FTDC criteria* for possible FTD Pure vascular dementia mimicking the behavioural variant of frontotemporal lobar degeneration : about 3 autopsied cases V. Deramecourt1, 2, 3, F. Lebert1, 2, C.A. Maurage1, 3, 4, F. Pasquier1, 2 1 Univ. Lille Nord de France, EA1046, UDSL, Lille, France 2 Lille University Hospital, Memory Clinic, French national reference centre for young onset Alzheimer patients, Lille, France 3 Univ. Lille Nord de France, Histology department, UDSL, Lille, France 4 Lille University Hospital, Pathology Department, Functional unit of Neuropathology, Lille, France INTRODUCTION Early behavioral disinhibition, apathy, loss of empathy, perseverative behavior, dietary changes and decline in executive tasks are core features of the behavioral variant of frontotemporal lobar degeneration (bvFTD). Recent reports have highlighted atypical cases (phenocopy cases) characterized by a long lasting, very slowly or non progressive presentation of bvFTD but neuropathological data are usually unavailable. Case n°1 Case n°2 Case n°3 gender male female Age at onset (y) 59 52 60 Duration of the disease (y) 17 3 5 Past medical history hypertension Hypertension Type 2 diabetes hypercholesterolemia Family history of dementia no « Frontal » dementia in her grandmother, her mother (aged 55 at onset) and uncle. FTDC criteria* for possible FTD yes Early behavioural disinhibition Socially inappropriate behaviour  (public urination, exhibitionism)  (rudeness, aggressiveness)  Loss of manner or decorum  (self neglect) Impulsive, rash or careless actions Early apathy or inertia apathy  severe, at foreground inertia  (pseudo catatonia) Early loss of sympathy or empathy Diminished responses to other people’s needs or feeling  (absence of emotion) Diminished social interest , interrelatedness or personal warmth Early perseverative stereotyped or compulsive ritualistic behaviour Simple repetitive movements  (scratching) Complex compulsive or ritualistic movements  (dressing/undressing)  (walking) (shaving) Stereotypy of speech  : « I’m screwed» : « that’s all »,«I don’t know » Hyperorality and dietary changes Altered food preference Binge eating, increased consumption of alcohol or cigarettes Oral exploration or consumption of inedible objects Neuropsychological profile Global cognition scores (MMSE/30 ; Mattis DRS/144) First : 28 ; 127 Last : 29 ; 128 First: 18 ; not done first: 28 ; 126 Decline in executive tasks Relative sparing of episodic memory Not applicable Relative sparing of visuospatial skills Functional decline No Other clinical features Gait impairment Mild left akinesia Rapid onset : catatonia Anxiety, akathisia. Perseverative ideas (about his tongue and teeth), agitation, Phobia about water Psychomotor instability treatments Serotonin recapture inhibitor Benzodiazepines, neuroleptics No psychoactive drug MRI data Periventricular leukoaraiosis, left lenticular lacune. Mild global atrophy. Left external capsule lacune Mild punctiform leukoaraiosis No atrophy Left caudate lacunar infarct. Small cerebellar infarct. Global atrophy. SPECT data normal Bilateral temporoparietal hypoperfusion Left frontotemporal hypoperfusion. CSF biomarkers data Not done Isolated low Ab-42 Cause of death Acute stroke, aspiration pneumonia Aspiration pneumonia Post mortem brain neuropathology Mild atrophy (brain weight=1400g) Multiple lacunes (hemispheric white matter, basal ganglia, pons, cerebellum), leukoaraiosis. Arteriolosclerosis No evidence of FTLD. Mild atrophy (brain weight=1350g) Multiple lacunes within the basal ganglia and hemispheric white matter Calcified arteriolosclerosis Numerous corpora amylacea Mild global atrophy (brain weight=1200g) No evidence of FTLD Diffuse arteriolosclerosis Microlacunes within the putamen, thalamus, temporal and frontal white matter. METHODS three case reports with a pathologically proven diagnosis of pure vascular dementia who presented with severe behavioral core features of bvFTD. these cases were investigated in the Lille University Hospital memory clinic: longitudinal follow-up with neurological, neuropsychological and behavioural evaluations. All cases had brain MRI and HMPAo SPECT Only one had a CSF sampling for Alzheimer’s biomarkers. Neuropathological assessment on the left hemisphere (the right one was frozen at -80°C). All cases were investigated with Tau, TDP-43, Ubiquitin, neurofilament, a-synuclein, Ab and PrP immunohistochemistry. Two large sections at the level of the mamillary body and pons were stained with H&E and Kluver-Barrera. RESULTS the 3 cases fulfilled the FTDC criteria for possible behavioural FTD* one of them had long lasting, non progressive variant (FTD phenocopy), the two others had  a rapid progression of 3 and 5 years from onset to death. They all lacked anterior atrophy and hypometabolism consistent with behavioural FTD Brain MRI only showed mild evidence for vascular pathology despite the final neuropathological diagnosis. FTLD pathology was excluded in each case. Microscopic examination showed prominent sub cortical chronic ischemic changes caused by arteriolosclerosis. Mild atrophy in case 2. Scattered white matter discoloration. Calcified arteriolosclerosis, perivascular space dilatation and microlacunes in case 2. (pallidum, H&E staining) « état criblé » of the putamen in case 3 (H&E staining) Mild atrophy in case 3, no macroscopic visible vascular lesion. CONCLUSIONS Isolated subcortical microvascular pathology may underlie atypical presentation of bvFTD including the long lasting, non-progressive variant. These observations also support the revised diagnosis criteria for bvFTD (international bvFTD criteria consortium) which require both functional decline and imaging results consistent with bvFTD to meet criteria for a probable diagnosis. REFERENCES * Rascovsky et al, Brain 2011, in press. (http://memory.ucsf.edu/ftd/medical/diagnosis/criteria/multiple/bvftd)