Exam 4 Deck 1 Flashcards
1
Q
What are primary headache syndromes?
A
Physiological disruption
Migraine
Tension type
Cluster
2
Q
What are secondary headache syndromes?
A
Pathology + physiology
Neoplasm
Infection
Aneurysm
3
Q
What is the most common type of headache?
A
Tension headache
4
Q
What is the most common type of headache that physicians see?
A
Migraines
5
Q
What defines a migraine without aura?
A
At least 5 attacks
Headache lasts 4-72 hours
Two of: unilateral, pulsatile, moderate/severe pain, aggravation or avoidance of physical activity
One of: N/V, photophobia and phonophobia
Not attributable to somethign else
6
Q
What defines a migraine with aura?
A
At least two of:
Aura with fully reversible visual, sensory, or dysphasic speech symptoms
Homonymous visual or unilateral sensory symptoms; 1 aura symptom developing over 5 minutes, or different symptoms in succession over 5 minutes
Headaches fulfill criterea for migraine without aura
7
Q
How does cerebral blood flow correlate with headache?
A
Prodrome - nothing
Aura - nothing
Headaceh - increased flow
8
Q
How do you determine whether the origin of a headache is opthalmic?
A
All ocular causes of headache are associated with changes in the external apperance of the eye
9
Q
How do the timing and topography of cerebral blood flow, aura, and headache relate to each other during migraine attacks?
A
Pain begins during hypoperfusion phase
Hyperperfusion may outlast pain
10
Q
What is cortical spreading depression?
A
Devleopment of waveform in brain that causes period of activation followed by refractory period of depression
Crawls at 3mm/minute from brainstem, up to occiput, and then forward through brain
I.e. activation = aura; depression = blindness
11
Q
Describe threshold of transcranial magnetic stimulation of a patient with migraines compared to normal.
A
Migraines - lower thereshold (brain is ‘excitable’)
12
Q
What brain structures get activated at the onset of migraines?
A
Brainstem centers - periaqueductal grey turns on during migraine attack
13
Q
What structures is primarily involved in migraines that can explain symptoms?
A
Meninges!
Cortical spreading depression causes release of vasodilatory mediators in the brain that cause meninges to expand/be inflamed
14
Q
What is the cheiro oral phenomenon?
A
Numbing/tingling of cheek and hand (which then spreads)
Almost pathognomonic for migraines
15
Q
If a patient walks in with headache symptoms and a tingling/numbing of the mouth and a hand, that progressively spreads up arm, what are you thinking?
A
Migraine
16
Q
What is the funciton of glial cells, and what about their normal physiology is important to migraines?
A
They redistribute K, Mg, and excitatory amino acids
Lowest numbers in primary occipital cortex (i.e. if glia aren’t working well, the occipital lobe will take a hit)
17
Q
What is the role of astrocytes in migraines?
A
Astrocyte calcium waves could mediate propagated cortical phenomena of migraine via release of neuroactive and vasoactive messengers
Astrocyte waves can explain cortical activity changes in the absence of cortical spreading depression
18
Q
What is a tension-type headache?
A
Bilateral, band-like pressing headache
Not aggravated by activity
Little or no nausea, photophobia, or phonophobia
19
Q
What are the diagnostic criteria for tension-type headache?
A
Essentially: not a migraine
Bilateral, steady non-pulsatile pain, not affected by movement,
Not associated with N/V, nor photophobia nor phonophobia
20
Q
Can migraines present with neck pain?
A
yes
Migraines are often misdiagnosed because of neck pain leading to the diagnosis of tension headache
21
Q
What is the physiology of neck pain that can be seen in migraines?
A
It is a referred pain phenomenon
Trigeminal nucleus caudalis extends to dorsal horn C2, C3, C4 => causes neck pain and posterior head pain.
22
Q
What is the trigeminal autonomic reflex?
A
Irritation of trigeminal nerve causes activaiton of parasympathetic nucleus which causes lacrimation, rhinorrhea, nasal congestion
23
Q
What is the tearing/sniffling/congestion reaction to cold/spicy/etc called?
A
Trigeminal autonomic reflex
24
Q
What are some symptoms of children with migraines?
A
Benign paroxysmal vertigo of childhood
Alternating hemiplegia
Cyclic vomiting
Recurring abdominal pain
Benign torticollis
Acute confusional migraine
Car sickness
25
What is sinus headache?
**NOT actually a thing.**
Commonly diagnosed as headache secondary to sinusitis in the US - leads to overprescription of antibiotics
26
What are more serious complications of migraines?
Progression in severity
Migrainous stroke
Persistent aura without infarction
Epilepsy
27
What neurological issues does migraine put you at an elevated risk for?
Stroke
Epilepsy
28
What are you likely to see if you order an MRI for a migraine patient?
White matter changes that may be misdiagnosed as MS plaques, vasculitis, etc.
29
Generally speaking, what is the timeframe of primary headache syndromes?
Months to years
Shorter is likely to be a secondary headache
30
Which structures in the head are pain sensitive?
Meninges
Neural Structures (Trigeminal, Glossopharyngeal, Vagus CNs)
Scalp + Superficial structures
Vasculature
31
What are red flags that a headache is not a primary headache syndrome?
• A new or different headache
– ≤5 years old
– ≥50 years old
* Abrupt onset
* Cancer, HIV, pregnancy
* Abnormal physical exam
* Neuro symptoms ≥ one hour
* Headache onset
– With seizure or syncope – With exertion, sex, or
Valsalva
32
How do headaches due to brain tumors present?
Similar to tension headaches in most patients
Can be migraine like
"Classical" brain tumor headache is only 8%
33
What type of headache do patients with brain abscesses get?
Same as brain tumor
Fever in 1/2 of cases
34
Patient with frontal headache which increase with straining and are awekening out of sleep. Also papiledema, and dysmenorrhea. What type of headache?
Idiopathic intracranial hypertension
Pseudotumor cerebri
35
What are characteristics of headaches of idiopathic intracranial hypertension?
brain tumor headache
Visual complaints (diploplia, TVOs, photopsias)
Cranial bruits, noises in head, pulsatile tinnitus
N/V
radiculopathies
36
What do you treat idiopathic intracranial hypertension with?
