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11
Clinical Neuropsychology.Clinical Neuropsychology.
Alan SunderlandAlan Sunderland
MSc Cognitive Neuroscience and Neuroimaging
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OverviewOverview
Contrasts between applied clinical and pure academicContrasts
between applied clinical and pure academicresearch in
neuropsychology. Challenges for the newresearch in neuropsychology.
Challenges for the newresearcher.researcher.
Common causes of acquired brain damage :Common causes of
acquired brain damage :--–– Head injuryHead injury–– StrokeStroke––
AlzheimerAlzheimer’’s Diseases DiseasePatterns of impairment,
methods of clinical assessment,Patterns of impairment, methods of
clinical assessment,
and current issues in clinical researchand current issues in
clinical research
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BackgroundBackground ReadingReading
Goldstein L.H. & McNeil, J.E.Clinical neuropsychology : a
practical guide to
assessment and management for clinicians. JohnJohnWiley 2004.
Especially, Chapter 9.Wiley 2004. Especially, Chapter 9.
Kolb, B. & Whishaw I.Q.Kolb, B. & Whishaw
I.Q.Fundamentals of human neuropsychology. Fifth
EditionFundamentals of human neuropsychology. Fifth Edition..
Worth Publishers 2003.Worth Publishers 2003.
Wilson, Barbara A.Wilson, Barbara A.Case studies in
neuropsychological rehabilitationCase studies in neuropsychological
rehabilitation..
Oxford University Press 1999.Oxford University Press 1999.
Contrasting Pure and Applied Research in
NeuropsychologyContrasting Pure and Applied Research in
Neuropsychology
Academic ResearchAcademic Research
Aim =Aim = to inform theoriesto inform theoriesof normal
cognitiveof normal cognitiveprocessing by studyingprocessing by
studyingeffects of brain damage.effects of brain damage.Methods =
novelMethods = novelexperimental studies withexperimental studies
withhighly selected cases e.g.highly selected cases
e.g.splitsplit--brain.brain.Outputs = scientificOutputs =
scientificjournals.journals.
Clinical ResearchClinical Research
Aim = to diagnose,Aim = to diagnose,assess and treatassess and
treatcognitive impairments.cognitive impairments.
Methods = standardisedMethods = standardisedassessments and
clinicalassessments and clinicaltrials with typical patients.trials
with typical patients.
Outputs = medical andOutputs = medical andrehabilitation
journals.rehabilitation journals.
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These are the extremes – some research spans both
approaches!
Challenges for the New ResearcherChallenges for the New
Researcher
PlanningPlanning –– Clarifying aims. Knowing what sorts
ofClarifying aims. Knowing what sorts ofimpairment occur and likely
incidence.impairment occur and likely incidence.
RecruitmentRecruitment –– Identifying target populations
andIdentifying target populations andobtaining ethical
approval.obtaining ethical approval.
CommunicationCommunication –– Interaction with both clinical
andInteraction with both clinical andacademic communities.academic
communities.
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Common disorders in neuropsychological practiceCommon disorders
in neuropsychological practice
1.1. Head InjuryHead Injury2.2. AlzheimerAlzheimer’’s Diseases
Disease3.3. Cerebrovascular diseaseCerebrovascular disease4.4.
EpilepsyEpilepsy5.5. Infections (viral, bacterial, AIDS)Infections
(viral, bacterial, AIDS)6.6. Multiple sclerosisMultiple
sclerosis7.7. Brain tumourBrain tumour8.8. ParkinsonParkinson’’s
Diseases Disease9.9. Other neurologicalOther neurological
diseasesdiseases
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Head injury = “traumatic” or “acquired brain injury”
Causes of serious head injury: 50% road accidents, 30% falls,
10%assaults.
But falls are the most common cause for children.
The vast majority are “closed” injuries, not “open”
penetratinginjuries.
Huge numbers of minor injuries (often seen in A&E depts)In
UK per year :
100,000 admitted to hospital: 10,000 transferred toneurosurgical
units.
Highest incidence for 18-24 year old males.
Incidence of head injury by sex and age.
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Head Injury – Mechanisms damage.
A shock wave travelsthrough the brain.Shearing forces forces
causediffuse axonal injury.
Focal damage under the blowand at the opposite side.
Bleeding or brain swelling can cause secondary damage
Head injury – brain damage in closed injuries.
Primary damage
Major damage often due toacceleration/deceleration
– DAI diffuse axonal injury (may only be
visiblemicroscopically).
Damage especially to deep white matter e.g.brainstem, corpus
callosum.
Bruising (contusion) under the blow and wherebrain hits/scrapes
against skull
(especially frontal & temporal poles ).
