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Uncovering hypothalamic network disruption in ALS.

Fabiola Freri1, Edoardo Gioele Spinelli1,2,3, Elisa Canu1,2

  • 1Neuroimaging Research Unit, Division of Neuroscience and Unit of Neurology, IRCCS San Raffaele Scientific Institute, Via Olgettina, 60, 20132, Milan, Italy.

Journal of Neurology
|December 22, 2025
PubMed
Summary
This summary is machine-generated.

Amyotrophic lateral sclerosis (ALS) patients exhibit altered hypothalamic functional connectivity, particularly with the caudate nuclei. These changes correlate with disease severity and progression, suggesting potential for early prognostic insights.

Keywords:
Amyotrophic lateral sclerosisFunctional connectivityHypermetabolismHypothalamusMRI

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Area of Science:

  • Neuroimaging
  • Neurology
  • Neuroscience

Background:

  • Structural MRI reveals hypothalamic atrophy and altered white matter (WM) connectivity in amyotrophic lateral sclerosis (ALS).
  • Hypothalamic functional connectivity and its clinical associations in ALS remain largely unexplored.
  • This study investigates resting-state functional connectivity (RS-FC) of the hypothalamus in ALS.

Purpose of the Study:

  • To compare hypothalamic RS-FC between ALS patients and healthy controls.
  • To examine the relationship between hypothalamic RS-FC and clinical parameters including disease severity (ALSFRS-r), BMI, duration, progression rate, survival, hypothalamic volume, and WM integrity.

Main Methods:

  • Seventy-one ALS patients and 39 controls underwent structural and resting-state functional MRI.
  • Seed-based analysis was used to assess hypothalamic RS-FC.
  • Correlations between RS-FC, clinical features, and WM integrity (using tract-based spatial statistics) were evaluated.

Main Results:

  • ALS patients displayed increased hypothalamic RS-FC with caudate nuclei compared to controls.
  • Greater disease severity correlated with enhanced hypothalamic RS-FC with the caudate nuclei and orbitofrontal cortex.
  • Hypothalamic RS-FC was associated with fractional anisotropy (FA) in the genu of corpus callosum/forceps minor and disease progression rate.

Conclusions:

  • Findings support the presence of hypothalamic alterations in ALS.
  • Hypothalamic changes may serve as a biomarker for prognostic stratification in ALS.
  • Early detection of hypothalamic alterations could aid in evaluating therapeutic intervention effects.