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H Chabriat CERVCO, INSERM U740, DHU NeuroVasc, Universit Denis Diderot, APHP Paris, France
Executive Dysfunction
Dementia
T2 WM abnormalities
10
20
30
40
50
60
70
80 Age (years)
Executive Dysfunction
Dementia
T2 WM abnormalities
10
20
30
40
50
60
70
80 Age (years)
N = 378 patients
50 40 30 20
percentage
women men
10
0
5 to 15
16 to 30
31 to 40 41 to 50 age (years)
51 to 60
> 60
6 5 7
26 9
Ischemic stroke
6085% of patients mean age of first stroke: 49 years (range from 19 to 70 years) average incidence: 104 per 100 patient-years (95% CI 5.6 to 15.2) average number: 2 to 5 recurrent strokes over several years ischemic events invariably subcortical lacunar syndrome in about 2/3 of cases (pure motor or sensory deficit, ataxic hemiparesis, sensory-motor deficit, dysarthriaclumsy hand syndrome) in most cases no conventional vascular risk factors but HT present in 20% of patients and high cholesterol and smoking present in 50% of patients in some series
Chabriat et al, Lancet, 1995 Dichgans et al, Ann Neurol, 1998 Peters et al, Stroke, 2004
Case 2 44 yo man, no vasc risk factor episodes of instability and paresthesias; sudden right sided dysarthria and hemiparesis BP 100-130/60-85 mmHg with episodes of hypotension 80/45 mm Hg Case 3 54 yo woman, no vasc risk factor, 4th stroke, acute right hemiparesis BP 105-130/60-75 mmHg
Case 1 48 yo woman, acute short term memory loss and word finding difficulty BP normotensive but no detail
ICH
Case 2: BP: 100/63 mm Hg, use of steroids MacLean et al, JNNP, 2005
4 hypertensive cases Rinnocciet al, J Neurol Sciences, 2013
Age, y, mean (SD) Range Men,%(n) Years of school, mean (SD) MMSE/30, mean (SD) MDRS/144, mean (SD) Modified Rankin Scale >3,%(n) IADL/8, mean (SD) Presence of vascular risk factors,%(n) History of psychiatric disorders,%(n) Migraine with aura,%(n) History of TIA or stroke,%(n) Presence of seizures,%(n) Presence of gait disorders,%(n) Dementia,%(n)
Structured Clinical Interview for DSMIV criteria by psychiatrists - N = 23 pts (mean age 53y, demented subjects excluded) - Lifetime episode of depression: n = 17 (74%)
- Main symptom: depressed mood, feelings of guilt, insomnia
Chabriat et al, Lancet Neurol, 2009 Valenti et al, Acta Neurol Scand, 2008 &2011
Cognitive decline
patients
Visuospatial abilities Reasoning Verbal fluency Attention Memory Executive functions < 50 ]50 60] > 60
Buffon F et al, JNNP, 2006
Percentage of
40%
20% 0%
Age
Memory impairment
INFORMATION
ENCODING immediate recall N = 44
Age (years) High educationlevel Sex male Cardiovascularrisk History of stroke or TIA Focal neurologica l deficit MADRS Barthel Index Rankin score MDRS <5th percentile,%(n) IADL, mean(S.E.) MMSE *adjustment for age, sex and education level 54.7(1.9) 13.0% 68.8% 67.5% 66.6% 42.9% 13.5(3.8) 91.6(3.2) 1.1(0.3) 42.3 (11) 6.7 (0.3) 28.3 (0.3)
30%
0.01 0.01 0.004 0.15 0.65 0.1 0.05 0.14 0.14 0.01 0.01 0.001 *
Hippocampic memory impairment is observed in one out of five CADASIL patients with memory deficit
INFORMATION
ENCODING STORAGE RETRIEVAL INFORMATION
poor free and delayed recall adequate encoding little or no improvement by cueing Hippocampic memory impairment (8) Mean age IADL Barthel index Rankin 56.8 5 (0.7) 77 (8) 2 (0.8) Other types of memory impairment (36) 55.1 6.8 (0.4) 92 (3) 1.1 (0.3)
MMSE
22.9 (0.8)
27 (0.4)
S Epelbaum et al, Neurobiol Aging, 2009
The cognitive profile does not differ between CADASIL pts with stroke and sporadic SVD
N = 20 N = 54 N = 14
Disability
Dementia 11%
1/3
1/3
1/10
Dementia
20-30% pts mean age = 58 9 years subcortical dementia
frontal-like symptoms (poor attention, perseverations, apathy) and memory impairment
stepwise or progressive deterioration isolated (no history of stroke) in 10% often associated with pseudobulbar palsy present in 90% of cases before death
Demented CADASIL patients can present without any history of stroke and without any focal symptoms
Gender effect
Spastic tetra-/hemiparesis Urinary incontinence Constant nursing care and attention Dementia Dysarthria Dysphagia Faecal incontinence Bedridden Pathological laughing or crying Decubital ulcer Transcutaneous gastric feeding Suprapubic catheter
55/62 (89) 48/60 (80) 51/65 (78) 49/64 (77) 47/61 (77) 41/56 (73) 42/58 (72) 41/65 (63) 30/56 (54) 18/55 (33) 18/59 (31) 12/58 (21)
C Opherk et al, Brain, 2004
Peripheral sensory symptoms with abnormal nerve conduction Myopathy Spinal cord manifestations with associated lesions Visual loss
Conclusion
CADASIL is a severe condition progressing over several decades the most frequent clinical manifestations are migraine with aura, TIAs and stroke, gait disturbances, mood disorders, cognitive decline from executive dysfunction to severe dementia associated with apathy, seizures can be also observed severe disability is more frequent in men than in women after 50y and can occur at different age from 45 to 80y, although > 75% pts are severely disabled after 65y
Lab
E Tournier Lasserve A Joutel and their team
Support Logistics
Jocelyne Ruffie Solange Hello
Imaging
Jean Pierre Guichard (MRI team) Eric Jouvent Franois De Guio
Neuropsychologists
Annie Kurtz Sonia Reyes Aude Jabouley
Main collaborators
Martin Dichgans Marco During Nicola Zieren Niels Peters Chahin Pachai
Acknowledgements
ARNEVA
Fondation Leducq