Head injury – brain damage in closed injuries.
Secondary damageDue to bleeding (haematoma)Or increased pressure
due to subdural haematoma and/or
brain swelling (oedema).
Progression ofsubdural haematoma
Head injury – brain damage in closed injuries.
Implications
- discrete, focal damage is unusual- preferred sites for damage,
but very variable
and not always visible- limited value of CT/MRI for
neuropsychology
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Injury Coma/PTA Recovery period Full recoveryor Permanent
deficits
Minutes weeks 6 months Several years
Head injuryHead injury –– sequence of events.sequence of
events.Head injury – acute assessment
Glasgow Coma Scale
Eye Opening E Best Motor Response M Best Verbal Response V
spontaneous 4 To Verbal Command:obeys 6 oriented and converses
5
to speech 3 To Painful Stimulus:localizes pain 5 disoriented and
converses 4
to pain 2 flexion-withdrawal 4 inappropriate words 3
no response 1 flexion-abnormal 3 incomprehensible sounds 2
extension 2 no response 1
no response 1
E + M+ V = 3 to 15
13-15=Mild or No Injury 9-12=Moderate Injury 3-8=Severe
Injury
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Head injury – acute assessment
Post-traumatic amnesia is the period from injury to the return
oforientation for time and place (and therefore includes coma).
From Kolb & Whishaw
PTA as a measure of severity of head injury
< 1 hour = “mild”>24 hours = “severe”
> 7 days = “very severe”
Can be estimated retrospectively (McMillan et al, 1996) , and
may be abetter predictor of cognitive outcome than coma
duration.
But certainty over PTA duration is only possible with repeated,
directrating such as the GOAT (Galveston Orientation & Amnesia
Test,Levin et al., 1975) 16-item assessment :-
– 10 items assessing orientation to person, place and time– 6
items assessing memory before and after injury
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Brooks et al. (1987). Most common problemsreported 2 to 7 years
after severe head injury .
Problem % relatives reporting % patients reporting
Slowness 77Personality change 76Poor memory 76
66Anger/irritability/impatience 74 62
Tiredness 70 43Tension/Anxiety/Worry 65 35Poor concentration 64
41Depression 63 49Mood changes 63Poor balance /coordination 59
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Some patients lack insight into the extent of their
problems.
Head injury – patterns of neuropsychologicalimpairment
Deficits apparent on tests – Slowing (RT), impaired
episodicmemory, dysexecutive problems, plus variable
selectivedeficits in individual cases e.g. anomia.
Some researchers suggest that these impairments relate to
areasof maximal damage:-memory problems = medial temporal
damage
dysexecutive problems = prefrontal damage. etc.This is dubious
given that damage is probably never focal and
always includes some DAI. However:-
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Head injury and Temporal lobe damageTate & Bigler, 2000
Correlation withmemory test scores= 0.33
86 patients 3 months after head injury.
Volume of hippocampus measuredfrom MR brain scans.
A significant but modest correlationwith scores on the Wechsler
MemoryScale
“memory disruption …is probably acombination of specific effects
at thehippocampal-fornix level andnonspecific effects that
disruptcerebral connectivity”
Learning & Memory, 7: 442-446
AlzheimerAlzheimer’’s diseases disease
3% to 11% of community3% to 11% of community--dwelling adults
older thandwelling adults older than65 years are diagnosed as
demented65 years are diagnosed as demented
AD as the most common form (>60% of cases?)AD as the most
common form (>60% of cases?)Other common causes are theOther
common causes are the LewyLewy Body dementiaBody dementiaand
vascular dementia.and vascular dementia.PathologyPathology--related
issues for neuropsychologyrelated issues for neuropsychology––
““dementiadementia”” vs domains of deficitvs domains of deficit--
disease vs agedisease vs age--related declinerelated decline
AlzheimerAlzheimer’’s diseases disease –– advanced
atrophyadvanced atrophy
Dilated ventricles – due to loss ofcortex
Normal brain – hippocampus outlined(from Digital Anatomist)
Galton et al. (2000). IntroductionGalton et al. (2000).
Introduction
Dominant view of AD starting with memory problems thenDominant
view of AD starting with memory problems thenprogressing to
involvement of attentional and executive processprogressing to
involvement of attentional and executive processes,es,semantic
memory, praxis and visuoperceptual abilities.semantic memory,
praxis and visuoperceptual abilities.
This reflects the current view of pathology which is thought
toThis reflects the current view of pathology which is thought
toinvolve initially the hippocampal complex and thereafter
theinvolve initially the hippocampal complex and thereafter
thetemporal lobes and beyond.temporal lobes and beyond.
