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151 Cards in this Set
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What is the infectious agent associated with progressive multifocal leukoencephalopathy (PML)
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Polyomavirus (JC) virus - infects oligodendrocytes causing demyelination
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Usually seen in immunocompromised individuals
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What is the infectious agent associated with subacute sclerosing panencephalitis (SSPE
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Measles paramoyxovirus - infects oligodendrocytes causing demyelination
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Describe anterograde amnesia, what is associated structure?
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impaired new declarative memory, medial temporal lobe
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Describe retrograde amnesia, what is associated structure?
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Affects stored declarative memory, most recently stored memories most vulnerable.
Cortical and/or white matter damage |
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Describe short-term memory impairment, what is associated structure
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Difficulty maintaining train of thought, prefrontal cortex/fronto-parietal connections
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Example of a multiple memory system impairment
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Example: Alzheimer's Disease, eventually affects both declarative and non-declarative memory
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Conditions Associated with Parietal Damage:
Constructional Apraxia Asomatognosia Anosognosia |
Constructional Apraxia: Inability to copy and object or put together parts of an object
Asomatognosia: denial that left side of body belongs to them (in right side attention dominant brain) Anosognosia: denial of illness |
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How do you treat Alzheimer's disease
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Cholinesterase inhibitors (Donepezil) - slows progression, but eventually trends downward
NDMA receptor antagonist (Memantine) |
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How to treat delirium
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Correct underlying etiology
High potency antipsychotics help with agitation Facilitate reality NO benzos or anticholinergics |
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Etiologies for delirium
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I WATCH DEATH
WHHHAM |
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Criteria for dementia dx
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decline in memory with impairment in at least one other domain of cognitive reasoning
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Criteria for delirium dx
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Disturbance of consciousness with reduced ability to focus, sustain or shift attention
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Differences between dementia and delirium
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Delirium has marked psychomotor changes
Delirium has altered and fluctuating levels of consciousness Delirium has short attention span |
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Differential dx for dementia
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Delirium
Focal neurologic symptoms Benign senescent forgetfulness Medications/drugs Depression |
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Clinical features of Alzheimer's disease (stages)
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Stage 1 - memory disturbance, poor judgement, carelessness
Stage 2 - aphasia, apraxia, acalculia, worsening stage I, incontinence Stage 3 - all cognitive functions affected, worsening stage II, motor disturbances |
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Gross findings of Alzheimer's disease
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medial temporal atrophy w/ hydrocephalus
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Gene mutations in familial Alzheimer's
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Amyloid precursor protein, presensilin-1, presensilin-2
All have autosomal dominant inheritance |
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Presentation of fronto-temporal dementia (early to late)
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Early presentation - behavioral changes associated with frontal lobe, speech and language related deficits (not memory)
Intermediate symptoms - anterior temporal lobe symptoms Late symptoms - diminished attention, abstraction, problem solving, attention, Parkinsonism |
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Compare and contrast early presentation of Alzheimer's disease, Lewy-body dementia, and fronto-temporal dementia
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AD - memory symptoms
FTD - behavior and speech symptoms LBD - attention, visuospatial deficits, visual hallucinations |
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Dx criteria for fronto-temporal lobe dementia (FTD)
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absence of plaques, tangles, and Lewy-bodes
Rule out other dementia causing diseases |
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Other causes for dementia (outside of FTD, AD, LBD)
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Huntington's disease (autosomal dominant inheritance and Chorea)
Vascular dementia (ie. stroke) |
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Features of genetically linked Alzheimer's disease
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Autosomal dominant
early onset (<60 years) |
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ApoE alleles are susceptibility factor for ____?
