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Mind Brain and Behavior
1.
2. 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.
3. IS A NUCLEUS IN THE CNS MADE UP OF GRAY
MATTER OR WHITE MATTER?
Gray matter
Tracts are white matter
4. 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
5. WHAT ARE THE GENERAL FUNCTIONS OF THE
FRONTAL LOBE?
Planning behavior
Language production
6. WHAT ARE THE GENERAL FUNCTIONS OF THE
PARIETAL LOBE?
Spatial orientation
Language comprehension
7. WHAT ARE THE GENERAL FUNCTIONS OF THE
TEMPORAL LOBE?
Audition
Visual processing
Recognition of stimuli
Learning and memory
8. WHAT ARE THE GENERAL FUNCTIONS OF THE
OCCIPITAL LOBE?
Vision
9. WHAT IS THE GENERAL FUNCTION OF THE
LIMBIC SYSTEM?
Emotional expression
Regulation of visceral motor activity
10. 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.
11. WHAT IS THE GENERAL FUNCTION OF THE
CEREBELLUM
Coordination of motor activity
Posture
Equilibrium
12. WHAT ARE THE THREE REGIONS OF THE CNS
THAT ARE IMPORTANT FOR CONSCIOUSNESS?
Cortical
Thalamic
Rostral reticular
14. WHAT ARE THE FOUR STEPS TO EVALUATE A
NEUROLOGICAL DISEASE?
Localize lesion
Determine type
Focal/diffuse
Mass/non-mass
Assess time course
Develop differential
15. WHAT ARE THE 5 NEUROLOGICAL SYSTEMS TO
WHICH DISEASE CAN LOCALIZE
Conscious
Motor
Sensory
Autonomic
Visual
16. WHAT ARE THE FIVE DIFFERENT TIME COURSES
OF A NEUROLOGICAL DISEASE
Acute – minutes to hours
Subacute – hours to days
Chronic
Relapsing and remitting
Static
23. LIST 2 CONDITIONS UNDER WHICH A LUMBAR
PUNCTURE ARE RISKY
Underlying coagulopathy
Increased intracranial pressure herniation
24. 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.
25. 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.
26. WHAT DO THE ARROWS POINT TO?
Thick arrow – arachnoid mater
Star – blood vessel
Thin arrow – pia mater
28. 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
32. WHY DOES THE SUBSTANTIA APPEAR DARK?
Located within cerebral peduncles
Appear dark due to presence of neuromelanin in neurons
33.
34. 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
35. 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
36. 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
38. DESCRIBE THE HISTOLOGICAL DIFFERENCES
BETWEEN RESTING AND ACTIVATED MICROGLIA
Resting – banana shaped, difficult to see without staining
Active – large foamy macrophages
39. NAME THE “ANATOMICAL” SITE OF THE BLOOD
BRAIN BARRIER
Cerebral capillary
Endothelial cells and astrocytes
40. 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.
41. WHAT ARE THE AREAS OF THE BRAIN THAT ARE
SENSITIVE TO HYPOXIA IN INFANTS?
CA1 hippocampus
diencephalon gray nuclei, thalami
midbrain nucleus
42. WHAT ARE THE COMMON REACTIONS OF THE
CNS TO INJURY
Cerebral Edema
Hydrocephalus
Raised ICP
Herniation
43. 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.
44. MOST CASES OF HYDROCEPHALUS OCCUR AS A
RESULT OF …
Impaired flow or resorption of CSF
NOT overproduction
45. 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
46.
47. WHAT IS THE MAIN POSTSYNAPTIC INHIBITORY
NEURON
GABA
Glycine is another
48. 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
49. 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
50. 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
51. 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)
52. 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.
53. 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
54. 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
55. 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.
56. 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
57.
58. WHAT ARE THE THREE AREAS OF MENTAL LIFE
THAT PSYCHIATRY CONSIDERS?
Thoughts
Moods
Behaviors
59. 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
60. WHAT ARE THE TWO EXPLANATORY METHODS
OF PSYCHIATRY
Form – descriptive – what?
Function – interpretive – why?
Looks at people as unique individuals
61. 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
62. WHAT ARE THE COMPONENTS OF A MENTAL
STATUS EXAM?
Appearance
Speech
Mood
Hallucinations
Delusions
Obsessions/Compulsions
Phobias
Cognition
Insight and Judgment
63. WHAT IS THE DIFFERENCE BETWEEN MOOD
AND AFFECT?
Affect – observable
Mood – subjective patient reported
64. 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
65. 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
66. WHAT IS THE DEFINITION OF A DELUSION
A belief (not a perception) that is FIXED, FALSE or IDIOSYNCRATIC
67. 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.
68. LIST THREE COMMON
OBSESSIONS/COMPULSIONS
Fear of germs/dirt
Pathologic doubt
Aggressive or sexual thoughts
Excessive need for order/symmetry
69. 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
70. 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?
71. 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
72. 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
73. 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
74. 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 .
75. 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
76.