This classic staging may fit the majority of cases but a
signifiThis classic staging may fit the majority of cases but a
significantcantproportion do not adhere to this orderly
pattern.proportion do not adhere to this orderly pattern.
Furthermore, diagnostic procedure for AD are heavily
weightedFurthermore, diagnostic procedure for AD are heavily
weightedtowards memory impairment as the central deficit and
may,towards memory impairment as the central deficit and
may,therefore, exclude atypical cases.therefore, exclude atypical
cases.
Brain, 2000, 123, 484-498.
Galton et al. (2000). PatientsGalton et al. (2000). Patients
Referrals to a specialist memory clinic.Referrals to a
specialist memory clinic.
Out of 180 cases of probable ADOut of 180 cases of probable
AD14% had14% had ““atypicalatypical””
presentations.presentations.
This study concerns 13 with postThis study concerns 13 with
post--mortems:mortems:--–– 4 presented as typical (poor memory as
the presenting4 presented as typical (poor memory as the
presenting
complaint).complaint).–– 9 as atypical (problems with vision,
language, or praxis).9 as atypical (problems with vision, language,
or praxis).
Galton et al. (2000). AGalton et al. (2000). A
““typicaltypical”” case.case.
69 yr retired antiques dealer, 12 month history of difficulty
in69 yr retired antiques dealer, 12 month history of difficulty
inremembering recent events such as conversations,
televisionremembering recent events such as conversations,
televisionprogrammes and family news.programmes and family
news.
Initial testing demonstrated only impaired memory (e.g.
delayedInitial testing demonstrated only impaired memory (e.g.
delayedstory recall), which was particularly marked for nonstory
recall), which was particularly marked for non--verbal
materialverbal material(Rey picture) . Language and spatial
abilities were intact.(Rey picture) . Language and spatial
abilities were intact.
Over the next 2 years, his memory worsened as measured byOver
the next 2 years, his memory worsened as measured bydelayed story
recall, but his semantic memory, language, attentidelayed story
recall, but his semantic memory, language,
attention,on,visuospatial and perceptual abilities all remained
intact.visuospatial and perceptual abilities all remained
intact.
The hippocampus and parahippocampal gyrus showed numerousThe
hippocampus and parahippocampal gyrus showed
numerousneurofibrillary tangles There was also some involvement of
BA 38neurofibrillary tangles There was also some involvement of BA
38(the temporal pole).(the temporal pole).
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Galton et al. (2000). AnGalton et al. (2000). An
““atypicalatypical”” case.case.
74y ex74y ex--secretary with a 2 year history of progressive
loss of speechsecretary with a 2 year history of progressive loss
of speechfluency. She complained of an inability to converse due to
hesitfluency. She complained of an inability to converse due to
hesitancy, wordancy, wordfinding difficulties and speech
distortion.finding difficulties and speech distortion.
Comprehension of single words was normal, but she had
difficultyComprehension of single words was normal, but she had
difficultyunderstanding syntactically complex sentences. Repetition
of shounderstanding syntactically complex sentences. Repetition of
short wordsrt wordswas good, but unable to repeat multisyllabic
words and phrases.was good, but unable to repeat multisyllabic
words and phrases.Visuospatial abilities were very well
preserved.Visuospatial abilities were very well preserved.
Over the subsequent 3 years, her language abilities declined
dOver the subsequent 3 years, her language abilities declined
dramatically,ramatically,in stark contrast to no deterioration in
general cognitive abiliin stark contrast to no deterioration in
general cognitive abilities or in herties or in herability to live
independently. By this time, she had almost no sability to live
independently. By this time, she had almost no
spontaneouspontaneousspeech but her visuospatial abilities and
nonspeech but her visuospatial abilities and non--verbal memory
remainedverbal memory remainednormal.normal.
Histologically there were features of AD but relative sparing
ofHistologically there were features of AD but relative sparing of
thethehippocampal complex contrasting with severe involvement of
superhippocampal complex contrasting with severe involvement of
superiorior--lateral temporal lobe.lateral temporal lobe.
Galton et al. (2000). ConclusionsGalton et al. (2000).
Conclusions
Proven Alzheimer's disease can present with a range of
cognitiveProven Alzheimer's disease can present with a range of
cognitivesymptoms.symptoms.Three main patterns identified:Three
main patterns identified:–– posterior cortical atrophy with either
major visual deficits orposterior cortical atrophy with either
major visual deficits or aa
predominantly biparietal syndromepredominantly biparietal
syndrome–– progressive aphasia which may be fluent, nonprogressive
aphasia which may be fluent, non--fluent or mixedfluent or mixed––
typical amnesic.typical amnesic.All of these are followed by global
impairment.All of these are followed by global impairment.