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Alzheimer's disease
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Dx criteria for dementia with Lewy-Bodies (DLB/LBD)
What is essential feature? |
Fluctuating cognition with pronounced variations in attention and alertness
Recurrent visual hallucnations Spontaneous Parkinsonism Lewy-bodies are essential for dx |
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Infectious causes of dementia
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HIV
neurosyphilis Cryptococal meningitis Whipple's disease PML SSPE CJD |
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Microscopic findings in HIV associated dementia
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microglial nodules commonly in white matter
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Creutzfeldt-Jakob disease types
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Familial
Sporadic Variant Iatrogenic |
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Clinical syndromes associated with sporadic CJD (early, late, end stage)
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Early: nonspecific malaise, fatigue, deficits in appetite, sleep and concentration
Late: dementia and non-behavioral symptoms (motor symptoms End stage: vegetative state, myoclonus, mutism, seizures, rigidity, autonomic dysfunction, hospital acquired infections |
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CSF and EEG findings in sCJD
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14-3-3 protein in CSF
Periodic complexes in EEG |
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Imaging findings in sCJD
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high signal in striatum, and least 2 cortical regions in diffusion-weighted imaging
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Microscopic findings in sCJD
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Neuronal loss, gliosis, NO INFLAMMATION/IMMUNE RESPONSE/VIRAL SYMPTOMS
Microvacuolation - all layers o cortex |
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Differences between sCJD and vCJD
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Younger patients compared to sCJD
Longer duration of illness than sCJD No abnormal EEG in vCJD 14-3-3 in only 50% of vCJD cases Earlier psychiatric and sensory symptoms in vCJD |
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Examples of tauopathies
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FTDP17 (frontal-temporal dementia w/ Parkinsonism linked to chromosome 17)
Pick's disease |
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Examples of synucleinopathies
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Lewy body dementia (diffuse Lew bodies)
Parkinson's disease (only brainstem Lewy bodies) |
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Describe the two types of Lewy bodies
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Classical (brainstem): eosinophilic w/ halo, multiple in one cell
Cortical: small neurons in layers V, VI, no halo |
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Describe etiology of Wernicke's encephalopathy
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Thiamine (B1) deficiency
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Clinical presentations of Wernicke's encephalopathy
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Anterograde amnesia, confabulations, loss of medial dorsal nucleus of thalamus
Slight retrograde amnesia |
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Gross findings of Pick's disease
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Atrophy (<1000 gms), fronto-temporal lobar atrophy, asymmetric atrophy, knife edge atrophy
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Where are NFTs found in AD
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Paired helical filaments in neocortex, hippocampus, amygdala, basal forebrain nuclei
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Composition of NFTs
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Tau, ubiquitin, amyloid-Beta
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Where and what are neuritic plaques in AD?
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neocortex, hippocampus, amygdala, basal forebrain nuclei (same as NFTs)
expanded dendrites (dystrophic neurites), mitochondria, central amyloid-Beta core |
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What is CERAD?
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Measurement of plaque density per age and history to establish AD dx
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What are the micro findings of FTDP17
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Accumulation of soluble and insoluble TAU in neurons and/or glia
NO amyloid deposits or other disease specific abnormalities |
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Micropathological findings of Pick's disease
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Neuronal loss and gliosis of outer cortex, caudate, thalamus, sparing of glboal pallidus
Presence of Pick bodies |
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Where and what are Pick bodies
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Introcytoplasmic inclusion
Found in dentate gyrus,amygdala, septal nuclei, cortex Consist of Tau and a-synuclein |
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Microscopic findings of Lewy body diseases
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Stain with ubiquitin and a-nuclein, but NOT tau
cortical microvacuolation but not to extent of CJD |
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What mutation is associated with prion diseases
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PNRP gene on chromosome 20
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What enzymes are present in normal APP processing?
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1) alpha-secretase
2) gamma-secretase |
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What enzymes are present in abnormal APP processing? What is formed?
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1) beta-secretase
2) gamma secretase Forms amyloid-beta-42 segments (prone to aggregation) |
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Describe role of presensilins, what happens when mutations occur?
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Interact with gamma-secretase
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What is the clinical triad of Wernicke's encephalopathy?
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Delirium, ataxia of gait, eye movement deficits with nystagmus
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What is the clinical triad of normal pressure of hydrocephalus?
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Dementia, gait disturbance, urinary incontinence
No mass effect or blockage |
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Who is most at risk for Wernicke's encephalopathy?
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Malnourished alcoholics
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What causes Korsakoff syndrome?
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untreated thiamine deficiency (Wernicke's encephalopathy)
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Understanding agent, host and environment in drug abuse
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Agent - drug itself (availability, effects, cost)
Host - user (hereditary, metabolism, co-morbidities, etc.) Environment - social setting, peer influence, conditioned stimuli, etc. |
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What is the Kindling model?
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Overlapping neurobiological pathways, repeated disruptions of brain functions sensitizes neurons that contribute to other disorders
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What is physical dependance?
