Reading...
Play button
Play button
Use LEFT and RIGHT arrow keys to navigate between flashcards;
Use UP and DOWN arrow keys to flip the card;
H to show hint;
A reads text to speech;
225 Cards in this Set
- Front
- Back
|
Where is REM sleep generated?
|
Pons
|
|
|
Major sleep induction nucleus that inhibits wake promoting neurons; *sleep center*
|
VLPO-Ventrolateral preoptic nucleus
|
|
|
REM-on neurons
|
SLD, PC, PB
|
|
|
REM-off neurons
|
vLPAG, LPT
|
|
|
Neuropeptides that are promoters of wakefulness
|
Hypocretin/orexin(modulates feeding) acts at lateral hypothalamus-inhibit REM; histamine from tuberomamillary nucleus
|
|
|
Has role in homeotic sleep drive, sleep induction, slow wave sleep (Stage 3 NREM)
|
Adenosine
|
|
|
Main pacemaker for circadian system
|
SCN of anterior hypothalamus
|
|
|
Abnormal events that intrude sleep
|
parasomnias
|
|
|
What is narcolepsy? Tetrad?
|
dysfunction in regulation of REM sleep, tetrad of daytime sleepiness, cataplexy (sudden loss of muscle tone), sleep paralysis, hypnagogic hallucinations
|
|
|
What substances reduce REM sleep?
|
Tricyclic antidepressants (TCAs), MAOinhibitors, Amphetamines, Opiods, alcohol
|
|
|
What substances reduce slow wave sleep?
|
Benzodiazepines, caffeine
|
|
|
What is made in TMN?
|
Histamine, an imp wake promoting nt
|
|
|
REM sleep characterized by?
|
EEG similar to wakefulness, muscle atonia, hippocampal THETA activity
|
|
|
EEG for
Stage 2 sleep? Stage 3 sleep? REM sleep? |
2- sleep spindles, K complex
3-delta waves, high voltage, slow waves REM- sawtooth waves |
|
|
What sleep stage is most of the nite spent in?
|
Stage N2
|
|
|
Caffeine is an example of what?
|
methyxanthine; adenosine receptor antagonist
|
|
|
What is sleep-wake cycle and two-process model?
|
Homeostatic drive-sleep dependent, governed by need for sleep; 1st part of nite high (high adenosine)
Circadian rhythm-sleep independent, entrained by light-dark cycle; 2nd part of nite its low |
|
|
How is REM atonia controlled?
|
By REM-on cells in PC, via glutamatergic pathways to IVMM and SLD
|
|
|
lesions of SLD, PC would cause what?
|
loss of REM-on neurons cause loss of REM sleep, atonia, and theta EEG
|
|
|
Main nucleus for sleep?
Main nucleus for wakefulness? |
Sleep-VLPO
Wakefulness- SCN |
|
|
What inhibits the SCN (the wakefulness nucleus)/causes drowsiness?
|
Melatonin; secretion is stimulated in dark
|
|
|
What is the drowsy phase of wakefulness char by on EEG?
|
alpha waves
|
|
|
Modafinil?
|
stimulates orexin/hypocretin neurons, used in narcolepsy to keep them awake
|
|
|
Hypothalamic nuclei involved in fluid-electrolyte balance
|
Supraoptic nucleus (SON), Paraventricular nucleus (PVN), Median pre-optic area (MnPO)-all have osmoreceptors
|
|
|
Hypothalamic nuclei involved in feeding behavior
|
PVN. Ventromedial Nucleus (VMN), Arcuate Nucleus (ARC), Lateral Hypothalamic area (LHA)
|
|
|
Lesion of VMN
|
INCREASE in body weight, levels off to new basal body wt
|
|
|
Lesion of lateral hypothalamus
|
DECREASE in body weight, but over time will gain wt to a point lower than pre-lesion body weight
|
|
|
NPY formation? Action?
|
made in ARC, goes to PVN to INCREASE food intake
|
|
|
Leptin formation? Action?
|
secreted by fat cells, acts on leptin receptors in hypothalamus to decrease NPY secretion; decrease NPY-->decrease food intake
|
|
|
Ghrelin formation? Action?
|
secreted by gut, increases NPY, signals hungers and increase food intake
|
|
|
CCK
|
secreted by gut, decreases food intake by signaling satiety
|
|
|
How does hypothalamus control posterior pituitary? (oxytocin, vasopressin) (neurohypophysis)
|
Neural control via MAGNOcellular (large) neurons in PVN (oxytocin) and SON (ADH); project axons to posterior pituitary to release hormones
|
|
|
How does hypothalamus control anterior pituitary? (adenohypophysis)
|
Humoral Control via PARVOcellular (small) neurons located thru-out hypothalamus; project axons to median eminence
|
|
|
What does the medial PARVOcellular neurons make?
