1. Mariano Musacchio 1 François Sellal 2 Frédéric Blanc 2 Jean-Marc Michel 2 Stephan Kremer 3 Jean-Louis Dietemann 3 1 Department of Neuroradiology - CHG Colmar 2 CMRR Strasbourg-Colmar 3 Department of Neuroradiology - CHU Strasbourg Neuroimaging and clinical spectrum of hippocampal sclerosis dementia

2. Hippocampal sclerosis Definition : Localized hippocampal neuronal loss and astrocytic gliosis, with predilection for CA1 and subiculum. Non epileptic elderly and/or demented patients a,b,c,d : Probst et al, 2007 e,f : Duvernoy e e f

3. Hippocampal sclerosis dementia Introduction Hippocampal sclerosis dementia FTLD FTD-ALS Alzheimer disease Argyrophilic grain disease Corticobasal degeneration Dementia with Lewy bodies Vascular dementia

4. Hippocampal sclerosis dementia Introduction The term hippocampal sclerosis dementia designates the presence of both hippocampal sclerotic lesions and a dementia syndrome

5. Purpose Hippocampal sclerosis dementia To describe neuroradiological findings and analyse clinical presentation of hippocampal sclerosis dementia

6. 9 patients (Colmar + Strasbourg in 4 years) Cognitive troubles or dementia Ecmnesia (anterograde memory) Hippocampal atrophy + sclerosis (T2/FLAIR, or after anatomopathological analysis) Population Hippocampal sclerosis dementia

7. Hypertension 3/9 Arrhythmia 1/9 Hypercholesterolemia2/9 Diabetes2/9 Smoking1/9 Antecedents Hippocampal sclerosis dementia Cardiovascular risk factors

8. 123456789 Score /30162926232227292530 Mean initial MMSE = 25,2 Initial MMSE Hippocampal sclerosis dementia

9. 123456789 MemoryXXXXXXXXX Visuo- constructive Apraxia XX AttentionXX Spatial Disorientation Facial Recognition XX Language Compartmental Troubles Sleep Disorder X Initial symptoms Hippocampal sclerosis dementia

10. Bilateral9 /9 R = L4 R > L2 R < L3 Hippocampal anomalies Anterior5 /9 Extended4 /9 Hippocampal sclerosis dementia

13. NAA/CrNAA/Cho+Cr Left hippocampus0,66* 0,35* Left peri-atrial area1,90 1,13 Case 3

14. Mild Cognitive Impairment 3 patients (n°2, 8, 9) Mild dementia, Alzheimer type 2 patients (n°4, 5) Moderate dementia, Alzheimer type 1 patient (n°1) Focal atrophy1 patient (n°3) Frontotemporal dementia 2 patients (n° 6,7) Initial Diagnosis Hippocampal sclerosis dementia

15. Final Diagnosis Hippocampal sclerosis dementia Frontotemporal lobar degeneration Alzheimer disease Mild Cognitive Impairment Focal atrophy Frontotemporal lobar degeneration 1 case 7 cases 3 cases 1 case 4 cases

16. Age at admission: Mean = 71,7 y-o [52-94] Diagnostic delay: Mean = 26 months [6 m - 6 y] Time of evolution: Mean = 63 months [3 - 11 y] Evolution Hippocampal sclerosis dementia

17. How? Hippocampal sclerosis dementia SPECT Temporal bilateral5 Temporal unilateral1 Fronto-temporal1 Biparietal1 8/8 non Alzheimer patients

18. How? Hippocampal sclerosis dementia CSF AD Biomarkers Aβ protNormal ↓ TauNormal P-tauNormal 6/8 non Alzheimer patients

19. Final Diagnosis Hippocampal sclerosis dementia Frontotemporal lobar degeneration Alzheimer disease Mild Cognitive Impairment Focal atrophy Frontotemporal lobar degeneration 1 case 7 cases 3 cases 1 case 4 cases

20. Monsieur R.C., 67 years old (2000) Antecedents : Diabetes Depression Complaints (wife) : Anxiety Memory troubles (anterograde) Difficulties in identifying people Independent, but less active

21. MMS = 29/30 Test de l’horloge = sp Mattis rating scale = 136/144 Attention = normal Judgement and abstraction = normal History recalls = abnormal Monsieur R.C., 67 years old (2000)

22. RL/RI-16 (Grober & Buschke) immediate recall : 16/16 free recalls : 5*-4*-8* (total : 17*) total recalls : 8*-8*-9* (total : 25*) recognition : 15/16 fausses reconnaissances : 0 deferred free recall : 9*/16 deferred total recall : 10*/16 intrusions : 13* Monsieur R.C., 67 years old (2000)

23. Isolated memory trouble Independent MCI (Mild Cognitive Impairment) Prodromal Alzheimer disease Monsieur R.C., 67 years old (2000) ?

24. Monsieur RC, evolution 5-word testTotal scoreIntrusions April 20017/103 August 20039/101 September 2004 9/100 October 200510/100 May 200610/100

25. MMSETotal scoreerreurs April 200129 memory 2/3 October 200129 id October 200229 id February 200428 memory 2/3 language 7/8 March 200527 memory 1/3 language 7/8 May 200628 memory 1/3 February 200826 memory 0/3 language 7/8 Monsieur RC, evolution

26. 2000 2008

28. Hippocampal sclerosis dementia Hippocampal sclerosis in dementia Clinical and radiologic follow-up ! Sligthly progressive isolated memory trouble No visuoconstructive apraxia in > 3-y follow-up No topographic memory trouble in > 3-y follow-up Localized hippocampal anomalies (unilateral or bilateral) Progressive (no other major associated anomaly)

29. Hippocampal sclerosis in dementia Discussion Hippocampal sclerosis FTLD ? Other ? Hippocampal sclerosis dementia ? Clinical evolution Localized/ extended atrophy + Dementia

30. Hippocampal sclerosis in dementia Discussion Blass et al. Neurology 2004; 63:492-497. White = HSclD, grey = FTD, black = AD. Symptoms at initial diagnosis

31. Hippocampal sclerosis in dementia Discussion White = HSclD, grey = FTD, black = AD. Blass et al. Neurology 2004; 63:492-497. Symptoms at 3-y follow-up

32. Hippocampal sclerosis in dementia Discussion

33. Hippocampal sclerosis in dementia Destruction of neuropil Gliosis FTLD-U HS HSD <<<<<<< + -

34. Conclusion Hippocampal sclerosis in dementia Hippocampal sclerosis in demented patients must orientate to a neurodegenerative disease, particularly FTLD Hippocampal sclerosis might be associated to vascular and some degenerative cerebral diseases Pure hippocampal sclerosis dementia is rare Neither visuoconstructive apraxia nor topographic memory troubles are seen during clincal follow-up. Atrophy and sclerosis of both hippocampi is its principal neuroradiologic anomaly

35. Thank you for your attention