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Lecture 21

PSY2301 Lecture 21: Disorders of Brain and Behaviour

11 Pages
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Department
Psychology
Course Code
PSY2301
Professor
Andra Smith

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Psychiatric*
Depression
Alzheimer's
Schizophrenia
Bipolar
Panic*Disorder
Drug*Abuse
Personality* Disorders
ADD*-ADHD
************Neurologic
Stroke
Head*injury
Congenital*
Epilepsy
Encephalitis
Meningitis
Autism
Multiple*Sclerosis
Scales
Glasgow*Coma*Scale*(3-15)
Mini*Mental*Assessment* (0-30)
ICD-10*=*The*International*Statistical*Classification* of*Diseases*and*Related*Health*Problems
DSM-IV*=*Diagnostic*and*Statistical*Manual*of*Mental*Disorders*-4th*Ed/*(Axis* I,*Axis*II)
Glasgow*Coma*Scale*(3-15)
Eye$Opening
None*1*=*Even*to*supra-orbital* pressure
To*pain*2*=*Pain*from*sternum/limb/supra-orbital* pressure
To*speech* 3*=*Non-specific* response,* not*necessarily*to*command
Spontaneous* 4*=*Eyes*open,*not*necessarily* aware
Motor$Response
None*1*=*To*any*pain;*limbs*remain*flaccid
Extension*2*=*Shoulder* adducted*and*shoulder* and*forearm*internally*rotated
Flexor*response* 3*=*Withdrawal*response* or*assumption* of*hemiplegic*posture
Withdrawal*4*=*Arm*withdraws*to*pain,* shoulder* abducts
Localizes*pain*5*=*Arm*attempts*to*remove*supra-orbital/chest* pressure
Obeys* commands*6*=*Follows* simple*commands
Verbal$Response
None*1*=*No*verbalization*of*any*type
Incomprehensible* 2*=*Moans/groans,* no*speech
Inappropriate*3*=*Intelligible,*no*sustained*sentences
Confused* 4*=*Converses* but*confused,* disoriented
Oriented*5*=*Converses* and*oriented
Mini*Mental*Assessment* (0-30)
!"#$%&'&#!%()*+,(-*.+/(0*1(,234(2+56,1
'57:*“What*is*the:*(year)(season)(date)(day)(month)?”* ____
'57:*“Where*are*we:*(state)(county)(town)(hospital)(floor)?”* ____
"$8#9&"'&#!%()53*1,(:;<;=(-*.+/5(233*1>.+?(/*(4*6(@2+A(21,(1,-,2/,>
%2@,(/41,,(*BC,3/5:*Give*the*patient*one*second* to*say*each.
'57(/4,(-2/.,+/(/*:*repeat*all*three*after*you*have*said*them.
Repeat*them*until*the*patient*learns*all*three.*____
'&&$%&#!%('%D(E'FEGF'&#!%( )*+,(-*.+/(0*1(,234(3*11,3/(5HB/123/.*+
'57(/4,(-2/.,+/(/*:*begin*from*100*and*count*backwards*by*7.*Stop*after*5*answers*-(93,*86,*
79,*72,*65)*____
"$E'FF()*+,(-*.+/(0*1(,234(3*11,3/(2+56,1
'57(/4,(-2/.,+/(/*:*name*the*three*objects*from*above.*____
F'%8G'8$
'57(/4,(-2/.,+/(/*:*identify* and*name*a*pencil*and*a*watch.*(2*points)* ____
'57(/4,(-2/.,+/(/*:*repeat*the*phrase*“No*ifs,* ands,* or*buts.”*(1*point)*____
'57(/4,(-2/.,+/(/*:*“Take*a*paper*in*your*right*hand,*fold* it*in*half,
and*put*it*on*the*floor*“*(1*point*for*each*task*completed* properly)*IIII
'57(/4,(-2/.,+/(/*:*read*and*obey*the*following:* “Close*your*eyes.”*(1*point)* IIII
'57(/4,(-2/.,+/(/*:*write*a*sentence.*(1*point)*IIII
'57(/4,(-2/.,+/(/*:*copy*a*complex*diagram*of*two*interlocking* pentagons.*(1*point)*IIII
Example
The*patient*fulfills* a*total*of*at*least*6*criteria*from*the*following* 3*lists,* distributed* as*
indicated:
#@-2.1,>(5*3.2J(.+/,123/.*+(K2/(J,25/(<LM
-Markedly*deficient*regulation*of*social*interaction*by*using*multiple* non-verbal* behaviours*
such*as*eye*contact,*facial*expression,* body* posture*and*gestures
-Lack*of*peer*relationships* that*are*appropriate*to*the*developmental* level
-Doesn't*seek*to*share*achievements,*interests*or*pleasure*with*others
-Lacks*social*or*emotional*reciprocity
#@-2.1,>(3*@@H+.32/.*+(K2/(J,25/(:LM
-Delayed*or*absent*development*of*spoken* language*for*which*the*patient*doesn't*try*to*
compensate*with*gestures
-In*patients*who*can*speak,*inadequate*attempts*to*begin*or*sustain*a*conversation
-Language*that*is*repetitive,*stereotyped*or*idiosyncratic
-Appropriate*to*developmental*stage,*absence*of*social*imitative*play*or*spontaneous,*
make-believe* play
'3/.N./.,5;(B,42N.*1(2+>(.+/,1,5/5(/42/(21,(1,-,/./.N,;(1,5/1.3/,>(2+>(5/,1,*/A-,>(K2/(J,25/(:(
*0LM
-Preoccupation* with*abnormal*(in*focus* or*intensity)* interests*that*are*restricted*and*
stereotyped*(such* as*spinning* things)
-Rigidly*sticks*to*routines*or*rituals*that*don't*appear*to*have*a*function
-Has*stereotyped,* repetitive*motor*mannerisms*(such* as*hand*flapping)
Persistently* preoccupied*with*parts*of*objects*
Histrionic
A*pervasive* pattern*of*excessive* emotionality*and*attention*seeking,* beginning*by*early*
adulthood* and*present*in*a*variety*of*contexts,*as*indicated*by*5*(or*more)*of*the*following:
-Discomfort*with*situations*in*which*the*patient*is*not*the*center*of*attention.
-Relationships*that*are*frequently*fraught*with*inappropriately*seductive*or*sexually*
provocative*behaviour.
-Expression* of*emotion* is*shallow* and*rapidly* shifting.
-Frequent*focusing* of*attention*on*self*through*use*of*physical* appearance.**
*****-Speech*is*vague*and*lacks*detail.
-Overly*dramatic*expression* of*emotion.
-Easy*suggestibility*(readily*influenced* by*opinions* of*other*people).
-Belief*that*relationships* are*more*intimate*than*they*really*are.*
Treatments
Biofeedback
Pharmacotherapy
Surgery
Psychotherapy
Cognitive*Therapy
Stem*Cells
Parkinson's*Disease
MPTP*-drug-induced*Parkinson's*symptoms*-depletion*of*substantia*negra*DA
Nigrostriatal*DA*pathway*=*substantia*nigra*to*striatum
Post-mortems*-<*100,000*nigral*neurons*=*DA*stared*striatum
~60%*of*nigral*neurons*have*to*be*lost,*with*an*80%*depletion*of*striatal*DA,*before*the*
symptoms*of*PD*develop
Treatment*for*Parkinson's
MAO*inhibitor*(ex.*Eldepryl)*slows*down*breakdown*of*DA
L-DOPA*is*initially* good*but*becomes*problematic*(eventual*dyskinesia)*and*is*required*
at*greater*and*greater*doses*as*the*disorder*progresses
Sinement*=*L-DOPA*+*carbodopa*(inhibitor*that*prevents*L-DOPA*from*being*absorbed*
by*tissue*other*than*the*brain)
Use*of*DA*agonists*delay*use*of*L-DOPA,*reduce*eventual*dose*of*L-DOPA*and*reduce*
motor*problems*(ex.*Requip*and*Mirapex)
Ex.*Rascol*Study
Subjects:*early*PD*untreated*patients*
Treatment*groups
treated*with*ropinerole*(agonist)*+*could*get*supplemental* L-DOPA*or1)
L-DOPA*and*could*only*have*dose*increased2)
After*5*years
46%*in*group*2)*had*dyskinesia
20%*in*group*1)*had*dyskinesia* whether*supplemented* with*
L-DOPA*or*not
PD*symptoms* were*same*in*each*group.