|
CRH-(for ACTH), TRH-(for TSH)
|
|
|
Difference in brain of dyslexics?
|
Planum temporale DOES NOT show left cortical asymmetry that normal ppl do; left temporoparietal cortex deficient functioning on fMRI; Microgyria; larger splenium
|
|
|
Signs of dyslexia
|
reading, spelling, writing difficulties, spelling reversals and poor spelling
|
|
|
Damage to arcuate fasciculus (aka superior longitudinal fasciculus)
|
conduction aphasia, auditory comprehension and speech articulation preserved, difficulty repeating heard speech
|
|
|
2 main skills for phonological processing
|
phonemic awareness-recognition of units of language, decoding-words to sounds of language
|
|
|
3 imp neural systems in reading
|
1. Anterior system in left inferior frontal (broca's) 2. dorsal parietotemporal (wernicke) 3. ventral occipitotemporal
|
|
|
what is the link betw written forms and auditory forms?
|
angular gyrus in temporoparietal junction (primary visual-->AG-->Wernickes)
|
|
|
Acquired dyslexia
|
dyslexia as a result of brain injury
|
|
|
Microgyria sx
|
impaired processing of rapid acoustic information
|
|
|
Differences in patterns of neural activation of dyslexics
|
increased activity of right hemisphere, increased activation of frontal areas such as Broca's, decreased activation of temporoparietal cortex (angular gyrus)
|
|
|
Where is working (short-term) memory localized to?
|
frontal lobe, anterior cingulate and dosolateral prefrontal brain
retained briefly, not stored |
|
|
Episodic vs. Semantic memory
|
Episodic-events
Semantic-facts and information Both are types of explicit memory which can be consciously demonstrated |
|
|
implicit memory
|
task-related memory
Priming (neocortex), conditioning (emotional-amygdala, motor-cerebellum), skills (striatum), habituation |
|
|
How do we form implicit memory vs. explicit memory?
|
implicit-via basal ganglia and cerebellum, not affected in amnesics
explicit-via hippocampus |
|
|
What can provoke generalized absence seizures?
|
hyperventilation
|
|
|
What is believed to be the cause of generalized seizures?
|
since discharges seen everywhere in the brain, thought to be THALAMO-cortical related
|
|
|
Ictus vs. interictal?
|
Ictus-point at which pt is striken
Interictal-between seizures |
|
|
Where do convulsive (tonic-clonic) seizures originate in humans?
|
in brainstem
|
|
|
What is the cause of PRIMARY convulsive (tonic-clonic) seizures?
|
due to genetic cause of having seizures
|
|
|
What are SECONDARY convulsive (tonic-clonic) seizures?
|
crescendo build-up of activity resulting from a focal incident, more likely than primary
|
|
|
Causes of Seizures
|
Microanatomical abnormalities, changes in excitation/inhibition ratio
|
|
|
Specific microanatomical abnormalities
|
Enhanced excitation=glutamate thru ionotropic and metabotropic receptors cause inward Na+ and Ca++ current
Loss of inhibition= GABA thru GABA-a(post) and GABA-b (pre) causes inward Cl- and outward K+ |
|
|
Specific changes in exc/inhib ratio
|
instead of single APs send BURSTS of APs; also, paroxysmal depolarizing shift where a balance shift in thalamic and purkinje neurons firing single and bursts changes
|
|
|
Phase 1 monitoring (Wada Test?)
|
EEG at scalp, neuroimaging, Wada test is unilaterally inject sodium amytal into internal carotid and asses memory and language in awake atmosphere (for partial seizures)
|
|
|
Phase 2 monitoring
|
EEG intracranially, language mapping of temporal lobe
|
|
|
When can you do a temporal lobe resection for seizures?
|
seizures from a single focus (partial seizures) in non-eloquent cortex
|
|
|
When is it good to use Vagal Nerve Stimulation for seizures?
|
Pts with difficult-to-treat epilepsy such as generalized seizures or partial seizures in an imp. area; control seizures better by stopping or decreasing duration, severity and recovery period
|
|
|
What is intractable epilepsy?
|
despite adequate pharm therapy, 40% of pts will continue to have seizures
|
|
|
What seizure classification is more effective with Anti-epileptic drugs?
|
Partial seizures may be more well-controlled than generalized, but types of seizures (absence vs. tonic clonic) does not have any difference in effectiveness
|
|
|
Status epilepticus? Tx?
|
seizures lasting more than 30 minutes, give benzodiazepines to sedate, phenytoin as treatment
|
|
|
1st generation drugs that block Na+ channels? Side effects?
