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2/10/2017
1
Clinicopathologic ConferenceRAIN 2017
Case Presenter: Scott Caganap, MDClinical Discussant: Gil Rabinovici, MD
Pathology Discussant: Lea Grinberg, MD, PhD
Outline• Case Presentation
1. History and Exam2. Expert Opinion3. Ancillary Testing4. Final Diagnosis?
• Pathology Presentation
• Closing Remarks
Case Presentation• 68 year-old left-handed man with progressive cognitive impairment
• Accompanied by his wife who does most of the reporting
Year 1• Difficulty fixing up cars
Year 2• Trouble understanding his wife in conversation• Hearing aid � no improvement
Year 3• Repeating conversations, word-finding difficulty, substitute/mispronounce words• Paucity of speech (down 25%), spoke with softer voice
Year 4
• Progressive difficulty with familiar tasks, stopped driving• Speech output down 80%, difficulty expressing himself � hand motions• No longer pursued hobbies, quit working, needed encouragement to keep up his hygiene• Increased sleep, daytime naps• Lacked insight, content mood
Year 5
• Nearly mute, unable to read or write• Excessive eating, weight gain, stuff large amounts of food in his mouth• Walk outside in only underwear• Repetitively paced in his yard in a particular pattern
68 year-old left-handed man with progressive cognitive impairment
2/10/2017
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Review of Systems• Cognition:
– No fluctuations in cognition or level of arousal– Unclear if memory is an issue because he speaks
so rarely– Does not get lost in familiar environments– No issues recognizing his family, but may not
recognize former co-workers occasionally
Review of Systems• Psychiatric:
– Approximately 10 years ago, he had a recurrent delusion in which he suspected his wife of infidelity, but this resolved with marriage counseling
– No illusions, misperceptions, or hallucinations
Review of Systems• Neurologic:
– No changes in vision– Difficulty swallowing (pills, large solids); coughs
during meals– Intermittently kicked his legs while sleeping– Generally slower movements– No tremor, weakness, incoordination, or recurrent
falls– Occasional urinary incontinence
Personal History• PMH: BPH s/p laser surgery• MEDS: tamsulosin, NKDA• FH: two healthy sons; biological family not known• Social History:
– Raised in foster care. Lost foster parents at a young age.
– Grew up in central California. Completed the twelfth grade without difficulty.
– Most recently worked a part-time job as a dishwasher. Previously employed as a mechanic at an auto shop.
– Rare alcohol consumption. No tobacco or illicit drug use.
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Examination• General:
– Normal vital signs, 137 lbs., 5’7”– Cooperative, well-groomed
Mental Status Exam• Alert, DSF 4• Flat affect, slow to respond• Unable to spell WORLD backward, DSB 0• Oriented to self, city, month, and date, but not season, year, or place
• Word registration 3/3, recall 0/3
Mental Status Exam• Sparse speech, up to 4-word sentences, grammatically correct
• Used hand gestures when attempting to speak• Named only a few simple objects• Can repeat a simple sentence• Unable to perform multi-step tasks
Mental Status Exam• Unable to copy intersecting pentagons• Could not pantomime blow-a-kiss or whistle• Unable to perform 3-step hand movement task (Luria test) on both sides
• MMSE 8/30
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Cranial Nerve Exam• VFF, no extinction to DSS• PERRLA• EOMI except for limitation in up-gaze, gaze impersistence
• Normal saccades, no nystagmus
Cranial Nerve Exam• Mild hypophonia and guttural dysarthria• Moderate hypomimia, full facial strength• Mildly diminished hearing bilaterally• Symmetric palate elevation• Normal tongue movements, no fasciculation
Motor Exam• Occasional BUE fasciculation• Paratonia in all extremities• Slowing of movements in all extremities (R>L)• Reduced amplitude finger/foot tapping• No postural or rest tremor• Full strength
Coordination Exam• Intention tremor during FNF testing on R• No dysmetria• Unable to perform RAMs
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Reflex Exam Reflex Exam• R palmar grasp• R palmomental & rooting reflex• Snout reflex
Sensory Exam• Normal sensation to all modalities• No extinction to DSS• Normal stereognosis• No instability during Romberg testing
Gait Exam• Slow, cautious• Short-stride length• Decreased arm-swing bilaterally• One step backwards during retropulsiontesting
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Expert Opinion• What are your thoughts Dr. Rabinovici?
