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November 10, 2015; 85 (19) Article

Lithium therapy in Kleine-Levin syndrome

An open-label, controlled study in 130 patients

Smaranda Leu-Semenescu, Thibault Le Corvec, Elisabeth Groos, Sophie Lavault, Jean-Louis Golmard, Isabelle Arnulf
First published October 9, 2015, DOI: https://doi.org/10.1212/WNL.0000000000002104
Smaranda Leu-Semenescu
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.
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Thibault Le Corvec
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.
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Elisabeth Groos
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.
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Sophie Lavault
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.
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Jean-Louis Golmard
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.
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Isabelle Arnulf
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.
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Citation
Lithium therapy in Kleine-Levin syndrome
An open-label, controlled study in 130 patients
Smaranda Leu-Semenescu, Thibault Le Corvec, Elisabeth Groos, Sophie Lavault, Jean-Louis Golmard, Isabelle Arnulf
Neurology Nov 2015, 85 (19) 1655-1662; DOI: 10.1212/WNL.0000000000002104

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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.

GLOSSARY

KLS=
Kleine-Levin syndrome;
LOCF=
last observation carried forward;
TSH=
thyroid-stimulating hormone

Footnotes

  • Go to Neurology.org for full disclosures. Funding information and disclosures deemed relevant by the authors, if any, are provided at the end of the article.

  • Editorial, page 1642

  • Received March 1, 2015.
  • Accepted in final form June 22, 2015.
  • © 2015 American Academy of Neurology
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