|
Phenytoin-gold standard for STATUS EPILEPTICUS; (F)osphenytoin is (f)aster
s/e-gingival hyperplasia, coarsening of facial features, hepatic enzyme INDUCER (C)arbamazepine-gold std for (C)OMPLEX PARTIAL SEIZURES s/e-hyponatremia, agranulocytosis |
|
|
1st generation drugs that promotes GABA channels (increase GABA by increasing Cl- conductance)? Side effects?
|
Phenobarbital (barbiDURATe); increase DURATION of Cl- channel
Diazepam (FREnzodiazepine); increase FREQUENCY of Cl- channel, used for detoxification s/e-sedation, tolerance, dependence, *Cyt P-450 induction w/Phenobarbital |
|
|
1st generation drug that blocks Na+ channels, blocks Ca++ channels, and increases GABA? Side effects?
|
Valproate-gold standard for primary (idiopathic) generalized seizures, also used for migraines
s/e-MANY ADVERSE, weight gain, tremor, hair loss, fatal hepatotoxicity |
|
|
What is the gold standard for primary (idiopathic) generalized seizures? Why?
|
Valproate; because it does everything! blocks Na+ channels, blocks Ca++channels, promotes GABA
|
|
|
3 common mechanism by which AEDs work
|
Block Na+ channels, enhance GABA receptor, block T-type Ca++ channels
|
|
|
What AED is used to treat absence seizures?
|
Ethosuximide; blockade of T-type calcium channels
|
|
|
What increases GABA release?
|
Gabapentin, off-label use
|
|
|
Lamotrigine- use, mech, side effects?
|
partial seizures; blocks Na+ channels; most favorable cognitive profile BUT major s/e: STEVEN's Johnson Syndrome, fatal, ulcerations of all mucosal surfaces
|
|
|
What two drugs should you never combine?
|
Lamotrigine and Valproate-causes SJS!!!
|
|
|
2nd generation Ca++ blocker used for add-on therapy of partial epilepsy
|
Levitiracetam, few side effects
|
|
|
What type of pt is a ketogenic diet effective?
|
children who have failed numerous drug trials, but many side effects
|
|
|
Anisocoria
|
unequal pupillary size
|
|
|
Papilledema; what does it indicate
|
swelling of the optic disc, indicates increase intracranial pressure
|
|
|
Aphasia
|
difficulty with language
|
|
|
Dysarthria
|
slurred speech
|
|
|
Global aphasia vs. Receptive aphasia vs. Expressive aphasia
|
Global-unable to understand or speak
Receptive-can't understand, able to speak Expressive-able to understand, can't speak |
|
|
Dementia vs. delirium
|
Dementia-impaired cognition
Delirium-impaired attention that produces disorientation Both have normal awareness |
|
|
Perseveration
|
repeating the same behavior
|
|
|
Meningismus
|
stiffness of the meninges, but various signs such as stiff neck that occur with irritation of the meninges
|
|
|
Paroxysmal
|
sudden (seconds or less)
|
|
|
Conversion disorder vs. Factitious disorder
|
Conversion: we know the pt caused this but the pt (really) doesnt know it
Factitious:the pt chose to cause the physical finding bc they are mentally disturbed |
|
|
Mydriasis; what does unilateral dilated pupil w/worst headache of life suggest? Bilateral?
|
dilated pupils
Unilateral: possible SAH, compression via PCA aneurysm Bilateral: very rare, eyedrops |
|
|
Diplopia. Intermittent?
w/worst headache and diabetes? w/worsening headaches and bradycardic? w/sudden onset R sided headache? |
Intermittent? neuromuscular prob (myasthenia graivs)
Worst headache + diabetes? microvascular infarct of 3rd nerve, pupils normal bc fibers lie on surface Worsening headaches+bradycardic? tumor w/increasing intracranial pressure Sudden onset R sided headache? retinal detachment |
|
|
What is the formula for Cerebral perfusion pressure? When does ischemia occur?
|
Mean arterial pressure-Intracranial pressure
Occurs when ICP > MAP |
|
|
Ways to reduce ICP
|
1. if a tumor, remove it
2. diuretics such as mannitol 3. steroids for inflammatory edema 4. hyperventilation to reduce CO2 causing vasoconstriction 5. give phenobarbital to reduce metabolism causing vasoconstriction |
|
|
Glasgow coma scale
|
used to assess if surgery is worthwhile, score<9(/15) will NOT get surgery
|
|
|
Paresis? w/decreased reflex in left leg? w/both legs and arms reflexes decreased? w/left calf/shin pain, foot drop after exercise? w/both legs and sensory loss to mid-abdomen?
|
Paresis=weakness
w/decreased reflex in left leg? SCIATICA w/both legs and arms reflexes decreased? Guillain-Barre w/left calf/shin pain, foot drop after exercise? anterior compartment syndrome w/both legs and sensory loss to mid-abdomen? cord compression from tumor |
|
|
Lethargic child that is difficult to arouse. @2am? after sporting accident? poorly behaved and recent falls?