Better*to*use*a*DA*agonist*for*as*long*as*possible.
Fetal*DA*Neuron*Transplants
Tissue*from*ventral*midbrain*of*aborted*fetuses* at*6-9*weeks*post-conception.
Surgically*placed*into*the*caudate*and/or* putamen.
Grafts*reinnervate*the*denervated*striatum,*form*synaptic*connections* with*host*neurons,*
release*DA*and*produce*some*functional* recovery.
Mild*to*moderate*improvement* in*motor*disturbances*without*major*side*effects.
Other*Treatments
1.*Deep*brain*stimulators* of*thalamus*and*subthalamic* nucleus.
2.*Stem*cells
1)*capable*of*dividing*and*renewing*themselves* for*long*periods* through*cell*division
2)*unspecialized
3)*can*give*rise*to*specialized*cell*types*under*certain*physiologic* or*experimental*
conditions,* e.g.*special*functions* such*as*the*beating*cells*of*the*heart*muscle*or*the*
DA*producing*cells*of*the*brain.*
Embryonic* Stem*Cells
Stem*cells*taken*from*a*human*embryo.
Added*a*gene*that*produces* an*antitumour*molecule*named*TRAIL.
Injected*the*stem*cells*into*mice*with*brain*tumours.
The*cells*localized*on*the*cancer*and*produced* enough*TRAIL*to*cut*the*tumour*size*by*
50%-70%.
The*cells*track*the*tumour*by*following* chemical*signals* emitted*by*the*immune*system*
molecules* that*attack,*but*fail*to*destroy,* the*cancer.*
There*have*been*other*animal*models* of*brain*injury*where*naturally*occurring*stem*cells*
will*travel*towards*and*try*to*repair*damaged*areas.
Stem*Cells* in*Humans
National*Institute*of*Neurological*Diseases*and*Stroke*
Brain*tissue*from*female*post*mortems*who*had*bone*marrow*transplant*from*male*donors.
All*patients*had*brain*tissue* with*clumps* of*Y-positive* cells.*
Suggesting*that*the*original*donor*cells*had*continued* to*multiply* after*differentiating*into*
brain*cells.*
Umbilical*Cord*Cells
Can*inject*into*jugular*vein*or*directly*transplant*into*the*brain.
Researchers*first*gave*the*drug,*mannitol,*to*provide*temporary*passage*through*the*blood-
brain*barrier*then*transfused* human*umbilical* cord*blood* cells*into*a*stroke*animal*model.
When*used* in*the*first*hours* and*days*following* a*stroke,* stroke*size*decreased*by*40*
percent*and*resulting*disability* was*significantly* reduced.
This*treatment*significantly* increased*brain*levels*of*neurotrophic* factors,*which*correlated*
positively* with*reduced*cerebral*infarcts*and*improved* behavioural*functions.*
Deprogramming*Stem*Cells
Kyoto*Japan,*University* of*Wisconsin
Created*pluripotent* human*stem*cells*using* ‘deprogramming’*human*somatic*cells*(skin*
fibroblasts).
Expose*skin* cells*to*specific*signaling*agents*that*reprogram*the*genetic*expression* pattern*
of*a*cell.
Cells*switch*from*skin* cell*precursors* to*more*embryonic-like,* capable*of*developing* into*
various*other*tissues* and*organ-specific* cells.
Controlling* Stem*Cells
How*cells*in*the*blood*enter*the*brain?
How*to*induce*them*to*enter*the*brain*in*larger*numbers?
How*to*promote*their*differentiation*into*neurons?
How*to*target*them*to*areas*of*need?
Are*the*internal*and*external*signals*for*cell*differentiation*similar* for*all*kinds*of*stem*cells?
Can*specific*sets*of*signals*be*identified* that*promote*differentiation* into*specific* cell*types?
Prevent*the*introduction* of*harmful* viruses* or*immune*reactions.*
Stem*Cells
In*the*3-to*5-day-old* embryo,* stem*cells*
in*developing* tissues*give*rise*to*the*
multiple*specialized*cell*types*that*make*
up*the*heart,*lung,*skin,* brain*and*other*
tissues.*
In*some*adult*tissues,*such*as*bone*
marrow,*muscle,*and*brain,*discrete*
populations* of*adult*stem*cells*generate*
replacements*for*cells*that*are*lost*
through*normal*wear*and*tear,*injury,* or*
disease.
Epilepsy
Elton*John,* Alexander*the*Great,*Charles* Dickens,*Vincent*Van*Gogh,*Peter*Tchaikovsky,*
Napoleon,* Danny*Glover,*and*Albert*Einstein*all*had*epilepsy!
Epilepsy* affects*1%*of*the*population* and*is*thus*one*of*the*most*common* neurological*
diseases.*It*can*begin*at*any*age.*
Epilepsy* is*defined*as*1,3H11.+? seizures*resulting*from*abnormal,*temporary,*cell*firing,*or*
electrical*function*in*the*brain*(~5%*of*all*people*have*a*seizure*at*some*point*but*do*not*
necessarily* develop*epilepsy).
In*approximately*30%*of*cases,*epilepsy*is*caused*by*such*events*as*head*trauma,*tumor,*
stroke,*or*infection.*Other*reasons*are*related*to*a*genetic*predisposition* for*epilepsy* or*an*
unknown* source.**
Epilepsy* can*produce*many*kinds* of*seizures,*depending* on*the*part*of*the*brain*that*is*
affected.*
Frontal*Lobe*Seizures
Can*be*generalized*of*partial*seizures
Many*triggers*and*causes
Causes* and*Triggers
Brain*damage*related*to*birth.
Brain*infection.
Brain*tumours.
Abnormalities* in*blood*vessels* of*the*brain.
Genetics.
Unknown.
Surgery*as*Treatment
The*following* conditions* must*be*fulfilled:
The*epilepsy* must*be*characterized*by*partial*seizures*with*or*without*generalized*seizures*
as*well.*
The*seizures*must*be*resistant*to*reasonable* efforts*at*control*with*medication.*
The*proposed* surgical*procedure*must*carry*a*sufficiently* low*risk*of*causing*unacceptable*
neurological*impairment.*
Epilepsy* must*be*the*persons* most*disabling* medical*problem.*
Alternate*Treatment
Vagus*nerve*stimulation*(VNS)*is*designed* to*prevent*seizures*by*sending*regular,*mild*
pulses* of*electrical*energy*to*the*brain*via*the*vagus*nerve.*These*pulses* are*supplied* by*a*
device*something*like*a*pacemaker.
This*pacemaker*for*the*brain*is*placed*under*the*skin*on*the*chest*wall*and*a*wire*runs*
from*it*to*the*vagus*nerve*in*the*neck.*
The*vagus*nerve*is*part*of*the*autonomic* nervous*system,* which*controls* functions* of*the*
body* that*are*not*under*voluntary* control,*such* as*heart*rate.*The*vagus*nerve*passes*
through*the*neck*as*it*travels*between*the*chest*and*abdomen*and*the*brainstem*of*the*
brain.
Vagus*Nerve*Stimulation
VNS*produces*desynchronization* of*cortical*EEG*and*measurable*changes*in*blood* flow*in*
the*cerebellum,* thalamus*and*cortex.*Perhaps*this*occurs*by*activating*inhibitory* structures*
in*the*brain*but*the*precise*mode*of*action*of*VNS*is*not*known.
