Mind Brain and Behavior

WHAT IS NEUROPIL
 Areas in which axons and dendrites synapse (2). More broadly described as
any area in the nervous system composed of mostly unmyelinated axons,
dendrites, and glial cell processes that forms a synaptically dense region
containing a relatively low number of cell bodies.

IS A NUCLEUS IN THE CNS MADE UP OF GRAY
MATTER OR WHITE MATTER?
 Gray matter
 Tracts are white matter

THE CEREBRAL HEMISPHERES CONSIST OF…
 An outer cerebral cortex consisting of gray matter and composed of four lobes:
frontal, parietal, temporal and occipital
 White matter
 Three deep nuclei: Basal ganglia, Hippocampus, Amygdala
 Gray matter
 **In the spinal cord the gray matter is on the inside

WHAT ARE THE GENERAL FUNCTIONS OF THE
FRONTAL LOBE?
 Planning behavior
 Language production

PARIETAL LOBE?
 Spatial orientation
 Language comprehension

TEMPORAL LOBE?
 Audition
 Visual processing
 Recognition of stimuli
 Learning and memory

OCCIPITAL LOBE?
 Vision

WHAT IS THE GENERAL FUNCTION OF THE
LIMBIC SYSTEM?
 Emotional expression
 Regulation of visceral motor activity

WHAT IS THE INTERNAL CAPSULE?
 White matter separating the caudate nucleus and thalamus from the globus
pallidus and putamen (Basal ganglia). Contains both ascending and
descending fibers.

WHAT IS THE GENERAL FUNCTION OF THE
CEREBELLUM
 Coordination of motor activity
 Posture
 Equilibrium

WHAT ARE THE THREE REGIONS OF THE CNS
THAT ARE IMPORTANT FOR CONSCIOUSNESS?
 Cortical
 Thalamic
 Rostral reticular

WHAT ARE THE CELL LAYERS OF THE
NEOCORTEX?

WHAT ARE THE FOUR STEPS TO EVALUATE A
NEUROLOGICAL DISEASE?
 Localize lesion
 Determine type
 Focal/diffuse
 Mass/non-mass
 Assess time course
 Develop differential

WHAT ARE THE 5 NEUROLOGICAL SYSTEMS TO
WHICH DISEASE CAN LOCALIZE
 Conscious
 Motor
 Sensory
 Autonomic
 Visual

WHAT ARE THE FIVE DIFFERENT TIME COURSES
OF A NEUROLOGICAL DISEASE
 Acute – minutes to hours
 Subacute – hours to days
 Chronic
 Relapsing and remitting
 Static

FOCAL AND ACUTE
 Vascular - infarct
 Traumatic - contusion

DIFFUSE AND ACUTE
 Toxic/Metabolic
 Traumatic – diffuse axonal injury

FOCAL AND SUBACUTE
 Inflammatory
 Infectious abscess

DIFFUSE AND SUBACUTE
 Diffuse infection
 Hepatic coma

CHRONIC AND FOCAL
 Neoplasm
 Neurosyphilis

CHRONIC AND DIFFUSE
 Degenerative – Alzheimers
 Metabolic – B12 deficiency

LIST 2 CONDITIONS UNDER WHICH A LUMBAR
PUNCTURE ARE RISKY
 Underlying coagulopathy
 Increased intracranial pressure  herniation

WHAT IS GFAP AND HOW IS IT USED IN
HISTOLOGY?
 Glial fibrillary acid protein (GFAP) is an intermediate filament type unique to
astrocytes.
 This protein is concentrated in the astrocytic processes which contribute to the
fibrous intercellular network called the neuropil.
 Staining with anti-GFAP antibodies (brown in image below) allows visualization
of astrocytes (A), especially astrocytic processes. Some astrocytic processes
terminate in perivascular feet (PF in image) which surround capillaries in the
CNS, contributing significantly to the blood-brain barrier.

DESCRIBE THE LOCATION AND FUNCTION OF
THE CHOROID PLEXUS AND THE EPENDYMAL
CELLS
 Ependymal cells line the ventricles of the brain and the central canal of the
spinal cord in a single layer of columnar or cuboidal cells.
 In some places, ependymal cilia project into the CSF to help circulate it.
Ependymal microvilli also project into the CSF to monitor its composition.
 In the choroid plexus, modified ependymal cells produce CSF.
 Unlike a true epithelium, the ependymal cell layer lacks a basal lamina. Instead,
it is anchored by processes that extend into the neuropil.

WHAT DO THE ARROWS POINT TO?
 Thick arrow – arachnoid mater
 Star – blood vessel
 Thin arrow – pia mater

DESCRIBE THE HISTOLOGICAL
CHARACTERISTICS OF THE CEREBELLUM
 The cerebellar cortex is convoluted with many distinctive small folds, each
supported at its center by cerebellar medulla (M), which is white matter
consisting of large tracts of axons.
 Immediately surrounding the white matter of the medulla is the granular layer
(GL) of the cortex, which is densely packed with very small, rounded neuronal
cell bodies.
 The outer, "molecular layer" (ML) consists of neuropil with fewer, more
scattered small neurons.
 At the interface between the granular and molecular layers is a single layer with
very large neuronal cell bodies of unique Purkinje cells (P), whose axons pass
through the granular layer (Gr) to join tracts in the medulla and whose multiple
branching dendrites ramify throughout the molecular layer

HIPPOCAMPUS: IDENTIFY AMMON’S HORN AND
DENTATE GYRUS

WHY DOES THE SUBSTANTIA APPEAR DARK?
 Located within cerebral peduncles
 Appear dark due to presence of neuromelanin in neurons

WHAT IS THE PRINCIPAL SIGN OF ACUTE
NEURONAL INJURY
 “Red neurons” refers to a spectrum of changes that accompany acute CNS
hypoxia/ischemia or other acute insults and reflect cell death, either necrosis or
apoptosis
 Red neurons” are evident with hematoxylin and eosin (H&E) preparations at about
12 to 24 hours after an irreversible hypoxic/ischemic insult.
 The morphologic features consist of shrinkage of the cell body, pyknosis of the
nucleus, disappearance of the nucleolus, and loss of Nissl substance, with intense
eosinophilia of the cytoplasm.
 1 hour: microvacuolation of cytoplasm (mitochondria swollen) & perineuronal
vacuolation (astrocytic processes swollen)
 4-12 hours: neuronal cytoplasm eosinophilia (nissl bodies disappear), nucleus
pykinosis, nucleoli not visible; red neuron
 15-24 hours: neutrophil leukocytes infiltration begins

WHAT ARE SIGNS OF SUBACUTE AND CHRONIC
NEURONAL INJURY?
 Pathologic Inclusions
 Hyperplasia and hypertrophy
 Gliosis
 Gemistocytic - acute
 Fibrillary – chronic
 Microglial proliferation/activation
 2 days: macrophagic infiltration begins (may stay for months)
 5 days: neutrophil infiltration ceases
 around 1 week: proliferation of reactive astrocytes
 around 10 days: area of infarction is characterized by the presence of
macrophages and surrounding reactive gliosis

DISTINGUISH BETWEEN PATHOLOGICAL
RESPONSES OF GEMISTOCYTIC ASTROCYTOSIS
AND FIBRILLARY ASTROCYTOSIS.
 gemistocytic astrocytosis
 nuclei of the astrocytes, which are typically round to oval with evenly
dispersed, pale chromatin, enlarge, become vesicular, and develop
prominent nucleoli
 previously scant cytoplasm expands to a bright pink, somewhat irregular
swath around an eccentric nucleus, from which emerge numerous stout,
ramifying processes
 short term
 fibrillary astrocytosis
 eosinophilic masses called rosenthal fibers can be seen within the
processes, especially when the lesion involves the white matter
 long term

DESCRIBE THE HISTOLOGICAL DIFFERENCES
BETWEEN RESTING AND ACTIVATED MICROGLIA
 Resting – banana shaped, difficult to see without staining
 Active – large foamy macrophages

NAME THE “ANATOMICAL” SITE OF THE BLOOD
BRAIN BARRIER
 Cerebral capillary
 Endothelial cells and astrocytes

DISTINGUISH THE ENDOTHELIAL AND
ASTROCYTIC SIDES OF THE BBB
 Endothelial side of the BBB has occluding intercellular (tight) junctions, low
pinocytotic (pinocytosis=cell uptake of fluid) activity, carrier facilitated & active
transport, and highly regulated cellular (monocytes) transfer
 The Astrocyte side of the barrier has foot processes and is important in
secretion of proteases, growth factors, and receptors as well as has
connections with neuronal elements.

WHAT ARE THE AREAS OF THE BRAIN THAT ARE
SENSITIVE TO HYPOXIA IN INFANTS?
 CA1 hippocampus
 diencephalon gray nuclei, thalami
 midbrain nucleus

WHAT ARE THE COMMON REACTIONS OF THE
CNS TO INJURY
 Cerebral Edema
 Hydrocephalus
 Raised ICP
 Herniation

WHAT ARE THE TWO TYPES OF CEREBRAL
EDEMA AND HOW ARE THEY CAUSED?
 Vasogenic edema
 caused by blood-brain barrier disruption and increased vascular permeability,
allowing fluid to shift from the intravascular compartment to the intercellular
spaces of the brain. The paucity of lymphatics greatly impairs the resorption
of excess extracellular fluid. Vasogenic edema may be either localized (e.g.,
adjacent to inflammation or neoplasms) or generalized.
 Cytotoxic edema
 increase in intracellular fluid secondary to neuronal, glial, or endothelial cell
membrane injury, as might be encountered in someone with a generalized
hypoxic/ischemic insult or with metabolic damage.

MOST CASES OF HYDROCEPHALUS OCCUR AS A
RESULT OF …
 Impaired flow or resorption of CSF
 NOT overproduction

WHAT IS THE
VIRCHOW ROBIN
SPACE
 When entering the brain
parenchyma, the vessels are
initially surrounded by the
perivascular space (also
known as the Virchow–Robin
space), which is connected
to the subarachnoid space

WHAT IS THE MAIN POSTSYNAPTIC INHIBITORY
NEURON
 GABA
 Glycine is another

WHAT IS FACILITATION AT THE SYNAPSE?
 Consistent influx of Ca++ in presynaptic neurons → higher level of
neurotransmitter release → progressively higher & higher EPSPs
 Short term effect

DESCRIBE SYNAPTIC DEPRESSION
 The presynaptic vesicles cannot keep up with the presynaptic electrical
stimulation → decrease in available neurotransmitter → progressively smaller
EPSPs
 Short term
 Generally occurs at synapses with high probability of release

WHAT IS POST-TETANIC POTENTIATION
 Enhancement of synaptic strength following a brief train of strikes. Higher
concentration of Ca++ available in the presynaptic neuron, so next stimulus
leads to higher EPSPs than normal. Same mechanism behind facilitation, with
many back-to-back stimuli (tetanic), so Ca++ accumulation & potentiation is
greater and lasts longer.
 Short term

LONG TERM POTENTIATION
 Brief, High Frequency Stimulation → Fast Increase in Ca++ →
Phosphorylation→ EXOcytosis of AMPAR→ Increased AMPAR at synapse→
Overall strength is increased
 LTP (Ca2+ comes in through NMDA channels)
 Ca++ binds to calmodulin which activates CaMKII which:
 Autophosphorylates
 Phosphorylates AMPAR to make them more permeable: goal is to keep
depolarization going
 Phosphorylates Ras-ERK signaling→ allows exocytosis of AMPAR contained
within vesicles
 Phosphorylates Stargazin on newly exocytosed AMPAR→ immobilizes
AMPAR at synapse (thereby increasing amount of AMPARs at synapse)

HOW ARE NMDA RECEPTORS ACTIVATED TO
INITITATE LTP?
 NMDA receptors (N-methyl-D-aspartate) are permeable to Na and Ca, but
have an Mg ion in pore that acts as a plug (blocking it at rest)
 NDMARs require a strong depolarization to first remove Mg ion from pore (>-
50mV)
 Therefore it needs (1) glutamate binding PLUS (2) strong depolarization to
dislodge the Mg and allow Ca++ and Na+ to flow through
 At rest, NDMARs will bind glutamate released from pre-synaptic neuron but will
not open due to lack of strong depolarization. NDMARs depend on AMPARs
opening first.

DESCRIBE THE STEPS OF LONG TERM
DEPRESSION
 Generated by prolonged (3-15min) low frequency (1-5Hz) stimulation, reduction
in sensitivity, small slow rises in the levels of Ca++ (not above threshold
though) in the postsynaptic cell; ultimately leads to endocytosis of AMPARs and
lower sensitivity to further stimuli.
 During LTD, low levels of Ca++ ions enter via the NMDA receptors. Low levels
of Ca++ ion activates protein phosphatases→ dephosphorylation of AMPAR→
endocytosis of AMPAR

WHAT IS A SILENT SYNAPSE?
 NMDA activation WITHOUT AMPA activation
 These synapses are “silent” because normal AMPA receptor-mediated signaling
is not present, rendering the synapse inactive under normal conditions.
 Remember that AMPAR are the only active receptors at rest
 NMDAR require initial depolarization from AMPAR activation to move the Mg++
block
 When an LTP is induced, there is a rapid expression of AMPA receptors at the
silent synapses  accounts for the depression of "failure" rate of postsynaptic
action potentials where there's an LTP

DESCRIBE THE MECHANISM UNDERLYING
EXCITOTOXICITY.
 Overactivation of NMDARs triggers excessive entry of Ca++ ions, which
activate a series of cytoplasmic and nuclear processes that promote neuronal
cell death
 Activation of Ca++-activated proteolytic enzymes like calpains that degrade
essential proteins
 ·Ca++ ions enter mitochondria, which enhances mitochondrial electron
transport leading to more ROS and free radical damage
 NMDA antagonist (memantine) given in Alzheimers in order to prevent further
cell death.

