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Frontotemporal
Dementia
05 November 2004
Heterogenous
group of neurodegenerative processes that involve lobar atrophy of the frontal
and temporal cortex.
Clinical
syndromes
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Frontotemporal
dementia
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Clinical:
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Early
personality changes including disinhibition, euphoria, apathy and
noncognitive symptoms such as hyperorality
Progressive
impairments of language, executive function, loss of insight and abstract
thinking.
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Neuropsych:
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Frontal
executive tasks are sensitive to dorsolateral rather than orbitobasal
Wisconsin
Card Sorting Test
Stroop
Test
Verbal
fluency eg spontaneous word generation (see frontal
lobe function testing)
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(HMPAO)
SPECT
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Probably
the most sensitive
Hypoperfusion
in the ventromedial frontal region (even before atrophy)
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MRI
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Atrophy
of frontal and anterior temporal lobes
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Progressive
aphasia
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Clinical
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Nonfluent
verbal output remains the only symptoms for 2 years
*Often
have Alzheimer’s
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Neuropsych:
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Phonologic
errors eg efelant for elephant
Semantic
tests (word picture matching, synonym tasks) usually perfect
Perform
poorly at phonologic competence: repetition of multisyllabic words,
blending and rhyming; Tests for the Reception of Grammar (TROG)
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(HMPAO)
SPECT
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Little
data
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MRI
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Widening
of the Sylvian fissure with atrophy of insula, inferior frontal lobes and
superior temporal lobes.
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Semantic
dementia
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Clinical
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Loss
of word and object meaning in the presence pf fluent verbal output eg
progressive anomia
Caregivers
note increasing use of substitute words & phrases such as “boy”
and “outdoor thing” and problems understanding less common words
Prosopagnosic
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Neuropsych:
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Naming
tasks
“Odd
man out” synonym tasks eg Which one is odd one out: “pond, lake,
river”?
Pyramids
& Palm Tress Test: asked to judge the semantic relatedness of pictures
Hodges
& Patterson semantic memory battery
Phonology
& syntax are preserved
Able
to read & spell words with regular spelling-to-sound correspondence,
virtually all cases have difficulty reading-and spelling-irregular words.
Eg reading PINT to rhyme with hint, flint etc. This pattern is known as
surface dyslexia (or dysgraphia)
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(HMPAO)
SPECT
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Hypoperfusion
in 1 or both temporal lobes
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MRI
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Severe
atrophy involving polar region, fusiform and inferolateral gyri with
relative sparing of hippocampal formation
Asymmetric
pattern
Left
temporal more involved than the right
Subtle
involvement of the orbitofrontal cortex
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Consensus
criteria: Neary D, Snowden JS, Gustafson L et al. Frontotemporal lobar
degeneration: a consensus on clinical diagnostic criteria. Neurology 1998; 51:
1546-1554.
Clinical
Lund-Manchester
criteria: Brun A, Englund B, Gustafson L et al. Clinical and neuropathological
criteria for frontotemporal dementia. J Neurol Neurosurg Psychiatry 1994;
57:416-418.
Consensus
criteria (as above)
Rosen
HJ, Hartikainen K, Jagust W et al. Utility of clinical criteria in
differentiating frontotemporal degeneration (FTLD) from AD. Neurology 2002; 58:
1622-1628.
Extrapyramidal
motor symptoms more likely to be present in FTD
5
features correctly classified 93% patients with FTD and 97% patients with AD.
1.Social
conduct disorders
2.Hyperorality
3.Akinesia
4.Absence
of amnesia
5.Absence
of a perceptual disorder
50%
patients have family history
Pathology
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Unspecified
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Most
frequent
Spongiform
degeneration
Mild
astrocytosis
Minimal
gliosis
Loss
of large neuronal cells
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Pick
type
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Widespread
gliosis
Severe
astrocytosis
Pick
cells: swollen neurons
Pick
bodies: tau & ubiquitin positive inclusions; usually in the
nonpyramidal cells of layers 2,3,6 of cerebral cortex and in dentate
granule cells; intraneuronal and intracytoplasmic argyrophilic inclusions.
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Notes
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Progressive
aphasia often have marked involvement of periSylvian language areas but
sparing of medial temporal structures; many cases are Alzheimer’s
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Amyloid
plaques & neurofibrillary tangles usually absent in both types
Neuropathology
of Pick’s disease
Hallmark
is circumscribed lobar atrophy
Atrophy
affects anterior temporal, and frontal lobes, orbitofrontal lobe, and medial
temporal lobes but spares the posterior part of the superior temporal gyrus and
the pre & postcentral gyri.
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Type
A Pick’s
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Classic
Pick’s
Frontotemporal
and limbic degeneration with Pick bodies and ballooned neurons
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Type
B Pick’s
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Many
have extrapyramidal signs, asymmetrical motor syndromes, degeneration of
substantia nigra and other deep nuclei in addition to cortical
degeneration
Often
have CBGD (corticobasalganglionic degeneration) or FTDP-17
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Type
C Pick’s
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Dementia
lacking distinctive histopathology
Neither
Pick bodies nor ballooned neurons but have circumscribed or diffuse
cortical atrophy with varying involvement of deep grey matter
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Diagnosis
CSF
Tau (also seen in any neurodegen such as CJD, AD, PSP, CBGD and vascular
dementia)
ŻCSF
Ab42
(HMPAO)SPECT
MRI
Neuropsychological
testing
Postmortem
Tau
analysis: Pick’s have tau
doublets of 55 & 64 kD doublets; CBGD have 65 & 69 kD doublets
Tauopathies
Disease
almost exclusively characterised by tau pathology: Pick’s, CBGD, progressive
supranuclear palsy, ALS/Parkinson dementia complex and FTDP-17.
Alzheimer’s
and Down also develop filamentous inclusions composed of abnormal tau protein,
but they also have extracellular amyloid b
protein (Ab)
as a histologic hallmark lesion.
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