Other*areas*possibly* activated*by*VNS*include* the*medulla,* parabrachial*nucleus,* locus*
coeruleus,* hypothalamus,* amygdala,*hippocampus,* cingulate*gyrus,*and*contralateral*
somatosensory* cortex.*
It*is*thought*that*perhaps*VNS*decreases*cortical*epileptiform*activity*indirectly*by*
influencing* the*reticular*activating*system*or*that*VNS*increases*the*seizure*threshold* by*
causing*widespread*release*of*GABA*and*glycine*in*the*brain.*
Studies*of*VNS
Ben-Menachem*et*al*measured*amino*acid*and*neurotransmitter*metabolite*
concentrations*in*cerebrospinal* fluid*(CSF)* samples*of*patients*on*clinical*trials*of*VNS*
before*and*3*months*after*VNS*placement.*
Responders* to*the*VNS*had*larger*amounts*of*GABA*and*less* glutamate*after*
treatment.*
Excitotoxicity
Glutamate*is*the*most*prevalent*neurotransmitter*in*the*brain*and*plays*a*role*in*several*
major*neurological*processes* like*LTP.*
When*the*brain*is*injured* it*releases*abnormally* large*amounts*of*glutamate,*over-
stimulating*the*glutamate*receptors*on*the*surface*membranes*of*postsynaptic* neurons.*
This*in*turn,*causes*unusually* large*amounts*of*calcium*to*enter*the*nerve*cells*which*
disrupts* biochemical*processes* within*the*neuron*and*activates*enzymes*that*produce* free*
radicals.*
Free*radicals*are*structurally*unbalanced*chemicals*capable*of*destroying* other*compounds*
that*form*the*internal*structure*of*neurons.*
Neuronal*cell*death*as*a*result*of*this*increase*in*glutamate*and*influx*of*calcium*that*results*
in*increased*free*radicals*=*Excitotoxicity.
Disorders*Involving*Excitotoxicity
Excitotoxicity*can*be*triggered*by*anything*that*deprives* the*brain*of*its*normal*supply* of*
oxygen*e.g.*Stroke.*That*is*why*there*is*cell*death*in*the*area*where*the*stroke*occurs.*
Most*treatments*to*help*stroke*sufferers*needs* to*be*administered* quickly* after*the*stroke*
begins.*These*drugs*include* glutamate*receptor*antagonists.
These*drugs*can*also*be*used*for*traumatic*brain*injury,* epilepsy* and*hypoglycemia* all*
disorders* that*can*lead*to*reduced*oxygenation* and*thus*excitotoxicity.*
Parkinson,* Huntingtons*and*Alzheimers* also*have*been*linked* to*excitotoxicity*so*these*
drugs*might*help*with*these*disorders* also.*
Stroke*Treatment
Thrombolytic* drugs*=*drugs*that*immediately*dissolve* the*blood* clots*that*cause*many*
strokes,* drastically*reducing*the*amount*of*damage*strokes*produce.*E.g.*Tissue*
plasminogen* activator*(tPA),*r-tPA,*streptokinase,* urokinase*and*prourokinase.*
Thrombolytics,* however,*only* work*if*delivered* directly*into*the*bloodstream,* either*through*
a*vein*or*an*artery*(intra-arterial)*and*only*if*administered*within*a*few*hours*of*the*stroke*
before*the*oxygen-deprived* nerve*cells*suffer* permanent*damage.*
The*time*window* for*getting*the*best*results*from*thrombolytic* drugs*is*three*hours* from*
the*first*signs*of*stroke.
O&.@,(.5(B12.+P
Alcohol* -heavy*drinking*
Stress*
Patterns*of*light,*especially*
flickering*or*rapid*strobe*light*
Late*nights,* shift*work,*and*
lack*of*sleep*
Illness,*especially*with*high*
fever*
Hormones*-seizures*can*be*
increased*just*before*or*
during*first*days*of*
menstruation*
Apoptosis
Not*just*excitotoxicity*causes*neuronal* death*but*an*internal*self*destructive*chemical*
program*=*cell*suicide*occurs*in*response* to*the*damage*caused*by*a*lack*of*oxygen*to*
neurons.*
Need*to*have*drugs*that*can*prevent*both*excitotoxicity*and*apoptosis.*
Apoptosis* is*implicated*in*the*progressive* loss* of*oligodendrocytes* in*multiple*sclerosis.
Free*radicals*are*also*thought*to*be*a*major*player*in*aging.*
Summary
Identify*and*classify*disorder.
Many*potential*sources* of*disorders* of*brain*and*behaviour* e.g.*anatomy,*chemistry,*
physiology,* genetics,*environment.
New*treatments*are*on*the*horizon.*
Disorders(of(Brain(and(Behaviour
Wednesday,* November* 30,*2016
7:45*PM
Psychiatric*
Depression
Alzheimer's
Schizophrenia
Bipolar
Panic*Disorder
Drug*Abuse
Personality* Disorders
ADD*-ADHD
Tourette’s*Syndrome
************Neurologic
Stroke
Head*injury
Congenital*
Epilepsy
Encephalitis
Meningitis
Autism
Multiple*Sclerosis
Scales
Glasgow*Coma*Scale*(3-15)
Mini*Mental*Assessment* (0-30)
ICD-10*=*The*International*Statistical*Classification* of*Diseases*and*Related*Health*Problems
DSM-IV*=*Diagnostic*and*Statistical*Manual*of*Mental*Disorders*-4th*Ed/*(Axis* I,*Axis*II)
Glasgow*Coma*Scale*(3-15)
Eye$Opening
None*1*=*Even*to*supra-orbital* pressure
To*pain*2*=*Pain*from*sternum/limb/supra-orbital* pressure
To*speech* 3*=*Non-specific* response,* not*necessarily*to*command
Spontaneous* 4*=*Eyes*open,*not*necessarily* aware
Motor$Response
None*1*=*To*any*pain;*limbs*remain*flaccid
Extension*2*=*Shoulder* adducted*and*shoulder* and*forearm*internally*rotated
Flexor*response* 3*=*Withdrawal*response* or*assumption* of*hemiplegic*posture
Withdrawal*4*=*Arm*withdraws*to*pain,* shoulder* abducts
Localizes*pain*5*=*Arm*attempts*to*remove*supra-orbital/chest* pressure
Obeys* commands*6*=*Follows* simple*commands
Verbal$Response
None*1*=*No*verbalization*of*any*type
Incomprehensible* 2*=*Moans/groans,* no*speech
Inappropriate*3*=*Intelligible,*no*sustained*sentences
Confused* 4*=*Converses* but*confused,* disoriented
Oriented*5*=*Converses* and*oriented
Mini*Mental*Assessment* (0-30)
!"#$%&'&#!%()*+,(-*.+/(0*1(,234(2+56,1
'57:*“What*is*the:*(year)(season)(date)(day)(month)?”* ____
'57:*“Where*are*we:*(state)(county)(town)(hospital)(floor)?”* ____
"$8#9&"'&#!%()53*1,(:;<;=(-*.+/5(233*1>.+?(/*(4*6(@2+A(21,(1,-,2/,>
%2@,(/41,,(*BC,3/5:*Give*the*patient*one*second* to*say*each.
'57(/4,(-2/.,+/(/*:*repeat*all*three*after*you*have*said*them.
