Abstract Details

Title Altered Hypothalamic Functional Connectivity in Amyotrophic Lateral Sclerosis

Topic Neuromuscular and Clinical Neurophysiology (EMG)

Presentation(s) S5 - Updates on Amyotrophic Lateral Sclerosis (4:18 PM-4:30 PM)

Poster/Presentation
Number 005

Background Hypermetabolism is a newly identified clinical feature of ALS, associated with shorter survival. Hypothalamic volume reduction and white matter structural connectivity alterations between hypothalamus, orbitofrontal and insular regions have been recently reported as a possible underlying cause. However, changes in functional connectivity of hypothalamus and its relationship with patients’ clinical severity have not been thoroughly investigated yet.

Objective To assess resting-state functional connectivity (RS-FC) of the hypothalamus in patients with amyotrophic lateral sclerosis (ALS) as compared to healthy controls (HC), and to evaluate its relationship with clinical measures.

Design/Methods Seventy-one ALS patients and 39 age- and sex- matched HC underwent brain structural and resting state functional MRI (rs-fMRI) on a 3 Tesla scanner. In each subject, the bilateral hypothalamus was manually segmented and a seed-based RS-FC analysis was performed between this region and the rest of the brain. Hypothalamic RS-FC was then compared among groups, and the relationship between RS-FC significant changes and ALS Functional Rating Scarle – revised (ALSFRS-r) scores was investigated.

Results The seed-based analysis showed that, compared to HC, ALS patients exhibited increased hypothalamic RS-FC with the caudate nuclei bilaterally. Additionally, greater disease severity in terms of ALSFRS-r scores in patients correlated with an increase of RS-FC between hypothalamus and both the bilateral caudate nucleus and orbitofrontal cortex.

Conclusions These findings support the presence of hypothalamic alterations in ALS. These RS-FC changes may be related to the hypermetabolic clinical feature in these patients. The early detection of the hypothalamic changes in ALS could be useful for prognostic stratification and for monitoring the effect of specific interventions.

Authors/Disclosures
Fabiola Freri, psychologist PRESENTER	Miss Freri has nothing to disclose.
Edoardo G. Spinelli, MD	Dr. Spinelli has nothing to disclose.
Elisa Canu (Ospedale San Raffaele)	The institution of Elisa Canu has received research support from Italian Ministry of Health .
Francesco Roselli (University of Ulm; and German Center for Neurodegenerative Diseases (DZNE))	No disclosure on file
Veronica Castelnovo, MSc (San Raffaele Scientific Institute, Vita-Salute San Raffaele University)	Dr. Castelnovo has nothing to disclose.
Ilaria Bottale, MD	Dr. Bottale has nothing to disclose.
Hans-Peter Müller (University of Ulm; and German Center for Neurodegenerative Diseases (DZNE))	No disclosure on file
Jan Kassubek, MD	Prof. Kassubek has nothing to disclose.
Albert C. Ludolph, MD	Dr. Ludolph has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Novartis. Dr. Ludolph has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Biogen. Dr. Ludolph has received personal compensation in the range of $0-$499 for serving as a Consultant for FundaMental Pharma . Dr. Ludolph has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Lilly. Dr. Ludolph has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Zambon . Dr. Ludolph 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. Ludolph has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Roche Pharma. Dr. Ludolph 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. Ludolph has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Alector. Dr. Ludolph has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Amylyx. Dr. Ludolph has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Biologix FZCo.. Dr. Ludolph has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Biogen. Dr. Ludolph has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Teva. Dr. Ludolph has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Biogen. Dr. Ludolph has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Biogen. Dr. Ludolph has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Zambon.
Federica Agosta (San Raffaele Scientific Institute)	Federica Agosta has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Philips. Federica Agosta has received personal compensation in the range of $500-$4,999 for serving as an Editor, Associate Editor, or Editorial Advisory Board Member for Elsevier INC.
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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