Try to correct predisposing factors (weight loss, diuresis, shunting)
Try to preserve vision - optic nerve sheath fenestration
Symptoms
37
What is a hypnic headache syndrome?
Rare disorder in older people (40-84 y/o)
Bilateral throbbing headache
Recurring 1-3 times nightly with no other associated symptoms
Treat with lithium, caffeine, flunarizine
38
What types of headaches are seen with patients who had strokes?
Abrupt or gradual
Severity not associated with size of infarct
Headache can be multifocal or migratory - pain can move down arms, etc)
Not migraine in older patients (would have had a history)
39
What must you consider in a patient with "complicated" migraine presentation who is older?
Not only migraine (but may be less likely due to age)
Consider tumors, strokes, sensory seizures, etc.
40
How do sub-arachnoid hemmorage present as?
Abrupt onset of severe headache (reaches full intensity instantly - or close)
(Aneurysm burst)
Seizures and diploplia can be seen
Perform non-contrast CT, LP
41
What is thunderclap headache?
Headache seen in survivors of Berry aneurysm
Can be caused by aneurysmal or nonaneurysmal subarachnoid hemmorrage
42
What distinguishes a thunderclap headache from a subarachnoid hemmorrhage?
Seizures adn diploplia seen in SAH
43
What is a cluster headache?
Intense, boring (knife-like pain, very severe), unilateral pain
Quicker onset (over span of minutes)
Eyes tear and nose runs - autonomic involvement
Horner's Syndrome (ptosis and miosis)
Episodic - bouts of headache that last 1-4 months. Follow circadian pattern within and between cycles
Chronic - may evolve from episodic form or be chronic from onset. Absence of circadian patterns
Headaches with manic symptoms - almost opposite of migraine
44
What is temporomandibular dysfunction?
Pain that can be around the ear while chewing
Can go away quickly, but can persist too
Click may be heard over ear while jaw opening.
45
What type of headache can present with giant cell arteritis (temporal arteritis)?
Generalized, throbbing, temporal pain
Claudication - worsens with exertion
Polymyalgia rheumatica in 50% (aches and pains, maybe fever)
Visual scintillations
CRP or ESR abnormalities indicate biopsy
TREAT WITH CORTICOSTEROIDS
46
What type of headaches can be seen with angina?
Jaw, tip of nose, brow, bregma, occiput, palate, .... (anywhere really)
Extremities, shoulder pain
Rarely below umbilicus
47
What type of headache do you see with sexual activity?
Explosive, throbbing, occipital or frontal
Lasts for hours
Confusional state or symptoms of ischemia
(occur with valsalva too)
48
What symptoms can you see withs pontaneous carotid artery dissection?
Seen in young and middle age
Risk factors include trauma, arteriopathies, family history, respiratory infection
**Headaches, neck pain, horner's syndrome**
Cerebral ischemia
Tx: anticoagulation
49
If a patient presents with unilateral throbbing headache with pain of the face, neck, worse with movement, Horner's Syndrome, and a recent URI; what do you suspect?
Spontaneous carotid artery dissection
50
What can cause low-pressure headache?
Meningeal diverticula
Dural root sleeve tears
Excessive coughs
Erosion of dura from adjacent lesions
Head trauma
overshunting/carbonic anhydrase inhibitors
**Lumbar puncture (esp. in thin females)**
51
What is a common issue that can develop in thin female patients who have lumbar punctures?
Low-pressure headacehs
52
How do you treat low-pressure headaches?
IV Na caffeine benzoate
Epidural blood patch (if post-LP)
53
What is beta-2-transferrin?
Indicator of CSF
If seen in rhinorrhea, indicative of CSF leak
54
What do you suspect if you identify beta-2-transferrin in rhinorrhea?
CSF leak
55
What is POTS?
Postural orthostatic tachychardia syndrome
Seen in young post pubertal females
See orthostatic and non-orthostatic headache
Fatigue, decreased concentration, exercise intolerance, syncope
56
How do you treat POTS?
Hydration and salts
Elastic stockings
Beta blockers, fludrocortisone, minodrine, indomethacin
57
72 year old male, developed sharp pains in his right cheek and lip. These increased with light touch and he was nearly unable to shave or eat. His neurological examination was entirely normal. What do you suspect?
Trigeminal Neuralgia
58
What is trigeminal neuralgia??
Brief paroxysms of electric-like, lancinating pains (stabbing)
Usually affects V2 and V3
Stimulation of trigger points induces attacks
Suggest structural disease - demyelinated nerve-root area
Seen more in older patients. In younger patients think neurodegenerative disease
59
How does trigeminal neuralgia occur in older patients?
Superior Cerebellar Artery rubs against trigeminal nerve root and causes demyelination - origin of pain
60
How does trigeminal neuralgia occurs in younger patients?
Demyelinating process of trigeminal nerve
61
What is primary stabbing headache?
New onset, sharp, shooting pain in temple and behind eye
Not triggered by cutaneous stimuli
Preceded by days of euphoria
62
What sequence of events occurs during excitotoxicity?
Injury (ischemia, trauma, etc) leads to a decreased ATP state in the neuron.
This causes increased Na and Ca levels, depolarizing membrane potential.
Glutamate is increased extracellularly, exciting neighboring neurons.
63
What is chromatolysis?
Apoptosis of neurons
Shown here surrounded by healthy neurons with intact Nissl bodies
64
What is neurapraxia?
Focal demyelination of a neuron
Leads to a loss in conduction velocity of the axon - neuron stays in tact
65
What is axonotmesis?
Axon is cut and the distal part is lost via Wallerian degeneration
Nerve can regrow back to original target (takes months)
66
What is neurotmesis?
Loss of axon and surrounding wrappings (endoneurium, perineurium, epineurium)
Poor prognosis, surgery may help
67
What is disrupted in neurotmesis?
Wrappings of the nerve beyond the myelin (endoneurium, perineurium, and/or epineurium)
68
What can you see in nerve conduction studies/electromyography in demyelination?