– Differential Diagnosis?– Further Workup?– Leading Diagnosis?– Expected Underlying Pathology?
Clinicopathological Conference:68 year-old with 5 years of cognitive and
behavioral decline
Gil Rabinovici, M.D.Associate Professor of Neurology, UCSF
50th Annual Recent Advances in NeurologyFebruary 10, 2017
Disclosures
• Research support – Avid Radiopharmaceuticals/Eli Lilly, GE Healthcare,
Piramal Imaging
– NIH (NIA, NINDS, NCATS), American College of Radiology, Alzheimer’s Association, Tau Consortium, Association for Frontotemporal Degeneration, Michael J Fox Foundation
• Consulting/honoraria– Eisai, Genentech, Lundbeck, Merck, Putnam, Roche
Approach to Patient with Cognitive Complaints
• HPI probes cognitive domains– Memory: misplacing items, repetitive questions, missing
appointments or bills, remote memory– Visuospatial: navigation, spatial relationships, object and
face recognition– Language: production and comprehension, motor speech,
reading and writing– Executive: decision-making, judgment, multi-tasking,
concentration/focus– Behavior: personality changes, depression, anxiety, apathy,
disinhibition, psychosis– Motor
• First or early symptoms particularly helpful• PMH, Meds, FH, SH may offer valuable clues
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Approach to Patient with Cognitive Complaints
• Mental Status exam and neuro-psychological testing– Better define cognitive domains
• Physical neurological exam– Cranial nerves– Motor: UMN/LMN, parkinsonism – Sensory loss– Ataxia– Gait
Approach to Patient with Cognitive Complaints
• Labs: exclude “treatable” metabolic or infectious causes– Mandatory
• Chem 20, CBC, B12, TSH
– Discretionary• RPR/FTA-ABS, HIV, homocysteine/methylmalonic acid,
LP, rheumatologic, paraneoplastic, heavy metals, etc.
– Imaging (MRI preferred)– Exclude tumor, SDH, NPH, etc.– Evaluate for vascular lesions– Pattern of atrophy
From Clinical Syndrome to PathologyAβ
Tau
α-synuclein
TDP-43
Common Causes of Neurodegenerative Dementia
Disease Protein Anatomy Early Sxs NeuropsychAD Aβ, tau Medial temporal
Posterior temporoparietalMemory loss,spatial disorientationBehavior spared
Episodic memoryVisuospatialDysexecutive
DLB α-synucleinAβ
FrontalOccipital/temporalBasal gangliaBrainstem
Parkinsonism, RBD,Psychosis, fluctuations
VisuospatialDysexecutiveMemory relatively spared
FTD TauTDP-43FUS
FrontalAnterior temporal
Disinihibition, apathy, personality changesAphasia, executive dysfunctionMotor-neuron disease
DysexecutiveMemory may be sparedVisuospatial usually spared
VascD N/A Often frontal predominant (but variable)
Often dysexecutive, memory, visuospatial, behavioral
Often executive functions worst, though variable
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History: Cognitive Symptoms• First symptom: “difficulty performing skilled tasks”
(e.g. car repairs)– Executive, motor planning or output, procedural memory
• Language decline– “Difficulty understanding his wife” – comprehension, attention– Decreased speech output, short sentences– Mispronouncing words, soft voice, mutism - motor speech– Repeating previous conversations
• Episodic memory, perseveration– Unable to read or write: pervasive language deficits
History: Behavioral Symptoms• Apathetic!