77. WHAT ARE THE MATURE DEFENSE
MECHANISMS
Anticipation
Humor
Sublimation
Suppression
Affiliation
78. 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
79. 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
81. DEFINE A TRAIT
Tendencies to react in circumstances in a particular fashion
82. 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
83. AXIS I
State related disorders
Delirium
Depression
Schizophrenia
Substance abuse
Eating disorder
84. AXIS II
Trait related disorders
Personality disorders
Mental retardation
85. 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
86. 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
87. 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
88. 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
89. 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.
90. 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
91. 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
92. 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
93. 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
94.
95. 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
96. 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
97. 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
98. 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
99. 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
100. 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
101. 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
102. 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
103. 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
104. 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)
105. 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
106. 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
107. 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
108. 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
109. 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
110. WHAT IS THE BEST PHARMACOLOGICAL
MANAGEMENT OF DELIRIUM
Haloperidol or atypical antipsychotic
Benzodiazepines
NOT ANTIDEPRESSANTS – tricyclic are anticholinergic exacerbate sx
112. 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).
113. SCHIZOPHRENIFORM DISORDER
Schizophreniform Disorder: Same criteria except for duration (1-6 months) and
no requirement for decline in functioning.
115. 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.
116. 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
117. 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”
118. 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
119. DESCRIBE THE DIFFERENCE BETWEEN A) FAMILY
STUDIES, B) TWIN STUDIES, C) ADOPTION
STUDIES, AND D) LINKAGE STUDIES.
120. 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.
121. 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
122. 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.
123. 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.
124. 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
125. 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
127. 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 -
128. 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)
129. 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
132. 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
133. 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
134. AGONISTS OF GABA TREAT _______ WHILE
ANTAGONISTS OF GABA CAN CAUSE _________
Agonist (Benzodiazepine) treat anxiety
Antagonists cause seizures
135. 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.
136. 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.
137. 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.
138. WHAT IS THE LOCATION OF DOPAMINE IN THE
BRAIN?
Midbrain
Substantia nigra
VTA
139. WHAT IS THE LOCATION OF SEROTONIN IN THE
BRAIN
Midbrain and pons
Raphe nuclei
140. WHAT IS THE LOCATION OF NE IN THE BRAIN
Locus ceruleus - pons
141.
142. 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
143. 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)
144. 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
145. 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
146. 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
147.
148. 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
149. 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.
150. 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
151. 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)
152. 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.
153. EXPLAIN HOW EPIDURAL AND SUBDURAL
HEMATOMAS CAN BE DISTINGUISHED IN
NEURORADIOGRAPHIC IMAGES.
Epidural – lens shaped and well-circumscribed
Subdural – follows shape of brain
154. 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
155. 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)
156.
157. WHAT IS THE MAJOR CAUSE OF CNS TRAUMA IN
INFANTS AND THE ELDERLY?
Falls
MVA for adults
159. 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
160. WHICH REGION OF THE SPINAL CORD IS MOST
VULNERABLE TO TRAUMATIC INJURY
Cervical
C1-C2
C4-C7
T11-L2
161. 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.
162. 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
163. 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
164. WHICH AREAS OF THE ADULT BRAIN ARE
PARTICULARLY VULNERABLE TO HYPOXIA?
CA1 of hippocampus
Purkinje cells of cerebellum
Layers 3 and 5 of cortex
165. WHICH CRANIAL NERVE IS OFTEN
COMPRESSED WITH AN UNCAL HERNIATION?
CN III – pupillary dilation
PCA may be compressed as well
166. WHY IS A TONSILLAR HERNIATION LIFE
THREATENING?
Brainstem compression compromises respiratory and cardiac centers in the
medulla
167. 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
168.
169. 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.
170. 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.
171. 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.
172. 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.
173. 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.
174. 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
175. 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
176. 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.
177. 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
178. 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.
179. STATE THE APPROXIMATE AGE AT WHICH THE
CRITICAL PERIOD FOR DEVELOPING
BINOCULAR VISION ENDS.
6 months to 2 years
180. STATE THE APPROXIMATE AGE AT WHICH THE
CRITICAL PERIOD FOR DEVELOPING LANGUAGE
ENDS.
0-12 years
181. 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.
182. 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.
183.
184. 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
185. 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
186. 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
187. 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
188. 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
189. EXPLAIN WHY EVEN LOW-GRADE OR BENIGN
CNS TUMORS CAN HAVE A POOR CLINICAL
OUTCOME
Tumor environment
Limited intracranial volume
Important structures
190. 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
191. 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
192. 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
193. WHAT FOUR CHARACTERISTICS CAN SUGGEST
POTENTIAL FOR MALIGNANCY OF A TUMOR
Atypia (cytological)
Mitotic activity
Endothelial microvascular proliferation
Necrosis
195. 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
197. 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
198. HISTOLOGY OF OLIGODENDROGLIOMA
Fried egg appearance
Chicken wire vessels
Hemorrhagic
Frontal and temporal preference
Calcifications seen on CT
200. STATE THE LOCATION AND MOST PREVALENT
AGE GROUP IN WHICH MEDULLOBLASTOMAS
ARISE.
