Focal degenerative disorders: a clinical approach

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Focal degenerative disorders a clinical approach

• Aberdeen 2007
• Tim Griffiths
• Cognitive Neurology Clinic, Newcastle General
  Hospital
• http//www.staff.ncl.ac.uk/t.d.griffiths/tdg.html
  

Supported by the Wellcome Trust (UK
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Key points

• An approach to focal dementias
• The late stages of many dementias are very
  similar
• At the early stages dementias can have different
  psychological profiles, that can be recognised on
  basis of the history and screening psychological
  measures
• The key to diagnosis is the recognition of those
  profiles
• IMAGING IS NOT THE KEY TO THE DIAGNOSIS OF
  DEMENTIA
• Early correct diagnosis has treatment
  implications and helps patients and their
  families
• Further information http//www.staff.ncl.ac.uk/t.d
  .griffiths/tdg/html
• cognitive neurology teaching cases

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Structure

• Four examples of patients who were referred to
  neurology
• Illustration of the approach history,
  psychological features, imaging

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Patient 1

• He is losing his memory, doc

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Patient 1

• 57R
• FH ve
• Birth development n
• School -gt 15
• Electrician
• No neurological event prior to cognitive Sx

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Patient 1

• 9 months of memory disturbance according to
  brother
• Forgetting to do jobs in plant (started writing)
• New tendency to lose keys and tools
• Language, praxis, visiospatial skills intact
• Increasing difficulty with complex multistage
  tasks (wired up a machine incorrectly)
• Frustrated, mood normal, no biological features
  depression or psychotic features

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Patient 1

• NEUROLOGICAL EXAMINATION NORMAL
• STRUCTURAL IMAGING WITH MRI NORMAL

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Patient 1 Cognitive assessment

• Screening assessment
• MMSE 27/30 ACE 72/100
• new learning deficit (learning of an address)
• anterograde verbal memory deficit (3 item 1
  minute recall and 5 minute address recall)

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Patient 1 Cognitive assessment

• Detailed neuropsychometry intellectual function
• WAIS III VIQ 96 (107) PIQ 117(108)
• Detailed neuropsychometry memory
• Striking deficits

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Patient 1 Memory (AMIPB)
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Patient 1

• Striking problem with new learning, anterograde
  verbal and visual memory
• Relative preservation of intellect
• Diagnosis of early onset AD later developed
  more striking features in non-memory domains
• NB1 MMSE not much help
• NB2 diagnosis from history and
  screening/detailed neuropsychological measures
• NB3 imaging no help (other than exclusion
  lesion)

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Distribution pathology in typical AD (Braak and
Braak 1991)
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Patient 2

• He cannot work out relationships in space, doc

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Patient 2

• 57R
• FH ve
• Birth development n
• Physical science degree
• University Lectuerer
• No neurological event prior to cognitive Sx

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Patient 2

• 1year of difficulties with spatial tasks
• Problems with reading maps
• Some difficulties putting clothes on correct way
  around
• Could not work out where all the wheel nuts were
  when changing wheel
• No Sx of forgetting spoken information or losing
  things (cf patient 1)
• Stress in job

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Patient 2

• NEUROLOGICAL EXAMINATION NORMAL
• STRUCTURAL IMAGING WITH MRI NORMAL

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Patient 2

• Screening cognitive assessment
• MMSE 29/30 ACE 97/100
• Isolated difficulty drawing intersecting
  pentagons
• Further testing in clinic showed difficulty with
  fragmented letters and rotated shapes

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Patient 2

• Detailed neuropsychometry intellect
• WAIS III VIQ 127(124) PIQ 70(125)
• Striking verbal performance discrepancy
• Detailed neuropsychometry perceptual testing
• VOSP (Visual object and spatial perception
  battery)
• Striking and significant deficit in all tests (eg
  failed on half trials of incomplete letters
  progressive silhouettes)
• Detailed neuropsychometry memory
• WMS III
• Normal verbal learning and anterograde verbal
  memory

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Patient 2

• Striking problem with visiospatial processing
  with preservation new learning and anterograde
  verbal memory (cf patient 1)
• Diagnosis of atypical AD later developed Sx in
  memory and other domains
• Form of AD called posterior cortical atrophy
• NB1 MMSE not much help
• NB2 diagnosis from history and
  screening/detailed neuropsychological measures
• NB3 imaging no help (other than exclusion
  lesion)

