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From INSERM (L.D., A.F., J.-L.G.D.A., J.-P.L.), U692, Laboratoire de Signalisations Moléculaires et Neurodégénérescence, Strasbourg; Université Louis Pasteur (L.D., A.F., J.-L.G.D.A., J.-P.L.), Faculté de Médecine, UMRS692, Strasbourg; Service de Neurologie (P.C.), Centre SLA, CHU Bretonneau, Tours; Laboratoire des Lipides (D.B.-R., R.B.), Groupe Hospitalier Pitié-Salpêtrière (AP-HP), Paris; Laboratoire de Neuropathologie (D.S., J.-J.H.) and Fédération des Maladies du Système Nerveux, Centre référent maladie rare SLA (L.L., V.M.), Hôpital de la Pitié-Salpêtrière (AP-HP), Paris; and Université Pierre et Marie Curie (D.B.-R., R.B., D.S., J.-J.H., L.L., V.M.), Paris, France.
* To whom correspondence should be addressed. E-mail: vincent.meininger{at}psl.ap-hop-paris.fr.
ABSTRACT
Background: Amyotrophic lateral sclerosis (ALS) is the most serious form of degenerative motor neuron disease in adults, characterized by upper and lower motor neuron degeneration, skeletal muscle atrophy, paralysis, and death. High prevalence of malnutrition and weight loss adversely affect quality of life. Moreover, two thirds of patients develop a hypermetabolism of unknown cause, leading to increased resting energy expenditure. Inasmuch as lipids are the major source of energy for muscles, we determined the status of lipids in a population of patients with ALS and investigated whether lipid contents may have an impact on disease progression and survival.
Methods: Blood concentrations of triglycerides, cholesterol, low-density lipoprotein (LDL), and high-density lipoprotein (HDL) were measured in a cohort of 369 patients with ALS and compared to a control group of 286 healthy subjects. Postmortem histologic examination was performed on liver specimens from 59 other patients with ALS and 16 patients with Parkinson disease (PD).
Results: The frequency of hyperlipidemia, as revealed by increased plasma levels of total cholesterol or LDL, was twofold higher in patients with ALS than in control subjects. As a result, steatosis of the liver was more pronounced in patients with ALS than in patients with PD. Correlation studies demonstrated that bearing an abnormally elevated LDL/HDL ratio significantly increased survival by more than 12 months.
Conclusions: Hyperlipidemia is a significant prognostic factor for survival of patients with amyotrophic lateral sclerosis. This finding highlights the importance of nutritional intervention strategies on disease progression and claims our attention when treating these patients with lipid-lowering drugs.
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