Repeat*them*until*the*patient*learns*all*three.*____
'&&$%&#!%('%D(E'FEGF'&#!%( )*+,(-*.+/(0*1(,234(3*11,3/(5HB/123/.*+
'57(/4,(-2/.,+/(/*:*begin*from*100*and*count*backwards*by*7.*Stop*after*5*answers*-(93,*86,*
79,*72,*65)*____
"$E'FF()*+,(-*.+/(0*1(,234(3*11,3/(2+56,1
'57(/4,(-2/.,+/(/*:*name*the*three*objects*from*above.*____
F'%8G'8$
'57(/4,(-2/.,+/(/*:*identify* and*name*a*pencil*and*a*watch.*(2*points)* ____
'57(/4,(-2/.,+/(/*:*repeat*the*phrase*“No*ifs,* ands,* or*buts.”*(1*point)*____
'57(/4,(-2/.,+/(/*:*“Take*a*paper*in*your*right*hand,*fold* it*in*half,
and*put*it*on*the*floor*“*(1*point*for*each*task*completed* properly)*IIII
'57(/4,(-2/.,+/(/*:*read*and*obey*the*following:* “Close*your*eyes.”*(1*point)* IIII
'57(/4,(-2/.,+/(/*:*write*a*sentence.*(1*point)*IIII
'57(/4,(-2/.,+/(/*:*copy*a*complex*diagram*of*two*interlocking* pentagons.*(1*point)*IIII
Example
The*patient*fulfills* a*total*of*at*least*6*criteria*from*the*following* 3*lists,* distributed* as*
indicated:
#@-2.1,>(5*3.2J(.+/,123/.*+(K2/(J,25/(<LM
-Markedly*deficient*regulation*of*social*interaction*by*using*multiple* non-verbal* behaviours*
such*as*eye*contact,*facial*expression,* body* posture*and*gestures
-Lack*of*peer*relationships* that*are*appropriate*to*the*developmental* level
-Doesn't*seek*to*share*achievements,*interests*or*pleasure*with*others
-Lacks*social*or*emotional*reciprocity
#@-2.1,>(3*@@H+.32/.*+(K2/(J,25/(:LM
-Delayed*or*absent*development*of*spoken* language*for*which*the*patient*doesn't*try*to*
compensate*with*gestures
-In*patients*who*can*speak,*inadequate*attempts*to*begin*or*sustain*a*conversation
-Language*that*is*repetitive,*stereotyped*or*idiosyncratic
-Appropriate*to*developmental*stage,*absence*of*social*imitative*play*or*spontaneous,*
make-believe* play
'3/.N./.,5;(B,42N.*1(2+>(.+/,1,5/5(/42/(21,(1,-,/./.N,;(1,5/1.3/,>(2+>(5/,1,*/A-,>(K2/(J,25/(:(
*0LM
-Preoccupation* with*abnormal*(in*focus* or*intensity)* interests*that*are*restricted*and*
stereotyped*(such* as*spinning* things)
-Rigidly*sticks*to*routines*or*rituals*that*don't*appear*to*have*a*function
-Has*stereotyped,* repetitive*motor*mannerisms*(such* as*hand*flapping)
Persistently* preoccupied*with*parts*of*objects*
Histrionic
A*pervasive* pattern*of*excessive* emotionality*and*attention*seeking,* beginning*by*early*
adulthood* and*present*in*a*variety*of*contexts,*as*indicated*by*5*(or*more)*of*the*following:
-Discomfort*with*situations*in*which*the*patient*is*not*the*center*of*attention.
-Relationships*that*are*frequently*fraught*with*inappropriately*seductive*or*sexually*
provocative*behaviour.
-Expression* of*emotion* is*shallow* and*rapidly* shifting.
-Frequent*focusing* of*attention*on*self*through*use*of*physical* appearance.**
*****-Speech*is*vague*and*lacks*detail.
-Overly*dramatic*expression* of*emotion.
-Easy*suggestibility*(readily*influenced* by*opinions* of*other*people).
-Belief*that*relationships* are*more*intimate*than*they*really*are.*
Treatments
Biofeedback
Pharmacotherapy
Surgery
Psychotherapy
Cognitive*Therapy
Stem*Cells
Parkinson's*Disease
MPTP*-drug-induced*Parkinson's*symptoms*-depletion*of*substantia*negra*DA
Nigrostriatal*DA*pathway*=*substantia*nigra*to*striatum
Post-mortems*-<*100,000*nigral*neurons*=*DA*stared*striatum
~60%*of*nigral*neurons*have*to*be*lost,*with*an*80%*depletion*of*striatal*DA,*before*the*
symptoms*of*PD*develop
Treatment*for*Parkinson's
MAO*inhibitor*(ex.*Eldepryl)*slows*down*breakdown*of*DA
L-DOPA*is*initially* good*but*becomes*problematic*(eventual*dyskinesia)*and*is*required*
at*greater*and*greater*doses*as*the*disorder*progresses
Sinement*=*L-DOPA*+*carbodopa*(inhibitor*that*prevents*L-DOPA*from*being*absorbed*
by*tissue*other*than*the*brain)
Use*of*DA*agonists*delay*use*of*L-DOPA,*reduce*eventual*dose*of*L-DOPA*and*reduce*
motor*problems*(ex.*Requip*and*Mirapex)
Ex.*Rascol*Study
Subjects:*early*PD*untreated*patients*
Treatment*groups
treated*with*ropinerole*(agonist)*+*could*get*supplemental* L-DOPA*or1)
L-DOPA*and*could*only*have*dose*increased2)
After*5*years
46%*in*group*2)*had*dyskinesia
20%*in*group*1)*had*dyskinesia* whether*supplemented* with*
L-DOPA*or*not
PD*symptoms* were*same*in*each*group.
Better*to*use*a*DA*agonist*for*as*long*as*possible.
Fetal*DA*Neuron*Transplants
Tissue*from*ventral*midbrain*of*aborted*fetuses* at*6-9*weeks*post-conception.
Surgically*placed*into*the*caudate*and/or* putamen.
Grafts*reinnervate*the*denervated*striatum,*form*synaptic*connections* with*host*neurons,*
release*DA*and*produce*some*functional* recovery.
Mild*to*moderate*improvement* in*motor*disturbances*without*major*side*effects.
Other*Treatments
1.*Deep*brain*stimulators* of*thalamus*and*subthalamic* nucleus.
2.*Stem*cells
1)*capable*of*dividing*and*renewing*themselves* for*long*periods* through*cell*division
2)*unspecialized
3)*can*give*rise*to*specialized*cell*types*under*certain*physiologic* or*experimental*
conditions,* e.g.*special*functions* such*as*the*beating*cells*of*the*heart*muscle*or*the*
DA*producing*cells*of*the*brain.*
Embryonic* Stem*Cells
Stem*cells*taken*from*a*human*embryo.
Added*a*gene*that*produces* an*antitumour*molecule*named*TRAIL.
Injected*the*stem*cells*into*mice*with*brain*tumours.
The*cells*localized*on*the*cancer*and*produced* enough*TRAIL*to*cut*the*tumour*size*by*
50%-70%.
The*cells*track*the*tumour*by*following* chemical*signals* emitted*by*the*immune*system*
molecules* that*attack,*but*fail*to*destroy,* the*cancer.*
There*have*been*other*animal*models* of*brain*injury*where*naturally*occurring*stem*cells*
will*travel*towards*and*try*to*repair*damaged*areas.
Stem*Cells* in*Humans
National*Institute*of*Neurological*Diseases*and*Stroke*
Brain*tissue*from*female*post*mortems*who*had*bone*marrow*transplant*from*male*donors.
All*patients*had*brain*tissue* with*clumps* of*Y-positive* cells.*
Suggesting*that*the*original*donor*cells*had*continued* to*multiply* after*differentiating*into*
brain*cells.*
Umbilical*Cord*Cells
Can*inject*into*jugular*vein*or*directly*transplant*into*the*brain.
Researchers*first*gave*the*drug,*mannitol,*to*provide*temporary*passage*through*the*blood-
brain*barrier*then*transfused* human*umbilical* cord*blood* cells*into*a*stroke*animal*model.
When*used* in*the*first*hours* and*days*following* a*stroke,* stroke*size*decreased*by*40*
percent*and*resulting*disability* was*significantly* reduced.
This*treatment*significantly* increased*brain*levels*of*neurotrophic* factors,*which*correlated*
positively* with*reduced*cerebral*infarcts*and*improved* behavioural*functions.*
Deprogramming*Stem*Cells
Kyoto*Japan,*University* of*Wisconsin
Created*pluripotent* human*stem*cells*using* ‘deprogramming’*human*somatic*cells*(skin*
fibroblasts).
Expose*skin* cells*to*specific*signaling*agents*that*reprogram*the*genetic*expression* pattern*
of*a*cell.
Cells*switch*from*skin* cell*precursors* to*more*embryonic-like,* capable*of*developing* into*
various*other*tissues* and*organ-specific* cells.
Controlling* Stem*Cells
How*cells*in*the*blood*enter*the*brain?
How*to*induce*them*to*enter*the*brain*in*larger*numbers?
How*to*promote*their*differentiation*into*neurons?
How*to*target*them*to*areas*of*need?
Are*the*internal*and*external*signals*for*cell*differentiation*similar* for*all*kinds*of*stem*cells?
Can*specific*sets*of*signals*be*identified* that*promote*differentiation* into*specific* cell*types?