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Altered physiological state produced by repeated drug use necessitating continuation to avoid withdrawal
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What is innate tolerance?
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Genetically determined sensitivity to a drug that is observed in naive user
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What are the types of acquired tolerance?
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Metabolic (pharmacokinetic) - increase in metabolism leading to less drug at receptor
Functional (pharmacodynamic) - less action at receptor despite same amount of drug Learned - reduced effects due to compensatory mechanisms and behaviors |
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What are 3 withdrawal techniques?
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Cross dependence - suppress physical dependence on drug with agonist (reinforcement)
Antagonist withdrawal - block reinforcing effects of drug with antagonist (extinction) Aversive withdrawal - induce negative effects when drug is administered (positive punishment) |
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Describe the ischemia cascade
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Ischemia --> Ca influx --> excitatory NTs, lactic acidosis --> free radical formation, NO release
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What is the rationale for hyperacute therapy of stroke?
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Preserve viable penumbra tissue
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How is blood flow restored during hyperacute therapy for stroke?
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T-PA thrombolytic
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What are the indications for T-PA use?
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Within 3 hours after onset of stroke (potentially effective after 4.5 hours)
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What is the recommended treatment for blood flow restoration after T-PA window has passed?
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Intra-arterial or mechanical thrombolysis
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What is the recommended evaluation and workup for ischemia stroke?
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Assessment
Imaging CTA/MRA Echocardiogram BMP, CBC/diff/coagulation fasting lipid thyroid EKG CXR |
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What is the mechanism of T-PA?
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Catalyzes conversion of plasminogen toplasmin
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Drugs used for anti-platelet Rx
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Aspirin
Dipyridamole Thienopyridines |
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Drugs used for anti-coagulant Rx
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LMW heparin
Warfarin Dobigatran Rivaroxaban |
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Indications for anti-coagulant RX
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Secondary prevention of cardiogenic stroke and primary prevention of stroke in A-fib
Do not use in patients within 24 hours of T-PA |
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Acute therapy for ischemic stroke
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Lower blood pressure over time
Antithrombotic RX (unless T-PA was used Protect airway Treat hyperglycemia DVT prophylaxis Treat fever or seizures Start PT/OT/ST early |
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How to treat intracranial hemorrhage
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Antihypertensive RX
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Metabolic vs. structural coma
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Delirium more common in metabolic
Global deficits more common in metabolic Posturing less common with metabolic Eye reflex remain in metabolic Asterixis and myoclonus in metabolic |
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From where does the hippocampus formation receive it's inputs?
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Entorhinal cortex
Parahippocampal cortex Piriform cortex - receives input from olfactory bulb |
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What structures make up the hippocampal formation?
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Hippocampus proper
Dentate Subiculum |
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Trace the hippocampal loop
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Cell bodies from entorhinal cortex --> dentate gyrus --> CA3 --> 2 branches
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Trace the two branches of the hippocampal loop
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branch I (from CA3) --> CA1 --> subiculum --> entorhinal cortex
branch II (from CA3) --> papez loop |
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Trace the Papez loop
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fibers from CA3 --> form fimbria and create fornix --> mammilary bodies --> anterior nucleus of thalamus --> cingulate cortex --> entorhinal cortex
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What are the amygdala's functions?
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Emotional memory and learning
- associated learning (fear conditioning) - appetite conditioning (addiction) - modulation of explicit memory (attaching emotional meaning to stimuli) |
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Describe the 3 loops of the amygdala
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Emotion loop - receives inputs and communicates with cingulate cortex and N.A.
Endocrine/autonomic loop - regulates septal basal forbrain Olfactory loop - similar to piriform-olfactory pathway |
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What occurs in patients with lesions in the amygdala?
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Tame placid behavior
Friendliness Inability to recognize emotion from facial expressions |
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What part of the brain is involved in attention guidance?
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Posterior parietal cortex - main one
Prefrontal cortex Subcortical structures (superior colliculus, Pulvinar nucleus of the thalamus) |
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Where is the source of norepinephrine? And where do these sources project?
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Local coeruleus --> forebrain
Lateral tegmental area --> subcortical structures |
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What is the role of acetylcholine in the higher cortical functions?
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Boost signal to noise ratio, arousal and attention
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What is the source of aceytlcholine?