|
@2am?ask if cough medicine taken
after sporting accident? epidural hematoma; emergent CT poorly behaved and recent falls? child abuse; emergent CT |
|
|
How to deal with suicidal or homicidal thoughts
|
Follow-up, the more detailed response, the higher the risk
|
|
|
Neck stiffness w/cough, fever, difficult to arouse. Child's neck NOT stiff? Man's neck is stiff? HIV w/stiff neck? man w/stiff neck but painting related?
|
Child's neck NOT stiff? still give LP
Man's neck is stiff? LP + antibiotics HIV w/stiff neck? brain abscess, risk of herniation so CT before LP man w/stiff neck but painting related? Meningismus if stiffness in anterior-posterior directions only |
|
|
65 w/confusion/wandering. severe in evening, but alert and follows commands? unable to follow commands, easily distracted? thinks you are evil, refuses to follow commands?
|
evening, but alert and follows commands?dementia *sundowning*
unable to follow commands, easily distracted? delirium thinks you are evil, refuses to follow commands? psychotic or delirious |
|
|
65yr old man talking in bed constantly. w/nonsensical speech, and R stimulation deficift? w/constant noises and right hand twitching?
|
w/nonsensical speech, and R stimulation deficift? fluent speech stroke in MCA affecting wernicke's area
w/constant noises and right hand twitching?complex partial status epilepticus, does not regain consciousness in between; risk of drying from excessive brain activity. Tx-intravenous anticonvulsant |
|
|
54 yr old woman blackout. w/feeling hot, spinning, vision going gray, twitching movts of legs? w/warm feeling in her stomach/bad smells and amnesia abt event?
|
w/feeling hot, spinning, vision going gray, twitching movts of legs? hypotensive episode w/ myoclonus
w/warm feeling in her stomach on and off and amnesia abt event? seizure w/aura |
|
|
For headaches, what is the nerve responsible for pain referred to the eyes, temple, forehead?
referred to the back of the head? |
Opthalmic division of trigeminal nerve
upper cervical spinal nerves |
|
|
Pain expression system in headaches?
Pain transmission system? |
trigeminal nerve, upper cervical roots
2nd order neurons which sit in trigeminal nucleus-->thalamus 3rd order neurons of thalamus-->sensory/limbic cortex |
|
|
What does the 1st branch of the trigeminal nerve innervate?
|
meningeal artery and vein in dura mater
|
|
|
For most primary headache disorders (migraines), what is the pain sensitive afferent?
|
Trigeminal nerve
|
|
|
Causes of secondary headache? (0.18% pts)
|
SNOOP:
Systemic or Secondary risk factors-fever, wt loss, HIV, cancer Neurologic symptoms-deficits, confusion Onset-sudden or abrupt Older- over 50 Previous history or Progressive headache |
|
|
Categories of primary headaches and features
|
Short duration-cluster headaches <4hrs
Recurrent long duration- migraines, tension-type; >4hrs, <15days/month Chronic Daily-chronic migraine or chronic tension, continua, daily; >4hrs, >15days/month |
|
|
Cluster headaches
|
unilateral short-lived headaches that occur in closely spaced intervals followed by relatively long pain free remissions
|
|
|
Migraine w/o aura
|
unilateral, pulsating, severe intensity, aggravation w/exercise
NAUSEA, photophobia, phonophobia Leading headache that causes ppl to seek treatment |
|
|
Tension type headache
|
bilateral, non-pulsating, mild to moderate intensity
most common primary headache |
|
|
Aura? proposed mechanism? Difference in seizures and migraine
|
focal neurologic deficits preceding h/a onset by hours or days
cortical spreading depression; wave of excitation followed by wave of inhibition, vascular changes follow Aura causes migraine, aura is a pre-symptom in seizure |
|
|
4 phases of migraine attacks
|
Prodrome, aura, headache, postdrome
|
|
|
Familial hemiplegic migraine?
Difference betw. type 1 and type 2. |
migraine w/aura that causes hemiparalysis; genetic disorder that leads to brain hyperexcitability via glutamate increase
1:gof, increase Ca++influx 2:lof, glia less able to take in glut. |
|
|
CNS activation during migraine.