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Posterior Cortical Atrophy

• The pathological process in AD sometimes breaks
  the rules and does not involve medial temporal
  lobe/memory first
• Atypical form of AD where pathology involves
  parietal lobes or ventral visual association
  areas
• Relative sparing of medial temporal lobe in early
  stages, unlike typical course pathology in Braak
  and Braak studies
• Syndrome 1 (parietal syndrome) Balints syndrome
  (optic ataxia, optic apraxia, simultaneous
  agnosia)
• Syndrome 2 (ventral occipital syndrome) visual
  agnosia

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Patient 3

• She cannot talk properly, doc

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Patient 3

• 70 R
• FH ve
• Birth development n
• School -gt 15
• Shop manageress -gt 10 y before assessment
• No neurological event prior to cognitive Sx

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Patient 3

• 4 year of speech disturbance

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Patient 3

• NEUROLOGICAL EXAMINATION NORMAL
• STRUCTURAL IMAGING WITH MRI NORMAL

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Patient 3

• Screening Assessment
• MMSE 24/30 ACE score 69/100
• Comprehension good
• Repetition impaired least for nouns
• Non-fluent agramatical output with phonemic
  paraphrasia
• 10/10 for naming on Cambridge
• Reading relatively preserved
• Verbal fluency 2P/1minute category fluency 8
• Detailed neuropsychometry
• WAIS III
• VIQ 76 PIQ 99
• AMIPB
• Anterograde visual memory normal
• Anterograde verbal memory poor 

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Patient 3

• Progressive non-fluent aphasia gt 2y
• No deterioration in language independent
  cognitive function NB verbal memory
• She meets criteria for Primary Progressive
  Aphasia, a focal dementia of the left hemisphere
• In terms of underlying, pathology, this can be an
  atypical form of AD, but is more commonly a form
  of frontotemporal dementia

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Patient 4

• He is losing his ability to name anything, doc

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Patient 4

• 57 R clerical worker
• Two year difficulty with naming
• Neurological examination normal

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Patient 4

• Screening assessment
• MMSE 23/30 ACE score 51/100
• Comprehension good
• Repetition normal
• Fluent output
• 0/10 for naming
• Surface dyslexia
• Detailed neuropsychometry
• WAIS III VIQ 80 PIQ 107
• Other tests
• 43/52 Pyramids and palm trees, three picture
  version

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Patient 4
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Patient 4

• Progressive fluent anomia gt 2y
• Associated surface dyslexia
• Features are of semantic dementia
• Not associated with AD pathology
• Associated with one of the pathological subtypes
  of frontotemporal dementia
• A focal dementia affecting the lateral temporal
  lobe (cf typical AD affecting medial temporal
  lobe)

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Dementia presenting with focal language
disturbance

• NON-FLUENT
• (Patient 3)
• PPA (Mesulam 1982)
• Output language gt 2y
• No other domains
• NOSOLOGICAL CATEGORY
• Diagnosis
• 60 non specific gliosis
• 20 Pick histology
• 20 AD (atypical sparing HC)
• Imaging
• VBM gt L perisylvian atrophy
• 1. Posterior superior temporal lobe
• 2. Inferior parietal lobe
• Sonty et al
• Ann Neurol 20035335-49

• FLUENT
• (Patient 4)
• Semantic dementia PPA(fluent)
• Progressive fluent aphasia
• Surface dyslexia (prosopagnosia)
• Diagnosis
• Always one of histological variants associated
  FTD
• Imaging
• VBM gt
• 1. AP gradient of atrophy
• 2. frontal atrophy
• Mummery et al
• Ann Neurol 20004736-45

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Focal temporal lobe dementia

• Recent imaging research

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Primary Progressive Aphasia (patients like
patient 3) Categorical 22 patient vs control
(RFX) Sonty et al (NorthWestern group) Ann Neurol
20035335-49
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Semantic dementia (patients like patient 4) 6
patient (individual FFX) Mummery et al Ann Neurol
20004736-45
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Focal dementia

• The practical message

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Focal dementiaYOU DO NOT NEED IMAGING TO
DISTINGUISH THESE CONDITIONS
R
L
PATIENT 3 ALZHEIMERS OR FTD PATHOLOGY LEFT
POSTERIOR SUPERIOR TEMPORAL LOBE ? non-fluent
aphasia
PATIENT 2 ALZHEIMERS PATHOLOGY PARIETAL
LOBE ? spatial sx
PATIENT 1 ALZHEIMERS PATHOLOGY HIPPOCAMPUS ?
memory sx
PATIENT 4 FTD PATHOLOGY LEFT LATERAL TEMPORAL
LOBE ? fluent aphasia