Prevent*the*introduction* of*harmful* viruses* or*immune*reactions.*
Stem*Cells
In*the*3-to*5-day-old* embryo,* stem*cells*
in*developing* tissues*give*rise*to*the*
multiple*specialized*cell*types*that*make*
up*the*heart,*lung,*skin,* brain*and*other*
tissues.*
In*some*adult*tissues,*such*as*bone*
marrow,*muscle,*and*brain,*discrete*
populations* of*adult*stem*cells*generate*
replacements*for*cells*that*are*lost*
through*normal*wear*and*tear,*injury,* or*
disease.
Epilepsy
Elton*John,* Alexander*the*Great,*Charles* Dickens,*Vincent*Van*Gogh,*Peter*Tchaikovsky,*
Napoleon,* Danny*Glover,*and*Albert*Einstein*all*had*epilepsy!
Epilepsy* affects*1%*of*the*population* and*is*thus*one*of*the*most*common* neurological*
diseases.*It*can*begin*at*any*age.*
Epilepsy* is*defined*as*1,3H11.+? seizures*resulting*from*abnormal,*temporary,*cell*firing,*or*
electrical*function*in*the*brain*(~5%*of*all*people*have*a*seizure*at*some*point*but*do*not*
necessarily* develop*epilepsy).
In*approximately*30%*of*cases,*epilepsy*is*caused*by*such*events*as*head*trauma,*tumor,*
stroke,*or*infection.*Other*reasons*are*related*to*a*genetic*predisposition* for*epilepsy* or*an*
unknown* source.**
Epilepsy* can*produce*many*kinds* of*seizures,*depending* on*the*part*of*the*brain*that*is*
affected.*
Frontal*Lobe*Seizures
Can*be*generalized*of*partial*seizures
Many*triggers*and*causes
Causes* and*Triggers
Brain*damage*related*to*birth.
Brain*infection.
Brain*tumours.
Abnormalities* in*blood*vessels* of*the*brain.
Genetics.
Unknown.
Surgery*as*Treatment
The*following* conditions* must*be*fulfilled:
The*epilepsy* must*be*characterized*by*partial*seizures*with*or*without*generalized*seizures*
as*well.*
The*seizures*must*be*resistant*to*reasonable* efforts*at*control*with*medication.*
The*proposed* surgical*procedure*must*carry*a*sufficiently* low*risk*of*causing*unacceptable*
neurological*impairment.*
Epilepsy* must*be*the*persons* most*disabling* medical*problem.*
Alternate*Treatment
Vagus*nerve*stimulation*(VNS)*is*designed* to*prevent*seizures*by*sending*regular,*mild*
pulses* of*electrical*energy*to*the*brain*via*the*vagus*nerve.*These*pulses* are*supplied* by*a*
device*something*like*a*pacemaker.
This*pacemaker*for*the*brain*is*placed*under*the*skin*on*the*chest*wall*and*a*wire*runs*
from*it*to*the*vagus*nerve*in*the*neck.*
The*vagus*nerve*is*part*of*the*autonomic* nervous*system,* which*controls* functions* of*the*
body* that*are*not*under*voluntary* control,*such* as*heart*rate.*The*vagus*nerve*passes*
through*the*neck*as*it*travels*between*the*chest*and*abdomen*and*the*brainstem*of*the*
brain.
Vagus*Nerve*Stimulation
VNS*produces*desynchronization* of*cortical*EEG*and*measurable*changes*in*blood* flow*in*
the*cerebellum,* thalamus*and*cortex.*Perhaps*this*occurs*by*activating*inhibitory* structures*
in*the*brain*but*the*precise*mode*of*action*of*VNS*is*not*known.
Other*areas*possibly* activated*by*VNS*include* the*medulla,* parabrachial*nucleus,* locus*
coeruleus,* hypothalamus,* amygdala,*hippocampus,* cingulate*gyrus,*and*contralateral*
somatosensory* cortex.*
It*is*thought*that*perhaps*VNS*decreases*cortical*epileptiform*activity*indirectly*by*
influencing* the*reticular*activating*system*or*that*VNS*increases*the*seizure*threshold* by*
causing*widespread*release*of*GABA*and*glycine*in*the*brain.*
Studies*of*VNS
Ben-Menachem*et*al*measured*amino*acid*and*neurotransmitter*metabolite*
concentrations*in*cerebrospinal* fluid*(CSF)* samples*of*patients*on*clinical*trials*of*VNS*
before*and*3*months*after*VNS*placement.*
Responders* to*the*VNS*had*larger*amounts*of*GABA*and*less* glutamate*after*
treatment.*
Excitotoxicity
Glutamate*is*the*most*prevalent*neurotransmitter*in*the*brain*and*plays*a*role*in*several*
major*neurological*processes* like*LTP.*
When*the*brain*is*injured* it*releases*abnormally* large*amounts*of*glutamate,*over-
stimulating*the*glutamate*receptors*on*the*surface*membranes*of*postsynaptic* neurons.*
This*in*turn,*causes*unusually* large*amounts*of*calcium*to*enter*the*nerve*cells*which*
disrupts* biochemical*processes* within*the*neuron*and*activates*enzymes*that*produce* free*
radicals.*
Free*radicals*are*structurally*unbalanced*chemicals*capable*of*destroying* other*compounds*
that*form*the*internal*structure*of*neurons.*
Neuronal*cell*death*as*a*result*of*this*increase*in*glutamate*and*influx*of*calcium*that*results*
in*increased*free*radicals*=*Excitotoxicity.
Disorders*Involving*Excitotoxicity
Excitotoxicity*can*be*triggered*by*anything*that*deprives* the*brain*of*its*normal*supply* of*
oxygen*e.g.*Stroke.*That*is*why*there*is*cell*death*in*the*area*where*the*stroke*occurs.*
Most*treatments*to*help*stroke*sufferers*needs* to*be*administered* quickly* after*the*stroke*
begins.*These*drugs*include* glutamate*receptor*antagonists.
These*drugs*can*also*be*used*for*traumatic*brain*injury,* epilepsy* and*hypoglycemia* all*
disorders* that*can*lead*to*reduced*oxygenation* and*thus*excitotoxicity.*
Parkinson,* Huntingtons*and*Alzheimers* also*have*been*linked* to*excitotoxicity*so*these*
drugs*might*help*with*these*disorders* also.*
Stroke*Treatment
Thrombolytic* drugs*=*drugs*that*immediately*dissolve* the*blood* clots*that*cause*many*
strokes,* drastically*reducing*the*amount*of*damage*strokes*produce.*E.g.*Tissue*
plasminogen* activator*(tPA),*r-tPA,*streptokinase,* urokinase*and*prourokinase.*
Thrombolytics,* however,*only* work*if*delivered* directly*into*the*bloodstream,* either*through*
a*vein*or*an*artery*(intra-arterial)*and*only*if*administered*within*a*few*hours*of*the*stroke*
before*the*oxygen-deprived* nerve*cells*suffer* permanent*damage.*
The*time*window* for*getting*the*best*results*from*thrombolytic* drugs*is*three*hours* from*
the*first*signs*of*stroke.
O&.@,(.5(B12.+P
Alcohol* -heavy*drinking*
Stress*
Patterns*of*light,*especially*
flickering*or*rapid*strobe*light*
Late*nights,* shift*work,*and*
lack*of*sleep*
Illness,*especially*with*high*
fever*
Hormones*-seizures*can*be*
increased*just*before*or*
during*first*days*of*
menstruation*
Apoptosis
Not*just*excitotoxicity*causes*neuronal* death*but*an*internal*self*destructive*chemical*
program*=*cell*suicide*occurs*in*response* to*the*damage*caused*by*a*lack*of*oxygen*to*
neurons.*
Need*to*have*drugs*that*can*prevent*both*excitotoxicity*and*apoptosis.*
Apoptosis* is*implicated*in*the*progressive* loss* of*oligodendrocytes* in*multiple*sclerosis.
Free*radicals*are*also*thought*to*be*a*major*player*in*aging.*
Summary
Identify*and*classify*disorder.
Many*potential*sources* of*disorders* of*brain*and*behaviour* e.g.*anatomy,*chemistry,*
physiology,* genetics,*environment.