Pain perception? Migraine generator? Where does sumatriptan act? |
Pain perception? anterior cingulate cortex; sumatriptan decreases pain
Migraine generator? raphe nuclei, locus coerulus, periaqueductal gray |
|
|
Primary pain producing process in migraine?
|
Trigeminal vascular jx releases mediators such as CGRP that activate meningeal BV causing pain
|
|
|
Triptans? Targets of triptans?
|
selective 5HT1D/1b AGONISTS, serotonin receptors on presynaptic terminal 5HT1D and blood vessel 5HT1B; reduce pain inducing vasodilation
|
|
|
Allodynia w/migraine
|
normal stimuli are considered painful, 2/3 of migraine sufferers, predicts better pain free response if allodynia absent
|
|
|
Modifiable Yellow flags for chronic daily headache
|
attack frequency, obesity, med overuse, stress, sleep disturbance
|
|
|
Pathway to stimulate reward centers (such as in addiction)
|
VTA to nucleus accumbens using dopamine
|
|
|
What is dopamine assoc. with?
|
euphoria as well as attention and learning
|
|
|
Opioid antagonist used in opiate overdose
|
Naloxone
|
|
|
Treatment for alcohol withdrawal/detoxification
|
Benzodiazepines
|
|
|
Opioid agonist therapy to prevent heroin relapse
|
Methadone; pts exhibit tolerance and withdrawal phenomena but do not fit criteria for dependence; good b/c cross tolerant with heroin to ease withdrawal
|
|
|
Conditioned place preference
|
prefer place that was assoc with drug intake
|
|
|
Withdrawal induced conditioned place aversion
|
prefer place where no withdrawal symptoms occurred
|
|
|
Sites of action of Stimulants
|
Nucleus Accumbens and Ventral Pallidum (terminal portion of mesocorticolimbic pathway)
|
|
|
Sites of action of Opiates
|
VTA and periaqueductal gray (origins of mesocorticolimbic pathway)
|
|
|
Where do most addictive substances act?
|
Mesocorticolimbic pathway
|
|
|
Target and mech of Nicotine
|
bind to nicotinic receptor located on CELL body of VTA neuron --> DA release in NA
|
|
|
Target and mech of Cocaine
|
binds to dopamine TRANSPORTER located on terminal axon of dopamine neuron in VTA -->prevents DA reuptake --> more DA in synapse of NA
|
|
|
Target and mech of Morphine
|
binds to u-opiate receptor on GABA neuron to inhibit GABA release --> more DA release in NA
|
|
|
What can cause a PHYSICAL withdrawal?
|
u-opiate receptor antagonist at Locus Coeruleus and Periaqueductal Gray
|
|
|
What can cause a MOTIVATIONAL withdrawal?
|
u-opiate receptor antagonist at Amygdal, VTA, NA, PeriAqGray
|
|
|
What drugs use Gi signalling to inhibit GABA firing and increase DA in synapse? receptors?
|
Opiates via opiate receptor and
Cannabinoids via CB1 receptor |
|
|
What drugs use Gs signalling to inhibit dopamine re-uptake and stimulate DA release, respectively? receptors?
|
Cocaine via dopamine reuptake transporter
Amphetamine |
|
|
Addictive substances may acutally improve psychological performance in these pts
|
Schizophrenia
|
|
|
Wernicke-Korsakoffs Syndrome
|
acute form of encephalopathy due to thiamine deficiency; vision changes, ataxia, and impaired memory
|
|
|
Central Pontine myelinolysis
|
locked-in syndrome, spastic quadriplegia, demyelination of pons
|
|
|
Marchiafaua-Bignami Syndrome
|
demyelination of corpus callosum, stupor, coma, seen in middle aged to elderly alcoholics
|
|
|
Naltrexone
|
blocks opioid receptors, reduces relapse rate
IMP! make sure pt is opioid free for 7-10 days before starting meds b/c can induce withdrawal |
|
|
Acamprosate
|
acts to inhibit GABA and increase glutamate, reduces symptoms of protracted abstinence
s/e diarrhea and somnolence |
|
|
Disulfaram
|
interferes with degradation of alcohol (blocks acetaldehyde dehydrogenase)
|
|
|
Narcan=Naloxone
|
given for opioid overdose for respiratory support and counteract CNS depression *different from naltexone-opioid receptor antagonist in making alcohol unrewarding*
|
|
|
Alternative opioid detox treatment? Mech? Benefits?
|
Buprenorphine-partial opiate agonist at low does, antagonist at high does, low risk of overdose/abuse, available in combination wtih naloxone (antagonist)
preferable for pts who want to avoid clinic daily settings of methadone maint. |
|
|
Where should you go to if impaired?
|
Committee for Physician Health (CPH)- anonymous, confidential, for substance use and psychiatric disorders
OPMC is bad. lose license. |
|
|
Volition
|
intentional behavior
|
|
|
Chronesthesia
|
consciousness that enables ppl to be aware of their personal past and future
|
|
|
3 big causes of coma
|
intoxication
trauma cerebrovascular disease |
|
|
Levels of Consciousness
|
Normal
Confusion-clouding of sensorium (dif. from delirium which includes hallucinations and agitation) Drowsiness and Stupor-sleepy state Coma-unresponsive |
|
|
Stages of memory
|
Encoding-attn/focus
Consolidation-short to long info Storage-dist of memories Retrieval-calling up memory from storage |
|
|
Where is short term memory converted to long term memory?