WHAT ARE THE MAJOR METABOLITES OF THE
MONOAMINES?
 Dopamine – HVA –
 ↑ Psychosis
 ↓ Parkinson’s
 Serotonin – 5-HIAA
 ↓ Severe depression and suicide, aggressiveness, impulsiveness
 Norepinephrine – VMA/MHPG
 ↓ Severe depression and attempted suicide

WHAT ARE THE THREE AREAS OF MENTAL LIFE
THAT PSYCHIATRY CONSIDERS?
 Thoughts
 Moods
 Behaviors

WHAT IS OPERATIONALISM IN PSYCHIATRY AND
WHAT ARE ITS LIMITATIONS?
 Seeks to define mental events by their public expression
 Limitations
 Patient must be verbal
 Patient must have insight into condition

WHAT ARE THE TWO EXPLANATORY METHODS
OF PSYCHIATRY
 Form – descriptive – what?
 Function – interpretive – why?
 Looks at people as unique individuals

DISTINGUISH BETWEEN FLIGHT OF IDEAS,
CIRCUMSTANTIALITY, AND LOOSE
ASSOCIATIONS.
 Flight of ideas
 Pressured and accelerated speech
 Goal directed with preserved associations
 Shifting goals, distractible
 *MANIA
 Circumstantiality
 Unnecessary digressions, parenthetical clarifications
 Excessive detail
 *OBSESSIVE
 Loose associations
 Loss of goal directed speech
 Derailments, word salad
 *SCHIZOPHRENIA

WHAT ARE THE COMPONENTS OF A MENTAL
STATUS EXAM?
 Appearance
 Speech
 Mood
 Hallucinations
 Delusions
 Obsessions/Compulsions
 Phobias
 Cognition
 Insight and Judgment

WHAT IS THE DIFFERENCE BETWEEN MOOD
AND AFFECT?
 Affect – observable
 Mood – subjective patient reported

WHAT ARE THE PRIMARY SYMPTOMS OF A
CLINICAL MOOD DISORDER?
 Sleep
 Interest
 Guilt
 Energy
 Concentration
 Appetite
 Psychomotor retardation
 Suicidal thoughts
 DIGFAST for Mania – distractibility, insomnia, grandiosity, flight of ideas,
activity, speech, thoughtlessness

WHAT IS A HALLUCINATION?
 Hallucination: true perception in the absence of an external stimulus
 Pseudohallucination: sensation is inside but foreign “voice inside my head”
 Illusions: external stimulus misperceived

WHAT IS THE DEFINITION OF A DELUSION
 A belief (not a perception) that is FIXED, FALSE or IDIOSYNCRATIC

DIFFERENTIATE OBSESSIONS FROM
HALLUCINATIONS, DELUSIONS AND
RUMINATIONS
 Obsessions - persistent ideas, thoughts, impulses or images that are
experienced as intrusive or inappropriate and that cause marked anxiety or
distress
 different from ruminations because the patient perceives them to be senseless.
 different from hallucinations because they are thoughts, and not sensory
perceptions.
 different from delusions because the patient acknowledges the irrationality in
his or her ideas.

LIST THREE COMMON
OBSESSIONS/COMPULSIONS
 Fear of germs/dirt
 Pathologic doubt
 Aggressive or sexual thoughts
 Excessive need for order/symmetry

LIST THE THREE GENERAL TYPES OF PHOBIAS
AND DESCRIBE THEM
 Specific phobias
 Fear of a clearly discernible circumscribed object/situation
 Agoraphobia
 Fear of situations/places that are difficult to escape
 Social phobia
 Fear of social situations where embarrassment may occur

WHY IS INSIGHT IMPORTANT AND WHAT ARE
ITS COMPONENTS?
 Strong correlations with prognosis
 Awareness of symptoms?
 Attribution of symptoms?
 Consider themselves ill?
 Treatment required?
 Medications required?

NAME FOUR PERSPECTIVES EMPLOYED IN
UNDERSTANDING MENTAL PHENOMENA
 Disease – what a person has
 Syndrome  pathology  etiology
 Dimensions – what a person is
 The trait is abnormal when it is excessive enough that the individual is
rendered vulnerable by it
 Behaviors – what a person does
 Pathological when object or strength of drive is socially unacceptable
 Life Stories – meaning of thoughts and feelings
 Emphasis on meaning of experience and emotions

DEFINE DELIRIUM AND EXPLAIN WHY IT IS
BEST APPROACHED USING A DISEASE
PERSPECTIVE.
 Change in the level of consciousness and change in the ability to sustain
attention
 Can wax and wane - ranges from normal (or even hypervigilant) through
drowsiness, stupor, or coma
 Treatment depends on pathology and etiology
 Can be tested

DEFINE DEMENTIA AND EXPLAIN WHY IT IS
BEST APPROACHED USING A DISEASE
PERSPECTIVE.
 Global decline in cognition with clear consciousness
 Use of disease perspective:
 syndrome is validated through serologic studies, radiographic studies, and
rarely brain biopsies
 treatment depends on the pathology and etiology of the illness

EXPLAIN WHY IT IS MORE DIFFICULT TO APPLY A
DISEASE PERSPECTIVE TO MOOD DISORDERS,
ANXIETY DISORDERS, AND SCHIZOPHRENIA
THAN TO DO SO FOR DELIRIUM AND DEMENTIA.
 There is continued uncertainty about the underlying pathology and etiology of
these disorders, so there is no “gold standard” ancillary tests to confirm or
refute the presence of these conditions such as mood disorders, anxiety
disorders, and schizophrenia .

WHAT ARE THE THREE CLUSTERS OF THE DSM
IV PERSONALITY DISORDERS
 Odd
 Paranoid
 Schizoid
 Schizotypal
 Dramatic
 Antisocial
 Borderline
 Histrionic
 Narcissistic
 Anxious
 Avoidant
 Dependent
 Obsessive-compulsive

WHAT ARE THE MATURE DEFENSE
MECHANISMS
 Anticipation
 Humor
 Sublimation
 Suppression
 Affiliation

WHAT ARE THE NEUROTIC DEFENSES
 Displacement – emotion placed elsewhere from source
 Externalization – blame on situation around
 Intellectualization
 Dissociation – detachment
 Repression – unconscious mechanism – emotion expressed in other ways
 Reaction formation – replaces impulse with exact opposite

WHAT ARE THE IMMATURE DEFENSES
 Denial – resistance in the face objective facts
 Autistic/Schizoid fantasy – out of touch with reality
 Passive aggressive behavior – insists that they are not angry but actions differ
 Acting out – behavior grossly out of proportion
 Splitting – everything is black and white, no gray area
 Projection - projecting emotions on other
 Projective identification – projection, and the person assumes that projection

DEFINE PERSONALITY
 The sum of an individual’s abiding and consistent traits

DEFINE A TRAIT
 Tendencies to react in circumstances in a particular fashion

DIFFERENTIATE THE CATEGORICAL FROM THE
DIMENSIONAL APPROACH IN DETERMINING AN
ABNORMAL TRAIT
 Categorical – inflexible and causing suffering
 Dimensional – excessive enough that the individual is vulnerable

AXIS I
 State related disorders
 Delirium
 Depression
 Schizophrenia
 Substance abuse
 Eating disorder

AXIS II
 Trait related disorders
 Personality disorders
 Mental retardation

NAME TWO DISADVANTAGES AND TWO
ADVANTAGES OF TYPOLOGICAL REASONING
 Disadvantages
 Proposes categories that are usually awkward and disjunctive
 Types are poorly tied to phenomena beyond themselves
 Advantages
 Important to understand why stressors affect people differently

PARANOID PERSONALITY DISORDER
0.5-2.5% of population
• Suspiciousness and distrust of others
• No hallucinations or delusions
• No “odd or magical” thinking as in Schizotypal Personality Disorder
• Genetic link to both Schizophrenia and Delusional Disorder
• Defense Mechanisms
- Externalization and projection
• Treatment
– Most are reluctant to engage in psychotherapy
– Need to avoid being overly confrontational but also overly friendly
– Low dose antipsychotic medication

SCHIZOTYPAL PERSONALITY DISORDER
3% of Population
• Social Withdrawal, impaired ability to form social relationships, “magical thinking”
– Thus resembles negative symptoms of Schizophrenia, or prodromal phase of
Schizophrenia
– Clear genetic link and about 10-20% go on to develop
Schizophrenia
– Often have biological markers of schizophrenia, e.g. smooth pursuit eye movement
abnormalities and enlarged ventricles on CT
•Defense Mechanisms
- Denial , projections
• Treatment
– May be brought in by family, or come in for depression, but little interest in
treatment; low dose antipsychotics

SCHIZOID PERSONALITY DISORDER
Detachment and social withdrawal as well as a restricted range of emotions
• Few friends but not bothered by this
• Often live at home with parents into adulthood
• Prevalence as high as 7% in community
• Defenses: Autistic Fantasy
• Score high on Introversion, likely with genetic basis
• Similar treatment limitations as for the other Cluster A disorders

ANTISOCIAL PERSONALITY DISORDER
DIAGNOSTIC CRITERIA
 A. Pervasive pattern of disregard for and violation of the rights of others occurring since
age 15 years, as indicated by three (or more) of the following:
 (1) Failure to conform to social norms with respect to lawful behaviors as indicated by
repeatedly performing acts that are grounds for arrest
 (2) Deceitfulness, as indicated by repeated lying, use of aliases, or conning others for
personal profit or pleasure
 (3) Impulsivity or failure to plan ahead
 (4) Irritability and aggressiveness, as indicated by repeated physical fights or assaults
 (5) Reckless disregard for safety of self or others
 (6) Consistent irresponsibility, as indicated by repeated failure to sustain consistent work
behavior or honor financial obligations
 (7) Lack of remorse, as indicated by being indifferent to or rationalizing having hurt,
mistreated, or stolen from another
 B. The individual is at least age 18 years.
 C. There is evidence of Conduct Disorder (see p. 90) with onset before age 15 years.
 D. The occurrence of antisocial behavior is not exclusively during the course of
Schizophrenia or a Manic Episode.

ANTISOCIAL PERSONALITY DISORDER
 Prevalence: 3% of men and 1% of women
 Not out of touch with reality
 Lack of conscience or empathy for others
 Preceded by childhood Conduct Disorder with onset before age 15
 50% of prison inmates
 Substance-abuse rehab setting: 20% of men and 10% of women
 May “burn out” in some after age 40
 Genetic Factors clearly involved
 More common in 1st degree relatives
 Monozygotic concordance > Dizygotic concordance
 Biological findings
 Violent individuals with more “soft” neurologic signs
 EEG with diminished response to novel stimuli
 Decreased galvanic skin response
 May be influenced by erratic parenting, ADHD, poverty, early substance abuse
 Treatment: Requires motivation by patient (may not be in the patient role); treat
comorbidity; avoid being conned

BORDERLINE PERSONALITY DISORDER
DIAGNOSTIC CRITERIA
 Pervasive pattern of instability of interpersonal relationships, self-image, and affects,
and marked impulsivity beginning by early adulthood and present in a variety of
contexts, as indicated by five (or more) of the following:
 (1) Frantic efforts to avoid real or imagined abandonment.
 (2) A pattern of unstable and intense interpersonal relationships characterized by
alternating between extremes of idealization and devaluation
 (3) Identity disturbance: markedly and persistently unstable self-image or sense of
self
 (4) Impulsivity in at least two areas that are potentially self-damaging (e.g., spending,
sex, substance abuse, reckless driving, binge eating).
 (5) Recurrent suicidal behavior, gestures, or threats, or self-mutilating behavior
 (6) Affective instability due to a marked reactivity of mood (e.g., intense episodic
dysphoria, irritability, or anxiety usually lasting a few hours and only rarely more than
a few days)
 (7) Chronic feelings of emptiness
 (8) Inappropriate, intense anger or difficulty controlling anger (e.g., frequent displays
of temper, constant anger, recurrent physical fights)
 (9) Transient, stress-related paranoid ideation or severe dissociative symptoms

BORDERLINE PERSONALITY DISORDER
 2-3% of Population, but 20% of Psychiatric Inpatients (the most common
among inpatients)
 Genetic Contribution
 5X more common in 1st degree relatives
 Family histories of Antisocial Personality Disorder, Substance Abuse, and
Mood Disorder
 Higher prevelence of neurologic “soft signs” in severe cases
 Lower CSF serotonin in more severe cases
 Developmental contributions
 Historical: Mahler’s rapprochement phase
 High rates of neglect and abuse, parental loss or separations/adoptions
 Chaotic family environment; Mother often with Borderline features; father
distant or absent
 Defenses: Acting out, splitting, projective identification

TREATMENT FOR BORDERLINE PERSONALITY
DISORDER
 Psychotherapy
 Keep the patient alive
 Keep the patient out of the hospital
 Avoid having sex with the patient or other boundary violations
 Avoid acting on countertransference
 Make appropriate use of projective identification
 Pharmacotherapy
 To treat comorbid mood disorder
 To treat features of the personality disorder

HISTRIONIC PERSONALITY DISORDER
DIAGNOSTIC CRITERIA
A pervasive pattern of excessive emotionality and attention seeking, beginning by
early adulthood and present in a variety of contexts, as indicated by five (or more)
of the following:
(1) is uncomfortable in situations in which he or she is not the center of attention
(2) interaction with others is often characterized by inappropriate sexually
seductive or provocative behavior
(3) displays rapidly shifting and shallow expression of emotions
(4) consistently uses physical appearance to draw attention to self
(5) has a style of speech that is excessively impressionistic and lacking in detail
(6) shows self-dramatization, theatricality, and exaggerated expression of emotion
(7) is suggestible, i.e., easily influenced by others or circumstances
(8) considers relationships to be more intimate than they actually are

HISTRIONIC PERSONALITY DISORDER
 Prevalence: 2-3% in community, but 15% in clinic population
 May have similar temperament to Borderline Personality Disorder but without
as much hostility and identity disturbance
 Defense mechanisms of repression and dissociation
 Treatment
 Psychotherapy: Beware of splitting, overidealization, sexualization of
relationship
 Antidepressants and anxiolytics depending on comorbidity

NARCISSISTIC PERSONALITY DISORDER
DIAGNOSTIC CRITERIA
A pervasive pattern of grandiosity (in fantasy or behavior), need for admiration, and lack of empathy,
beginning by early adulthood and present in a variety of contexts, as indicated by five (or more) of the
following:
(1) has a grandiose sense of self-importance (e.g., exaggerates achievements and talents, expects to be
recognized as superior without commensurate achievements)
(2) is preoccupied with fantasies of unlimited success, power, brilliance, beauty, or ideal love
(3) believes that he or she is "special" and unique and can only be understood by, or should associate with,
other special or high-status people (or institutions)
(4) requires excessive admiration
(5) has a sense of entitlement, i.e., unreasonable expectations of especially favorable treatment or automatic
compliance with his or her expectations
(6) is interpersonally exploitative, i.e., takes advantage of others to achieve his or her own ends
(7) lacks empathy: is unwilling to recognize or identify with the feelings and needs of others
(8) is often envious of others or believes that others are envious of him or her
(9) shows arrogant, haughty behaviors or attitudes

NARCISSISTIC PERSONALITY DISORDER
• 1% of General Population; 2-16% of clinic population
• 50-75% are male (gender bias?)
• May have fragile self-esteem, with “narcissistic bubble” and tendency toward suicidal despair or
severe rage when faced with failure
• Therefore may present for treatment of depression or “mood swings”
• Lack of acceptance in childhood
• Defenses:
• Same biological factors as other cluster B disorders (overlap with Antisocial, Borderline, and
Histrionic)
• Treatment
– Psychotherapy: Debate over whether to confront or support defenses, based on theory involved
– Medications for comorbid depression or anxiety
– Similar pharmacologic options to treat affective or impulsive element of temperament as with
Borderline Personality Disorder, although not well studied