New*treatments*are*on*the*horizon.*
Disorders(of(Brain(and(Behaviour
Wednesday,* November* 30,*2016 7:45*PM
Psychiatric*
Depression
Alzheimer's
Schizophrenia
Bipolar
Panic*Disorder
Drug*Abuse
Personality* Disorders
ADD*-ADHD
Tourette’s*Syndrome
************Neurologic
Stroke
Head*injury
Congenital*
Epilepsy
Encephalitis
Meningitis
Autism
Multiple*Sclerosis
Scales
Glasgow*Coma*Scale*(3-15)
Mini*Mental*Assessment* (0-30)
ICD-10*=*The*International*Statistical*Classification* of*Diseases*and*Related*Health*Problems
DSM-IV*=*Diagnostic*and*Statistical*Manual*of*Mental*Disorders*-4th*Ed/*(Axis* I,*Axis*II)
Glasgow*Coma*Scale*(3-15)
Eye$Opening
None*1*=*Even*to*supra-orbital* pressure
To*pain*2*=*Pain*from*sternum/limb/supra-orbital* pressure
To*speech* 3*=*Non-specific* response,* not*necessarily*to*command
Spontaneous* 4*=*Eyes*open,*not*necessarily* aware
Motor$Response
None*1*=*To*any*pain;*limbs*remain*flaccid
Extension*2*=*Shoulder* adducted*and*shoulder* and*forearm*internally*rotated
Flexor*response* 3*=*Withdrawal*response* or*assumption* of*hemiplegic*posture
Withdrawal*4*=*Arm*withdraws*to*pain,* shoulder* abducts
Localizes*pain*5*=*Arm*attempts*to*remove*supra-orbital/chest* pressure
Obeys* commands*6*=*Follows* simple*commands
Verbal$Response
None*1*=*No*verbalization*of*any*type
Incomprehensible* 2*=*Moans/groans,* no*speech
Inappropriate*3*=*Intelligible,*no*sustained*sentences
Confused* 4*=*Converses* but*confused,* disoriented
Oriented*5*=*Converses* and*oriented
Mini*Mental*Assessment* (0-30)
!"#$%&'&#!%()*+,(-*.+/(0*1(,234(2+56,1
'57:*“What*is*the:*(year)(season)(date)(day)(month)?”* ____
'57:*“Where*are*we:*(state)(county)(town)(hospital)(floor)?”* ____
"$8#9&"'&#!%()53*1,(:;<;=(-*.+/5(233*1>.+?(/*(4*6(@2+A(21,(1,-,2/,>
%2@,(/41,,(*BC,3/5:*Give*the*patient*one*second* to*say*each.
'57(/4,(-2/.,+/(/*:*repeat*all*three*after*you*have*said*them.
Repeat*them*until*the*patient*learns*all*three.*____
'&&$%&#!%('%D(E'FEGF'&#!%( )*+,(-*.+/(0*1(,234(3*11,3/(5HB/123/.*+
'57(/4,(-2/.,+/(/*:*begin*from*100*and*count*backwards*by*7.*Stop*after*5*answers*-(93,*86,*
79,*72,*65)*____
"$E'FF()*+,(-*.+/(0*1(,234(3*11,3/(2+56,1
'57(/4,(-2/.,+/(/*:*name*the*three*objects*from*above.*____
F'%8G'8$
'57(/4,(-2/.,+/(/*:*identify* and*name*a*pencil*and*a*watch.*(2*points)* ____
'57(/4,(-2/.,+/(/*:*repeat*the*phrase*“No*ifs,* ands,* or*buts.”*(1*point)*____
'57(/4,(-2/.,+/(/*:*“Take*a*paper*in*your*right*hand,*fold* it*in*half,
and*put*it*on*the*floor*“*(1*point*for*each*task*completed* properly)*IIII
'57(/4,(-2/.,+/(/*:*read*and*obey*the*following:* “Close*your*eyes.”*(1*point)* IIII
'57(/4,(-2/.,+/(/*:*write*a*sentence.*(1*point)*IIII
'57(/4,(-2/.,+/(/*:*copy*a*complex*diagram*of*two*interlocking* pentagons.*(1*point)*IIII
Example
The*patient*fulfills* a*total*of*at*least*6*criteria*from*the*following* 3*lists,* distributed* as*
indicated:
#@-2.1,>(5*3.2J(.+/,123/.*+(K2/(J,25/(<LM
-Markedly*deficient*regulation*of*social*interaction*by*using*multiple* non-verbal* behaviours*
such*as*eye*contact,*facial*expression,* body* posture*and*gestures
-Lack*of*peer*relationships* that*are*appropriate*to*the*developmental* level
-Doesn't*seek*to*share*achievements,*interests*or*pleasure*with*others
-Lacks*social*or*emotional*reciprocity
#@-2.1,>(3*@@H+.32/.*+(K2/(J,25/(:LM
-Delayed*or*absent*development*of*spoken* language*for*which*the*patient*doesn't*try*to*
compensate*with*gestures
-In*patients*who*can*speak,*inadequate*attempts*to*begin*or*sustain*a*conversation
-Language*that*is*repetitive,*stereotyped*or*idiosyncratic
-Appropriate*to*developmental*stage,*absence*of*social*imitative*play*or*spontaneous,*
make-believe* play
'3/.N./.,5;(B,42N.*1(2+>(.+/,1,5/5(/42/(21,(1,-,/./.N,;(1,5/1.3/,>(2+>(5/,1,*/A-,>(K2/(J,25/(:(
*0LM
-Preoccupation* with*abnormal*(in*focus* or*intensity)* interests*that*are*restricted*and*
stereotyped*(such* as*spinning* things)
-Rigidly*sticks*to*routines*or*rituals*that*don't*appear*to*have*a*function
-Has*stereotyped,* repetitive*motor*mannerisms*(such* as*hand*flapping)
Persistently* preoccupied*with*parts*of*objects*
Histrionic
A*pervasive* pattern*of*excessive* emotionality*and*attention*seeking,* beginning*by*early*
adulthood* and*present*in*a*variety*of*contexts,*as*indicated*by*5*(or*more)*of*the*following:
-Discomfort*with*situations*in*which*the*patient*is*not*the*center*of*attention.
-Relationships*that*are*frequently*fraught*with*inappropriately*seductive*or*sexually*
provocative*behaviour.
-Expression* of*emotion* is*shallow* and*rapidly* shifting.
-Frequent*focusing* of*attention*on*self*through*use*of*physical* appearance.**
*****-Speech*is*vague*and*lacks*detail.
-Overly*dramatic*expression* of*emotion.
-Easy*suggestibility*(readily*influenced* by*opinions* of*other*people).
-Belief*that*relationships* are*more*intimate*than*they*really*are.*
Treatments
Biofeedback
Pharmacotherapy
Surgery
Psychotherapy
Cognitive*Therapy
Stem*Cells
Parkinson's*Disease
MPTP*-drug-induced*Parkinson's*symptoms*-depletion*of*substantia*negra*DA
Nigrostriatal*DA*pathway*=*substantia*nigra*to*striatum
Post-mortems*-<*100,000*nigral*neurons*=*DA*stared*striatum
~60%*of*nigral*neurons*have*to*be*lost,*with*an*80%*depletion*of*striatal*DA,*before*the*
symptoms*of*PD*develop
Treatment*for*Parkinson's
MAO*inhibitor*(ex.*Eldepryl)*slows*down*breakdown*of*DA
L-DOPA*is*initially* good*but*becomes*problematic*(eventual*dyskinesia)*and*is*required*
at*greater*and*greater*doses*as*the*disorder*progresses
Sinement*=*L-DOPA*+*carbodopa*(inhibitor*that*prevents*L-DOPA*from*being*absorbed*
by*tissue*other*than*the*brain)
Use*of*DA*agonists*delay*use*of*L-DOPA,*reduce*eventual*dose*of*L-DOPA*and*reduce*
motor*problems*(ex.*Requip*and*Mirapex)
Ex.*Rascol*Study
Subjects:*early*PD*untreated*patients*
Treatment*groups
treated*with*ropinerole*(agonist)*+*could*get*supplemental* L-DOPA*or1)
L-DOPA*and*could*only*have*dose*increased2)
After*5*years
46%*in*group*2)*had*dyskinesia
20%*in*group*1)*had*dyskinesia* whether*supplemented* with*
L-DOPA*or*not
PD*symptoms* were*same*in*each*group.