Decreased conduction velocity
69
What do you see in nerve conduction studies/electromyography in axonal loss?
decreased action potential amplitude
70
What occurs during wallerian degeneration?
Intra-axonal organelle and microtubule breakdown (mins-hours)
Schwann cells begin breakdown of axons and recruit macrophages
Macrophages do their thing
Then the path is cleared for axons to regrow from proximal to distal
71
Which is more conducive to nerve regeneration, CNS/PNS?
PNS
72
Does Wallerian degeneration occur in the PNS? CNS?
PNS only!
Oligodendrocytes not as good at initiating degradation as Schwann cells
CNS - astrocytes and microglia not as helpful as macrophages
73
Which cells (PNS/CNS) have greater intrinsic growth potential and why?
PNS cells - have greater expression of regeneration-associated genes (RAGs)
PNS neurons possess receptors and signal transduction machinery allowing them to grow in response to neurotrophins - retrograde injury signals
74
What are neurotrophins?
Retrograde injury signals - promote growth towards higher concnetration
75
What is a growth cone?
Very tip of a regenerating axon - sense the milieu and decide to grow or not (sense neurotrophins, for instance) and direct growth of axon
76
What is the molecular basis of a growth cone?
Cytoskeletal rearrangement - actin bundles and microtubules
Attachment of cytoskeleton to the signal transduction machinery is key
77
What are retraction bulbs (of Cajal)?
Failed regeneration growth cones of the CNS
78
What types of changes are seen in CNS plasticity?
Molecular and structural changes
Molecular include synapse, receptor, transmitter regulation
Help adapt instead of regrowing in CNS
79
What opportunities arise from the complexity of neuronal connetions in the brain?
Complexity allows for recovery in the case of injury - you can reroute or use other mechanisms - don't have to fix the original pathway
80
How does activity help lead to neuronal plasticity?
Leads to increases in grwoth factors, especially BDNF (important in exercise)
Leading to increased neurogenesis, glial cell support.
Also, angiogenesis, synaptogenesis
81
What parallels are there between normal brain developmenta nd recovery from injury?
Birth-\>child age -\> maturity
Injury-\>regrowth-\>consolidation
You need to prune the neuronal connections
82
What types of activities are best for helping regrow/recover from neuronal injuries?
A variety of skilled, task-specific, repetitive tasks - these are better than general exercise alone
e.g. real life skills (reaching into cupboard)
83
What are natural sources for stem cells?
Embryonic - inner cell mass from 4-5d blastocyst - usually from excess IVF cells - plurpotent
Fetal - from extra-fetal or fetal tissue (amniotic, cord blood, placental tissue) - multipotent
Adult - from BM, skin, GI, fat, heart, brain, dental pulp - multipotent or oligopotent - huge advantage is they are autologous
84
What is a difference between adult, fetal and embryonic stem cells?
adult - oligo or multipotent - autologous
fetal - multipotent
embryonic - pluripotent
85
What is somatic cell nuclear transfer?
Take nucleus from adult somatic cell and insert it into enucleated egg cell - get early embryo
Not 100% autologous - mitochondrial genome is still present
86
What are induced pluripotent stem cells (iPS) and their advantages?
Turn on four genes - myc, sox, oct, nanog - in a somatic cell and you get a stem cell
Pluripotent
100% autologous
87
What are the best targets for stem cel therapies?
Neurodegenerative diseases - Huntington's (one type of neuron, isolated), ALS, Parkinson's, Alzheimers (but it is very diffuse)
Stroke
Traumatic Brain Injury, Spinal Cord Injury
88
How many approved indications are there for pluripotent stem cells?
ZERO
Hematopoeitic stemm cells are used in bone marrow transplants
89
What are dysmyelinating diseases?
Disease where myelin sheath is abnormally **formed** (mostly related to inherited metabolic disorders)
90
What are demyelinating diseases?
Disease wher ethe myelin sheath is normally formed but is the target of **destruction** (e.g. MS)
91
What cells comprise the gray matter?
Neuron cell bodies
Dendrites
Synapses
Axons
92
What comprises the white matter?
Myelinated axons
93
What makes up the myelin of the CNS?
Oligodendroglial cells wrapped around the axon
94
Where in the brain are grey and white matter generally located?
Cortex - grey matter
Tracts underneath - white matter (including corpus callosum)
95
What are examples of dysmyelinating diseases?
Adrenoleukodystrophy - primarily affects white matter
Tay Sachs disease - primarily involves ccumulation of myelin byproducts in neurons
96
What is the general course of MS?
Initially begins with relapse/recover periods (something like IBD)
Then morphs into a progressive disease (something like Alzheimers)
97
What is multiple sclerosis?
Inflammatory, autoimmune disease of CNS
Characterized by relapsing neurologic symptoms, and progressive impairement of function
Variable symptoms and signs - monocular vision loss, brainstem, motor/sensory impairments, imbalance
98
What are common early features of MS?
Motor weakness, parasthesias, impaired vision, double vision, intention tremor, ataxia
These are symptoms common of other diseases, so you must work it up or look back at it later
99
What is Charcot's triad?
Intention tremmor, nystagmus, scanning speech
Points to white matter pathways to and from cerebellum (vulnerable to demyelination)
Common presentation of MS
100
What is the most common form of involvement of the visual pathway of MS?
optic neuritis
Inflammation of optic nerve - **painful**
101
What is a very common first presenting feature of MS?
Optic neuritis - inflammation of optic nerve - presents with pain
102
What type of eye involvement is common in MS?
Optic neuritis - painful upon movement
Common to have a scotoma - isolated area of visual field with absent vision
103
What is the prognosis of optic neuritis that is seen early in MS?
1/3 will recover completely, the rest will improve substantially
Half of patients who present with optic neuritis alone will develop other signs of MS
104
What is RR-MS?
Relapsing-remitting MS
Relapses, recovery, and **stability** between
105
What are the different clinical patterns of MS?
Relapsing-remitting, secondary progressive, primary progressive, progressive relapsing
106
What is secondary progressive MS?
Relapse with recovery, then gradual worsening of symptoms over time
107
What is primary progressive MS?
gradual worsening of symptoms - no cardinal features of relapses
108
What is the relationship between brain lesions and disability in MS?