AVOIDANT PERSONALITY DISORDER
Wish for social contact, but fear humiliation
– Distinguishes it from Schizoid Personality Disorder
• 1% in Community; 10% in clinic
• Overlap with Social Phobia
• Genetics
– Introversion and Behavioral Inhibition highly heritable
– May be reinforced behaviorally by teasing by peers as children
• Defenses: Displacement
• Treatment
– Supportive psychotherapy to help bolster fragile self-esteem, followed by encouragement to
do more
– challenge expectations of failure
– SSRI’s, Benzodiazepines, Beta-blockers

DEPENDENT PERSONALITY DISORDER
• Excessive need to be cared for by others, with difficulty being alone, difficulty making
independent decisions, submissive behaviors, often taken advantage of in their
interpersonal relationships, often belittle themselves (e.g. “stupid”) and at higher risk for
depression and anxiety
• 15% in community, making it one of most common Personality Disorders. Diagnosed in 2-
3% in clinic, but 20% if using standardized interview (may be ignored due to more
prominent Axis I features)
• Genetics
– Submissiveness appears heritable
• Treatment
– Supportive Psychotherapy
– Assertiveness Training
– Avoid dependence on therapy by patient
– Treatment of comorbid Axis I

OBSESSIVE COMPULSIVE DISORDER
DIAGNOSTIC CRITERIA
A pervasive pattern of preoccupation with orderliness, perfectionism, and mental and interpersonal control, at
the expense of flexibility, openness, and efficiency, beginning by early adulthood and present in a variety of
contexts, as indicated by four (or more) of the following:
(1) is preoccupied with details, rules, lists, order, organization, or schedules to the extent that the major point
of the activity is lost
(2) shows perfectionism that interferes with task completion (e.g., is unable to complete a project because his
or her own overly strict standards are not met)
(3) is excessively devoted to work and productivity to the exclusion of leisure activities and friendships (not
accounted for by obvious economic necessity)
(4) is overconscientious, scrupulous, and inflexible about matters of morality, ethics, or values (not accounted
for by cultural or religious identification)
(5) is unable to discard worn-out or worthless objects even when they have no sentimental value
(6) is reluctant to delegate tasks or to work with others unless they submit to exactly his or her way of doing
things
(7) adopts a miserly spending style toward both self and others; money is viewed as something to be
hoarded for future catastrophes
(8) shows rigidity and stubbornness

OBSESSIVE COMPULSIVE DISORDER
Prevalence: 1% in Community; 3-10% in the clinic
• Twice as prevalent in men as in women
Bruce Cohen, M.D.- Personality Disorders, p. 13
• No higher risk of depression or OCD, but they often present for this
• Comorbidity includes Avoidant and Paranoid Personality Disorder
• Etiology uncertain
Defenses include externalization, isolation, rationalization,
displacement, and reaction formation
• Treatment is psychotherapy
– Help the patient learn to set priorities, to laugh at self, to deal with uncertainty, not
to set such high standard for self (and for others), to help patient get in touch with
emotions

THE TRAITS OF IMPULSIVITY AND AGGRESSION
HAVE BEEN LINKED TO…
 Low CNS serotonin
 Side effect of SSRIs can be loss of affect, flatness
 GABA enhancement can decrease aggressiveness
 Benzodiazepine
 High dopamine and norepinpehrine – increased impulsivity and aggression

IN THE HOSPITAL, DESCRIBE: A) PREVALENCE
OF DELIRIUM B) MORBIDITY C) MORTALITY
 a.) prevalence: Delirium is present in 15-25% of hospital pts at the time of
admission and it prolongs hospitalization.
 b.) morbidity: Have longer hospital stays, have worse medical or surgical
recovery, hit nurses, pull out their NG tubes, IV's, arterial lines, central lines,
and aortic balloon pumps, have much higher risk of decubitus ulcers and
aspiration pneumonia, cost money (due to medical complications and longer
hospital stays)
 c.) mortality: Highest mortality of any psychiatric diagnosis (25-75% of patients,
either in that hospital stay, or within the next 6 months)

LIST THE KEY SIGNS AND SYMPTOMS
OBSERVED CLINICALLY IN DELIRIUM
 Delirium is change in level of consciousness; may have hallmarks of other
disease like cognitive change (dementia), mood change (depression), or
hallucinations/delusions (schizophrenia), but consciousness change is what
distinguishes it
 Signs and symptoms of delirium from lecture: Rapid onset, fluctuating course,
reduced level of consciousness (EEG slowing), reversible (usually), impaired
attention, disturbance in cognition or perception

NAME FACTORS THAT CAN PREDISPOSE A
PATIENT TO DELIRIUM
 Elderly
 Decreased clearance of pharm (pharmacokinetic)
 Decreased brain mass/ catecholamines (pharmacodynamic)
 comorbidities
 Post op
 Burn
 Brain Injury
 Alcohol/Drug Withdrawal

LIST THE PNEUMONIC AND COMMON
ETIOLOGIES OF DELIRIUM
 I WATCH DEATH
 Infectious
 Withdrawal
 Acute Metabolic
 Trauma
 CNS Disease
 Hypoxia
 Deficiencies
 Environmental
 Acute vascular
 Toxins/drugs
 Heavy metals

DESCRIBE HOW AN EEG CAN BE USEFUL IN
VALIDATING THE DIAGNOSIS OF DELIRIUM AND
DESCRIBE THE MOST COMMON EEG FINDING IN
DELIRIUM
 Most delirious patients have reduced cerebral metabolic activity
 EEG studies show slowing of background brainwave activity
 Not seen in patients with schizophrenia or major depression

HOW CAN DELIRIUM BEST BE APPROACHED
 Symptomatic management
 Keep the patient safe
 Initial focus should be on diagnosing and treating those conditions which will
lead to increased morbidity/mortality
 Discontinue all nonessential meds
 Daily labs and physical exam if cause of delirium remains undetermined
 Check vital signs frequently and check for clinical deterioration
 Pulling out lines
 Crawling over bedrails
 Fluid input/output
 oxygenation

WHAT IS THE BEST PHARMACOLOGICAL
MANAGEMENT OF DELIRIUM
 Haloperidol or atypical antipsychotic
 Benzodiazepines
 NOT ANTIDEPRESSANTS – tricyclic are anticholinergic  exacerbate sx

DESCRIBE THE PREVALENCE OF
SCHIZOPHRENIA IN THE GENERAL
POPULATION.
 1%

SCHIZOPHRENIA
 Schizophrenia: > 6 months of symptoms (> 1 month active), including
hallucinations, delusions, thought disorder, disorganized or catatonic behavior,
or "negative” symptoms; decline in functioning.
 Mood Disorder excluded (treatment and prognostic implications).

SCHIZOPHRENIFORM DISORDER
 Schizophreniform Disorder: Same criteria except for duration (1-6 months) and
no requirement for decline in functioning.

BRIEF PSYCHOTIC DISORDER
 Brief Psychotic Disorder: Lasts from < 1 month

SCHIZOAFFECTIVE DISORDER
 Schizoaffective Disorder: Meets criteria for both schizophrenia and Mood
Disorder.
 Mood episode and active-phase symptoms of Schizophrenia occur together,
preceded or followed by at least 2 weeks of delusions or hallucinations without
prominent mood symptoms.

OTHERS
 Delusional Disorder: Non-bizarre delusions in the absence of other active-phase
symptoms of Schizophrenia, lasting > 1 month.
 Shared Psychotic Disorder (folie a deux): Disturbance develops in an individual
who is influenced by someone else who has an established delusion with similar
content.
 Psychotic Disorder Due to a General Medical Condition: Psychotic symptoms
judged to be direct physiological consequence of a general medical condition.
 Substance-Induced Psychotic Disorder: Psychotic symptoms are judged to be
direct physiological consequence of a drug of abuse, a medication, or toxin
exposure.
 Psychotic Disorder Not Otherwise Specified: Psychotic presentations that do not
meet the criteria for any of the specific Psychotic Disorders, or psychotic
symptomatology about which there is inadequate or contradictory information

DISCUSS POSITIVE VS NEGATIVE SX IN
SCHIZOPHRENIA
 Positive Symptoms: Phenomena that are present in Schizophrenia aren’t seen
in normals, i.e. psychotic symptoms (Hallucinations, Delusions, Formal Thought
Disorder and grossly disorganized behavior) – Mesolimbic Dopamine
 Negative Symptoms: Also called “deficit” symptoms; areas of functioning where
patients with Schizophrenia are lacking normal abilities. (Apathy, Affective
blunting, Poverty of speech or thought content, Social withdrawal & inability to
relate, Attention problems, Dishevelment) – Mesocortical Dopamine
 Negative symptoms are the major source of life disability, even for when
patients who are taking medication and responding to them to the extent that
they are no longer actively “psychotic”

DESCRIBE THE TYPICAL COURSE OF
SCHIZOPHRENIA AND LIST FACTORS
ASSOCIATED WITH A BETTER PROGNOSIS.
 1. Prodromal Phase: Slow and gradual
development of negative symptoms
(often Schizotypal Personality Disorder
features
 2. Active Phase: Development of positive
symptoms, often occurs abruptly with
“psychotic break.”
 3. Residual Phase: Resembles
prodromal, but positive symptoms might
be present in attenuated form; need to
watch for harbingers of relapse
Better Prognostic Factors
- Good premorbid adjustment (rather than “odd”
personality)
- Acute onset (rather than gradual decline)
- Later age at onset
- Being female
- Precipitating events
- Associated mood disturbance
- Brief duration of active-phase symptoms
- Good interepisode functioning, minimal residual
symptoms
- Absence of structural brain abnormalities
- Normal neurological functioning
- A family history of Mood Disorder
- No family history of Schizophrenia

DESCRIBE THE DIFFERENCE BETWEEN A) FAMILY
STUDIES, B) TWIN STUDIES, C) ADOPTION
STUDIES, AND D) LINKAGE STUDIES.

DESCRIBE HOW DELUSIONAL DISORDER
DIFFERS FROM SCHIZOPHRENIA IN ITS
PHENOMENOLOGY AND IN ITS IMPACT ON THE
AFFECTED INDIVIDUAL’S FUNCTIONING.
 Patients with delusional disorder will be have delusions (fixed, false,
idiosyncratic beliefs) without the “active-phase” symptoms of schizophrenia (i.e.
hallucinations, disorganized speech). Unlike patients with schizophrenia,
patients with delusional disorder do not have any functional impairment beyond
that due to delusions themselves.
 Dr. Cohen gives the example in his PRL of a patient with delusional disorder
who was convinced he had syphilis despite repeat negative syphilis tests. The
guy had a high level of functioning, but was still sure he had syphilis.

DESCRIBE THE FOUR PRIMARY DOPAMINE
PATHWAYS IN THE BRAIN
 Mesolimbic Tract: DA activity to nucleus accumbens is thought to be cause pleasurable sensations that reinforce
motivated behaviors, including the euphoria associated with addictive drugs
 Overstimulation might increase hallucinations and delusions
 D2 blockers might work here to treat positive symptoms
 Nigrostriatal tract: Degeneration increases Parkinson’s Disease (resting tremor, rigidity, bradykinesia, postural
instability)
 Increased dopaminergic activity increases choreoform, dyskinetic, and dystonic movements
 D2-blockade of this pathway increases Parkinsonism
 Increased D2 sensitivity with longer-term antipsychotic use causes Tardive Dyskinesia
 Mesocortical tract: Believed to mediate effects of DA on attention and planning
 Negative symptoms of Schizophrenia resemble frontal lobe injury
 Evidence on functional neuroimaging of lower frontal lobe activity in Schizophrenia
 Reciprocal connections between frontal lobes and basal ganglia  traditional antipsychotics may worsen
negative symptoms due to Nigrostriatal dopamine (Parkinsonism), OR Mesocortical dopamine
 Tuberoinfundibular tract
 DA inhibits prolactin release
 D2 –blockade increased serum prolactin  gynecomastia and galactorrhea.
 Antipsychotics also suppress levels of luteinizing hormone (LH) and follicle stimulating hormone (FSH), which
can cause amenorrhea and anorgasmia in women

DISTINGUISH THE CNS MECHANISMS BY WHICH
AMPHETAMINES, LSD, AND PCP CAN CAUSE
PSYCHOTIC SYMPTOMS
 Amphetamines: increase brain levels of dopamine. Causes a paranoid psychotic
state resembling schizophrenia and also can exacerbate psychotic symptoms when
they are taken by people with preexisting schizophrenia.
 LSD: serotonin receptor agonist. More serotonin → less DA in nigrostriatal and
mesocortical systems. Causes pseudo psychotic state. Effects are different than
schizophrenia in that it produces visual illusions, rather than visual and auditory
hallucinations, insight is often preserved and negative symptoms are absent. Take-away:
5HT is not as important as DA
 PCP: glutamate antagonist. Less glutamate → more dopamine. Causes true
psychotic state. Glutamate fibers from the cortex to subcortical limbic structures
stimulate interneurons that modulate with inhibitory GABA. These same interneurons
are inhibited by DA fibers as well. So maybe in schizophrenia the interneurons are
inhibited by DA, and in PCP induced psychosis the interneurons are not inhibited by
glutamate.

DESCRIBE HOW ANTICHOLINERGIC AGENTS
MINIMIZE EXTRAPYRAMIDAL SIDE EFFECTS OF
TYPICAL ANTIPSYCHOTIC MEDICATIONS.
 DA neurons from the substantia nigra synapse on cholinergic neurons in the
basal ganglia, inhibiting ACh release. So, blocking DA receptors on these ACh
neurons with antipsychotics triggers excessive ACh release, triggering
excessive inhibition of motor behavior - parkinsonism.
 Anticholinergic drugs combat this effect without affecting the drugs effects
along the mesolimbic pathway.