– Loss of initiative, interest in hobbies, personal hygiene, hyper-somnolence
• Blissfully unaware– Poor insight, not perturbed by deficits
• Repetitive motor behaviors, pacing• Disinhibition
– Walking around in underwear• Overeating
Frontal Circuits: Cognition & Behavior
Seeley et al. J Neurosci. 2007Rosen et al. Brain 2005
Aberrant Motor Behavior
Apathy
DisinhibitionT-score
T-score
T-score
Executive Control Network – Lateral, fronto-parietalCognitive
Salience Network –Medial, fronto-insularSocial-emotional behavior
Speech Production Networks
Key nodes: inferior frontal gyrus (BA 44), supplementary motor area (SMA), caudate
Key tracts: aslan tract (AT), superior longitudinal fasciculus (SLF), fronto-striatal
Gorno-Tempini et al. Neurology 2006Mandelli et al. Brain 2016
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Additional History• Dysphagia • Occasional urinary incontinence• Delusion of marital infidelity 10 years ago, no hallucinations
• No sleep disturbance• No major medical co-morbidities, Rx• Family history unknown
Exam: Pertinent Positives and Negatives• Thin (5’7”, 137 lbs.) despite over-eating• Cognitively globally impaired (but knows exact date)• Slow, apathetic, little speech output, orobuccal
apraxia• Digits forwards 4, backwards 0; working memory
disproportionately affected vs. repetition• Saccades intact; hypophonic, guttaral dysarthria• UE fasciculations; mild hyper-reflexia, R Babinski• Hypomimia, bradykinesia R>L, slow gait with
decreased arm swing• Intention tremor on R, no truncal or limb ataxia
Rabinovici et al., Continuum 2015
Case Summary• Chronic, progressive course and absence of co-morbidities consistent with primary neurodegenerative disease
• Cognitive: Early and disproportionate executive dysfunction and motor speech
• Behavior: Apathy > disinhibition, overeating• Motor: UMN/LMN; mild extra-pyramidal• Localization:
– Dorsolateral and dorsomedial prefrontal cortex, L>R
– UMN and C-spine LMN, basal ganglia
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Common Causes of Neurodegenerative Dementia
Disease Protein Anatomy Early Sxs NeuropsychAD Aβ, tau Medial temporal
ParietalFrontal
Memory loss,spatial disorientation,social graces preserved
Episodic memoryVisuospatialDysexecutive
DLB α-synucleinAβ
FrontalOccipital/temporalBrainstem
Parkinsonism, RBD,Psychosis, fluctuations
VisuospatialDysexecutiveMemory relatively spared
FTD TauTDP-43FUS
FrontalAnterior temporal
Disinihibition, apathy, personality changes,Aphasia, executive dysfunctionMotor-neuron disease
DysexecutiveMemory usually sparedVisuospatial always spared
VascD N/A Often frontal predominant (but variable)
Often dysexecutive, memory, behavioral
Often executive functions worst, though variable
Frontotemporal Dementia• Family of clinicopathologic syndromes
– Progressive changes in behavior or language– Neurodegeneration of frontal or anterior temporal lobes
• Common cause of pre-senile dementia– 5% of all dementia, most common cause of early-onset dementia (<65 years)
– Incidence 3-4/105, prevalence 15-22/105
– Even more common when include associated disorders ALS, HS, CBD, PSP, CTE
PSP CBD nfvPPA bvFTD svPPA FTLD-ALS
FTLD-TAU FTLD-TDP
MAPT PGRN
Clinical Syndromes: FTD
Pathology: FTLD
Genes
FTLD-FUS
C9ORF72
Rabinovici and Miller. CNS Drugs 2010
Behavioral-Variant FTD: Clinical Criteria(3 of 6 for “Possible bvFTD”)
• Early behavioral disinhibition • Early apathy or inertia -• Early loss of emotional reactivity/sympathy and empathy
• Perseverative, stereotyped or compulsive/ritualistic behavior
• Hyper-orality and dietary changes -• Executive-predominant cognitive dysfunction
Rascovsky et al. Brain 2011
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Behavioral-Variant FTD: Clinical Criteria(3 of 6 for “Possible bvFTD”)
• Early behavioral disinhibition - +/-• Early apathy or inertia - �• Early loss of emotional reactivity/sympathy and empathy - No
• Perseverative, stereotyped or compulsive/ritualistic behavior - �
• Hyper-orality and dietary changes - �• Executive-predominant cognitive dysfunction –perhaps early on, now too impaired to judge
Rascovsky et al. Brain 2011
Atrophy Patterns in FTLD vs. ADPathology-proven AD/FTLD vs. NC
Common atrophy in AD and FTLD
Distinct atrophy in AD and FTLD
Rabinovici et al. AJADOD 2007