We can see lesions more readily than attacks, and are indicators of progression of MS
Looking below the surface of symptoms reveals worsening picture of lesions in the brain
109
What is clinically isolated syndrome?
First presentation of what is liekly to become MS - (singular sclerosis)
Within 10 years, 50% wil develop secondary-progressive MS
110
Who gets MS?
young people: 20-40 (big spread)
Particularly women (3:1)
111
What is the most common cause of medical disability in young adults?
MS
112
In what ethnicity is MS more common?
North European descent
Seen more common in latitudes further from equator too
113
What are the genetic fators of MS?
Complex - but twins at 30% chance of getting MS, siblings 2-5%
Both more common than general population
114
What helps you make the diagnosis for MS?
Dissemination in space and time of disease activity
Based on history and neurological exam
No single diagnostic test
MRI can help
115
What is the significance of contrast-enhanced lesions in the brain on MRI?
Indicate **active** inflammation. Lesion associated with MS
In non-contrast MRI - indicate history of MS lesions
116
In non-contrast-enhacned MRI, what is the significant of lesions in white matter tracts?
Old MS plaques. Active inflammation can be seen by contrast enhancement
117
What is this MRI indicative of?
**Multiple Sclerosis**
Periventricular lesions - radiating upward and outward from ventricles + white matter tracts
Radiating upwards from corpus callosum
Brainstem, cerebellum lesions
118
How do MRI lesions predict development of MS after presentation with optic neuritis (or other first attack)?
Increased likelihood
119
What must you be sure of before diagnosing MS?
That there is no better explanation, e.g.:
Infectious: Lyme, Syphilis, HIV, HTLV-1, PML
Inflammatory: SLE, Sjogren’s syndrome, vasculitis,
sarcoidosis, Bechet’s syndrome, APLS
Metabolic: Vitamin B12 deficiency, dysmyelinating
diseases (lysosomal/leukodystrophies), toxins, CPM,
mitochrondrial disorders, Copper deficiency,
Vascular: CADASIL, susac’s syndrome
Neoplastic: CNS lymphoma, metastatic disease
Structural Spine disease: AVMs, degenerative disc
disease, syrinx, arnold-chiari
Genetic- hereditary spastic paraparesis
**Psychogenic**-Depression, anxiety, conversion
120
What occurs from an immunological perspective in Multiple Sclerosis?
Th1 cells become activated and self-reactive T cells enter brain and mistake myelin for antigens
Without regulatory cells, they are reactivated and release proinflammatory cytokines that increase inflammation, cause edema, and damage myelin and nerves
121
What type of disregulation is thought to occur in MS with respect to Th cells?
Th1 more than Th2 (inflammatory more than anti-inflammatory)
122
What do you see in the CSF of MS patients?
Oligoclonal bands - identified by electrophoresis of CSF
Two or more bands needed to be seen for it to be useful
IgG bands
123
What are oligoclonal bands?
When you electrophorese CSF in MS patients, you will see excess of bands instead of smear, of IgG
124
What is seen in histological sections of MS lesions?
Peri-venular inflammatory infiltrates
125
What are the goals of treating MS?
Treat relapses and exacerbation
Prevent relapses
Reduce devleopment of disability
Treat symptoms
126
What can be used to directly treat MS relapses/exacerbations?
High dose IV steroids - remember, this is an inflammatory event.
127
What are some limitations of treating MS?
Disease modifying agents are only partially effective
All injectible (IV)
Side effects of interferons (flu-like, headche, fever)
Risk/Benefit
128
How can you identify an acute exacerbation of MS that you should treat?
Must distinguish from Uhthoff's phenomenon (which is sudden onset of neurological dysfunction as a result of elevated body temperature)
Episode of neurological dysfunction lasting more than 24 hours in the absence of fever or infection
129
What is Uhthoff's phenomenon?
A sudden onset of neurological dysfunction as a result of elevated body temperature
130
What drug do you use to treat acute exacerbations of MS?
IV methylprednisone - high dose
131
What are common causes of head injury?
Motor vehicle crash
Pedestrian Accidents
Assault
Falls
Gunshot or stab wounds
Occupational
Child abuse
132
How do you diagnose head injury?
Examine the patient's level of consciousness, motor response, pupillary light response, ability to talk (orientation), ability to breathe
133
What is used to assess degree of head trauma?
Glasgow Coma Scale - correlates with outcome (lower scores = worse outcomes)
134
What defines a mild head injury?
GCS 13-15 (glasgow coma scale)
135
What defines a moderate head injury?
GCS 9-12 (glasgow coma scale)
136
What defines a severe head injury?
GCS 3-8 (glasgow coma scale)
137
What tests are done for most patients with head injury?
X-rays (but nowadays more commonly CT scans)
CT can detect blood in and around brain acutely; fractures; is easy and quick; Gold Standard
138
What is the gold standard in acute head injury diagnosis?
CT scan
139
What is wrong here? 
Depressed skull fracture
140
What occurs in an epidural hematoma?
Fracture causes rupture of middle meningeal artery, causing blood accumulation between calvarium and dura
May cause uncal herniation
Lucid interval - recover quickly from concussion, but then are fine until the hematoma causes you to further problems
141
What is wrong here?
Epidural hematoma
142
What occurs in subdural hematoma?
Blood accumulation between dura and pia/arachnoid layer. Bridging veins are sheared during acceleration/deceleration injury
143
What is a difference between the localization of a subdural and epidural hematoma?
Epidural - the brain sutures prove to be too strong of attachments for the dura - blood does not pass beyond them
Subdural - below dura, so there are no restrictions of where blood can go
144
What occurs in the progression of a subdural hematoma?
Acute - can visibly see crescent shaped lesion.
Subacute - harder to see, spreads out
Chronic - hypodensities and thickening and mixed-age images
145
What are cerebral contusions?
Intra-parenchymal lesions
146
Where are cerebral contusions more likely to be found?
Frontal and temporal lobes - they can get caught in wings of sphenoid bone or in the ridges of the roof of the orbit
Particularly during accelerations/deccelerations
147
What is the most common cause of subarachnoid hemmorrhage?