DESCRIBE HOW SEROTONIN RECEPTOR HELPS
TO MINIMIZE EXTRAPYRAMIDAL SIDE EFFECTS
BY SECOND GENERATION (“ATYPICAL”)
ANTIPSYCHOTIC AGENTS.
 Serotonin fibers from the dorsal raphe area project to the substantia nigra,
where they synapse on somatodendritic 5HT2 receptors located on the DA
neurons that project to the striatum. Thus, serotonin has an inhibitory effect on
the nigrostriatal DA system. A serotonin antagonist counteracts D2-blocking
effects by antipsychotics, minimizing EPS

DESCRIBE THE DIFFERENCE BETWEEN A)
ANTIPSYCHOTIC-INDUCED PARKINSONISM, B)
AKATHISIA, C) DYSTONIA, AND D) TARDIVE
DYSKINESIA.
 Parkinsonism: resting tremor, rigidity, bradykinesia, and postural instability →
decreased motor activation
 Akathisia: severe motor restlessness
 Dystonia: sustained, involuntary muscle spasms, most often of the face, neck,
and back
 Tardive dyskinesia: abnormal, involuntary movements of the tongue and jaw,
limbs, and/or trunk. → increased motor activation

WHAT DOPAMINE PATHWAY CAUSES
PARKINSONISM
 Nigrostriatal

DESCRIBE THE SX AND RX OF NEUROLEPTIC
MALIGNANT SYNDROME
 Symptoms:
 -Severe muscle rigidity & elevated temperature (mild: 99 F; severe 106 F)
 -Diaphoresis
 -Dysphagia
 -Tremor
 -Incontinence
 -Delirium (can progress to coma or death)
 -Mutism
 -Tachycardia, elevated or labile blood pressure
 -Leukocytosis (WBC or labile blood pressure)
 -Increased creatine phosphokinase (severe elevations can cause myoglobinuria & renal
failure)
 Treatment:
 Sepsis workup + Immediate discontinuation of antipsychotic medication
 Antipyretics, IV fluids, cooling blankets, dopamine agonists/ peripheral muscle relaxants
(dantrolene) can be adjuncts
 Often resolves after approx. 2 weeks -

RECEPTOR PROFILE ASSOCIATED WITH EACH
OF THE FOLLOWING: A) SEDATION AND WEIGHT
GAIN, B) DRY MOUTH AND CONSTIPATION, C)
PROTECTION AGAINST DRUG-INDUCED
PARKINSONISM, D) HYPOTENSION, AND E)
PROLACTIN ELEVATION.
 Sedation & Weight Gain: H1 histamine receptor
 Dry Mouth & Constipation: M1 acetylcholine receptor
 Protection from drug-induced Parkinsonism: D2 dopamine receptor
(nigrostriatal)
 Hypotension: Alpha 1 Norepinephrine Receptor
 Prolactin Elevation: D2 dopamine receptor (tuberoinfundibular)

LIST THE ADVANTAGES AND DISADVANTAGES
OF PRESCRIBING TYPICAL ANTIPSYCHOTIC
DRUGS
 Advantages: good at treating the positive symptoms
 Haloperidol & Fluphenazine in long acting (Decanoate) forms especially useful
in non-compliant patients (only need dosing once a month)
 Disadvantages: antagonistic activity at many receptor types
 Histamine – sedation & weight gain
 NE – hypotension;
 M1 ACh – blurred vision, dry mouth & constipation)
 D2 antagonism in nigrostriatal system – parkinsonism and EPSs

IN WHICH DOPAMINE SYSTEM DOES 5-HT NOT
PLAY A ROLE?
 Mesolimbic

STRESS DIATHESIS MODEL
 Stress-Diathesis Model: environmental stressors act on a genetically vulnerable
individual, and the disease ultimately becomes independent of these
environmental stressors once it has taken hold.
 Life stress likely plays an important role in precipitating “first-break” episodes as
well as later relapses

DISTINGUISH THE INHIBITORY AND EXCITATORY
SEROTONIN AND DOPAMINE RECEPTORS
 5-HT1 – Inhibitory – presynaptic autoreceptors
 5-HT2 – Excitatory
 Acts on dopamine receptor
 D1 – Excitatory
 D2 – Inhibitory – presynaptic autoreceptor
 Interacts with acetylcholine receptor

AGONISTS OF GABA TREAT _______ WHILE
ANTAGONISTS OF GABA CAN CAUSE _________
 Agonist (Benzodiazepine) treat anxiety
 Antagonists cause seizures

DISTINGUISH BETWEEN SEROTONIN RECEPTOR
1 AND 2 FAMILIES AND HOW THEY ARE
INVOLVED IN THE TREATMENT OF PSYCHIATRIC
ILLNESSES.
 5-HT1 receptor family:
 -5HT1A is an autoreceptor in the limbic area that affects mood. Desensitization of 5HT1A
may help raise synaptic cleft 5-HT during chronic SSRI administration. If 5HT1A is
postsynaptic, it exacerbates anxiety (anxiogenic). If presynaptic, it alleviates anxiety
(anxiolytic).
 -5HT1B and 5HT1D are both presynaptic autoreceptors that inhibit cell firing and 5HT
release.
 5-HT2 receptor family:
 -5HT2A is postsynaptic and the main excitatory receptor for serotonin. Psychedelic drugs
work as 5HT2A agonists, and new generation antipsychotics are 5HT2A antagonists (fewer
side effects than previous generations).
 -5HT2B is presynaptic and regulates serotonin release via the serotonin transporter.
 -5HT2C activation is responsible for side effects of SSRI and SNRI medications by
inhibiting dopamine and norepinephrine release.

EXPLAIN THE INTERACTION BETWEEN
DOPAMINE AND SEROTONIN NEURONS IN THE
BASAL GANGLIA AND HOW IT AFFECTS THE
SIDE EFFECT PROFILE OF CONVENTIONAL
ANTIPSYCHOTICS VERSUS THE SECOND
GENERATION ANTIPSYCHOTICS
 Summary of Anti-Psychotics:
 1st gen: D2 antagonists. Block dopamine everywhere, including basal ganglia
→ extrapyramidal symptoms.
 2nd gen: D2 & 5HT2 antagonists: Block dopamine everywhere but increase
dopamine in basal ganglia (by blocking serotonin receptors which in turn block
dopamine thus resulting in more dopamine)→ less extrapyramidal symptoms.

EXPLAIN THE INTERACTION BETWEEN
DOPAMINE AND ACETYLCHOLINE NEURONS IN
THE NIGROSTRIATAL DOPAMINE PATHWAY AND
HOW D2 BLOCKADE BY ANTIPSYCHOTICS CAN
AFFECT MOVEMENT.
 Dopamine signaling to cholinergic neurons inhibits ACh release. D2 blockade
by antipsychotics removes this inhibitory effect and increases ACh signaling,
which exacerbates extrapyramidal symptoms.

WHAT IS THE LOCATION OF DOPAMINE IN THE
BRAIN?
 Midbrain
 Substantia nigra
 VTA

WHAT IS THE LOCATION OF SEROTONIN IN THE
BRAIN
 Midbrain and pons
 Raphe nuclei

WHAT IS THE LOCATION OF NE IN THE BRAIN
 Locus ceruleus - pons

WHAT IS THE BEST WAY TO DISTINGUISH
BETWEEN T1 AND T2
 On T1 water/CSF (the spaces in the brain) appear dark
 On T2 water/CSF appears bright

DISCUSS CONTRAST AGENTS FOR CT AND MRI
 In x-ray based studies, they are higher density materials (e.g., iodine, barium)
that absorb more x-rays and appear brighter
 In MRIs, they are chelates of paramagnetic ions and exert an effect on protons
to alter their relaxation times
 CT contrast agents = iodine compounds
 Iohexol (Omnipaque)
 Iodixanol (Visipaque)
 MR contrast agents = gadolinium compounds
 gadopentetate dimeglumine (Magnevist)
 gadobutrol (Gadavist)
 gadobenate (MultiHance)

CATHETER ANGIOGRAPHY
 Small flexible catheter inserted into femoral artery
 X-ray fluoroscopy used guide catheter tip into neck or head
 Iodinated contrast injected through catheter into artery
 X-rays taken simultaneously over 6-20 seconds
 May be combined with endovascular treatment at same setting

CT ANGIOGRAPHY
 Timed IV bolus contrast injected as neck and head are rapidly (< 1 min)
scanned with CT
 Vasculature depicted at high resolution with white contrast opacification
 Post-processed as 2D or 3D images

MRA AND MRV
 Depends on moving hydrogen protons in blood
 Detects fast moving flow of arterial blood
 Detects slow moving venous blood in sinuses
 May or may not use contrast
 Typically used to identify sites of impeded or absent arterial blood flow due to
atherosclerosis, thrombosis, dissection, or aneurysm

DISTINGUISH BETWEEN CLOSED AND OPEN
HEAD INJURY.
 Closed head injury = blunt trauma and is associated with acceleration and
deceleration forces. In other words, there is a traumatic force to the head but
the dura and skull remain intact.
 Open head injury = penetrating trauma. This is when you actually get
penetration of the skull or brain by an object

DISTINGUISH BETWEEN LINEAR, DEPRESSED
AND CONTRECOUP FRACTURES. LIST THE
COMPLICATIONS OF SKULL FRACTURES.
 Linear skull fractures: fractures in the skull that traverse the full thickness of the bone, are fairly
straight, and do not displace bone. Linear skull fractures are of clinically little significance unless
they occur close to or in a suture or if they involve a venous sinus or vascular channel. The
resulting complications of a linear fracture is suture diastasis (separation in sutures), venous
sinus thrombosis, and epidural hematoma.
 Depressed skull fractures: These are comminuted fractures in which broken bones are displaced
inwards. These fractures carry the risk of increasing pressure on the brain and hemorrhage. If the
scalp and dura are lacerated, these types of fractures carry a risk of infection.
 Contrecoup fractures: These fractures occur when there is an initial impact to the skull, but the
injury occurs on the opposite side or far away from the site of impact. The example in the handout
is occipital area impact leads to fracture of the roofs or orbits/ethmoid bone.
 Complications of skull fractures: If you get a vascular tear- epidural hematomas. If trauma causes
a dural tear and or depressed skull fractures- susceptible to infections. Contusions are another
complication of skull fracture.

EXPLAIN THE PHYSIOLOGICAL CONSEQUENCES
OF BRAIN CONTUSIONS
 Contusions are caused by rapid displacement of brain tissue, disruption of
vascular channels, and subsequent hemorrhage, tissue injury and edema. The
most susceptible structures for contusion are the crests of the gyri because
they are close to the surface.
 The physiological consequence of brain contusions are focal subarachnoid
hemorrhages. To expand on this a little; Contusions are wedge-shaped, with
the widest aspect close to the point of impact. Within a few hours, blood
extravasates throughout the injury. The inflammatory response to the injury
follows, with neutrophil invasion and subsequent macrophage invasion. The
superficial layers of cortex are most severely affected

IDENTIFY THE MOST COMMON LOCATIONS OF
CONTUSIONS. DISTINGUISH BETWEEN COUP
LESIONS AND CONTRE-COUP CONTUSIONS.
 The most common locations of contusions are regions of the brain overlying
rough and irregular inner skull surfaces, such as the orbitofrontal regions and
the temporal lobe tips.
 A coup contusion occurs at the same site of injury. A contrecoup contusion is
when the contusion occurs on the other side of the brain (opposite the impact)

DISTINGUISH BETWEEN EPIDURAL HEMATOMA,
SUBDURAL HEMATOMA AND SUBARACHNOID
HEMORRHAGE IN TERMS OF THEIR TRAUMATIC
CAUSES AND LOCATIONS IN THE SKULL.
 Epidural hematoma: Dural vessels, especially the MIDDLE MENINGEAL A., are vulnerable to traumatic
injury. In infants, traumatic displacement of the easily deformable skull may tear a vessel, even in the
absence of a skull fracture. In children and adults, by contrast, tears involving dural vessels almost always
stem from skull fractures. Once a vessel is torn, blood accumulating under arterial pressure can dissect
the tightly applied dura away from the inner skull surface, producing a hematoma that compresses the
brain surface. Clinically, patients can be lucid for several hours between the moment of trauma and the
development of neurologic signs
 Subdural Hematoma: Rapid movement of the brain during trauma can tear the BRIDGING VEINS that
extend from the cerebral hemispheres through the subarachnoid and subdural space to the dural sinuses.
Their disruption produces bleeding into the subdural space. LESS ACUTE SYMPTOMS, SLOW
DEVELOPMENT
 Subarachnoid hemorrhage: This is bleeding into the subarachnoid space, between the arachnoid and pia
mater. This can occur from a ruptured cerebral aneurysm or from head trauma. **often due to rupture of
CORTICOMENINGEAL A. in association with cerebral contusion.

EXPLAIN HOW EPIDURAL AND SUBDURAL
HEMATOMAS CAN BE DISTINGUISHED IN
NEURORADIOGRAPHIC IMAGES.
 Epidural – lens shaped and well-circumscribed
 Subdural – follows shape of brain

STATE THE CAUSE AND CONSEQUENCE OF
TRAUMATIC INTRAPARENCHYMAL
HEMORRHAGES.
 Tend to be multiple
 Commonly ‘delayed’ hemorrhages
 > 24 hours following trauma
 Common locations:
 Cortex in association with contusion
 Frontal and temporal lobes
 Intraventricular extension

DEFINE DIFFUSE AXONAL INJURY. EXPLAIN
HOW ACUTE AND CHRONIC PHASES OF EACH
CAN BE RECOGNIZED HISTOPATHOLOGICALLY.
 DIFFUSE AXONAL INJURY (DAI): widespread damage of axons resulting from
severe
 acceleration or deceleration of the head.
 Common locations: Locations of long myelinated (white) axons in the brain
 - corpus callosum
 - cerebral hemisphere white matter
 - subcortical fiber tracts (fornix, internal and external capsules)
 - brain stem (long white tracts)
 - cervico medullary junction

 Histology:
 Acute- Axonal retraction balls and swelling in acute phases
 (these lesions are best seen by APP immunohistochemistry)

WHAT IS THE MAJOR CAUSE OF CNS TRAUMA IN
INFANTS AND THE ELDERLY?
 Falls
 MVA for adults

PENETRATING VS. PERFORATING INJURY
 Perforating enters and exits

FACTORS OTHER THAN DIRECT LACERATION
THAT IMPACT BULLET WOUNDS
 1) Explosive forces
 - due to the exploding gases from the barrel of the gun causing expansive
forces on the head
 -will result in a larger entrance wound than exit wound when the barrel is
held near the head
 2) Expansive forces
 - the wave of tissue compression and expansion as a result of the energy of
the bullet
 -Will diminish as the energy of the bullet diminishes
 3) Infectious elements:
 -Bullets carry contaminated scalp and hair into the brain, increasing the risk
of infection

WHICH REGION OF THE SPINAL CORD IS MOST
VULNERABLE TO TRAUMATIC INJURY
 Cervical
 C1-C2
 C4-C7
 T11-L2

EXPLAIN THE COMBINATION OF ETIOLOGIES
THAT UNDERLIE ISCHEMIC/HYPOXIC BRAIN
DAMAGE SECONDARY TO TRAUMATIC INJURY.
 Hypoxic-ischemic damage is common after head trauma and is highly likely in
patients that have had clinical evidence of hypoxia and/or hypotension for at least 15
minutes
 Etiologies are:
 1) Intracranial arterial spasm→ ischemia/hypoxia
 2) Edema/hematomas→ increased intracranial pressure→ decreased blood flow
 3) Increased metabolic activity due to post-trauma status epilepticus (epilepsy
following head trauma leading to increased metabolic activity and subsequent
ischemia)
 Secondary brain damage often leads to diffuse brain edema leading to a buildup of
fluid in the brain. This can be the result of both vasogenic (leakage of fluid from the
capillaries) or cytotoxic (leakage of contents from cells) edema. This buildup of fluid
in the brain is what can cause increases in inracranial pressure.