|
Hippocampus
|
|
|
What region of the brain is responsible for memory of OBJECTS?
|
Parahippocampal and entorrhinal areas
|
|
|
What region of the brain is responsible for SPATIAL memory?
|
Right hippocampus
|
|
|
What region of the brain is responsible for memory of WORDS, PEOPLE?
|
Left hippocampus
|
|
|
What area of the brain shows increased activity when thinking about FUTURE events?
|
anterior portion of the superior frontal gyrus
|
|
|
How is synaptic strength increased
|
more efficient synapse
change in diameter of spine location of synapse NMDA synchrony addition of new synapses AMPA receptors NOT static, traffic continuously |
|
|
Factors that consolidate memory
|
Transmitters (ACh, dopamine...)
Stress/Emotions (adrenaline, NE) Sleep (REM sleep critical for learning) Practice |
|
|
Up-regulation of AMPA receptors is most likely to result in what to memory?
|
Increased memory
|
|
|
ACh; what reduces memory?
What improves memory? |
what reduces memory? decrease ACh
What improves memory? increase ACh |
|
|
What is the major nucleus that controls executive function and is the major projection nucleus to the prefrontal cortex (makes us human)
|
Medial Dorsal Nucleus
|
|
|
What part of the brain has an amazing ability for face recognition?
|
Inferior Temporal Region
|
|
|
Schizophrenia?
When does it present? Duration of illness? |
alteration of perception, thinking, speaking, emotions, movts and behavior with DELUSIONS and HALLUCINATIONS (auditory)
onset in late teens lifelong illness |
|
|
What is an illness that has no clear disctinction from schizophrenia?
|
Bipolar disorder
|
|
|
Risk factors for schizophrenia
|
Family Hx
Genes- COMT gene, change in gray matter density (cannabis susceptib) Neuroregulin gene, psychosis Paternal Age>50, immigrants, northern latitude, RUBELLA |
|
|
Describe course of schizophrenia
|
premorbid
prodromal psychosis RELAPSE- pt normal, multiple times deficit |
|
|
Neurobiological changes in schizophrenia
|
reduced gray matter and loss of gyrification
INCREASED activity in Brocas, hippocampus, cingulate gyrus (cause hallucinations, positive symptoms, delusions) Abnormal EEG REDUCED GAD7, Reelin, precursors of phospholipids |
|
|
What do you give to schizophrenia pts?
How do they work? |
Anti-psychotics (haloperidol)
dopamine (D2) antagonist-block D2 dopamine receptors |
|
|
What are the first generation anti-psychotics?
Used for? s/e? |
Haloperidol, D2 receptor antagonist
Schizophrenia Extra-pyramidal symptoms: parkinsonism, dystonia, tardive dyskinesia |
|
|
What are the second generation anti-psychotics?
Benefits? |
serotonin receptor antagonism
prevents Extrapyramidal symptoms typical of D2 receptor antagonists by selective dopamine stimulation of nigro-striatal pathway |
|
|
How long does meds help in schizophrenia?
Relapse rate? |
10-20 yrs
relapse rate is 80% in 5 yrs |
|
|
Serotonin hypothesis of Schizophrenia
|
LSD (5HT2a agonist)--causes vivid hallucinations and psychosis
Pure serotonin antagonists drugs are not anti-psychotic |
|
|
NMDA hypothesis of Schizophrenia
|
PCP blocks ion channel gated by NMDA glutamate receptor-->similar positive, negative and cognitive symptoms
|
|
|
Dopamine hypothesis of Schizophrenia
|
Positive symptoms due to increased meso-LIMBIC activity (hyperdopaminergia)
Negative symptoms due to decreased meso-CORTICAL activity (hypodopaminergia) Does not account for cognitive symptoms |
|
|
Anterior cingulate and Schizophrenia
|
Decreased activity-->thought disorder and attention deficits
|
|
|
Hippocampus and Schizophrenia
|
Increased activity-->Responsible for positive symptoms
|
|
|
Neurodevelopmental hypothesis of Schizophrenia
|
Early insults-->pathological neuron circuits
Multiple hits-->schizophrenia Need genes |
|
|
Phenylketonuria
|
Deficiency in phenylalanine hydroxylase-->prevents phenylalanine to tyrosine conversion
|
|
|
Rate limiting enzyme in sythesis of dopamine
|
Tyrosine Hydroxylase
Tyrosine-->Dopa |
|
|
What drugs cause dopamine release and prevents reuptake?
