Abstract Details

Title In-Vivo Mapping of Thalamic Pathological Mechanisms in Pediatric Patients With MS

Topic Child Neurology and Developmental Neurology

Presentation(s) S19 - Child Neurology: Updates in Autism, Migraine, MS, and Stroke (4:25 PM-4:36 PM)

Poster/Presentation
Number 006

Background Both local inflammatory demyelination and changes secondary to axonal transection of fibers passing through focal white matter (WM) lesions can account for thalamic abnormalities in MS patients. Assessing location of microstructural abnormalities within the thalamus as a function of distance from cerebrospinal fluid (CSF) in pediatric MS patients could help to individuate whether at beginning of disease, thalamic damage is due to CSF-mediated factors or thalamic neurodegeneration associated with macroscopic damage.

Objective To investigate, in-vivo, pathological mechanisms underlying microstructural thalamic damage in pediatric multiple sclerosis (MS) patients by applying quantitative MRI techniques.

Design/Methods Sixty-eight pediatric MS patients and 24 age and sex-matched healthy controls (HC) underwent 3T MRI and clinical evaluation. As quantitative MRI metrics, we assessed diffusion tensor imaging measures - fractional anisotropy (FA) and mean diffusivity (MD)- and T1/T2-weighted ratio. We tested for: differences in thalamic volume and quantitative MRI measures globally and within concentric bands originating from CSF/thalamus interface; relation between thalamic, cortical, and WM metrics; and contribution of MRI metrics to clinical disability.

Results Compared to HC, pediatric MS patients had reduced thalamic FA (p=0.009) and no thalamic atrophy. In pediatric MS, significant reduction of FA was observed in bands nearest to CSF and in those nearest to WM, while significant abnormalities of MD and T1/T2-weighted ratio were respectively observed in thalamic regions next to CSF and to WM. Global and regional FA abnormalities as well as T1/T2-weighted ratio abnormalities showed significant correlations with disease duration, MD alterations showed significant correlations with cortical thinning. No correlations between thalamic damage and T2 lesion volumes or clinical disability were observed.

Conclusions The abnormalities observed suggest that thalamic damage occurs from the earliest stages of MS and is determined by heterogeneous pathological processes, individuating the thalamus as a critical barometer of diffuse neuronal pathology in MS.

Authors/Disclosures
Ermelinda De Meo (San Raffaele, Vita-Salute University, Milan) PRESENTER	Ms. De Meo has nothing to disclose.
Loredana Storelli	Loredana Storelli has nothing to disclose.
Lucia Moiola, MD, PhD (Fondazione Centro San Raffaele)	Dr. Moiola has nothing to disclose.
Maria P. Amato, PhD (Ospedale Di Careggi)	Dr. Amato has received personal compensation for serving as an employee of AOUCareggi. Dr. Amato has received personal compensation for serving as an employee of AOUCareggi. Dr. Amato has received personal compensation for serving as an employee of AOUCareggi. Dr. Amato has received personal compensation for serving as an employee of AOU Careggi. Dr. Amato has received personal compensation for serving as an employee of AOUCareggi. Dr. Amato has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Roche. Dr. Amato has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Novartis. Dr. Amato has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Sanofi Genzyme. Dr. Amato has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Novartis. Dr. Amato has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Biogen. Dr. Amato has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Merck. Dr. Amato has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Roche. Dr. Amato has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Novartis. Dr. Amato has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Sanofi genzyme. The institution of Dr. Amato has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Celgene BMS. The institution of Dr. Amato has received research support from Merck. The institution of Dr. Amato has received research support from Biogen. The institution of Dr. Amato has received research support from Roche.
Angelo Ghezzi, MD	No disclosure on file
	No disclosure on file
Ruggero Capra, MD	Dr. Capra has nothing to disclose.
Maria A. Rocca (Neuroimaging Research Unit)	Maria Assunta Rocca has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Biogen, Bristol Myers Squibb, Eli Lilly, Janssen, Roche. Maria Assunta Rocca has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for AstraZaneca, Biogen, Bristol Myers Squibb, Bromatech, Celgene, Genzyme, Horizon Therapeutics Italy, Merck Serono SpA, Novartis, Roche, Sanofi and Teva. The institution of Maria Assunta Rocca has received research support from MS Society of Canada, the Italian Ministry of Health, the Italian Ministry of University and Research, and Fondazione Italiana Sclerosi Multipla.
Massimo Filippi, MD, FAAN (Ospedale San Raffaele, Neuroimaging Research Unit)	Dr. Filippi has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Alexion, Almirall, Biogen, Merck, Novartis, Roche, Sanofi. Dr. Filippi has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Alexion, Biogen, Bristol-Myers Squibb, Merck, Novartis, Roche, Sanofi, Sanofi-Aventis, Sanofi-Genzyme, Takeda. Dr. Filippi has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Bayer, Biogen, Celgene, Chiesi Italia SpA, Eli Lilly, Genzyme, Janssen, Merck-Serono, Neopharmed Gentili, Novartis, Novo Nordisk, Roche, Sanofi, Takeda, and TEVA. Dr. Filippi has received personal compensation in the range of $10,000-$49,999 for serving as an Editor, Associate Editor, or Editorial Advisory Board Member for Springer Nature. The institution of Dr. Filippi has received research support from Biogen Idec, Merck-Serono, Novartis, Roche, the Italian Ministry of Health, the Italian Ministry of University and Research, and Fondazione Italiana Sclerosi Multipla.

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