WHAT IS KERNOHAN’S NOTCH?
 The Kernohan's notch is an imaging finding resulting from extensive midline
shift due to mass effect.
 Indentation of the Crus against the cerebellar tentorium secondary to
transtentorial herniation due to mass effect (tumor, etc)
 Contrecoup injury: injury to right brain results in left Kernohan’s Notch, which
then affects the right side of the body (freakin CNS mind games).
 source: http://radiopaedia.org/articles/kernohans-phenomenon

WHAT IS A DURET HEMORRHAGE?
 crushing of the midbrain between herniating temporal lobe and opposite leaf of
tentorium  leads to hemorrhage and necrosis of the midbrain and pons
 Symptoms:
 -Cheyne-Stokes respirations- pattern of breathing where person goes
through cycles of breathing deeply and quickly at first, followed by decline
and then pause in breathing before starting again
 -Stupor or coma
 -Fixed pupils and gaze alterations
 -Bipyramidal signs

WHICH AREAS OF THE ADULT BRAIN ARE
PARTICULARLY VULNERABLE TO HYPOXIA?
 CA1 of hippocampus
 Purkinje cells of cerebellum
 Layers 3 and 5 of cortex

WHICH CRANIAL NERVE IS OFTEN
COMPRESSED WITH AN UNCAL HERNIATION?
 CN III – pupillary dilation
 PCA may be compressed as well

WHY IS A TONSILLAR HERNIATION LIFE
THREATENING?
 Brainstem compression compromises respiratory and cardiac centers in the
medulla

HERNIATIONS
 Subfalcine herniation = cingulate herniation is when the cingulate gyrus herniates under the
cerebral falx
 remember that the cingulate gyrus is superior to the corpus callosum
 this herniation may lead to compression of branches of the anterior cerebral artery
(and therefore I'm guessing deficits along the midline of the brain)
 Transtentorial herniation = uncal herniation = mesial temporal herniation is when the medial
aspect of the temporal lobe is compressed against the free margin of the tentorium
 increased displacement in this area compresses CN III, resulting in pupillary dilation
(“blown pupil”) and impairment of ocular movement on the side of the lesion
 may also compress the posterior cerebral artery, resulting in ischemic injury to the
brain tissue it supplies (including the primary visual cortex)
 extreme herniation may compress the contralateral cerebral peduncle, resulting in
hemiparesis on the ipsilateral side (Kernohan’s Notch)
 uncal herniation is often accompanied by hemorrhagic lesions in the midbrain and pons
called secondary brainstem hemorrhages or Duret hemorrhages
 Tonsillar herniation is when the cerebellar tonsils are displaced through the foramen
magnum
 this is life threatening! because it causes brainstem compression and compromises vital
respiratory and cardiac centers in the medulla oblongata

DESCRIBE THE ROLE OF SHH GENES IN
PATTERNING THE DORSAL/VENTRAL AXIS OF
THE NERVOUS SYSTEM.
 Shh (sonic hedgehog) patterns the dorsal-ventral axis of the spinal cord. It is
expressed first in the notochord and then in the floor plate and induces ventral
differentiation in the neural tube. Shh expressed in the prechordal plate induces
ventral midline structures in the telencephalon as well as midline facial
structures.
 Facial midline defect associated with loss of Shh or Shh pathway genes include
cyclopia, nasal, palate, and dental defects.
 Mutations in Shh and its signaling pathway can cause human
holoprosencephaly (HPE), which is the failure of hemispheric cleavage.

DESCRIBE THE LOCATION OF NEURAL
PROGENITOR CELLS IN THE DEVELOPING
FOREBRAIN AND IN THE ADULT FOREBRAIN.
 In the developing forebrain, neural progenitor cells are found in the ventricular
zone of the neural tube in ALL brain regions (intermediate progenitors also
found in the subventricular zone)
 In the adult forebrain, there are much fewer neural progenitor cells. They are
found in a thin subventricular zone and in the dentate gyrus of the
hippocampus.
 NPCs in the SVZ make neurons that migrate to the olfactory bulb.
Neurogenesis in the hippocampus can be enhanced by exercise and
antidepressants.

LIST THE TWO MAJOR ROLES OF A RADIAL
GLIAL CELL IN THE CEREBRAL CORTEX.
 A radial glial cell is both 1) a progenitor cell, and 2) a guiding scaffold for
migration of its daughters.
 The earliest neural progenitor cells are called neuroepithelial cells, or
neuroepithelial stem cells. Later in development, these neuroepithelial cells are
called radial glia. In order for the cortex to grow layers, neurons need to migrate
out of the ventricular zone. This migration is glial guided.

DESCRIBE THE DIFFERENCE IN DAUGHTER
CELLS PRODUCED BY A SYMMETRIC VERSUS
AN ASYMMETRIC DIVISION OF A
NEUROEPITHELIAL PROGENITOR CELL.
 Symmetric division of a neuroepithelial cell produces two apical progenitors.
Symmetric division increases area. Too few symmetric divisions may cause
microcephaly
 Asymmetric division produces one progenitor and one neuron. Asymmetric
division increases thickness.

DESCRIBE WHAT IS MEANT BY INSIDE-OUT
FORMATION OF THE NEURONAL LAYERS OF THE
CEREBRAL CORTEX.
 In normal development, neurons migrate out of the ventricular zone, past their
earlier-born sisters. Therefore, the innermost layer of the cerebral cortex
contains the first-born neurons, and the outermost layer contains the last-born
neurons. This is called inside-out development.

DEFINE EACH OF THE FOLLOWING CLINICAL
TERMS RELATED TO DEVELOPMENTAL
ABNORMALITIES: LISSENCEPHALY, CORPUS
CALLOSUM AGENESIS.
 Lissencephaly: agyria; “smooth brain” with no gyri or sulci; can be caused by
defects in neurogenesis as well as neuron migration
 Reelin important
 Dcx important
 Corpus callosum agenesis: defect in axon tract formation of the CC
 Netrin important

DESCRIBE THE DEVELOPMENTAL BASIS OF
LISSENCEPHALY.
 Can be caused by mutations in reelin gene. Reelin is secreted in the marginal
zone (layer 1 of cortex) and instructs cortical neuron migration and lamination.
(not sure how much of that molecular crap we need to know so will edit if
needed after class)
 Mutations in DCX gene can also result in lissencephaly

DESCRIBE THE PROCESS BY WHICH THE
NUMBER OF POSTMITOTIC NEURONS IN THE
DEVELOPING NERVOUS SYSTEM IS REDUCED TO
REACH THE NUMBER IN THE ADULT BRAIN.
 This process is similar to what we saw at the NMJ. Once a neuron grows an
axon to its target, it needs neurotrophins from its target to survive and persist.
Multiple neurons at a single target compete for trophic factors. The neurons
that do not receive enough undergo apoptosis, which is a normal part of
development.

DEFINE THE TERM “ACTIVITY DEPENDENT
PRUNING” OF NEURAL CONNECTIONS.
 This refers to the refinement of circuits, where axon and dendrite branches are
“pruned” based on electrical activity and competition for space and trophic
factors. Again this is similar to the NMJ. Active synapses will get stronger and
inactive ones will get weaker and will get eliminated.
 Neurons that fire together wire together – Hebb’s rule

DESCRIBE WHY THE LOSS OF VISION IN ONE
EYE DURING THE CRITICAL PERIOD FOR
DEVELOPMENT OF VISION CAN LEAD TO
IMPAIRED VISION OR BLINDNESS.
 This all depends on the critical periods for any system in the brain. For vision, it
occurs in the first few years of life. Plasticity will allow a certain amount of time
for a behavior to “crystallize,” kind of like putting a stick in cement-- it will move
at first but then will solidify. For binocular vision, it develops in 6 months-2
years.
 Recovery of binocular vision after 6 months is difficult and almost impossible
after 2 years. So, a cataract in one eye, or closing one eye any time before 5
years of age can lead to amblyopia or cortical blindness. Prolonged deprivation
of that eye firing signals will cause rewiring in the visual cortex and will lead to
vision loss even if the cataract or blockage is removed later. The sooner you
can repair the eye, the fuller recovery will be because more plasticity is
available.

STATE THE APPROXIMATE AGE AT WHICH THE
CRITICAL PERIOD FOR DEVELOPING
BINOCULAR VISION ENDS.
 6 months to 2 years

STATE THE APPROXIMATE AGE AT WHICH THE
CRITICAL PERIOD FOR DEVELOPING LANGUAGE
ENDS.
 0-12 years

DISTINGUISH SPINA BIFIDA (OCCULT AND
CYSTIC FORMS) FROM NEURAL TUBE CLOSURE
DEFECTS.
 Spina bifida is incomplete formation of the vertebral (neural) arches. Failure of
the neural tube itself to close is known as rachischisis. Spina bifida and
rachischisis are both forms of neural tube defects.

DISTINGUISH MENINGOMYELOCELE,
MENINGOCELE, AND SPINA BIFIDA OCCULTA IN
TERMS OF MORPHOLOGY AND CLINICAL
PRESENTATION AND SYMPTOMS.
 Spina bifida is a failure of the bony vertebral arch to form, which normally
occurs due to signals from the roof plate. There are two types of spina bifida -
spina bifida occulta and spina bifida cystica, which can be subdivided into
meningocele and meningomyelocele.
 Spina bifida occulta: defect is restricted to laminae of one or two vertebrae.
Adjacent skin develops normally. The location is sometimes indicated by a
thick tuft of long hair. Patients are usually asymptomatic.
 Spina bifida cystica: one or more vertebral arches completely fail to develop.
This can lead to a herniation of the meninges through a defect in the skin
(meningocele) or herniation of both meninges and spinal cord
(meningomyelocele). Patients with severe meningomyelocele usually present
with neurological symptoms.

DISTINGUISH BETWEEN CHILDREN AND ADULT
POPULATIONS IN TERMS OF THE INCIDENCE
AND THE LOCATION OF CNS TUMORS.
 Adults: Supratentorial
 2% of primary tumors
 Gliomas, meningiomas
 Metastatic more common
 Children: Infratentorial
 2nd most common malignancy
 Pilocytic astrocytoma, medulloblastoma

NAME THE BASIS FOR THE CLASSIFICATION OF
CNS TUMORS ACCORDING TO THE WHO,
 NOT staged and the TNM staging system is not applicable
 Rarely metastasize outside the nervous system
 No lymphatics in the brain
 Location is critical to treatment, prognosis, and outcome.
 Histological grading is also critical for prognosis
 Tumor Nomenclature
 Classified according to their resemblance to mature and immature cells of the CNS
 Histological Grade
 Grade I: Slow-growing, non-malignant, associated with long-term survival
 Grade II: Relatively slow-growing but sometimes recur as higher grade tumors. Can
be malignant or non-malignant
 Grade III: Malignant and often recur as high grade tumors
 Grade IV: Malignant, aggressive

NAME THE COMMON PATHOPHYSIOLOGIC
EFFECTS OF CNS TUMORS IN THE BRAIN.
 Space occupying lesion
 Increased ICP
 Hydrocephalus
 Altered function of Tissues
 Seizures
 Focal neurological defects
 Paraneoplastic syndrome
 Signs and Symptoms
 headaches
 vomiting (particularly children)
 confusion, lethargy, coma
 papilledema

DESCRIBE THE GROWTH PATTERNS OF
GLIOMAS, MENINGIOMAS, AND METASTATIC
TUMORS.
 Gliomas = infiltrative, disseminate
 Exclusions (gliomas that do not show infiltrative growth pattern):
Ependymomas, choroid plexus papillomas, circumscribed astrocytomas
 Meningiomas = grow by expansion
 Metastatic tumors = hematogenous spread or direct invasion from adjacent
tissues

DESCRIBE THE DISSEMINATION PATTERNS OF
GLIOMAS
 Spread along white matter tracts (i.e. cross into other hemisphere by corpus
callosum) BUTTERFLY LESIONS
 Spread along the pial membrane (i.e. “travel” along subpial surface of brain,
invade into subarachnoid space and diffusely spread through the
leptomeninges)
 Spread along perivascular space (i.e. Virchow-Robin space = fluid-filled space
surrounding perforating arteries and veins in the parenchyma of the brain)
 Spread across the ependyma and ventricular lining (ventricular and CSF
seeding)
 RARELY metastasize outside CNS

EXPLAIN WHY EVEN LOW-GRADE OR BENIGN
CNS TUMORS CAN HAVE A POOR CLINICAL
OUTCOME
 Tumor environment
 Limited intracranial volume
 Important structures

NAME 4 MOST COMMON GENETIC SYNDROMES
ASSOCIATED WITH NS TUMORS AND THE
TUMORS ASSOCIATED
Syndrome Gene Locus Nervous syst. tumors
Neurofibromatosis 1 NF1 17q11 Neurofibroma, optic nerve glioma,
MPNST
Neurofibromatosis 2 NF2 22q12 Bilateral vestibular schwannoma,
peripheral schwannoma,
meningioma, ependymoma
Tuberous Sclerosis TSC1/TSC2 9q34/16p13 Subependymal Giant Cell
Astrocytoma (SEGA)
Von Hippel-Lindau VHL 3p25 Hemangioblastoma

NAME ENVIRONMENTAL FACTORS THAT HAVE
BEEN LINKED TO THE PATHOGENESIS OF
NERVOUS SYSTEM TUMORS.
 There is a definitive link between ionizing radiation and nervous system tumors
 Radiation-induced tumors:
 Meningiomas
 Gliomas
 Malignant nerve sheath tumors
 Uncertain
 Electromagnetic Fields
 Cell Phones
 Diet (e.g. N-nitroso compounds, vitamins, EtOH, tobacco)
 Viruses

LIST THE TUMOR TYPES THAT ARE CLASSIFIED
AS NEUROEPITHELIAL TUMORS AND THE
TUMORS THAT ARE USUALLY DESIGNATED
“GLIOMAS.”
 Tumors of Neuroepithelial tissue: (red tumors are referred to as gliomas)
 Astrocytic Tumors
 Oligodendroglial Tumors
 Oligoastrocytic Tumors
 Ependymal Tumors
 Choroid Plexus Tumors
 Neuronal and Mixed Neuronal-Glial Tumors
 Pineal Tumors
 Embryonal Tumors

WHAT FOUR CHARACTERISTICS CAN SUGGEST
POTENTIAL FOR MALIGNANCY OF A TUMOR
 Atypia (cytological)
 Mitotic activity
 Endothelial microvascular proliferation
 Necrosis

HISTOPATHOLOGY OF PILOCYTIC
ASTROCYTOMA
 Piloid cells with microcystic areas
 Rosenthal fibers

WHAT IS THE POPULATION, LOCATION, AND
GRADE OF PILOCYTIC ASTROCYTOMA?
 Children
 Midline structures
 Cerebellum
 Optic nerve and chiasm – Optic Nerve Glioma
 Third ventricle region/hypothalamus
 Brainstem (often dorsal exophytic)
 Spinal cord in adults
 Grade I

HISTOLOGY OF DIFFUSE ASTROCYTOMAS
 Nuclear pleomorphism
 Atypia/ Mitotic figures
 Geographic Necrosis
 Microvascular endothelial proliferation (absence of BBB)
 Palisading Necrosis

DESCRIBE THE CLINICAL PRESENTATION AND AGE
GROUP AFFECTED BY OLIGODENDROGLIOMAS.
 Long clinical histories
 Slow clinical evolution
 Seizures in 90% of cases
 Location mostly in frontal and temporal lobe (supratentorial areas)
 Age group:
 Majority of tumors occur in adults, with a peak incidence in the 40s and 50s.
 Only 6% of oligodendrogliomas are from pediatric patients. Rare in children