Trauma
148
What is a coup injury?
Injury on the side of the impact
Counter-coup is on the opposite side
149
What is a counter-coup injury?
Injury on the opposite side to that of impact
Coup injury is that on the same side
150
What defines a concussion?
transient alteration of consciousness due to an impact to the head
Temporary alteration of ion channels and energy balance
Can be associated with normal head CT
151
What are the diffuse brain injuries?
Concussion
Diffuse Axonal Injury
152
What is diffuse axonal injury?
longer periods of unconsciousness or coma
CT scan is often normal or with evidence of punctate hemorrhages within grey/white junctions
Exam may be disproportionate to radiographic appearance
153
What are clinical signs of concussion?
Confusion
Amnesia (retrograde or anterograde)
May report "seeing stars" or "white/black out" visually
154
What is post-concussion syndrome?
Often resolves within a few days or weeks, but can persist for months
Symptoms: Headache, N/V, dizziness, visual complaints, fatigue, depression, difficulty concentrating, reading, memory, insomnia, sleeping more
155
What is chronic traumatic encephalopathy (CTE)?
Repetitive brain injury (dementia pugilistica - boxers; but seen in other sports i.e. football)
Possible repetitive axonal stretching and deformation - especially in those with unresolved concussive events
156
What can you see in gross pathology in CTE patients?
Atrophy - general cortical;mesial temporal/mammillary bodies
Cavum septum pellucidum - septal fenestrations
Pallor - locus ceruleus/substantia nigra
157
What is this patient likely to have suffered from? 
Chronic Traumatic Encephalopathy
158
What do you see on a molecular level in chronic traumatic encephalopathy?
Tau-protein immunoreactivity (but more in cortical layers and sulci vs in AD)
Also found perivascularly, in mammillary bodies, and hippocampus
β-amyloid plaque formation is less consistently found than in AD
159
What are clinical features of CTE patients?
Early - short term memory impairment; cognitive dysfunction; depression/emotional instability; impulse control problems; suicidality
Late - Dementia; Parkinsonism
160
What are potential genetic risk factors for CTE?
Apolipoprotein E allele 4
161
What is severe head injury defined by?
Glasgow Coma score 3-8
must ensure your ABCs!
162
What is done to a patient with a severe head injury?
Place patient on ventilator
Place monitor ot measure brain pressure (ICP)
Perform surgery on any large hematomas within brain for significant swelling
163
Why is ICP monitoring important in severe head injury?
Allows for early warning for significant intracranial developments
Enables cerebral perfusion pressure measurement
164
What is the cerebral perfusion pressure?
CPP = MAP - ICP
(Inflow - outflow)
165
What are contributors to the ICP?
Cranial vault which is a closed cavity
The three components therein - brain, blood, CSF
166
What is the Monro-Kellie Doctrine?
Calvarium is a fixed volume - increases in volume wil cause increasingly bigger increases in pressure
167
What is the primary injury in severe head injury?
Moment of impact - irreversible
168
What is the secondary injury in severe head injury?
Anytime after primary impact - especially first 24 hours and preventible, mostly
ISCHEMIA
169
What are causes of ischemia in head injury?
Decreased perfusion due to high ICP (due to hemorrhage/edema)
Hypoxia
Hyoptension
170
What are the biochemical changes in ischemia?
Influx of calcium - calcium release from ER due to decreased ATP, increase in glutamate release, due to increased activation of NMDA Ca++ channels
171
What is Poiseulle's Law?
Q = flow
P = Transmural pressure gradient
r = radius
l = length
η = viscosity
172
What is normal cerebral blood flow?
50 cc/100g/min
173
What is cerebral blood flow in reversible ischemia?
10-20 cc/100g/min
174
What is cerebral blood flow in irreversible ischemia?
\<10 cc/100g/min
175
What is brain oxygen monitoring useful for?
Early indication of ischemic events
Variable correlation with SjvO2 - good correlation with global insults
CPP \< 60 with negative effect
BTPO2 \< 15-20 mmHg = impending hypoxia
BTPO2 \< 10 mmHg = hypoxia and increased glutamate seen
176
What can help prevent secondary injury in severe head injuries?
Maintaining good oxygen delivery to brain cells
177
What is the basis for most classifications of psychiatric illnesses?
Clinical observation and symptom description
178
Is the etiology of any psychiatric disorder known?
No
Limited understanding of pathyphysiology
179
What is automaticity?
Unconscious mental activity directs behavior, thoughts, feelings.
You respond before you know you're responding
180
What does non-conscious mean?
Mental functioning that is not represented in consciousness and of which one is unaware
(unconscious)
181
What is unconsciousness?
Lack of consciousness or responsiveness to people and other environmental stimuli
182
What is subliminal?
That which is below an individual's threshold for conscious perception
183
What is id?
Totally unconscious
Instincutal drives (sex, aggression, eating, power, physical contact)
Primary process that demands gratification and ignores reality
184
What is ego?
Conscious and unconscious
Moderates between id and superego and seeks compromises to pacify both
Executive of the psyche, involved in regulatory functions
185
What is superego?
Conscious and unconscious
Morals, conscience, internalized parents, self-criticism
Denies gratification
186
What is psychodynamics?
Concept that unconscious mental life directs behavior, thoughts, feelings, responses, etc
Parts of the mind are in conflict
The mind regulates or disavows experiences to preserve equilibrium and avoid dissonance
Past being alive in the present and relationship patterns being repeated
Symptoms have meaning/purpose to a patient
Psychodynamic psychotherapy helps us recognize the ways in which we disavow aspects of our experience so as to permit us to have more choice in present situations.
187
What is a defense mechanism?
This process of Implicit Emotion Regulation is provided by Defense Mechanisms, whereby people unconsciously adjust perceptions/experiences to preserve equilibrium, protect self- esteem, avoid more severe aversive feelings, etc.
Distort one’s representation of reality to create emotionally preferable conclusions & determine what reaches awareness
188
When are defense mechanisms pathological?
When there is a rigid use of a limited repertoire of defenses
When they are immature or maladaptive
189
What is repression?
Blocking ideas/impulses from conscious mind
190
What is forgetting?