Children
Cerebellum
Malignant Grade IV
High CSF dissemination
202. LIST TWO TUMORS ARISING FROM THE NERVE
SHEATH CELLS AND TWO GENETIC SYNDROMES
ASSOCIATED
203. 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
205. WHAT IS THE MOST COMMON LOCATION OF
CNS METASTASES
Cerebral hemispheres
Gray white matter border
206. 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
207.
208. 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
209. 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
210. 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
211. WHAT IS THE MOST COMMON ENTRY SITE OF
BACTERIAL MENINGITIS
Upper respiratory
212. 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
214. WHAT ARE THE COMPLICATIONS OF BACTERIAL
MENINGITIS?
Cerebral infarcts
Hydrocephalus
Abscesses
Hearing loss
Mental retardation
215. STATE THREE CAUSES OF NON-VIRAL CHRONIC
MENINGITIS
TB
Lyme
Syphilis
216. 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
217. 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
219. WHAT ARE THE PATHOLOGIC SIGNS OF
TUBERCULOSIS MENINGITIS
Base of brain and cranial nerves are affected
Granulomas
Gelatinous exudate
Hydrocephalus early
220. COMPLICATIONS OF TB MENINGITIS
Infarcts: occlusive endarteritis
Abscesses: tuberculomas
Hydrocephalus
Severe leptomeningeal fibrosis
OSTEOMYELITIS
221. 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)
222. 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
223. 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
224. WHAT ARE THE CHARACTERISTICS OF
ASPERGILLUS ABSCESS
Poorly defined hemorrhagic lesions
Vascular invasion infectious vasculisit
Seen in immunocompromised
225. COMPLICATIONS OF ABSCESS
Cerebral Edema
Mass effect
Herniations
Rupture into ventricles
Secondary abscess
226. 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
228. 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
231. 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
232. WHICH RESPECTIVE GANGLION DO HSV1 AND
HSV2 INHABIT?
HSV1 – trigeminal
HSV2 – dorsal root ganglion
233. WHY ARE RED BLOOD CELLS COMMON IN
HERPES SIMPLEX ENCEPHALITIS.
It is a hemorrhagic encephalitis
234. WHAT IS THE CORTICAL DISTRIBUTION OF
HERPES ENCEPHALITIS?
Frontotemporal
235. 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)
236. 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
237. MENINGITIS VACCINES
H. Influenzae
BEST
Has almost eradicated meningitis of this cause
N. Meningitidis
S. pneumoniae
238. NAME THE CRITERIA FOR DEFINING A
NEUROLOGICAL EMERGENCY.
In the nervous system
TREATABLE
239. EXPLAIN WHY ADDITIONAL ANTIBIOTICS MAY
BE NECESSARY TO TREAT BACTERIAL
MENINGITIS.
Drug resistance
240. 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)
241. WHAT IS XANTHOCHROMIA AND ITS CAUSE
Yellow CSF
Bilirubin released from ruptured RBCs
242. 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.
243. WHAT IS THE TEST OF CHOICE FOR HERPES
ENCEPHALITIS?
The CSF PCR for herpes simplex is now the test of choice for diagnosis.
244. 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
245. ARE THERE RISK FACTORS FOR HERPES
ENCEPHALITIS?
NO
Anyone can get it
No seasonal variation either
246. CHRONIC VIRAL ENCEPHALITIS
Long incubation period
Many end in death
Rubella – progressive rubella panencephalitis
Measles – SSPE
JC virus – PML
All rare
252. 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
253. 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)
255. 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.
257. WHEN SHOULD ANTIBIOTICS BE STARTED?
IMMEDIATELY – BEFORE LP
Empiric therapy
Ampicillin + Ceftriaxone unless 3-7 yrs old
258. WHAT ARE THE SPECIFIC THERAPIES FOR
BACTERIAL MENINGITIS
S. pneumonia – vanc + ceftriaxone
N. meningitidis – ceftriaxone
259. WHAT IS THE PROPHYLACTIC RX FOR
EXPOSURE TO BACTERIAL MENINGITIS?
Cipro
Rifampin (for children)
260. LIST THE COMMON CAUSES OF BACTERIAL
MENINGITIS AND THEIR EMPIRIC TREATMENTS
IN NEONATES, OLDER CHILDREN, AND ADULTS.
261. 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
262. 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.
263. 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
265. 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
266.
267. 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
268. 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
269. 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.
270. 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
274. 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)
275. 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
276. WHAT IS THE MILWAUKEE PROTOCOL
Induced coma + antiviral treatment
277. WHAT ARE THE TWO ENTITIES FOR
PREVENTION OF RABIES?
Rabies immunoglobulin
Rabies killed vaccine
278.
279. 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
280. 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
281. 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
282. 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
283. NAME THE TYPICAL OUTCOME OF THE WADA
TEST ON MOTOR FUNCTION.
Contralateral flaccid hemiparesis
284. 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
285. 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.