HISTOLOGY OF OLIGODENDROGLIOMA
 Fried egg appearance
 Chicken wire vessels
 Hemorrhagic
 Frontal and temporal preference
 Calcifications seen on CT

IMPORTANT PROGNOSTIC PARAMETER OF
OLIGODENDROGLIOMA
 1p, 19q codeletion

STATE THE LOCATION AND MOST PREVALENT
AGE GROUP IN WHICH MEDULLOBLASTOMAS
ARISE.
 Children
 Cerebellum
 Malignant Grade IV
 High CSF dissemination

HISTOLOGY OF EMBRYONAL TUMORS
 Small round blue cell
 Homer-Wright rosettes

LIST TWO TUMORS ARISING FROM THE NERVE
SHEATH CELLS AND TWO GENETIC SYNDROMES
ASSOCIATED

STATE THE CELL TYPE OF ORIGIN OF
MENINGIOMAS. LIST COMMON LOCATIONS
WHERE MENINGIOMAS ARISE.
 Arise from meningioepithelial cells – arachnoid cells  mesenchymal origin
 Location
 Convexity, skull base, spine
 Intradural, extra-cerebral and extra-medullary tumors
 Intraventricular tumors may occur but are rare

HISTOLOGY OF MENINGIOMA
Meningothelial Fibrous
Psommatous Syncytial

WHAT IS THE MOST COMMON LOCATION OF
CNS METASTASES
 Cerebral hemispheres
 Gray white matter border

STATE THE 5 MOST COMMON SOURCES OF
METASTATIC TUMORS TO THE CNS
 Intracranial
 Lung
 Breast
 Skin
 Kidneys/Colon
 Unknown
 Intraspinal
 Breast
 Lung
 Prostate
 Leukemia/lymphoma

WHAT ARE THE THREE MAJOR CLINICAL
PRESENTATIONS OF INFECTION IN THE CNS?
 Meningitis – inflammation of leptomeninges
 Pia and arachnoid
 Acute or Subacute
 Abscess
 Central necrotic mass and capsule formation
 Mass lesion
 Few fibroblasts, think immunodeficiency
 Encephalitis
 Inflammation either diffuse or localized, can involve spinal cord
 Regional selectivity due to specific viruses

WHAT ARE THE MOST IMPORTANT MODES OF
TRANSMISSION IN THE CNS
 Blood stream
 Most common
 Direct spread
 Bones and sinuses
 Direct implantation
 Iatrogenic, trauma surgeries
 Centripetal spread: retrograde from PNS
 Rabies, Herpes
 Axonal transport

EXPLAIN THE PATIENT’S CHARACTERISTICS
INCLUDING AGE AND IMMUNOLOGICAL STATUS
AND TYPES OF INFECTION THAT MAY OCCUR.
 Age – young and old are at high risk
 Adolescents/young adults  epidemics
 Immunocompromised
 Post-transplant, post-chemo, AIDS
 Chronic steroid treatment
 Time of year
 Seasonal infections

WHAT IS THE MOST COMMON ENTRY SITE OF
BACTERIAL MENINGITIS
 Upper respiratory

ACUTE BACTERIAL MENINGITIS
 Purulent infiltrate in subarachnoid space
 PMN infiltrate
 Perivascular inflammatory cuffings
 Cerebral edema
 CSF
 PMN
 10-10,000 cells/mm3
 Glucose – low
 Protein – high
 Gram - reactive

SUBACUTE BACTERIAL MENINGITIS
 Mononuclear infiltrates (lymphocytes, macrophages, plasma cells)
 Inflammatory vasculitis: thrombosis/infarcts
 Leptomeningeal fibrosis
 CSF: low white cell count, predominantly mononuclear cells

WHAT ARE THE COMPLICATIONS OF BACTERIAL
MENINGITIS?
 Cerebral infarcts
 Hydrocephalus
 Abscesses
 Hearing loss
 Mental retardation

STATE THREE CAUSES OF NON-VIRAL CHRONIC
MENINGITIS
 TB
 Lyme
 Syphilis

ASEPTIC MENINGITIS
 Aseptic meningitis is inflammation of the meninges with CSF lymphocytic
pleocytosis and no apparent cause after routine CSF stains and cultures.
 Viruses are the most common cause of aseptic meningitis. Other causes may
be infectious or non-infectious.
 Headaches, mild fever
 CSF – lymphocytic infiltrate, negative gram culture
 More benign than bacterial meningitis

VIRAL MENINGITIS
 Viral Meningitis
 Most common viral infection of the CNS
 More benign condition than bacterial meningitis, self-limited with none or few sequelae
 Affects frequently children and young adults
 CSF profile:
 – Low cellularity (50 to < 1000 cells/mm3); predominance of lymphocytic cells
 – Glucose: mostly normal
 – Protein: mostly normal to slightly elevated
 – Gram: non-reactive
 Histopathology:
 Mild to moderate lymphocytic infiltration of the leptomeninges
 Common Viral Meningitis
 Enteroviruses – most common cause of meningitis
 Herpes simplex virus (HSV)-2
 Mumps (paramyxovirus) – vaccination has ↓ incidence
 HIV
 Lymphochoriomeningits virus, arbovirus, measles, parainfluenza virus, adenovirus

FUNGAL AGENTS OF ASEPTIC MENINGITIS
 Candida
 Aspergillus
 Cryptococcus
 Coccidiodes
 Blastomyces

WHAT ARE THE PATHOLOGIC SIGNS OF
TUBERCULOSIS MENINGITIS
 Base of brain and cranial nerves are affected
 Granulomas
 Gelatinous exudate
 Hydrocephalus early

COMPLICATIONS OF TB MENINGITIS
 Infarcts: occlusive endarteritis
 Abscesses: tuberculomas
 Hydrocephalus
 Severe leptomeningeal fibrosis
 OSTEOMYELITIS

FUNGAL MENINGITIS
 Major concern in immunocompromise
 Most are SECONDARY infections
 FIND PRIMARY
 Blood stream spread and sinuses!
 Involvement of base of brain and cranial nerves
 Granulomatous reaction less prominent
 Immunocompetent
 Blastomyces (SE)
 Coccidiodes (SW)

WHAT ARE THE THREE TYPES OF FUNGAL
INFECTION IN THE CNS?
 1) Chronic Meningitis: inflammatory process of leptomeninges & CSF within the
subarachnoid space
 usually tuberculous, spirochetal, or cryptococcal
 2) Vasculitis: direct fungal invasion of blood vessel walls => causing vascular
thrombosis => producing infarction (potential to be hemorrhagic & become
septic)
 mucormycosis and aspergillosis (most common); candidiasis (sometimes)
 3) Parenchymal Invasions:
 Candida: (hematogenous dissemination) produces multiple microabscesses
+/- granular formation)
 Cryptococcus: (hematogenous dissemination)
 Mucormycosis: (direct extension invasion) commonly in diabetics with
ketoacidosis

DEFINE CEREBRITIS AND ABSCESS.
 Abscess:
 Space-occupying infectious lesion
 Well-defined lesion with necrotic center and capsule formation
 Ring-enhancing at neuroimaging
 Results from the ‘maturation’ of cerebritis
 Cerebritis:
 Poorly-defined lesion with acute inflammatory reaction
 necrotic (“soupy-like”) appearance
 surrounded by high degree of edema
 Progresses to abscess

WHAT ARE THE CHARACTERISTICS OF
ASPERGILLUS ABSCESS
 Poorly defined hemorrhagic lesions
 Vascular invasion  infectious vasculisit
 Seen in immunocompromised

COMPLICATIONS OF ABSCESS
 Cerebral Edema
 Mass effect
 Herniations
 Rupture into ventricles
 Secondary abscess

STATE THE MOST COMMON ROUTE OF ENTRY OF
ABSCESSES.
 Usually the consequence of a secondary infection.
 Blood stream dissemination from an extra-cerebral primary source
 Adults: lungs, teeth, pelvic or abdominal sources
 Children: congenital cardiac lesions
 Contiguous spread from adjacent structures
 Examples: Otitis media, sinusitis, osteomyelitis
 Iatrogenic causes
 Examples: Trauma, post-surgical procedures
 Cryptogenic abscess
 Note: Obligatory workup for ruling out cardiac shunts

VIRAL ENCEPHALITIS ROUTES OF INFECTION
 Hematogenous
 Centripetal
 HSV, Rabies, maybe arbovirus

WHAT ARE THE FOUR COMMON PATHOLOGICAL
FEATURES OF VIRAL ENCEPHALITIS
 Mononuclear infiltrates
 Microglial activation
 Rod and gitter cells, nodules, neuronophagia
 Inclusion bodies
 Specific for viruses
 Intranuclear or intracytoplasmic
 Necrosis
 Variable amongst ages
 Infants get microcephaly

COWDRY, NEGRI, JC VIRUS INCLUSION

STATE THE MOST COMMON GROSS AND
MICROSCOPIC FEATURES SEEN IN HERPES
(HSV) ENCEPHALITIS
 Temporo-frontal and limbic distribution
 Hemorrhagic/necrotic lesions with edema
 Dense inflammatory infiltrates
 Parenchymal and perivascular cuffings
 Neuronal inclusions
 Intranuclear – Cowdry A
 Intracytoplasmic may be seen
 Chronic lesions – infarct like lesions

WHICH RESPECTIVE GANGLION DO HSV1 AND
HSV2 INHABIT?
 HSV1 – trigeminal
 HSV2 – dorsal root ganglion

WHY ARE RED BLOOD CELLS COMMON IN
HERPES SIMPLEX ENCEPHALITIS.
 It is a hemorrhagic encephalitis

WHAT IS THE CORTICAL DISTRIBUTION OF
HERPES ENCEPHALITIS?
 Frontotemporal

STATE THE CAUSATIVE AGENT OF PML, THE
LOCATION OF THE LESIONS AND THE
PREFERENTIAL CELL INFECTED
 JC Virus
 Oligodendrocyte
 White matter of CNS
 Reactive astrocytosis and macrophagic infiltration (gitter cells)

DESCRIBE WHY CORTICOSTEROIDS MAY BE
IMPORTANT IN THE TREATMENT OF BACTERIAL
MENINGITIS.
 Dexamethasone
 To dampen immune response which can cause much of the damage of the
disease

MENINGITIS VACCINES
 H. Influenzae
 BEST
 Has almost eradicated meningitis of this cause
 N. Meningitidis
 S. pneumoniae

NAME THE CRITERIA FOR DEFINING A
NEUROLOGICAL EMERGENCY.
 In the nervous system
 TREATABLE

EXPLAIN WHY ADDITIONAL ANTIBIOTICS MAY
BE NECESSARY TO TREAT BACTERIAL
MENINGITIS.
 Drug resistance

DESCRIBE THE SIGNS AND SYMPTOMS OF
HERPES SIMPLEX ENCEPHALITIS AND HOW IT
IS DIAGNOSED AND TREATED AS WELL AS THE
PROGNOSIS.
 Sx: Change in personality, altered mentation and decreased level of consciousness,
fever, cortical focal neurologic findings, headache, papilledema, nausea and
vomiting and focal and generalized seizures
 Lumbar puncture - CSF WBC 10s, 100s to 1000-2000 /mm3, predominantly
lymphocytes, may contain 10s to 1000s of RBCs, opening pressure may be
elevated, PCR of cerebral spinal fluid test of choice (96% sensitivity, 99%
specificity)
 CT – Rarely may show hypodensities in the region of the temporal or frontal lobes
 MRI – Hyperintensities onT2 and gadolinium enhancement around lesion
 Rx: Acyclovir (10 mg/kg every 8 hrs for 21 days)
 Prognosis:
 Mortality rates: 19% at 6 months, 28% at 18 months, 70% for placebo treated
patients
 Poor outcomes: >30 yo, comatose or semi-comatose with a GCS<6 (70% mortality)

WHAT IS XANTHOCHROMIA AND ITS CAUSE
 Yellow CSF
 Bilirubin released from ruptured RBCs

WHAT IS VIEWED ON AN MRI OF HERPES
ENCEPHALITIS?
 The MRI is well regarded as a test for diagnosing herpes encephalitis. It is
common to see hyperintensities on T2 and gadolinium enhancement around
the lesion in the lobe that is infected. As the temporal lobe is the most common
cortical structure to be infected by herpes this is frequently well delineated with
gadolinium enhancement.

WHAT IS THE TEST OF CHOICE FOR HERPES
ENCEPHALITIS?
 The CSF PCR for herpes simplex is now the test of choice for diagnosis.

DISTINGUISH HSV 1 AND HSV 2 IN TERMS OF
ENCEPHALITIS
 HSV 1 – most common, most grave form of acute encephalitis
 HSV 2 – neonatal encephalitis
 TORCH

ARE THERE RISK FACTORS FOR HERPES
ENCEPHALITIS?
 NO
 Anyone can get it
 No seasonal variation either

CHRONIC VIRAL ENCEPHALITIS
 Long incubation period
 Many end in death
 Rubella – progressive rubella panencephalitis
 Measles – SSPE
 JC virus – PML
 All rare

WHICH IMMUNOSUPPRESSIVE DRUG IS HIGHLY
ASSOCIATED WITH PML
 Natalizumab

WHAT IS THE CELL INFECTED IN PML?
 Oligodendrocyte

STATE THREE PATTERNS OF DISEASES CAUSED
DIRECTLY BY HIV-1.
 Aseptic meningitis
 AIDS dementia – subacute encephalitis
 AIDS acute encephalitis

TORCH
 Toxoplasmosis
 Other (syphilis)
 Rubella
 Cytomegalovirus
 Herpes and HIV
 Chorioretinitis****
 Microcephaly
 Calcification
TRANSMISSION
 Tranplacental vs. transvaginal – (HSV-2) and breast feeding

DEFINE MENINGISMUS.
 Meningismus: Marked signs of meningeal irritation
 Meningismus is present in all of the following conditions:
 Infectious meningitis
 Subarachnoid hemorrhage
 Carcinomatous meningitis
 Chemical meningitis

LIST 5 SYMPTOMS OF MENINGEAL IRRITATION.
 Headache
 Lethargy
 Sensitivity to light (photophobia) and noise (phonophobia)
 Fever
 Nuchal rigidity (stiff neck, unable to touch chin to chest)

MENINGOCOCCAL NON-BLANCHING PURPURA
 Due to Coagulopathy
 Can be positive for organism

EXPLAIN WHY A HEAD CT SHOULD BE DONE
PRIOR TO AN LP IN BACTERIAL MENINGITIS
 Performing a head CT allows the clinician to determine whether a mass lesion
is present. If a mass lesion is present, lumbar puncture is contraindicated.
 Mass lesions may produce increased ICP. In conditions of increased ICP,
removal of CSF may precipitate herniation.