Is AD accelerated ageing or a separate disease process?
Buckner RL (2004). Memory and executive function in aging and
AD: Multiplefactors that cause decline and reserve factors that
compensate. Neuron 44 (1):195-208.
Loss of hippocampus in ADLoss of hippocampus in ADseems more
than normal ageing.seems more than normal ageing.
Jack et al. : Neurology, Volume 51(4).October 1998.993-999
Head et al., 2005
But the 2 patterns are intermingled trends only. So this remains
speculative.Also, there is no clear evidence of qualitatively
distinct cognitive profiles.
Plus individual variation related to sited of maximal
damage:-
Most common in older people, but there is no lower age
limit.Brain haemmorhage is the commonest cause of stroke inyounger
people.
30
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Site and extent ofdamage depends onwhich arterial branchis
affected.
Therefore there isgreat variability inthe type and degreeof
impairments.
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Contralateral weakness(hemiparesis).
Dysphasia afterdominant (left)hemisphere lesions.
Visuospatial problemsafter non-dominant(right)
hemispherelesions.
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Small, deep penetratingarteries known as thelenticulostriate
arteriesbranch from the middlecerebral artery.
15-25% of all ischemicstrokes.
Damage to motor andsensory pathwayscauses hemiparesis butno
cognitive problems
The anterior cerebralartery extendsupward and forwardfrom the
internalcarotid artery.
It supplies most ofthe medialhemisphere and thefrontal pole
Dysexecutive and“alien hand”syndromes may occur
Supplies thetemporal andoccipital lobes.
Occlusion often leadsto hemianopia, visualprocessing deficitsand
dyslexia.
But hemianopia ismost commonly seenafter MCA stroke.
Speed on the 9-Hole Peg Test with the paretic hand.
0.0
0.1
0.2
0.3
0.4
0.5
0.6
0.7
0 100 200 300 400
Days since stroke
Peg
s/s
Mean for age-matched healthy controls
Case 122. Age 55.Lesion of posteriorright internal capsule.
Data from Sunderland, Fletcher et al. JNNP 1994;57:856-858.
Recovery After StrokeFast early, slow late and spanning
>6months.
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Indications from imaging studies of recovery fromaphasia and
paresis.
1. Homologous areas in theintact hemisphere can onlytake-over
function to avery limited extent.
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Indications from imaging studies of recovery fromaphasia and
paresis.
2. The primary recoveryprocess may be increasedactivity in
surviving areasof the intact hemisphere,especially areas close
tothe lesion.
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Indications from imaging studies of recovery fromaphasia and
paresis.
3. Initially there is greaterthan normal activity inmany brain
areas.
4. During recovery there is are- focusing to a morenormal
pattern.
XX
X
X X
X
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Indications from imaging studies of recovery fromaphasia and
paresis.
This points in the direction ofrestitution rather
thancompensation as the majormechanism of recovery.
But very few imaging studies haveattempted to
investigatestrategy change, socompensation may also beinvolved.
X
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Ward et al. Brain (2003), 126, 2476-2496
Patient 7 A left-sided pontine infarct resulting in right
hemiparesis.
Red areas = recovery-related decreases in task-related
activation acrosssessions.
Green areas = recovery-related increases.• Decreases in
motor-related areas seen in all 8 patients.
• No consistent pattern of increases across patients.
Key Points
• Clinical neuropsychology is concerned with issues ofclinical
importance in typical patient groups.
• Head injury, Alzheimer’s Disease & Stroke are themost
common causes of acquired brain damage.
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Key Points
• Head injuries vary in severity and are gradedby duration of
coma or PTA
• They involve focal contusions and diffuseaxonal damage, and
typical impairments aremental slowing and poor memory.
• It is dangerous to assume localised effects,but hippocampal
damage may be predictor ofpoor episodic memory.
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Key Points
• Alzheimer’s Disease is the most common formof dementia.
• Typical cases have impaired memory as thecentral feature but
atypical presentations alsooccur. This is consistent with different
patternsof cortical atrophy.
• AD and normal ageing are probably differentprocesses, but
evidence for medial temporalversus fronto-striatal patterns
remainscontroversial and there are no clearneuropsychological
markers.
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Key Points
• Stroke is the most common cause of focalbrain damage.
• Patterns of impairment are variable anddependent on location
of disrupted bloodsupply.
• Significant functional recovery occurs over themonths after
stroke and has been a focus forresearch into neuroplasticity.
• Functional imaging suggests a progressiontowards a more normal
pattern of activation butthere has been limited behavioural
researchinto whether true restoration of function occurs.
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