Lithium therapy in Kleine-Levin syndrome
An open-label, controlled study in 130 patients
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.
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Information & Authors
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Copyright
© 2015 American Academy of Neurology.
Publication History
Received: March 1, 2015
Accepted: June 22, 2015
Published online: October 9, 2015
Published in print: November 10, 2015
Disclosure
S. Leu-Semenescu received honoraria for traveling to congresses from UCB Pharma. T. Le Corvec, E. Groos, S. Lavault, and J. Golmard report no disclosures relevant to the manuscript. I. Arnulf received honoraria and board for a speaking engagement from UCB Pharma, and reported another study on brain imaging in KLS founded by the KLS Foundation in Boston. Go to Neurology.org for full disclosures.
Study Funding
This report was not an industry-sponsored study. It was financed by the Hospital Clinical Research Program AOM07-138 from the French Health Ministry to I.A. and sponsored by Assistance Publique-Hôpitaux de Paris.
Authors
Author Contributions
S.L.-S. collected the information regarding treatment into medical files, entered it in a database, and drafted the first manuscript with I.A. T.L.C. contacted all patients and gathered additional information. E.G. helped diagnose KLS and ruled out psychiatric diagnoses. S.L. collected general information on the disease in a database. J.-L.G. performed the statistical analysis. I.A. obtained the grant for the research program on KLS, diagnosed, treated, and followed up the patients with KLS (helped by E.G.), and drafted the manuscript. The final manuscript was approved by all coauthors.
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