WHEN SHOULD ANTIBIOTICS BE STARTED?
 IMMEDIATELY – BEFORE LP
 Empiric therapy
 Ampicillin + Ceftriaxone unless 3-7 yrs old

WHAT ARE THE SPECIFIC THERAPIES FOR
BACTERIAL MENINGITIS
 S. pneumonia – vanc + ceftriaxone
 N. meningitidis – ceftriaxone

WHAT IS THE PROPHYLACTIC RX FOR
EXPOSURE TO BACTERIAL MENINGITIS?
 Cipro
 Rifampin (for children)

LIST THE COMMON CAUSES OF BACTERIAL
MENINGITIS AND THEIR EMPIRIC TREATMENTS
IN NEONATES, OLDER CHILDREN, AND ADULTS.

DESCRIBE THE STRUCTURE, GROWTH
PROPERTIES, AND VIRULENCE FACTORS OF S.
PNEUMONIAE.
 Gram-positive cocci in short chains or pairs (lancet-shaped diplococcic)
 Fastidious facultative anaerobes, Microaerophilic (lack catalase)
 Grow on agar, alpha-hemolytic
 Fermentive metabolism – produce acids like lactic acid
 Optochin-sensitive and produce peroxide.
 Anti-phagocytic capsule, pneumolysin, cell wall

DESCRIBE THE MECHANISMS OF
PATHOGENESIS FOR S. PNEUMONIAE FOR THE
CNS DISEASE IT CAUSES.
 Meningitis is acquired as a result of bacteremia, typically through the
respiratory tract or other sometimes at other sites.
 Can happen as a primary disease following head trauma or Eustachian tube
obstruction.

IF A CT FOR MENINGITIS IS ALMOST ALWAYS
NORMAL WHY IS IT DONE?
 To look for a mass lesion that may be mimicking the symptoms of bacterial
meningtis

CAN INCREASED ICP BE SEEN ON A CT/MRI
SCAN? **
 NO

WHAT IS THE GOLD STANDARD FOR CNS
INFECTION?
 Lumbar puncture
 Safe with generalized icp but not mass lesio/hydrocephalus
 Bacterial meningitis
 Almost all have increased opening pressure
 Elevated WBC 100-1000 - PMNs
 Low glucose
 High protein

PATHOGENESIS OF RABIES
 1. Inoculation with saliva of infected animal
 2. Slow replication in muscles and/or skin
 3. Binding and entry into peripheral motor nerve
 4. Retrograde transport
 5. Replication in motor neurons of spinal cord and dorsal root ganglia
 6. CNS infection (concentrated in brainstem)
 Negri bodies
 BH4 deficiency leads to neurotransmission failure
 7. Anterograde transport to organs, salivary glands

DESCRIBE THE STRUCTURE AND TAXONOMIC
CLASSIFICATION OF RABIES VIRUS
 Rabies virus structure:
 -Bullet-shaped, negative-sense, single-stranded, helical enveloped RNA virus
 N protein coats the RNA with M protein at the tip to attach to membrane, G,L, P
 -Negri bodies, prominent cytoplasmic inclusion bodies, are seen at autopsy of
human and animal victims
 NO NUCLEAR INVOLVEMENT, RNA dependend RNA polymerase present in
virion
 Taxonomic classification:
 -Family Rhabdoviridae, genus Lyssavirus
 -There are 7 Lyssavirus genotypes, all of which have been known to transmit
rabies in humans, but type 1 accounts for the majority of cases
 -Within genotype 1 genetic variants have been defined

AT WHAT POINT IS THE VACCINE NO LONGER
ABLE TO AID THE PATIENT?
 As soon as the virus reaches the peripheral nervous system, the virus cannot
be stopped.

WHAT IS THE TEMPORAL COURSE OF RABIES?
 Clinical rabies develops after incubation period of 1 month to 1 year
 a. Prodromal period (2-10 d)
 Nonspecific symptoms
 Specific early symptoms
 b. Acute neurological phase (“furious”, paralytic)
 Hydrophobia
 c. Coma
 d. Death

SX
 Nonspecific
 Fever
 Malaise
 Sore throat
 Nausea/ vomiting/ weakness
 Severe encephalitis
 Agitation
 Depressed mentation
 Seizures
 Hydrophobia/aerophobia
 Drooling
 Coma
 Death

WHAT IS THE MOST SENSITIVE DIAGNOSTIC
TEST FOR RABIES?
 RT-PCR

ONCE RABIES ENCEPHALITIS
DEVELOPS, NO THERAPY HAS
PROVEN EFFECTIVE

POST EXPOSURE PROPHYLAXIS
 Postexposure prophylaxis (PEP)
 Effective only when given promptly.
 PEP includes wound cleansing
 HRIG (human-rabies Ig)
 Immunization with killed vaccine virus produced in cell culture
(HDCV=human diploid cell vaccine)

WHAT ARE THE TWO MOST IMPORTANT
VECTORS IN THE U.S. CURRENTLY?
 Bats
 Racoons
 Dogs used to be a threat, still exists in other countries

WHAT IS THE MILWAUKEE PROTOCOL
 Induced coma + antiviral treatment

WHAT ARE THE TWO ENTITIES FOR
PREVENTION OF RABIES?
 Rabies immunoglobulin
 Rabies killed vaccine

IDENTIFY WHICH GENDER HAS LESS
FUNCTIONAL BRAIN ASYMMETRY. IDENTIFY
WHETHER RIGHT-HANDERS OR LEFT-HANDERS
HAVE LESS FUNCTIONAL BRAIN ASYMMETRY.
 Females and left-handers have less functional asymmetry
 More diffusely distributed

EXPLAIN TWO REASONS WHY LATERALIZATION
OF BRAIN FUNCTION IS ASSESSED IN ADVANCE
OF BRAIN SURGERY.
 To preserve patients ability to speak and comprehend language, surgery is
limited in the language dominant hemisphere.
 The hippocampus is assessed to ensure that an adequate amount will be
preserved to support memory. If an inadequate amount is preserved then the
patient may develop dense anterograde amnesia

DESCRIBE HOW THE WADA TEST IS
PERFORMED AND INTERPRETED.
 The Wada test is used to lateralize speech processes so that surgery can be planned to
minimize post-op aphasia.
 Procedure:
 Inject sodium amytal (barbiturate with sedative-hypnotic properties, wiki) into R carotid,
sodium amytal essentiatlly deactivates the entire hemisphere, mimicking the post-op
effects of excision
 Assess expressive functions
 have patient name objects, count, recite days of the week
 Additional assessments
 Naming - whole and parts
 Repeating familiar and unfamiliar phrases
 Reading
 Following complex commands - inverted syntax
 Repeat assessment after injection into L carotid

NAME THE TYPICAL OUTCOME OF THE WADA
TEST ON THE LANGUAGE DOMINANT AND
NONDOMINANT HEMISPHERES.
 Speech disruption/aphasia after L injection
 One patient had disruption after R injection

NAME THE TYPICAL OUTCOME OF THE WADA
TEST ON MOTOR FUNCTION.
 Contralateral flaccid hemiparesis

STATE THE DEGREE TO WHICH SPEECH IS
LATERALIZED IN RIGHT-HANDERS.
 96% Left
 4% Right
 0% bilateral
 Left handers
 70% left
 15% right
 15% bilateral

DESCRIBE THE MEMORY DEFICITS IN PATIENT
HM WHO UNDERWENT BILATERAL TEMPORAL
LOBE SURGERY.
 Patient HM suffered from severe epilepsy without a clearly localized epileptic
focus. The patient underwent bilateral temporal ressections. The patient
developed dense anterograde memory deficit (aka dense anterograde
amnesia), but retained normal intellectual functioning postoperatively.

DESCRIBE THE PROCEDURE FOR IAP MEMORY
TESTING. EXPLAIN HOW THIS TEST
DISSOCIATES FOR ANOMIA AND AMNESIA.
 Inject sodium amytal (barbiturate with sedative-hypnotic properties, wiki) into R
carotid, sodium amytal essentiatlly deactivates the entire hemisphere, mimicking the
post-op effects of excision
 Present items during period of drug effect
 Patient is asked to recall and recognize these items after recovery
 Assessment of new learning
 Anomia vs. amnesia
 Anomia = inability to recall or recognize the names of objects
 Amnesia = inability to recall past events or form new memories
 When memory is tested by this method patients are able to recognize items they
were shown during the confusional period. Thus they retained the ability to recall the
objects name (no anomia) even if they didn’t remember being shown the item
(amnesia).

DISTINGUISH BETWEEN THE TWO
HEMISPHERES IN TERMS OF WHICH PRIMARILY
CODES FOR EACH OF THE FOLLOWING: WORDS,
SHAPES, FACES, LETTERS, FAMILIAR MATERIAL,
NOVEL MATERIAL.
 Left Hemisphere: words, letters, familiar material (Left = Language)
 Right Hemisphere: shapes, faces, novel material

NAME THE MOST COMMON ANESTHETIC
INDUCTION AND A3 CLINICALLY USED INHALED
ANESTHETICS.
 The most commonly used drug for the induction of anesthesia: Propofol (IV)
 - Works on GABAa R which are chloride channels to increase inhibition –
increasing chloride ion flux
 - Antiemetic
 - Pain on injection (not understood, some pt pain is severe) and can cause
hypotension
 Inhaled anesthetics:
 -Volatile: halothane, enflurane, isoflurane, desflurane, sevoflurane
 -Gaseous: nitrous oxide, xenon


DESCRIBE THE MAIN RECEPTOR TARGET FOR
ANESTHETIC DRUGS
 -Chloride channels (GABAa and glycine receptors) and potassium channels
(K2P, possibly Kv, and Katp channels) remain the primary inhibitory ion
channels for anesthetic action. Anesthetics are agonists at these receptors (net
inhibitory effect)
 -Excitatory ion channels targets include those activated by acetylcholine
(nicotinic and muscarinic receptors), by excitatory AAs (AMPA, kainate, and
NMDA receptors), or by serotonin (5-HT2 and 5-HT3 receptors). Anesthetics
are antagonists at these receptors (net inhibitory effects)
 GABAa is the main mechanism!
 N2O and ketamine are antagonists at NMDA receptors!

EXPLAIN THE CONCEPT OF MINIMAL ALVEOLAR
CONCENTRATION AND WHY IT IS USEFUL IN
ADMINISTERING INHALED ANESTHETICS.
 The concentration of gas at which 50% of individuals are immobile upon cutting
 Increased tissue solubility leads to lower MAC
 Expressed in % atm
 High MAC – faster kinetics
 MAC is lowered by CNS depressants
 MAC is lower in the elderly (higher potency)

WHICH INHALANT IS USED MOST COMMONLY IN
CHILDREN
 Sevoflurane (if they won’t tolerate IV)

WHAT CLASS OF DRUGS ARE MOST COMMONLY
USED FOR “PREMEDICATION”
 Benzodiazepines (GABAa Receptor)
 Midazolam
 Anxiolytic
 Sedation
 Anterograde amnesia
 Painless IV injection
 Rapid brief action and can be reversed with flumazenil
 Modest respiratory depression

WHAT IS THE MINIMUM RISK OF POSTOP
NAUSEA AND VOMITING?
 40%
 RISK FACTORS
 Female gender
 Non-smoker
 History of PONV
 Post-op opiods
 0-10%
 1-20%
 2- 40%
 3-4 – 60-80%

HOW CAN WE PREVENT PONV?
 Propofol
 Limit inhaled anesthetics
 Don’t use nitrous oxide
 Limit opiate requirement
 Ketorolac
 Nerve blocks
 Anti-emetic drug
 Odansetron

WHICH INHALED ANESTHETIC IS NO LONGER
USED IN THE US
 Halothane – no longer availability
 Also Isoflurane is decreasing
 The difference is mainly speed of onset and offset.
 We want drugs that are very fast and very controllable
 Also big Pharma
 HUGE PRICING DIFFERENCE

CHARACTERISTICS AND SIDE EFFECTS OF
NITROUS OXIDE, DESFLURANE AND
SEVOFLURANE
 Nitrous Oxide (gas)
 Colorless, odorless tasteless
 MAC 100%
 Minimum CV effects
 Desflurane
 Least soluble volatile, MAC 6%
 Pungent
 Hypotension
 Bronchoconstrictor
 Malignant Hyperthermia
 Sevoflurane
 MAC 2.0%
 Hypotension
 Bronchodilator
 Slightly pungent
 Useful for induction
 Malignant Hyperthermia
 Delivered through vaporizers,
 ET tube
 Contribute to postop nausea

BALANCED ANESTHESIA
 Limit side effects by combining drugs
 Nitrous Oxide – short acting, no hypotension ,may cause nausea
 Opiates – short acting, fentanyl, remifentanil
 Local anesthetics

DESCRIBE THE MAJOR PERIOPERATIVE
INDICATIONS FOR BENZODIAZEPINES, OPIATES,
AND MUSCLE RELAXANTS.
 Analgesia
 Sedation
 Amnesia
 Relaxation – easier to cut and operate, prevent reflex responses

NAME THE MAIN CLASSES OF DRUGS USED TO
TREAT POSTOP PAIN, AND THEIR MOAS.
 Opioid analgesics:
 Activate opioid receptors in the CNS, leads to analgesia
 SE: respiratory suppression (can cause death with apnea), hypoxia, sedation, nausea,
decreased blood pressure, urinary retention, itching, flaccid skeletal muscles,
constipation
 Ketamine:
 Partially water-soluble and highly lipid-soluble; differs from most other IV anesthetics in
that it produces significant analgesia
 Also has significant amnestic effects (“dissociative” anesthetic)
 Preserves muscle tone - can maintain protective airway reflexes and spontaneous
respiration
 Produced through inhibition of the NMDA receptor complex
 SE: increases in BP, HR, and cardiac output, increased ICP, unpleasant emergence
reactions after administration (vivid colorful dreams, hallucinations, out-of-body
experiences, increased and distorted visual, tactile, and auditory sensitivity) – pair with
benzodiazepines
 Also - Tylenol

WHAT DRUG CAN YOU USE TO TREAT
MALIGNANT HYPERTHERMIA?
 Dantrolene – inhibits ryanodine receptor

WHAT IS THE IMPORTANT ADVANTAGE OF IV
ADMINISTRATION?
 Increases bioavailability of drug

WHY CAN’T THE PATIENT WITH A LUMBAR
LAMINECTOMY GET SPINAL OR EPIDURAL
ANESTHESIA
 Not able to do neurologic exam after surgery
 Confusion about etiology of neurological complication

DEFINE THE FOLLOWING TERMS: STROKE, TIA,
ISCHEMIA.
 Stroke: is a focal neurologic deficit occurring in a vascular distribution, typically
lasting greater than 24 hours and producing infarction. It is a cardiovascular
disease that affects the blood vessels supplying the brain.
 Transient Ischemic Attack (TIA): is a transient episode of neurological
dysfunction caused by focal brain, spinal cord, or retinal ischemia that does not
produce acute infarction.
 Ischemia: is an insufficiency of cerebral blood flow that results in oxygen and
glucose deficits to neural tissue. Neurons are particularly susceptible to
ischemia due to their high rates of metabolism.