|
Cocaine and amphetamine
|
|
|
What is an antidepressant that is a DA and NE reuptake inhibitor?
|
Bupropion
|
|
|
What are dopamine agonists that are approved for use in Parkinsons and RLS?
|
PramipexOLE and RopinorOLE
|
|
|
Which dopamine system is responsible for the amenorrhea and galactorrhea seen with some antipsychotic meds?
|
Tuberoinfundibular
|
|
|
What is happening when someone has ADHD? What can you take?
|
dopamine is deficient in mesocortical system, take a dopamine agonist
|
|
|
Of the 4 dopamine systems, what are the two involved in schizophrenia and what symptoms are they responsible for?
|
Mesolimbic-increased DA resp for positive symptoms of schizophrenia, such as hallucinations, delusions
Mesocortical-increased DA resp for negative symptoms of apathy, affective flattening, anergy; also mediates focus, conc, attn of frontal lobes *4As* |
|
|
Of the 4 dopamine systems, what are the two that experience negative anti-dopaminergic effects for schizophrenia treatment and what symptoms are they responsible for?
|
Nigrostriatal- D2 blockade can cause parkinson's symptoms
Tuberoinfundibular- HPA axis, hyperprolactinemia; can give Bromocriptine, a dopamine agonist for these symptoms |
|
|
What post-synaptic enzymes breakdown DA?
|
COMT, MAO
|
|
|
If your pt has hyper prolactinemia from a dopamine antagonist, what can you give them?
|
Bromocriptine, a dopamine agonist
|
|
|
What drugs can interact with tyramines (cheeses, wine) and cause HTNsive crisis?
|
MAOIs-->norepinephrine
|
|
|
How do TCAs work?
What are TCAs good for? name one |
5-HT/serotonin reuptake inhibition, NE reuptake inhibition, serotonin antagonist
treating SEVERE depression Amitriptyline |
|
|
How do SSRIs work?
What are SSRIs good for? name one s/e |
5-HT reuptake inhibition
Anti-depressant, anti-anxiety Fluoxetine s/e-sex dysfunction |
|
|
How do MAOIs work?
What are MAOIs good for? name one Avoid? |
inhibit MAO, increase NE
Anti-depressant (ATYPICAL) Phenylzine avoid TYRAMINE!!! |
|
|
Advantage to SARIs over SSRIs?
|
less sexual dysfunction
|
|
|
What herbal can cause serotonin syndrome if paired with an SSRI or MAOI?
|
St. john's wart
|
|
|
What cell body is NE made
|
locus ceruleus
|
|
|
What cell body is Serotonin (5HT) made?
|
Raphe nuclei
|
|
|
What is found to be low in pts who have committed violent suicide? What is it?
|
5-HIAA, metabolite of serotonin
|
|
|
How do 2nd gen SNRIs work?
What are 2nd gen SNRIs good for? name one s/e |
increase 5HT (+) *increase NE*!
Anti-depressant, anti-anxiety (+) CHRONIC PAIN s/e sex dysfunction |
|
|
How do 2nd gen NaSSAs work?
What are 2nd gen NaSSAs good for? (Advantage of NaSSAs) |
universal blocker, tricks brain into thinking its catecholamine poor, increases 5HT activity
favorable s/e profile |
|
|
Serotonin syndrome
|
Altered mental status, autonomic dysfunction, tremor, ataxia, myoclonus, anxiety, agitation, hyperkineasia, hyperreflexia
From overstimulation of 5-HT receptors by SSRIs, TCAs, MAOIs |
|
|
Dysthymic Disorder
|
chronic, unremitting, low lying depression
2+ YEARS Poorer prognosis (personality based) |
|
|
INAH3
|
Interstitail nucleus of anterior hypothalamus
Present in males, hard to define in females No significant difference between heterosexual and homosexual men |
|
|
SDN-POA neurons
|
At birth, women shown to have a large drop in cell numbers
Estrogen (aromatized from testosterone) in men reduces programmed cell death |
|
|
Amygdala processing differences
Right Left |
Right-associated with memory for central information (big picture)=greater in men
Left-associated with memory for details=greater in women |
|
|
Males vs. Females Prevalence for Personality Disorders
|
Males: schizoid, antisocial, OCD
Females: dependent, histrionic, borderline |
|
|
Personality Disorder Clusters
A B C |
A-"Weird"--schizotypal, paranoid, schizoid; first degree relatives
B-"Wild"--Borderline, Antisocial, Narcissistic, Histrionic; in families C-"Worried"--Avoidant, Dependent, OCD; in families Cluster B and C are highly comorbid |
|
|
Panic Attack
|
Period of intense fear/discomfort with rapid onset and short duration accompanied by a feeling of impending doom
Characteristic autonomic findings (sweating, nausea, dizziness) |
|
|
Malingering
|
Voluntary and intention production of symptoms created to achieve secondary gain (avoidance of punishment, financial compensation/drugs, retaliate for legal penalty/job loss)
|
|
|