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Basal forebrain --> septal nuclei, diagonal band of Broca, nucleus basalis
Pedunculopontine nucleus, dorsal tegmental nucleus --> subcortical structures |
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What is the role of domapine in higher cortical functions?
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Euphoria system
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What is the source of domapine and it's targets
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Ventral tegmental areas, substantia nigra --> frontal cortex, striatum, limbic system
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What is the role of serotonin
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Mood regulation
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What are the sources of serotonin?
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Midbrain raphe --> forebrain
Pontine, medulla raphe --> subcortical structures |
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What area of the brain controls functions such as restraint, judgement, initiative and order?
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Prefrontal cortex
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What RX is indicated for opiate addiction?
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Methadone
Buprenorphine - partial mu agonist Maltrexone - mu antagonist for OD |
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Opiates exhibit what type of tolerance?
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pharmacodynamic tolerance
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Alcohol exhibits what type of tolerance?
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pharmacodynamic and kinetic
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What RX is indicated for alcohol addiction?
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benzodiazepines (diazepam) - for withdrawal seizures
Carbamazepine - for withdrawal seizures Disulfiram - blocks metabolism Naltrexone - mu antagonist Acamprosate- NDMA antagonist |
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What type of tolerance is exhibited by barbituates?
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Pharmacodynamic and kinetic
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Why is overdose common with benzodiazepines?
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Tolerance develops to many effects except for lethality
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What type of tolerance is exhibited by benzodiazepines?
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Pharmacodynamic
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What RX indicated for benzodiazepine or barbituate addiction?
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Carbamazepine or phenobaritol (long half life)
Flumazenil for overdose |
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What RX is indicated for nicotine addiction?
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nicotine replacement therapy
Buproprion - sustained release antidepressent Varenicline - partial nicotinic agonist |
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What is the mechanism for cocaine and amphetamines?
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Dopamine reuptake block
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Benzoylecgonine is found in urine after use of what drug?
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Cocaine and amphetamines
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What RX is indicated for stimulant addiction?
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Symtptom RX
Modafinil - for narcolepsy Disulfiram - unkonwn mechanism |
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What is the endogenous cannabinoid ligand?
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anadamide
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Describe the difference between functional and ischemic hypoxia
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functional - low pO2, low O2 carrying capacity, inhibition of O2 use by tissue
Ischemia - low blood flow |
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What causes global cerebral ischemia?
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Systemic hypotension
Cardiac arrest |
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What causes focal cerebral ischemia?
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Large vessel occlusion - fixed occulsions (thrombosis), embolus
Small vessel occlusion - arteriolosclerosis (lacunar infarct) |
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What regions of the brain are most sensitive to global ischemia?
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CA1 - hippocampus
Cerebellum Cortical neurons in layers 3 and 5 |
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What are some etiologies for large vessel occlusion cerebral ischemia?
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Thrombosis
Atherolosclerosis Vasculitis Hypercoagulation Dissecting aneurysm Drugs CADASIL |
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Why do watershed infarcts commonly include hemorrhage?
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Watershed infarcts are usually caused by systemic hypotension, hemorrhage occurs when re-perfusion occurs
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What is laminar necrosis?
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Deep cortical necrosis in watershed regions with scarring due to microglial insult
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What is most common cause of a bland infarct?
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Embolism
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What are the most common causes of emboli to the brain?
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Vegetation on valves from infections
Cardiac mural thrombus (from M.I.) Carotid plaques |
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Were are lacunar infarcts typically found?
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Tissues perfused by penetrating small vessels
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What is the most common cause of subarachnoid hemorrhage?
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Saccular aneurysms - dissection can lead to sudden death
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What conditions are associated with venous sinus thrombosis
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Bilateral hemorrhagic infarcts
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What are some etiologies of intracerebral hemorrhage?
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Arteriolosclerosis
Hypertension Coagulopathy Vascular malformations Aneurysms Neoplasm Drug use (cocaine, ampethamines) |
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What are some "organic" etiologies for a patient with psychotic symptoms?
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Trauma
Infection Organ failure Brain lesions Drugs or toxins |
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What are some psychiatric etiologies for psychosis
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Delusional disorders
Mood disorders Cognitive disorders CD Dissociative disorder Personality disorder Schizophreniform |
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what are positive symptoms of schizophrenia?
