Hypothalamic atrophy correlates with onset of disease-defining symptoms in patients with ALS

author: Martin Gorges, University of Ulm
published: July 21, 2017,   recorded: May 2017,   views: 754


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Background: Alterations in energy metabolism have been described in the context of ALS but direct evidence of hypothalamic involvement is lacking. The hypothalamus plays a key role in controlling the energy metabolism. Objective: To study whether possible morphologic alterations of the hypothalamus in manifest ALS and asymptomatic ALS mutation carriers are associated with the course of the disease. Methods: High-resolution whole-brain based T1-weighted 3D-MRI data together with clinical and laboratory parameters were acquired in a large monocentric cohort including 270 manifest ALS patients, 32 asymptomatic ALS mutation carriers, and 116 healthy controls. The hypothalamic volumes were semimanually quantified following a well-established procedure that was optimized to sensitively detect hypothalamic volume alterations. The hypothalamic volumes for all subjects were measured by an experienced rater who was blinded for any clinical information. The determined hypothalamic volumes were normalized for the intracranial volume and corrected for age. Results: The hypothalamic volumes were significantly atrophied in both manifest ALS patients (p<0.0001) and asymptomatic ALS mutation carriers (p<0.01) compared with controls. There was no significant correlation with global brain atrophy, metabolic indices (among others BMI), or hypothalamic-associated hormones (leptin, adiponectin). In contrast, the disease onset was significantly correlated with the hypothalamic volume (p=0.012) and survival was better (p=0.022) the less the hypothalamus was atrophied. Conclusions: The hypothalamus appears to be selectively atrophied even in an asymptomatic phase of ALS. The volume loss of the hypothalamus is likely to be associated with the onset of ALS-defining symptoms and possibly a prognostic factor for survival

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