DEFINE THE MAJOR TYPES OF STROKE AND
THEIR PREVALENCE.
 Ischemic (Intraluminal Occlusive) Stroke
 Thrombotic stroke: occurs when a blood clot (thrombus) forms and blocks
blood flow in a cerebral artery. Blood clots usually form in arteries damaged
by atherosclerosis. Prevalence of 53%.
 Embolic Stroke: results when a detached blood clot (or a particle) flows into
and clogs a cerebral artery. An embolus typically forms in the heart or large
artery and is carried in the blood supply to the brain where it encounters
progressively smaller vessels, and eventually becomes lodged. Prevalence
of 31%.
 Hemorrhagic Stroke
 Intracerebral hemorrhage: occurs when a parenchymal artery bursts,
flooding the surrounding tissue (parenchyma) of the brain. Common causes
of intracerebral hemorrhage are severe hypertension and the rupture of an
aneurysm. Prevalence of 10%.
 Subarachnoid hemorrhage (SAH): occurs when a blood vessel on the
surface of the brain ruptures and bleeds into the subarachnoid space.
Prevalence of 6%.

DISTINGUISH BETWEEN THE SUBTYPES OF
ISCHEMIC (OCCLUSIVE) AND HEMORRHAGIC
STROKES.
 Ischemic (occlusive) stroke: occurs when there is some type of blood clot
(thrombus) that forms and blocks/clogs blood flow in a cerebral artery. Ischemic
challenge to the brain tissue is created downstream from the occlusion.
 Hemorrhagic stroke: results from an artery in the brain rupturing/bursting which
leads to increased intracranial pressure, accumulation of blood in the
parenchyma, and ischemia downstream from the rupture.

NAME THREE KEY FEATURES OF ISCHEMIC
STROKE THAT DETERMINE THE PROGNOSIS
FOR THE PATIENT.
 Duration
 Intensity
 Location

DISTINGUISH BETWEEN THE ISCHEMIC CORE
AND THE ISCHEMIC PENUMBRA IN TERMS OF
THE FOLLOWING: DEGREE OF ISCHEMIA,
PROGNOSIS FOR RECOVERY, POTENTIAL FOR
THERAPY.
 Ischemic core (area at center of crisis): dense ischemia, poor prognosis, and
undergoes infarction if reflow is delayed.
 Ischemic penumbra (area surrounding core): partial blood flow, prognosis
improves with early intervention, and can exhibit infarction or selective neuronal
loss.
 Ischemia  INJURY CASCADE

DISTINGUISH BETWEEN THE GENERAL
VULNERABILITY AND SELECTIVE
VULNERABILITY OF NEURONS TO ISCHEMIA
 Neuron vulnerability
 General vulnerability : neurons are very vulnerable to ischemia
 most can only survive short periods of deep ischemia
 infarction = generalized cell death
 necrotic cell death is common in cerebral infarction
 pannecrosis: neurons, glial cells, and vascular cells are all affected
 penumbral zone is what enables many neurons to survive longer ischemic
periods
 Selective vulnerability
 some neurons are especially vulnerable to ischemia
 they can have delayed death after ischemic events of less than 3 min.
 CA1 of hippocampus
 Purkinje cells of cerebellum
 Layers 3 and 5 of cortex
 loss of neurons is delayed since it involves apoptotic mechanisms (not
necrosis)

WHY DO NEURONS DIE?
 High metabolic demands
 ATP runs down with ischemia
 Injury mechanisms
 Excitotoxicity

DESCRIBE THE EXCITOTOXICITY HYPOTHESIS
FOR CELL LOSS DURING ISCHEMIC INJURY.
 Dying neurons release high amounts of glutamate
 too much glutamate (excitatory NT) activates both ionotropic (AMPA, NMDA)
and metabotropic (GluR) receptors
 activation of these neurons leads to elevated intracellular Ca2+
 too much intracellular Ca2+ leads to deleterious calcium cascades, like
proteolytic + lipolytic enzyme systems

EXPLAIN HOW CEREBRAL EDEMA CAN BE A
POTENTIALLY LETHAL COMPLICATION OF
STROKE.
 Normally peaks between 3-5 days after onset of stroke and leads to mass
effect
 increase ICP
 restrict blood flow
 compress ventricles
 shift midline structures
 intracellular cytotoxic edema (more brain volume from swollen cells)
 cells fail to maintain normal osmotic gradient  cellular swelling
 extracellular vasogenic edema (more brain volume from more space between
cells)
 increase in fluids in interstitial space that originates from leaky vasculature

EXPLAIN WHY STROKE IS A MEDICAL
EMERGENCY.
 Prompt treatment is crucial
 Early action can minimize brain damage and potential complications

WHY IS IT IMPORTANT TO DISTINGUISH
BETWEEN ISCHEMIC AND HEMORRHAGIC
STROKE AND HOW IS THE DX MADE?
 It is important to distinguish between ischemic and hemorrhagic stroke
because optimal treatment modalities differ in different types of strokes. Rapid
diagnosis is critical to survival chances.
 Major goals in treating strokes include:
 Re-establishing/maintaining blood flow for occlusive (ischemic) strokes
 Limiting progression of cellular injuries
 Remove blood around arteries (avoid delayed deficits)
 Computerized tomography is typically used to distinguish between ischemic
and hemorrhagic stroke

DEFINE THE PURPOSE OF T-PA TREATMENT AND
STATE THE TIME COURSE OVER WHICH IT CAN
BE USED.
 TPA (tissue plasminogen activator) is a clot dissolving drug used for the
treatment of ischemic stroke.
 t-PA works by converting inactive plasminogen into plasmin which is a serine
protease that dissolves fibrin clots
 Treatment with t-PA should be initiated within 3 to 4.5 hours of stroke onset.

DEFINE “TRIPLE H” THERAPY FOR SAH AND
DESCRIBE HOW IT WORKS.
 SAH (subarachnoid hemorrhage) can be treated using the “Triple H” therapy.
The three H’s stand for
 Hypertension: involves increasing the blood pressure to force blood through
the narrowed arteries
 Hypervolemia: involves increasing IV fluids to increase blood volume
 Hemodilution: involves making the blood thin and watery in order for it to flow
more easily through the narrowed arteries.

LIST 3 NON-MODIFIABLE RISK FACTORS FOR
STROKE.
 Age: older population at higher risk (according to CDC and AHA according to
comments)
 Sex: males are more likely to suffer from stroke (CDC and AHA) but women are
more likely to die of stroke (CDC)
 Race: African Americans at higher risk (CDC and AHA)

LIST 3 MODIFIABLE RISK FACTORS FOR STROKE
 Hypertension
 Heart disease
 Diabetes mellitus

WHAT ARE STRATEGIES FOR REPERFUSION
 Thrombolytic agents
 Mechanical disruption
 Bypassing obstruction

IPSP
20 pA
100 ms
20 pA
100 ms
+ Benzodiazepine
Sedative, anxiolytic, analgesic

DISTINGUISH BETWEEN THE TWO MAIN
CLASSES OF GABA RECEPTORS.
 : Two main classes
 GABA-A – ionotropic, chlorine channels
 GABA-B - metabotropic – 2nd messengers  K/Ca channels
 GABA-A and nicotinic cholinergic receptors = ionotropic pentamers; GABA-A
conducts Cl-, nicotinic nonspecifically conducts Na+, Ca++, K+
 GABA-B inhibits adenylate cyclase (PKA pathway), activates post-synaptic K+
channels, inhibits pre-synaptic Ca++ conductance

IDENTIFY THE MEDICAL USE OF THE GABA-B
RECEPTOR AGONIST BACLOFEN IN NEUROLOGY
 Alcohol Dependence

DESCRIBE THE EFFECT THAT BDZ BINDING TO
GABA-A CHANNELS HAS ON THE ACTIVITY OF
CNS NEURONS.
 The binding site for GABA is between the alpha and beta units
 The binding site for BDZ is between the beta and gamma units
 This induces conformational change and increases affinity for GABA
 ALLOSTERIC MODULATION

DEFINE ALLOSTERIC MODULATION. PROVIDE
EXAMPLES OF DIFFERENT TYPES OF
ALLOSTERIC MODULATION.
 Allosteric modification: modulation achieved by binding of a drug to a site
distinct from the site required for activation
 Positive (agonism): benzodiazapines
 Negative (inverse agonism): CCE (reduces effect of positive agonism)
 Antagonist (blocker): Flumazenil
GABA
GABA
+ pos mod
GABA
+ neg mod
GABA
+ antag
Relative GABA-induced
current
0
0.5
1.0
2.0
- Rudolph & Knoflach, 2011

DEFINE WHAT A BDZ RECEPTOR ANTAGONIST IS
AND GIVE AN EXAMPLE OF ONE.
 Flumenazil

DISTINGUISH BETWEEN A GABA-A RECEPTOR
ANTAGONIST AND A BDZ RECEPTOR
ANTAGONIST
 GABA-A antagonists block (or compete for) the binding of GABA to the GABA-A
receptor, and therefore prevents activation of the receptor (opening of the Cl-channel).
 The BDZ receptor antagonist binds to the BDZ binding site, which is at an
allosteric site on the GABA receptor. It therefore does not inhibit GABA binding.
BDZs work by increasing the probability of activation of the GABA-A receptor in
response to GABA.

LIST IN ORDER, FROM MILD TO MOST SEVERE,
THE PROGRESSIVE DOSE-DEPENDENT EFFECTS
OF BDZS ON THE BRAIN.
 Side effects from Mild to Severe
 Anxiolysis= reduction in anxiety
 Sedation= decreases activity, moderates excitement, calms
 Hypnosis= drowsiness, facilitates onset & maintenance of sleep
 Even at high doses, will not cause death (unlike barbiturates)
 Can however reduce fatal dose of other substances (alcohol)

NAME TWO FACTORS THAT CAN INFLUENCE
DOSING OF BENZODIAZEPINES
 Age
 Sex

SIDE EFFECTS OF BENZODIAZEPINES
 Sedation
 Tolerance
 Dependence
 Respiratory depression
 Coma (less risk than with barbiturates)
 Additive CNS depression effects with alcohol

DESCRIBE WHY DIFFERENT ALPHA SUBUNITS
ARE ASSOCIATED WITH DIFFERENT BEHAVIORS
 They are expressed in different parts of the brain
 Alpha1 – hypnosis
 Alpha2 - anxiety
 Alpha3 and Alpha5 – muscle relaxation
 Z compounds – alpha 1 selective agents
 SEDATION – sleep aids
 Technically not benzodiazepines
 Imidazopyridine - zolpidam

STRUCTURE OF BENZODIAZEPINES
 Benzene ring fused to a diazepine ring
 Diazepam
 Clonazepam
Cl
CH3 O
diazepam
O2N
H O
Cl
clonazepam

IDENTIFY THE VARIOUS CLASSES OF BDZS AND
DESCRIBE THEIR MAIN CLINICAL USES.
 Sedation-Hypnosis
 True Benzodiazepines
 Triazolam (closest to ‘ideal hypnotic’)
 Flurazepam (less ‘early morning insomnia’)
 Z Compounds
 Zolpidem (Ambien)
 Zaleplon (Sonata)
 Eszopiclone (Lunesta)
 Anxiolysis
 Most benzodiazepines, with medium to long T1/2
 Low doses often used
 Alpha-2 selective benzodiazepines are actively being developed
 Severe Anxiety:
 Associated with prominent autonomic signs (e.g. panic disorders)
 High-potency benzodiazepines are used:
 Alprazolam (Xanax)
 Clonazepam (Klonopin): absence seizures
 Lorazepam (Ativan): status epilepticus
 Anticonvulsant
 Only a few used
 e.g. lorazepam (status epilepticus), clonazepam (absence seizures), clorozepate

EXPLAIN THE CHARACTERISTICS OF
TOLERANCE/DEPENDENCE TO BDZS.
 Tolerance:
 primarily observed with anticonvulsant actions
 limited tolerance observed with sedative-hypnotic and anxiolytic effects
 Dependence/Addiction:
 physical dependence is usually mild
 follows general rules of drug dependence:
 higher dosage = more severe withdrawal
 longer t1/2 = less severe withdrawal
 estimated 0.1-0.2% of adult population abuse or are dependent on BDZs (300K -
600K in the U.S.)
 GABA receptors are located in the VTA (ventral tegmental area)
 modulating GABA receptor activity in the VTA hypothesized to increased
dopamine release (reward system)

IDENTIFY THE MEDICAL USES OF FLUMAZENIL.
 It is used to reverse conscious sedation, general anesthesia and
benzodiazepine overdose aka stupor. However, there is a potential risk of
seizures.

WHY DO BARBITUATES HAVE MORE SERIOUS
SIDE EFFECTS?
 Bind to GABA site  open Cl conductance channel
 High doses are fata

DESCRIBE THE MOLECULAR AND SYNAPTIC
EFFECTS OF AMPHETAMINES. HOW DO THEY
INFLUENCE CNS NORADRENALINE AND
SEROTONIN NEURONS THAT MEDIATE WAKING.
 Amphetamine structures mimic catecholamines, so they can bind to the same transporters as
catecholamines and also induce concentration-dependent effects.
 1. Amphetamines are taken up by the same transporter (Norepinephrine transporter) and
increases concentration of catecholamine within the cells. When the concentration is high
enough, NET reverse transports NE out of the cell, enabling post-synaptic binding and effects.
 Indirect release of NE into synapse
 2. Amphetamines are transported into vesicles by vesicular monoamine transporter VMAT2,
increasing the intravesicular pH.
 The increase in pH inhibits VMAT2, causing a further buildup of intracellular catecholamine
and causing more reverse transport and more catecholamine effects.
 Dopamine - reward + psychosis/addiction
 NE - fight or flight effects, increased BP/HR/stroke risk (+vigilance and anorexia)
 5HT (Serotonin) - increased vigilance and anorexia

DESCRIBE SOME COMMON PROBLEMS AND
SIDE EFFECTS THAT ARE ASSOCIATED WITH
PROLONGED USE OF
 Restlessness, dizziness, insomnia (Basically an extension of its clinical effects!)
 Addiction/Dependency
 CV/GI effects
 Neurotoxicity and neuronal degeneration
 Psychosis

EXPLAIN WHY MODAFINIL REPRESENTS A NEW
APPROACH TO THE TREATMENT OF
HYPERSOMNIA.
 Modafinil is a psychostimulant but doesn’t have the same side effects
(jitteriness, anxiety, or excess locomotor activity or rebound effect) as
amphetamine or the same addiction tendencies. The mechanism isn’t fully
understood but it does increase glutamine release and diminish GABA release.
It’s new because it was approved in 2004 for use in hypersomnia?
 Also doesn’t have cardiovascular side effects

Mind Brain and Behavior

More Related Content

What's hot (20)

Viewers also liked (9)

Similar to Mind Brain and Behavior (20)

More from Jess Little (17)

Recently uploaded (20)

Mind Brain and Behavior