Smaranda Leu-Semenescu1, Thibault Le Corvec1, Elisabeth Groos1, Sophie Lavault1, Jean-Louis Golmard1, Isabelle Arnulf2. 1. From the Sleep Disorders Unit and National Reference Center for Narcolepsy, Hypersomnia and Kleine-Levin Syndrome (S.L.-S., T.L.C., E.G., S.L., I.A.), and Department of Biostatistics (J.-L.G.), Pitié-Salpêtrière University Hospital; AP-HP (S.L.-S., I.A.), Brain Research Institute (CRICM-UPMC-Paris 6; Inserm UMR_S 975; CNRS UMR 7225), Sorbonne Universities, UPMC Univ Paris 06; and AP-HP and ER4 (J.-L.G.), Pierre and Marie Curie University, Paris, France. 2. From the Sleep Disorders Unit and National Reference Center for Narcolepsy, Hypersomnia and Kleine-Levin Syndrome (S.L.-S., T.L.C., E.G., S.L., I.A.), and Department of Biostatistics (J.-L.G.), Pitié-Salpêtrière University Hospital; AP-HP (S.L.-S., I.A.), Brain Research Institute (CRICM-UPMC-Paris 6; Inserm UMR_S 975; CNRS UMR 7225), Sorbonne Universities, UPMC Univ Paris 06; and AP-HP and ER4 (J.-L.G.), Pierre and Marie Curie University, Paris, France. isabelle.arnulf@psl.aphp.fr.
Abstract
OBJECTIVE: To compare the benefits and risks of lithium therapy vs abstention/other treatments in Kleine-Levin syndrome (KLS). METHODS: In a KLS cohort followed in a single center, 130 patients regularly took lithium carbonate (median dose 1,000 mg/day; n = 71; 40 children), valproate (n = 5), contraceptive pill (n = 5), or no treatment (n = 49). The disease characteristics (frequency, mean, and longest durations of episodes, time incapacitated per year) were compared before and after follow-up in the lithium vs abstention groups. RESULTS: The time between KLS onset and therapeutic onset was 69 ± 92 months. The patients were then followed up for a mean of 21.5 ± 17.8 months. Before treatment, the 71 patients treated with lithium tended to have a higher frequency of episodes per year (3.8 ± 2.9 vs 2.9 ± 2.6) and had a longer time spent incapacitated (57 ± 51 vs 37 ± 35 days) than the untreated patients. The mean (-8 ± 20 vs 2 ± 13 days) and longest (-18 ± 35 vs -5 ± 13) episode duration, the time spent incapacitated (-37 ± 65 days vs -10 ± 38), as well as the frequency of episodes per year (-2.6 ± 2.9 vs 1.3 ± 2.78) decreased significantly more in the treated than in the untreated patients. Side effects (reported by 50% of the patients) were mild and classical with lithium (tremor, increased drinking, diarrhea, and subclinical hypothyroidism). CONCLUSIONS: In this large, prospective, open-label, controlled study, the benefit/risk ratio of lithium therapy is superior to that of abstention, supporting the concept that lithium has anti-inflammatory/neuroprotective effects. CLASSIFICATION OF EVIDENCE: This study provides Class IV evidence that for patients with KLS, lithium decreases the frequency and duration of KLS episodes.
OBJECTIVE: To compare the benefits and risks of lithium therapy vs abstention/other treatments in Kleine-Levin syndrome (KLS). METHODS: In a KLS cohort followed in a single center, 130 patients regularly took lithium carbonate (median dose 1,000 mg/day; n = 71; 40 children), valproate (n = 5), contraceptive pill (n = 5), or no treatment (n = 49). The disease characteristics (frequency, mean, and longest durations of episodes, time incapacitated per year) were compared before and after follow-up in the lithium vs abstention groups. RESULTS: The time between KLS onset and therapeutic onset was 69 ± 92 months. The patients were then followed up for a mean of 21.5 ± 17.8 months. Before treatment, the 71 patients treated with lithium tended to have a higher frequency of episodes per year (3.8 ± 2.9 vs 2.9 ± 2.6) and had a longer time spent incapacitated (57 ± 51 vs 37 ± 35 days) than the untreated patients. The mean (-8 ± 20 vs 2 ± 13 days) and longest (-18 ± 35 vs -5 ± 13) episode duration, the time spent incapacitated (-37 ± 65 days vs -10 ± 38), as well as the frequency of episodes per year (-2.6 ± 2.9 vs 1.3 ± 2.78) decreased significantly more in the treated than in the untreated patients. Side effects (reported by 50% of the patients) were mild and classical with lithium (tremor, increased drinking, diarrhea, and subclinical hypothyroidism). CONCLUSIONS: In this large, prospective, open-label, controlled study, the benefit/risk ratio of lithium therapy is superior to that of abstention, supporting the concept that lithium has anti-inflammatory/neuroprotective effects. CLASSIFICATION OF EVIDENCE: This study provides Class IV evidence that for patients with KLS, lithium decreases the frequency and duration of KLS episodes.
Authors: Aditya Ambati; Ryan Hillary; Smaranda Leu-Semenescu; Hanna M Ollila; Ling Lin; Emmanuel H During; Neal Farber; Thomas J Rico; Juliette Faraco; Eileen Leary; Andrea N Goldstein-Piekarski; Yu-Shu Huang; Fang Han; Yakov Sivan; Michel Lecendreux; Pauline Dodet; Makoto Honda; Natan Gadoth; Sona Nevsimalova; Fabio Pizza; Takashi Kanbayashi; Rosa Peraita-Adrados; Guy D Leschziner; Rosa Hasan; Francesca Canellas; Kazuhiko Kume; Makrina Daniilidou; Patrice Bourgin; David Rye; José L Vicario; Birgit Hogl; Seung Chul Hong; Guiseppe Plazzi; Geert Mayer; Anne Marie Landtblom; Yves Dauvilliers; Isabelle Arnulf; Emmanuel Jean-Marie Mignot Journal: Proc Natl Acad Sci U S A Date: 2021-03-23 Impact factor: 11.205
Authors: Kiran Maski; Lynn Marie Trotti; Suresh Kotagal; R Robert Auger; Todd J Swick; James A Rowley; Sarah D Hashmi; Nathaniel F Watson Journal: J Clin Sleep Med Date: 2021-09-01 Impact factor: 4.324