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Hallucinations in all sensory modalities
Delusions Thought disorders (disorganized speech, cognitive impairment) |
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What are negative symptoms of schizophrenia?
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Ahedonia-asociality
Inattentiveness Affective flattening (lack of expression) Alogia (thought blocking) Apathy |
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What are the 3 phases of schizophrenia?
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Prodrome
Active phase Residual phase |
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What symptoms are most prevalent in active phase schizophrenia?
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Positive schizophrenic symptoms (hallucinations, delusions, etc.)
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What symptoms are most prevalent in residual phase schizophrenia?
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Negative schizophrenic symptoms (social withdrawal,
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Describe the first rank symptom for schizophrenia
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Complete auditory hallucination - when sounds are heard from outside your head
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DSM-IV criteria for schizophrenia includes
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At least two of the following:
delusions hallucinations disorganized speech disorganized behavior negative symptoms |
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What are the subtypes of schizophrenia?
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paranoid
disorganized catatonic residual undifferentiated |
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What RX is indicated for schizophrenia?
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Hospitalization for safety and monitoring
Antipsychotic medication Psychosocial rx |
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How is white matter volume correlated with schizophrenic symptoms?
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Complete auditory hallucination is correlated with less white matter volume
Internal hallucinations is correlated with more white matter volume |
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What commonly mimics schizophrenia?
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Schizotypal personality (Cluster A disorders)
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What are the two models of sleep-wake regulation?
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Homeostatic (sleep load) - the more you're awake the sleepier you get
Circadian alert signal - histamine keeps you awake |
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What is the mechanism of sleeping pills?
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pro-GABA release to inhibit histamine
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What structures localize sound?
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Medial superior olive - time delay
Lateral superior olive - level differences |
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Explain connections of olivocochlear efferent system
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lateral superior olive - connects to IHC
medial superior olive connects to OHC |
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What are the functions of different GABA-a receptor classes?
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alpha-2 - anxiety
alpha-1 - sedation alpha-5 - learning and memory |
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Treatment for alcohol abuse
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disulfiram - blocks acetaldehyde metabolism and causes severe withdrawal
acamprosate - reduces cravings in abstinent alcoholics Naltrexone - reduces rewarding effects of alcohol in abstinent alcoholics Topiramate - reduces active drinking Onedastron - 5ht3 antagonist, reduces cravings |
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Most common pathogen in neonatal CNS infection
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Group B strep
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Most common pathogen in pediatric CNS infection
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N. meningitidis
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Most common pathogen in adult CNS infection
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S. pneumoniae
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Most common viral pathogen in CNS infection
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enteroviruses
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Why do SSRIs work better in children than adults?
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More sensitive seratoninergic system
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Rx for aggressive autism patients
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Use antipsychotics:
aripiprazole risperidone |
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What is first line RX for children an adolescents with ADHD?
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Stimulants:
amphetamine Methylphenidate |
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What are the 3 pathways of dopamine?
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Mesostriatal: SN to striatum
Mesolimbic: Ventral tegmentum to limbic system Mesocortical: SN, VT to cortex |
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What are the long GABA pathways?
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striatum to SN
hypothalamus to forebrain |
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What is the mechanism of phenothiazine (and other typical) neuroleptics?
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D2 (dopamine receptor) antagonists
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What are the most potent "typical neuroleptics?
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Piperazine (trifluoperazine)
Butyphenones/Haloperidol |
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What are examples of atypical neuroleptics?
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Clozapine - binds at D4; causes potentially fatal agranulocytosis
Olanzapine - safe than clozapine Risperidone - D2 antagonist but also potent at other receptors |
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What are non-dopa related side effects of neuroleptics
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Sedation
Orthostatic hypertension Extrapyramidal symptoms (acute Parkinsonism, chronic tardive dyskinesia) |
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What are dopa-related side effects of neuroleptics?
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Anti-nausea (nausea produced at chemoreceptor trigger zone by dopa)
Endocrine effects |
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What is the correlation of dopa with schizophrenia
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anti-Dopanergic drugs relieve schizophrenia symptoms
Increase in dopa causes psychotic symptoms |
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What are the sidechain classes of phenolthiazines?
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Aliphatic - chorpromazine
Piperidine - Thioridazine Piperazine - Trifluoperazine |
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