Repression of an emotion that manifests as forgetting
191
What is altruism?
Unselfishness in response to unconcsiously distressing feelings
Unselfishness to maintain consistent sense of self
192
What is humor?
unconsciously dealing with distressing feeling/thought by joking (more maladaptive if resentment, hostility)
193
What is suppression?
Consciously pushing a thought or feeling out of awareness
194
What is sublimation?
Expressing a socially or personally unacceptable feeling or thought in an acceptible way
195
What is displacement?
Directing the object of one's feelings to a safer one
196
What is rationalization?
making excuses
Dealing with emotional distress or internal/external stressors by concealing the true motivations for one's own thoughts, actions, or feelings through making reassuring but **incorrect** explanations
197
What is intellectualization?
Using excessive and abstract thinking to avoid difficult feelings
Flight into reason
Involves emotionally removing one's self from a stressful event
A person studies or works to explain something rather than to have an understandable emotional reaction to it
198
What is isolation of affect?
Remainig aware of the descriptive details of an event but losing connection with the feelings about the event
199
What is identification with the aggressor?
Reversing the power roles
Instead of being object of threat, you become the one making the threat; allowing the victim to achieve some feeling of strength in an otherwise humiliating/painful situation
**stockholm syndrome**
****
200
What is reaction formation?
Your behaviors, thoughts or feelings are the complete opposite of your unconscious desires/etc
201
What is somatization?
Directing intolerable thoughts or feelings towards your body
202
What are mature defenses? vs immature?
Allow flexible adaptation to reality, cognitively complex
immature distort reality
203
What are immature defenses? vs mature ones?
Distort reality, appear early, maladaptive residues of childhood experiences
vs cognitively complex defenses that allow flexible adaptation
204
What is acting out?
Dealing with emotional distress by actions rather than reflection or words
Primitive defense
205
What is splitting?
Primitive defense
Compartmentalizing internal representations of self and others into all-good and all-bad so that conflict is avoided
206
What is projection?
primitive defense
To avoid ownign an intolerable thought or feeling, a person attributes it to another person
207
What is projective identification?
primitive defense mechanism
Defense involving subtle interpersonal pressure so that the target of a projection takes on characteristics of that which is being projected
208
What is denial?
Primitive defense mechanism
By dismissing perceptions that are obvious to everyone in the environment, the person avoids awareness of aspects of external realities that are difficult to face
209
What is withdrawal?
Primitive defense
Retreating into one's private internal world to avoid anxiety about interpersonal situations
210
What is dissociation?
Primitive defense mechanism
Separating off parts of ones self to avoid acknowledgement of distressing experiences
211
Who uses defenses?
Everyone
They are not necessarily unhealthy
212
What is transference?
The unconscious transfer of past relationship patterns onto someone in the present
Emotionally charged interpersonal memories hold center court
Both conscious and subliminal present stimuli activate such procedural memory traces and shape present perception
The neural signature of an activated memory can be similar to that of true external stimuli
213
What is concordant countertransferance?
One person experiences another's feelings (empathy)
214
What is complementary countertransferance?
Person experiences feelings similar to what other people in the other person's life have felt in response to that peson
Role responsiveness
215
What is the diagnostic criteria for major depressive disorder?
At least 5 symptoms present for at least 2 weeks and impair function:
Sad mood\*
Anhedonia\*
Sleep disturbance
Change in appetite
Low energy/fatigue
Psychomotor agitation or retardation
Impaired concentration
Guilty feelings, self blame
Suicidal/thoughts of death
\*Need one of these two for a diagnosis
216
What are symptoms that must be present for a diagnosis of major depressive disorder?
One of:
Sad mood
Anhedonia
217
How do you screen for depresion?
PHQ-9
PHQ-2 (preliminary, if positive, do PHQ-9)
218
What is the gender that suffers from major depressive disorder more commonly?
Females (2x as common)
219
What is the course of illness in major depressive disorder?
May be triggered by an event
Untreated may last 6-13 months; treated last 3 months
Tends to be chronic with relapses - previous episodes increase risk of future episodes
220
What are consequences of untreated or undertreated major depressive disorder?
Suicide (30% attempt, 15% complete)
Divorce or relationship issues
Decreased productivity/ability to work
Poor hygiene
Can't care for children
Decreased quality of life
Effects on caregivers
Medical comorbidities
221
What is the psychodynamic theory of depression?
Disturbances in infant-mother relationship during oral phase causes damaged self esteem and unresolved conflict from real or imagined object loss
Anger toward lost object turns inward
Goal of treatment should be symptom relief and personality change through understanding of unconscious conflicts
222
What is the cognitive theory of depression?
Depression results from specific cognitive distoritons
Learned negative views about self, environment and future
Treat with cognitive behavioral therapy
223
What are neurobiological theories of depression?
Monoamine deficiency hypothesis
Amino acid neurotransmiter system dysregulation
Neuroendocrine dysregulation
Structural and functional brain changes
Neuropathological changes
Impairments in neuroplasticity
224
What is the monoamine deficiency hypothesis of depression?
Early antidepressants block reuptake or degradation of serotonin and norepinephrine
Led to belief that depression resulted from deficiency of monamines
Studies have yet to reliably demonstrate this - depletion of monoamines doesn't cause depression in healthy subjects; Also, antidepressants take 4-6 weeks for clinical benefit, but work to increase monoamine transmission instantly
225
What is the glutamate dysfunction theory of depression?
Chronic stress = excess glutamate
Hyperactivation of NMDA type glutamate receptors on neurons and glial cells
End result is atrophy and death of neurons and glial cells
IV ketamine (NMDA antagonist) has rapid antidepressant effect
226
What is the neuroendocrine theory of depression?
Excess cortisol present - can have damage to brain areas (hippocampus -atrophy)
Decreased supression of hypothalamus and anterior pituitary (decreased negative feedback effect)
227
What is the dexamethasone test?
Test where you give exogenous steroid in order to attempt to induce the negative feedback fo HPA axis to test its functionality
Not specific or sensitive for depression, but about 50% of patients with depression will fail the test
228
What happens to your hippocampal volume the longer you go with untreated depression?
