MRI in ALS. Federica Agosta, MD, PhD
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1 MRI in ALS Federica Agosta, MD, PhD Neuroimaging Research Unit, Institute of Experimental Neurology, Division of Neuroscience, San Raffaele Scientific Institute, Vita-Salute San Raffaele University, Milan, Italy
2 Background Proposed staging of ptdp-43 pathology in ALS Stage 1 Stage 2 Stage 3 Stage 4 Motor cortex, bulbar and spinal somatomotor neurons Reticular formation, precerebellar nuclei Prefrontal cortex and basal ganglia Anteromedial areas of the temporal lobe and the hippocampal formation Braak et al., Nat Rev Neurol 2013
3 p=0.05 p=0.01 ALS vs controls Anterior Posterior p= T-value C-statistic ALS vs. controls 0.75 Progression rate: r=-0.33, p= Agosta et al., PlosONE 2012 GM damage / Motor cortex & clinical correlations Bulbar and limb-onset ALS vs controls Verstraete et al., JNNP 2012 Bede et al., JNNP 2012
4 GM damage / Extramotor damage & cognition MND-MOTOR vs controls MND-PLUS vs controls t values Agosta et al., Hum Brain Mapp 2007 Agosta et al., PlosONE 2012 MND-PLUS vs MND-MOTOR Agosta et al., Hum Brain Mapp 2016
5 CST FA vs UMN score and disease duration Filippini et al., Neurology 2010 WM damage / CST CST damage vs progression rate and survival CST average FA r=-0.42 p=0.04 CST FA decrease in patients without UMN signs at the time of MRI Disease progression rate Sach et al., Brain 2004 Independent predictors of survival: ALSFRS deterioration rate (p=0.01, HR=2.2, 95% CI= ) CST FA (p=0.06, HR=0.94, 95% CI= ) Agosta et al., Eur J Neurosci 2010
6 Extramotor WM damage Cognitive impairment vs WM damage in ALS Corpus callosum Bilateral Partial R 2 =0.25 Bilateral Partial R 2 =0.30 PLS without cognitive deficits vs controls PLS with cognitive deficits vs controls Right ILF Right Partial R 2 =0.30 Right Partial R 2 =0.29 FA vs semantic fluency Left IFOF Left Partial R 2 =0.46 Left Partial R 2 =0.43 FA vs action naming Sarro et al., AJNR 2011 Canu et al., PlosONE 2013
7 Functional connectivity ALS vs controls Increased FC in PLS vs controls Sensorimotor Network Frontal Network ALSFRS-R Progr-rate FA CC-PMC FA CC-SMA Fluency FA CC-body Left frontoparietal Network Increased FC Reduced structural connectivity Douaud et al., Brain 2011 Agosta et al., Neurobiol Aging 2013
8 RS networks Functional connectivity ALS vs controls DMN Salience Executive DMN: WCST score vs connectivity of L precuneus (β=-0.087) and L angular gyrus (β=-0.040) Right fronto-parietal: WCST score vs connectivity of R angular gyrus (β=-0.055) and L PCC (β=-0.022) Right frontoparietal Left frontoparietal Agosta et al., Neurobiol Aging 2013
9 Network analysis Affected subnetwork after 6 months Verstraete et al., Hum Brain Mapp 2013
10
11 Spinal cord Controls ALS Cord FA r = 0.74 p < Cord MD [/1000 mm 2 s -1 ] Cord FA ALSFRS Valsasina et al., JNNP 2007 Carew et al., Neurology 2012
12 Healthy control STIR STIR MRI in ALS Peripheral NS Nerve root increased signal 3D T2 VISTA Nerve root T2 signal vs disease progression: r = 0.40 Gerevini et al., Radiology 2016 Healthy control T2 T2 Supraspinatus muscle edema STIR T1 Adipose tissue deposition between trapezius and supraspinatus muscle
13 OSR DIVISION OF NEUROSCIENCE M. Absinta F. Agosta L. Cacciaguerra E. Canu F. Caso S. Basaia M. Copetti E. Molteni Neuroimaging Research Unit Physicians, Neuropsychologists, & fellows Physicists A. D Ambrosio E. De Meo P.M. Ferraro S. Fumagalli S. Galantucci E. Pagani L. Storelli P. Valsasina Director: M. Filippi F. Imperiale R. Messina F. Pirro P. Preziosa G. Riccitelli L. Dall Occhio A. Meani P. Misci M. Petrolini Technicians E. Sarasso M.A. Rocca L. Sarro F. Savoldi E. G. Spinelli S. Sala M. Sibilia E. Silvestri R. Vuotto Department of Neurology G. Comi, N. Riva Department of Neuroradiology A. Falini
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