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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

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 23

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).

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.

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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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