Decreases!
229
What are brain changes in depression?
Structural: decreased volume of hippocampus, dorsolateral PFC, anterior cingulate, amygdala, OFC
Functional: decerased anterior cingulate, dorsolateral PFC activity; increased amygdala, orbitofrontal cortex activity
**Relative lack of cortical regulation of the limbic system during adversity**
230
What is the most prominent feature of cell pathology in depression?
Reduction in glial cell density and number
Seen in orbital cortex, dorsolateral PFC, anterior cingulate, hippocampus, amygdala
231
What is BDNF?
Brain-derived neurotrophic factor
Important for axonal growth, neuronal survival, and for synaptic plasticity
BDNF levels affected by stress and cortisol
232
What is the relationship between BDNF and sensitivity to stress in healthy people?
Inverse correlation
Low BDNF found in hippocampus, PFC and serum of depressed patients
Polymorphism in BDNF gene may be associated with hippocampal hypersensitivity to stress and increased vulnerability to depression
233
What is the neurotrophic hypothesis of depression?
Depression may be in part cuased by decrease in neurotrophic factors and the subsequent failure of neuronal plasticity
Enhancement in neural plasticity and cellular resilience is final common pathway for all effective therapies
234
What are the genetics of depression?
It is 37% heritable
No single depression gene
Gene x environment
Epigenetics may play a role
235
What are treatments for depression?
Medications - SSRIs, Tricyclics, Monoamine oxidase inhibitors, others
Psychotherapy
Electroconvulsive Therapy (80% response)
Vagal Nerve stimulation
236
What are the diagnostic criteria for bipolar I disorder?
At least one week of abnormally and persistently elevated, expansive, or irritable mood
PLUS 3 or more of:
Inflated self esteem/grandiosity
Decreased need for sleep
More talkative
Flight of ideas/racing thoughts
Distractibility
Increased goal-directed activity/psychomotor agitation
Excessive involvement in pleasurable activities with high potential for painful consequences
Impaired functioning/need for hospitalizaiton
237
What is the lifetime prevalence of Bipolar I disorder?
0.5-1% (less than depression)
238
What gender is more commonly afflicted with bipolar I disorder?
Equal in men and women
239
What is the typical range of onset of bipolar I disorder?
18-44 (typically on the younger end)
240
What is the neurobiology of bipolar disorder?
Structural and functional changes (dysregulation in limbic and PFC circuitry)
Endocrine (HPA/HPT axis dysregulation)
Cellular (decreased neuronal size and density in key areas)
241
What are the genetics of bipolar disorder?
8-10x increased risk of bipolar disorder in first degree relatives of bipolar individuals
2-10x increased risk of major depressive disorder in first degree relatives of bipolar individuals
65% heritable - no genes found yet
242
What demographic has the highest rates of suicide?
Men older than 75
243
What are risk factors for suicide?
Family history
Demographics - older white males
Previous attempts
Psychiatric disorders
Substance abuse
Chronic pain, illness, etc
244
What are protective factors for suicide?
Good clinical care
Easy access to clinical interventions, support
Connectedness
Religion
Skills in problem solving
Children
245
What are things that are important in the development of resilience (10)?
Positive attitude, optimism
Cognitive flexibility through cognitive reappraisal - reframe, assimilate, accept and recover from stress. Failure is essential for growth
Embrace a personal moral compass - develop core set of beliefs that few things can shatter; Altruism is strongly related to resilience
Find a resilient role model
Face your fears
Develop active coping skills
Establish and nurture a supportive social network
Attend to physical well being
Train regularly and rigorously in multiple areas
Recognize, utilize, and foster signature strengths
246
What is the stockdale paradox?
Retaining faith that you will prevail in the end, regardless of the difficulties, while at the same time confronting the most brutal facts of your current reality, whatever they might be
247
Which sex gets anxiety disorders more commonly?
Females
248
What are the anxiety disorders?
* Panic Disorder with/without Agoraphobia
* Social Anxiety Disorder
* Generalized Anxiety Disorder
* SpecificPhobia
* Separation Anxiety Disorder
* SelectiveMutism
* Substance/Medication Induced Anxiety Disorder
* Anxiety Disorder due to Medical Condition
249
What is the most common anxiety disorder?
Specific phobia
250
What are subjective symptoms common to all anxiety disorders?
Apprehension
Worry
Anticipation
Fear
Hypervigilence
Restlessness
Impaired concentration
Depression
251
What are physiological symptoms common to all anxiety disorders?
Neuromuscular (tension, fatigue, tremor)
GI - dry mouth, difficulty swallowing
Hyperventilation
Cardiovascular (palpitations)
252
What is Panic Disorder?
Recurrent, unexpected panic attacks
Anticipatory anxiety - more than 1 month of concern about having additional attacks, worrying about their implications, or change in behavior related to anticipatory anxiety (avoidance)
Not attributable to substance or another medical condition
+/- Agoraphobia (Fear or avoidance of situations from which escape might be difficult/embarrassing or in which help might not be readily available if have panic attack)
253
What is agoraphobia?
Fear or avoidance of situations from which escape might be difficult/embarrassing or in which help might not be readily available if have panic attack
254
What is a panic attack?
Abrupt surge of intense fear that builds ot crescendo pattern
Sudden onset, peaks within minutes, lasts 5-30 minutes
Often out of the blue, presents with physical symptoms
Emotional symptoms of fear of dying, or losing control
Can occur in non-physiologically ill people
Can occur in other disorders besides panic disorder
255
What are physical symptoms of panic attacks?
Hyperventilation
Palpitations
Sweating
Trembling or shaking
Feelings of choking
Chest pain or discomfort
Nausea or abdominal distress
Parasthesias
Chills or hot flashes
Derealization or depersonalization
Dizzy, unsteady, lighteaded, syncope
Dyspnea or air hunger, frequent sighing
256
What is the cardianl symptom of panic?
Hyperventilation
257
What is significant about hyperventilation and panic?
Cardinal symptom
Panic patients are chronic hyperventilators who also acutely hyperventialte during panic attacks
Hyperventilation -\> hypocapnia (reduced CO2) and alkalosis -\> decreased cerebral blood flow -\> dizziness, confusion, derealizaiton.