Amyloid vs. FDG-PET in Differential Diagnosis of AD vs. FTD
Rabinovici et al. Neurology 2011
AD (N=62, age 65, MMSE 22)FTD (N=45, age 65, MMSE 22)Amyloid (PIB) PET visual reads
90% sensitivity, 83% specificityInter-rater agreement κ=0.96
FDG-PET visual reads78% sensitivity*, 84% specificityInter-rater agreement κ=0.72*
70 autopsy-proven casesPIB: Sensitivity 96%, Specificity 88%FDG: Sensitivity 88%, Specificity 89%
* - p<0.05 vs. PIB
bvFTD – Probable or Definite• Probable bvFTD
– Meets criteria for possible bvFTD– Significant functional decline– Frontal/anterior temporal pattern on MRI/FDG
• bvFTD with definite FTLD pathology– Histopathological evidence on bx/autopsy– Presence of a known pathogenic mutation
• Exclusions– Deficits better accounted for by other medical,
neurological or psychiatric disorder– Biomarkers strongly indicative of AD or other
process Rascovsky et al. Brain 2011
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Primary Progressive Aphasia
• Non-fluent/agrammatic variant (nfvPPA)– Effortful speech, agrammatism, motor speech deficits– Pathology: FTLD-Tau > FTLD-TDP
• Semantic variant (svPPA)– Fluent, grammatically correct speech with loss of word and object meaning– Pathology: FTLD-TDP
• Logopenic variant (lvPPA)– Hesitant speech with word finding difficulty, poor repetition– Pathology: AD
Mesulam, Ann Neurol 1982Gorno-Tempini et al. Neurology 2011
Progressive loss of language with relative preservation of other cognitive functions
Progressive Supranuclear Palsy
• Richardson’s Syndrome– Vertical gaze palsies, postural instability with early
falls, axial-predominant parkinsonism– Highly specific but not sensitive at early stages
• Cognitive decline– Executive dysfunction, slowed processing speed,
impaired working memory
• Behavioral symptoms– Apathy, depression, impulsivity
• Atypical phenotypes– PSP-parkinsonism, pure akinesia with gait
freezing (PAGF), nonfluent PPA, bvFTD
Clinical Phenotypes of Corticobasal Degeneration
• Corticobasal syndrome (CBS)– Asymmetric limb rigidity/akinesia, dystonia, myoclonus– Orobuccal/limb apraxia, cortical sensory loss, alien limb
• Frontal behavioral-spatial syndrome– Executive dysfunction, behavior/personality changes,
visuospatial deficits• Nonfluent primary progressive aphasia
– Effortful speech, agrammatism, apraxia of speech• PSP syndrome
– Symmetric, supranuclear gaze palsies, early fallsArmstrong et al. Neurol 2013
bvFTD FTLD-ALS
FTLD-TAU FTLD-TDP
MAPT PGRN
Clinical Syndromes: FTD
Pathology: FTLD
Genes
FTLD-FUS
C9ORF72
Rabinovici and Miller. CNS Drugs 2010
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Pick’s PSP CBD
TDP-A TDP-B TDP-C
FTLD-TDP
FTLD-tau
DPR(C9ORF72)
FTLD-FUSNeuropathological Dx in Clinical bvFTDUCSF Neurodegenerative Brain Bank, N=117
Courtesy of David Perry, Lea Grinberg & Bill Seeley
� None � Delusions more common (and more severe on NPI)
� More signs of MND
� None with visual misperception
FTLD-tau: FTLD-TDP� Younger age at onset,
presentation, and death
� More oral exploration
� More severe NPI anxiety, euphoria, apathy, disinhibition, aberrant motor, sleep disturbance, eating behavior
� Worse verbal memory and more design fluency repetitions
FTLD-FUS
� FTDC criteria
• No difference in 6 core FTDC features at presentation or throughout follow-up
• Frequency of meeting possible or probable FTDC criteria
� Parkinsonism
Not helpful
Predicting Pathology in bvFTD: Clinical Pearls FTD Autosomal Dominant MutationsMutation C9orf72 MAPT GRN
Age of DX 56 52 62
Clinical bvFTD, ALSFTD-ALS, (AD)
bvFTD, PSP. CBS, (AD)
bvFTD, nfvPPA, CBS, (AD)
MRI Diffuse cortical, can be mild, thalamus,cerebellum
Frontotemporaltemporal > frontal
Asymmetric frontotemporal, parietal
Unique clinical
ALS, psychiatricprodrome with slow progression
Symmetry, addiction
Asymmetric syndromes
Neuropath FTLD-TDP BFTLD-TDP AFTLD-TDP (U)
FTLD-Tau(usually 4R)
FTLD-TDP A
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Genetic vs. Sporadic FTD
Whitwell et al. Brain 2012
Tau PET in FTD: [18F]AV1451
Spina et al. Neurology 2017
Final Conclusions• Clinical dx: behavioral-variant FTD (with
prominent language disturbance)
• Predicted pathology (in order of likelihood):1. FTLD-TDP, type B; sporadic or C9ORF722. FTLD-TDP, type A/U3. FTLD-Tau (Pick, PSP, CBD) less likely4. AD unlikely to be primary pathology