Better*to*use*a*DA*agonist*for*as*long*as*possible.
Fetal*DA*Neuron*Transplants
Tissue*from*ventral*midbrain*of*aborted*fetuses* at*6-9*weeks*post-conception.
Surgically*placed*into*the*caudate*and/or* putamen.
Grafts*reinnervate*the*denervated*striatum,*form*synaptic*connections* with*host*neurons,*
release*DA*and*produce*some*functional* recovery.
Mild*to*moderate*improvement* in*motor*disturbances*without*major*side*effects.
Other*Treatments
1.*Deep*brain*stimulators* of*thalamus*and*subthalamic* nucleus.
2.*Stem*cells
1)*capable*of*dividing*and*renewing*themselves* for*long*periods* through*cell*division
2)*unspecialized
3)*can*give*rise*to*specialized*cell*types*under*certain*physiologic* or*experimental*
conditions,* e.g.*special*functions* such*as*the*beating*cells*of*the*heart*muscle*or*the*
DA*producing*cells*of*the*brain.*
Embryonic* Stem*Cells
Stem*cells*taken*from*a*human*embryo.
Added*a*gene*that*produces* an*antitumour*molecule*named*TRAIL.
Injected*the*stem*cells*into*mice*with*brain*tumours.
The*cells*localized*on*the*cancer*and*produced* enough*TRAIL*to*cut*the*tumour*size*by*
50%-70%.
The*cells*track*the*tumour*by*following* chemical*signals* emitted*by*the*immune*system*
molecules* that*attack,*but*fail*to*destroy,* the*cancer.*
There*have*been*other*animal*models* of*brain*injury*where*naturally*occurring*stem*cells*
will*travel*towards*and*try*to*repair*damaged*areas.
Stem*Cells* in*Humans
National*Institute*of*Neurological*Diseases*and*Stroke*
Brain*tissue*from*female*post*mortems*who*had*bone*marrow*transplant*from*male*donors.
All*patients*had*brain*tissue* with*clumps* of*Y-positive* cells.*
Suggesting*that*the*original*donor*cells*had*continued* to*multiply* after*differentiating*into*
brain*cells.*
Umbilical*Cord*Cells
Can*inject*into*jugular*vein*or*directly*transplant*into*the*brain.
Researchers*first*gave*the*drug,*mannitol,*to*provide*temporary*passage*through*the*blood-
brain*barrier*then*transfused* human*umbilical* cord*blood* cells*into*a*stroke*animal*model.
When*used* in*the*first*hours* and*days*following* a*stroke,* stroke*size*decreased*by*40*
percent*and*resulting*disability* was*significantly* reduced.
This*treatment*significantly* increased*brain*levels*of*neurotrophic* factors,*which*correlated*
positively* with*reduced*cerebral*infarcts*and*improved* behavioural*functions.*
Deprogramming*Stem*Cells
Kyoto*Japan,*University* of*Wisconsin
Created*pluripotent* human*stem*cells*using* ‘deprogramming’*human*somatic*cells*(skin*
fibroblasts).
Expose*skin* cells*to*specific*signaling*agents*that*reprogram*the*genetic*expression* pattern*
of*a*cell.
Cells*switch*from*skin* cell*precursors* to*more*embryonic-like,* capable*of*developing* into*
various*other*tissues* and*organ-specific* cells.
Controlling* Stem*Cells
How*cells*in*the*blood*enter*the*brain?
How*to*induce*them*to*enter*the*brain*in*larger*numbers?
How*to*promote*their*differentiation*into*neurons?
How*to*target*them*to*areas*of*need?
Are*the*internal*and*external*signals*for*cell*differentiation*similar* for*all*kinds*of*stem*cells?
Can*specific*sets*of*signals*be*identified* that*promote*differentiation* into*specific* cell*types?
Prevent*the*introduction* of*harmful* viruses* or*immune*reactions.*
Stem*Cells
In*the*3-to*5-day-old* embryo,* stem*cells*
in*developing* tissues*give*rise*to*the*
multiple*specialized*cell*types*that*make*
up*the*heart,*lung,*skin,* brain*and*other*
tissues.*
In*some*adult*tissues,*such*as*bone*
marrow,*muscle,*and*brain,*discrete*
populations* of*adult*stem*cells*generate*
replacements*for*cells*that*are*lost*
through*normal*wear*and*tear,*injury,* or*
disease.
Epilepsy
Elton*John,* Alexander*the*Great,*Charles* Dickens,*Vincent*Van*Gogh,*Peter*Tchaikovsky,*
Napoleon,* Danny*Glover,*and*Albert*Einstein*all*had*epilepsy!
Epilepsy* affects*1%*of*the*population* and*is*thus*one*of*the*most*common* neurological*
diseases.*It*can*begin*at*any*age.*
Epilepsy* is*defined*as*1,3H11.+? seizures*resulting*from*abnormal,*temporary,*cell*firing,*or*
electrical*function*in*the*brain*(~5%*of*all*people*have*a*seizure*at*some*point*but*do*not*
necessarily* develop*epilepsy).
In*approximately*30%*of*cases,*epilepsy*is*caused*by*such*events*as*head*trauma,*tumor,*
stroke,*or*infection.*Other*reasons*are*related*to*a*genetic*predisposition* for*epilepsy* or*an*
unknown* source.**
Epilepsy* can*produce*many*kinds* of*seizures,*depending* on*the*part*of*the*brain*that*is*
affected.*
Frontal*Lobe*Seizures
Can*be*generalized*of*partial*seizures
Many*triggers*and*causes
Causes* and*Triggers
Brain*damage*related*to*birth.
Brain*infection.
Brain*tumours.
Abnormalities* in*blood*vessels* of*the*brain.
Genetics.
Unknown.
Surgery*as*Treatment
The*following* conditions* must*be*fulfilled:
The*epilepsy* must*be*characterized*by*partial*seizures*with*or*without*generalized*seizures*
as*well.*
The*seizures*must*be*resistant*to*reasonable* efforts*at*control*with*medication.*
The*proposed* surgical*procedure*must*carry*a*sufficiently* low*risk*of*causing*unacceptable*
neurological*impairment.*
Epilepsy* must*be*the*persons* most*disabling* medical*problem.*
Alternate*Treatment
Vagus*nerve*stimulation*(VNS)*is*designed* to*prevent*seizures*by*sending*regular,*mild*
pulses* of*electrical*energy*to*the*brain*via*the*vagus*nerve.*These*pulses* are*supplied* by*a*
device*something*like*a*pacemaker.
This*pacemaker*for*the*brain*is*placed*under*the*skin*on*the*chest*wall*and*a*wire*runs*
from*it*to*the*vagus*nerve*in*the*neck.*
The*vagus*nerve*is*part*of*the*autonomic* nervous*system,* which*controls* functions* of*the*
body* that*are*not*under*voluntary* control,*such* as*heart*rate.*The*vagus*nerve*passes*
through*the*neck*as*it*travels*between*the*chest*and*abdomen*and*the*brainstem*of*the*
brain.
Vagus*Nerve*Stimulation
VNS*produces*desynchronization* of*cortical*EEG*and*measurable*changes*in*blood* flow*in*
the*cerebellum,* thalamus*and*cortex.*Perhaps*this*occurs*by*activating*inhibitory* structures*
in*the*brain*but*the*precise*mode*of*action*of*VNS*is*not*known.