258
What is the epidemiology of panic disorder?
Females \> males (2-3:1)
Young adults in 3rd decade more commonly, but can be later
Women during childbearing years
259
What is the course of panic disorder?
Highly variable
– 30-40% symptom free
– 50% mild symptoms
– 10-20% significant symptoms
Ideal is to treat panic attacks before you get phobic avoidance - often leads to complete remission
Can lead to suicidality
260
What are common comorbidities with panic disorder?
Major depressive disorder
Other anxiety disorders
Alcohol (in 20%) and other substance dependence
Medical unexplained syndromes
Other medical conditions (peptic ulcer disease, asthma, migraines, HTN)
261
What is generalized anxiety disorder (GAD)?
Excessive anxiety and worry, most days, for at least six months
Difficult to control the worry
At least three of:
- restlessness/keyed up
- poor concentration
- muscle tension
- easily fatigued
- irritability
- sleep disturbance
That leads to impaired functioning
262
What gender is afflicted by generalized anxiety disorder more?
Females
263
When is generalized anxiety disorder typically onset?
early 20s but can develop at any age
264
What is social phobia (social anxiety disorder)?
Fear of 1 or more social or performance situations in which exposed to unfamiliar people or to possible scrutiny by others
Exposure to feared situation provokes anxiety
Fear or anxiety is **out of proportion** to actual threat
Tend to avoid situations or endure with intense anxiety
Causes functional impairment
Lasts at least 6 months
265
What are typical fears of social phobia?
Fear of speaking
Fear of meeting people
Fear of eating in public
Fear of using public phone
Fear of using public bathroom
Fear of attending parties
266
What is the basis for the fear in social phobia?
Fear of appearing nervous or foolish
Fear of being embarrassed/humiliated
Fear of making mistakes
Fear of beign criticized
Fear of being laughed at
Fear that actions will lead to being rejected or offending others
267
What is the gender distribution of social phobia?
No difference between men and women
268
Which anxiety disorder shows no gender bias?
Social phobia
269
When is the typical onset of social phobia?
Late childhood/early adolescence
Can be acute, following humiliating social experience; or can be insiduous
270
What is the course and outcome of social phobia?
Can be asymptomatic unless confronted with phobic situation or can be demoralizing, isolating and disabling vocational and interpersonal impairments
271
What is the key to treating anxiety disorders?
Cognitive Behavroral Therapy
In concert with medications
272
What are the cognitive-behavioral theories of anxiety disorders?
Learned response from parental behavior
Classical conditioning
Faulty thinking patterns, catastrophic thinking, accompany or precede maladaptive behaviors and emotional disorders
273
What neurobiological factors are implicated in anxiety disorders?
Disordered fear circuitry
False suffocation/abnormal sensitivity
Neurotransmitter abnormalities
Structural and functional brain changes
Genetics
274
What may be the neurobiological basis of panic?
Abnormally sensitive fear network (PFC, thalamus, insula, amygdala, amygdalar projections to brainstem and hypothalamus)
Potential deficit in cortical processing pathways -\> misinterpretation of sensory information -\> inappropriate activaiton of fear network
275
What is the role of the hippocampus in panic?
Formation of contextual memory
May be important for phobic avoidance, whcih in part arises from an association of panic attacks with teh context in which they occurred
276
What are neurotransmitters implicated in panic disorder?
Serotonin
Norepinephrine
GABA
277
What evidence exists to support the theory that serotonergic dysfunction is important in panic disorder?
SSRIs treat panic disorder
Decreased 5HT1A receptor binding in cingulate cortex and raphe nucleus
Works on downstream sites to dampen autonomic arousal:
278
What evidence is there to suggest that there is noradrenergic dysregulation in panic disorder?
Increased noradrenergic transmission from locus ceruleus
Increased NE concentrations in serum cause panic/anxiety
Panic disorder associated with increased activity and sensitivity of noradrenergic system
279
What evidence is there to suggest that GABA is important in panic?
Decreased benzodiazepine receptor binding to GABA-A receptor in hippocampus and amygdala in panic disorder may imply fewer GABA-A receptors or a decreased sensitivity of the receptors
Lower concentrations of cortical GABA in panic disorder patients vs controls
280
What is the genetics of anxiety disorders?
Genes contribute, but environmental influences are substantial
Complex non-mendelian inheritance
Maybe you inherit the tendency for fearfulness/susceptibility to panic
281
What is behavioral inhibition?
Reticence when faced with novel situations/people
Linked to risk for social phobia and other anxiety disorders
282
What are environmental contributors to anxiety disorders?
Disruption of early attachment and childhool trauma may be associated with later development of panic disorder
Those with panic disorder may be more susceptible to the effects of trauma than those without
80% of patients with panic disorder report major stressor in previous 12 months
Interaction b/w life stress + genetic susceptibility that contributes to panic disorder
283
How do you treat anxiety disorders pharmacologically?
SSRIs, SNRIs
Tricyclic antidepressatns, MAOIs
Benzodiazepines
Anticonvulsants
However, often found to be very sensitive to side effects of these drugs
284
What are non-pharmacological therapies for panic disorders?
Cognitive Behavioral Therapy
Robust and effective treatment
Psychoeducation about panic to correct misconceptions
Cognitive restructuring to identify and correct distortions in thinking
Exposure to feared bodily sensation and situations
285
How does CBT work to treat panic?
Operates upstream from amygdala
Strengthens ability of cortical projections to assert reason over (and inhibit) automatic behavioral and physical responses
286
Anxiety disorders might be characterized by [...] of subcortical emotion-processing areas and hypoactivity of cognitive processing/"top-down control" areas
Anxiety disorders might be characterized by hyperactivity of subcortical emotion-processing areas and hypoactivity of cognitive processing/"top-down control" areas
287
Anxiety disorders might be characterized by hyperactivity of subcortical emotion-processing areas and [...] of cognitive processing/"top-down control" areas
Anxiety disorders might be characterized by hyperactivity of subcortical emotion-processing areas and hypoactivity of cognitive processing/"top-down control" areas