Year 1• Difficulty fixing up cars
Year 2• Trouble understanding his wife in conversation• Hearing aid � no improvement
Year 3• Repeating conversations, word-finding difficulty, substitute/mispronounce words• Paucity of speech (down 25%), spoke with softer voice
Year 4
• Progressive difficulty with familiar tasks, stopped driving• Speech output down 80%, difficulty expressing himself � hand motions• No longer pursued hobbies, quit working, needed encouragement to keep up his hygiene• Increased sleep, daytime naps• Lacked insight, content mood
Year 5
• Nearly mute, unable to read or write• Excessive eating, weight gain, stuff large amounts of food in his mouth• Walk outside in only underwear• Repetitively paced in his yard in a particular pattern
68 year-old left-handed man with progressive cognitive impairment
ROSROS• Dysphagia• Bradykinesia• Incontinence
2/10/2017
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Ancillary Testing• Basic serum studies including B12 and TFTs were unremarkable
• MRI Brain: – No mass lesions or ischemic changes– Subtle generalized atrophy, ? anterior predominance,
no lateralization
• FDG-PET: global hypometabolism with sparing of bilateral occipital cortices and posterior cingulate
Year 1• Difficulty fixing up cars
Year 2• Trouble understanding his wife in conversation• Hearing aid � no improvement
Year 3• Repeating conversations, word-finding difficulty, substitute/mispronounce words• Paucity of speech (down 25%), spoke with softer voice
Year 4
• Progressive difficulty with familiar tasks, stopped driving• Speech output down 80%, difficulty expressing himself � hand motions• No longer pursued hobbies, quit working, needed encouragement to keep up his hygiene• Increased sleep, daytime naps• Lacked insight, content mood
Year 5
• Nearly mute, unable to read or write• Excessive eating, weight gain, stuff large amounts of food in his mouth• Walk outside in only underwear• Repetitively paced in his yard in a particular pattern
68 year-old left-handed man with progressive cognitive impairment
ROSROS• Dysphagia• Bradykinesia• Incontinence
MRI T1-Weighted Sequences
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Ancillary Testing• MRI Brain: severe L>R atrophy
– Lateral and medial frontal lobes– Anterior and medial temporal lobes
• PIB-PET: negative
Expert Opinion• Interpretation of Imaging?• Final Diagnosis and Pathology? Change your mind?
Year 1• Difficulty fixing up cars
Year 2• Trouble understanding his wife in conversation• Hearing aid � no improvement
Year 3• Repeating conversations, word-finding difficulty, substitute/mispronounce words• Paucity of speech (down 25%), spoke with softer voice
Year 4
• Progressive difficulty with familiar tasks, stopped driving• Speech output down 80%, difficulty expressing himself � hand motions• No longer pursued hobbies, quit working, needed encouragement to keep up his hygiene• Increased sleep, daytime naps• Lacked insight, content mood
Year 5
• Nearly mute, unable to read or write• Excessive eating, weight gain, stuff large amounts of food in his mouth• Walk outside in only underwear• Repetitively paced in his yard in a particular pattern
68 year-old left-handed man with progressive cognitive impairment
2/10/2017
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Year 6• Marked progression of apathy• Decline in mobility and functional independence• No longer following commands
Year 7• No longer responding to voice• Significant weight loss, feeding tube placement• Bedridden• Hospice
68 year-old left-handed man with progressive cognitive impairment Pathology Discussion• Dr. Grinberg, what are the range of pathological findings that can be seen in a patient presenting with these signs and symptoms?
• What did the autopsy show?
RAIN 2017CPC
Pathology
Lea T. Grinberg, M.D Ph.DAssociate Professor of Neurology and PathologyUCSF
Frontotemporal lobar degeneration (FTLD)
SD FTD-MNDbvFTD PSPSCBSPNFA
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Frontotemporal lobar degeneration (FTLD)
SD FTD-MND
FTLD-tau FTLD-TDP*
Pick’s3R tau
CBD4R tau
PSP4R tau
FTDP-17(MAPT)
Tau NOSMST/AGD
FTLD-FUSFTLD-3
(CHMP2b)
bvFTD PSPSCBS
Alzheimer’sDisease
PNFA
Type CType D(VCP)
Type B(C9orf72)(TARDP?)
