TY  - JOUR
AU  - Freri, Fabiola
AU  - Spinelli, Edoardo Gioele
AU  - Canu, Elisa
AU  - Basaia, Silvia
AU  - Castelnovo, Veronica
AU  - Müller, Hans-Peter
AU  - Kassubek, Jan
AU  - Ludolph, Albert C
AU  - Krishnamurthy, Sruthi Sankari
AU  - Roselli, Francesco
AU  - Filippi, Massimo
AU  - Agosta, Federica
TI  - Uncovering hypothalamic network disruption in ALS.
JO  - Journal of neurology
VL  - 273
IS  - 1
SN  - 0367-004X
CY  - [Darmstadt]
PB  - Steinkopff
M1  - DZNE-2025-01454
SP  - 37
PY  - 2026
AB  - Structural MRI studies have shown hypothalamic atrophy and altered white matter (WM) connectivity in amyotrophic lateral sclerosis (ALS), as a possible substrate of hypermetabolism in this condition. However, hypothalamic functional connectivity and its association with clinical features in ALS remain unclear. This study explored hypothalamic resting-state functional connectivity (RS-FC) in ALS patients compared to controls and its relationship with disease severity defined by the ALS Functional Rating Scale (ALSFRS-r), body mass index (BMI), disease duration, progression rate, survival, hypothalamic volume, and WM integrity.Seventy-one ALS patients and 39 healthy controls underwent structural and RS functional MRI. The bilateral hypothalamus was segmented, and a seed-based RS-FC analysis was performed. Group differences in hypothalamic RS-FC and their correlations with ALSFRS-r scores, BMI, disease duration, progression rate, survival, hypothalamic volume, and WM integrity were assessed. Tract-based spatial statistics was performed to estimate the correlation between WM damage in ALS and hypothalamic RS-FC.ALS patients showed increased hypothalamic RS-FC with caudate nuclei compared to controls. Additionally, greater disease severity correlated with increased hypothalamic RS-FC with the caudate nuclei and orbitofrontal cortex. Hypothalamic RS-FC mean values also associated with FA in the genu of corpus callosum and forceps minor and disease progression rate. No significant correlations were observed with other clinical features.These findings support hypothalamic alterations in ALS. Early detection of hypothalamic changes could be useful in prognostic stratification and evaluating intervention effects.
KW  - Humans
KW  - Amyotrophic Lateral Sclerosis: diagnostic imaging
KW  - Amyotrophic Lateral Sclerosis: physiopathology
KW  - Amyotrophic Lateral Sclerosis: pathology
KW  - Female
KW  - Male
KW  - Middle Aged
KW  - Hypothalamus: diagnostic imaging
KW  - Hypothalamus: physiopathology
KW  - Hypothalamus: pathology
KW  - Magnetic Resonance Imaging
KW  - Aged
KW  - Adult
KW  - White Matter: diagnostic imaging
KW  - White Matter: pathology
KW  - Nerve Net: diagnostic imaging
KW  - Nerve Net: physiopathology
KW  - Disease Progression
KW  - Connectome
KW  - Amyotrophic lateral sclerosis (Other)
KW  - Functional connectivity (Other)
KW  - Hypermetabolism (Other)
KW  - Hypothalamus (Other)
KW  - MRI (Other)
LB  - PUB:(DE-HGF)16
C6  - pmid:41428120
C2  - pmc:PMC12722382
DO  - DOI:10.1007/s00415-025-13574-3
UR  - https://pub.dzne.de/record/283047
ER  -