Body Dysmorphic Disorder
|
Preoccupation with imagined physical defect
Major depression, delusinoal disorder, OCD, social phobias females, Adolescence Treat with SSRI |
|
|
Hypochondriasis
|
Preoccupation with having or contracting a serious illness
Persists in spite of negative medical work-up Belief not delusional |
|
|
Cluster C DIsorders
|
"Worried" personality type
High degree of comorbidity with cluster B Reduction in dopaminergic activity and increased serotonergic activity |
|
|
Narcissistic Personality Disorder
|
inflated self esteem, sense of self importance, grandiosity and entitlement; unempathic, fragile self esteem
Interpersonal exploitation Coexists with other cluster Bs Intolerant of criticism Devalue others Idealization and omnipotence |
|
|
Antisocial Personality Disorder
|
Disregard for social norms, violation of other's rights, lack of remorse
Lack anxiety in stressful situations Appear pleasant or charming Criminal activity common Associated with ADHD Receitful, remorseless and aggressive **Cannot be diagnosed before the age of 18** EEGs abnormal--reduction in prefrontal grey |
|
|
Obsessive Compulsive Personality Disorder
|
Perfectionism, inflexibility, emotional constriction, indecisiveness
Preoccupation with rules and perfectionism Hoard worthless objects |
|
|
What Personality disorder is associated with increased levels of HVA? what is it?
|
Schizotypal; dopamine metabolite
|
|
|
Schizotypal vs. paranoid vs. schizoid
|
Schizotypal: ODDBALL
paranoid: DISTRUSTING schizoid: NO EMOTION |
|
|
Hypochondriasis
|
fears of having a serious illness
GI and cardiac complaints most common |
|
|
Conversion disorder
|
loss of sensor or motor function suggesting a neurological deficit
|
|
|
Common sx seen in pain disorder?
What should you give? |
unremitting pain that does not fluctuate in intensity or with changes in emotion;
Analgesics NOT Helpful Antidepressants drugs of choice |
|
|
Posttraumatic Stres Disorder
|
Direct cause implied
Symptoms experienced after exposure to a traumatic event in which the event involved death or threat of death or serious injury followed by the response of fear/helplessness or horror Re-experience the event Overreactivity to cues or reminders Avoidance behaviors, detachment and decreased interest Children--foreshortened future Not necessarily appear immediately after the actual trauma |
|
|
For all anxiety disorders, you should give SSRIs as first line treatment, except for what disorder? What drug should you give?
|
PTST; give MAO Inhibitors
|
|
|
Astrocytoma
|
Grades 1-2
ening form of diffuse infiltrating astrocytic neoplasia Tumor progresses to more malignant form Hits cerebral hemispheres 20-40 Survival >5 years |
|
|
Anaplastic astrocytoma
|
Grade 3: Malignant form
M > F Cerebral hemispheres No necrosis Survival 2-3 years |
|
|
Glioblastoma multiforme
|
Grade 4: most malignant form--80% from previous existing astrocytoma
Amplification of growth factor receptors and p53 mutation M > F, aged 50+ Necrosis with pseudopalisading and vascular proliferation Survival 8-10 months |
|
|
Meningioma
|
Tumor of arachnoid cells (from villi)
F > M Excellent prognosis if completely resected |
|
|
Medulloblastoma
|
Tumor of undifferentiated blasts
Exclusively in cerebellum of children Radiosensitive 5 year survival 75% |
|
|
Pilocytic astrocytoma
|
A tumor of children
|
|
|
Isolation Aphasia
|
Variety of fluent aphasia
Can ONLY repeat--repeat everythign that is said Infarction in watershed area Develop demential, cortical blindness, hemiparesis Cannot name objects, cannot follow requests-->general cognitive impairment |
|
|
Conduction Aphasia
|
Variant of fluent aphasia
Lesion in arcuate fasciculus between Wernicke's and Broca's area Can hear, speak, follow commands, name objections **CANNOT REPEAT** |
|
|
Fluent Aphasia
|
Wernicke's aphasia
Inability to express oneself, problem with content of words or phrasing Can be substitutes and neologisms **Paraphasias-individual abnormal words** Temporal or parietal damage-trauma, tumor (usually structural) Alzheimer's No cognitive or physical deficit Contralateral homonomous hemianopsia (cannot see right visual field-->damage of optic radiations) |
|
|
Non-fluent aphasia
|
Broca's aphasia
Non-verbal, <50 WPM, dysarthric (area near motor strip--weakness of arm and lower face), speak only when spoken to, nouns and verbs, no demential, normal emotion Left middle cerebral artery |