*Harmonized scheme
aFTLD-U
NIFID???
(FUS)
BIBDType A
(PGRN)(C9orf72)
Courtesy W. Seeley, UCSF
Frontotemporal lobar degeneration (FTLD)
SD FTD-MND
FTLD-tau FTLD-TDP*
Pick’s3R tau
CBD4R tau
PSP4R tau
FTDP-17(MAPT)
Tau NOSMST/AGD
FTLD-FUSFTLD-3
(CHMP2b)
bvFTD PSPSCBS
Alzheimer’sDisease
PNFA
Type CType D(VCP)
Type B(C9orf72)(TARDP?)
*Harmonized scheme
aFTLD-U
NIFID???
(FUS)
BIBDType A
(PGRN)(C9orf72)
Courtesy W. Seeley, UCSF
Weight: 1066 g
R
UCSF/MAC Neurodegenerative Disease Brain Bank
2/10/2017
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1. Moderate dorsolateral frontal and insula atrophy2. Mild ventral frontal and temporal atrophy3. Caudate is flat4. Hippocampus is relatively spared
Example of negative immunohistochemical assay
100 µm
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Beta-amyloid
Scarce number of diffuse and
neuritic plaques in the primary
visual area (occipital cortex)
TDP-43
*
ITG
Scale bars: 10 µm
unclassifiable: neuronal cytoplasmatic and nuclear inclusions, threads, glial inclusions in all cortical layers
SN
ITG
IFG
3R- and 4 Repeat-tau
RD4 RD3
Entorhinal cortex
Scale bars: 10 µm
Atypical neuronal/glial 4R-tauopathy (limbic and peri-limbic
Ubiquitin IHC, cerebellar granule cells
The signature pathologyImmunohistochemistry for p62 - cerebellum
pathognomonic of C9orf72 expansions
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Final Neuropathological DiagnosesPrimary diagnosis: Frontotemporal lobar degeneration with TDP-43 immunoreactive inclusions FTLD-TDP, unclassifiable
Contributing diagnosis : 4-repeat tauopathy, not otherwise specified
Incidental diagnosis: Alzheimer’s disease neuropathological change (ADNC)2
Low ADNC, NIA-AA Criteria (A1, B1, C0)Thal Amyloid Plaque Phase 1Braak Neurofibrillary Degeneration Stage 1CERAD Neuritic Plaque Score none,
Case Summary• Our patient developed cognitive impairment in his mid-60’s that progressed over 7 years– Cognitive domains:
1. Executive2. Behavior + Language
– Brain Imaging:1. Anterior-predominant hypometabolism2. Severe L>R frontal & anterior temporal lobe atrophy
• Clinical Dx: behavioral-variant FrontotemporalDementia
• Pathological Dx: FTLD-TDP associated with mutation in C9ORF72
behavioral-variantFrontotemporal Dementia
Epidemiology• FTD is 2nd most common cause of early-onset neurodegenerative dementia (after AD)
• Prevalence:– 15-22 per 100K persons 45-64 yo– 10% occurs in patients <45 yo– 30% occurs in patients >65 yo
• bvFTD accounts for >50% of autopsy-confirmed FTLD
Knopman et al, J Mol Neurosci 2011Snowden et al, Brain 2011
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Genetics• 40% of FTD is associated with autosomal dominant inheritance
• bvFTD & agrammatic PPA are most common phenotypes
• Mutations in 8 genes account for 50% of familial FTD
• C9ORF72 mutation is most common genetic abnormality in familial FTD (12%) and familial ALS (23%) Rohrer et al, Neurology 2009
Le Ber, Rev Neurol 2013DeJesus-Hernandez et al, Neuron 2011
Criteria for bvFTD• Gradual onset and progressive deterioration of behavior and/or cognition– Disinhibition– Apathy– Ritualistic behavior– Hyperorality
• Frontal and/or anterior temporal pattern on MRI or PET
Rascovsky et al, Brain 2011
Management• No approved therapies for FTD• Supportive care
– Power of attorney– Swallow evaluation– Physical therapy
• Genetic counseling
Finger, Continuum 2016
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Acknowledgements• The patient and his family• UCSF Memory and Aging Center• Discussants:
– Dr. Gil Rabinovici– Dr. Lea Grinberg
• RAIN 2017 Co-Chairs:– Dr. Stephen Hauser– Dr. Andy Josephson