1. 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. (