propofol?
the 1990s answer to thiopental
used for sedation, induction and maintenance of anaesthesia (TIVA–total intravenous anaesthesia)
smooth induction, “pleasant dreams”, rapid and clear headed awakening
antiemetic properties
MOA of propofol?
facilitation of inhibitory neurotransmission via GABA a receptors
pharmacokinetics of propofol?
rapid induction similar to thiopental, with even more rapid awakening (3 min after IV bolus)
rapid metabolism in the liver (half life of one hour)
no significant redistribution which is useful for infusion
adverse effects of propofol?
pronounced hypotension (greater than thiopental, marked dose reductions necessary in the elderly)
respiratory depression and apnea
injection pain
potential for sepsis
what is ketamine derived from?
its a PCP derivative
what does ketamine do?
produces a state of “dissociative anaesthesia”–patient appears conscious, yet is unable to process or respond to sensory input (catatony, amnesia, analgesia)
produces little cardiorespiratory depression and maintains airway reflexes
has bronchodilator effect
unpleasant dreams are common
clinical uses of ketamine?
induction of anesthesia in trauma or shock
battlefield surgery
analgesia in burn patients
i.m induction in kids
MOA of ketamine?
antagonist at NMDA receptors (type of glutamate receptor)
what type of receptor is the NMDA receptor?
glutamate
pharmacokinetics of ketamine?
rapid induction after IV bolus (slower than propofol or thiopental)
hepatic metabolism with half life of 3 hours