Other*areas*possibly* activated*by*VNS*include* the*medulla,* parabrachial*nucleus,* locus*
coeruleus,* hypothalamus,* amygdala,*hippocampus,* cingulate*gyrus,*and*contralateral*
somatosensory* cortex.*
It*is*thought*that*perhaps*VNS*decreases*cortical*epileptiform*activity*indirectly*by*
influencing* the*reticular*activating*system*or*that*VNS*increases*the*seizure*threshold* by*
causing*widespread*release*of*GABA*and*glycine*in*the*brain.*
Studies*of*VNS
Ben-Menachem*et*al*measured*amino*acid*and*neurotransmitter*metabolite*
concentrations*in*cerebrospinal* fluid*(CSF)* samples*of*patients*on*clinical*trials*of*VNS*
before*and*3*months*after*VNS*placement.*
Responders* to*the*VNS*had*larger*amounts*of*GABA*and*less* glutamate*after*
treatment.*
Excitotoxicity
Glutamate*is*the*most*prevalent*neurotransmitter*in*the*brain*and*plays*a*role*in*several*
major*neurological*processes* like*LTP.*
When*the*brain*is*injured* it*releases*abnormally* large*amounts*of*glutamate,*over-
stimulating*the*glutamate*receptors*on*the*surface*membranes*of*postsynaptic* neurons.*
This*in*turn,*causes*unusually* large*amounts*of*calcium*to*enter*the*nerve*cells*which*
disrupts* biochemical*processes* within*the*neuron*and*activates*enzymes*that*produce* free*
radicals.*
Free*radicals*are*structurally*unbalanced*chemicals*capable*of*destroying* other*compounds*
that*form*the*internal*structure*of*neurons.*
Neuronal*cell*death*as*a*result*of*this*increase*in*glutamate*and*influx*of*calcium*that*results*
in*increased*free*radicals*=*Excitotoxicity.
Disorders*Involving*Excitotoxicity
Excitotoxicity*can*be*triggered*by*anything*that*deprives* the*brain*of*its*normal*supply* of*
oxygen*e.g.*Stroke.*That*is*why*there*is*cell*death*in*the*area*where*the*stroke*occurs.*
Most*treatments*to*help*stroke*sufferers*needs* to*be*administered* quickly* after*the*stroke*
begins.*These*drugs*include* glutamate*receptor*antagonists.
These*drugs*can*also*be*used*for*traumatic*brain*injury,* epilepsy* and*hypoglycemia* all*
disorders* that*can*lead*to*reduced*oxygenation* and*thus*excitotoxicity.*
Parkinson,* Huntingtons*and*Alzheimers* also*have*been*linked* to*excitotoxicity*so*these*
drugs*might*help*with*these*disorders* also.*
Stroke*Treatment
Thrombolytic* drugs*=*drugs*that*immediately*dissolve* the*blood* clots*that*cause*many*
strokes,* drastically*reducing*the*amount*of*damage*strokes*produce.*E.g.*Tissue*
plasminogen* activator*(tPA),*r-tPA,*streptokinase,* urokinase*and*prourokinase.*
Thrombolytics,* however,*only* work*if*delivered* directly*into*the*bloodstream,* either*through*
a*vein*or*an*artery*(intra-arterial)*and*only*if*administered*within*a*few*hours*of*the*stroke*
before*the*oxygen-deprived* nerve*cells*suffer* permanent*damage.*
The*time*window* for*getting*the*best*results*from*thrombolytic* drugs*is*three*hours* from*
the*first*signs*of*stroke.
O&.@,(.5(B12.+P
Alcohol* -heavy*drinking*
Stress*
Patterns*of*light,*especially*
flickering*or*rapid*strobe*light*
Late*nights,* shift*work,*and*
lack*of*sleep*
Illness,*especially*with*high*
fever*
Hormones*-seizures*can*be*
increased*just*before*or*
during*first*days*of*
menstruation*
Apoptosis
Not*just*excitotoxicity*causes*neuronal* death*but*an*internal*self*destructive*chemical*
program*=*cell*suicide*occurs*in*response* to*the*damage*caused*by*a*lack*of*oxygen*to*
neurons.*
Need*to*have*drugs*that*can*prevent*both*excitotoxicity*and*apoptosis.*
Apoptosis* is*implicated*in*the*progressive* loss* of*oligodendrocytes* in*multiple*sclerosis.
Free*radicals*are*also*thought*to*be*a*major*player*in*aging.*
Summary
Identify*and*classify*disorder.
Many*potential*sources* of*disorders* of*brain*and*behaviour* e.g.*anatomy,*chemistry,*
physiology,* genetics,*environment.
New*treatments*are*on*the*horizon.*
Disorders(of(Brain(and(Behaviour
Wednesday,* November* 30,*2016 7:45*PM

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Description
Disorders of Brain and Behaviour Wednesday, November 30, 2016 7:45 PM Psychiatric Neurologic Depression Stroke Head injury Alzheimer's Congenital Epilepsy Schizophrenia Bipolar Encephalitis Meningitis Panic Disorder Autism Multiple Sclerosis Drug Abuse Personality Disorders ADD - ADHD Tourettes Syndrome Scales Glasgow Coma Scale (3-15) Mini Mental Assessment (0-30) ICD-10 = The International Statistical Classification of Diseases and Related Health Problems DSM-IV = Diagnostic and Statistical Manual of Mental Disorder-4th Ed/ (Axis I, Axis II) Glasgow Coma Scale (3-15) Eye Opening None 1 = Even to supra-orbital pressure To pain 2 = Pain from sternum/limb/supra -orbital pressure To speech 3 = Non-specific response, not necessarily to command Spontaneous 4 = Eyes open, not necessarily aware Motor Response None 1 = To any pain; limbs remain flaccid Extension 2 = Shoulder adducted and shoulder and forearm internally rotated Flexor response 3 = Withdrawal response or assumption of hemiplegic posture Withdrawal 4 = Arm withdraws to pain, shoulder abducts Localizes pain 5 = Arm attempts to remove supra -orbital/chest pressure None 1 = To any pain; limbs remain flaccid Extension 2 = Shoulder adducted and shoulder and forearm internally rotated Flexor response 3 = Withdrawal response or assumption of hemiplegic posture Withdrawal 4 = Arm withdraws to pain, shoulder abducts Localizes pain 5 = Arm attempts to remove supra -orbital/chest pressure Obeys commands 6 = Follows simple commands Verbal Response None 1 = No verbalization of any type Incomprehensible 2 = Moans/groans, no speech Inappropriate 3 = Intelligible, no sustained sentences Confused 4 = Converses but confused, disoriented Oriented 5 = Converses and oriented Mini Mental Assessment (0-30) ORIENTATION one point for each answer Ask: What is the: (year)(season)(date)(day)(month)? ____ Ask: Where are we: (state)(county)(town)(hospital)(floor)? ____ REGISTRATION score 1,2,3 points according to how many are repeated Name three objects: Give the patient one second to say each. Ask the patient t: repeat all three after you have said them. Repeat them until the patient learns all three. ____ ATTENTION AND CALCULATION one point for each correct subtraction Ask the patient t: begin from 100 and count backwards by 7. Stop after 5 answers- (93, 86, 79, 72, 65) ____ RECALL one point for each correct answer Ask the patient t: name the three objects from above. ____ LANGUAGE Ask the patient t: identify and name a pencil and a watch. (2 points) ____ Ask the patient t: repeat the phrase No ifs, ands, or buts. (1 point) ____ Ask the patient t: Take a paper in your right hand, fold it in half, and put it on the floor (1 point for each task completed prope____ Ask the patient t: read and obey the following: Close your eyes. (1 poi____ Ask the patient t: write a sentence. (1 point) ____ Ask the patient t: copy a complex diagram of two interlocking pentagons. (1 point____ Example The patient fulfills a total of at least 6 criteria from the following 3 lists, distributed as indicated: Ask the patient t: write a sentence. (1 point) ____ Ask the patient t: copy a complex diagram of two interlocking pentagons. (1 point____ Example The patient fulfills a total of at least 6 criteria from the following 3 lists, distributed as indicated: Impaired social interaction (at least 2): -Markedly deficient regulation of social interaction by using multiple non-verbal behaviours such as eye contact, facial expression, body posture and gestures -Lack of peer relationships that are appropriate to the developmental level -Doesn't seek to share achievements, interests or pleasure with others -Lacks social or emotional reciprocity Impaired communication (at least 1): -Delayed or absent development of spoken language for which the patient doesn't try to compensate with gestures -In patients who can speak, inadequate attempts to begin or sustain a conversation -Language that is repetitive, stereotyped or idiosyncratic -Appropriate to developmental stage, absence of social imitative play or spontaneous, make-believe play Activities, behavior and interests that are repetitive, restricted and s
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