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16-10-2015 | Neurology | News | Article

Lithium benefits found in Kleine–Levin syndrome

medwireNews: Researchers have provided Class IV evidence that lithium reduces the frequency and duration of Kleine–Levin syndrome (KLS) episodes.

They found that when treated with lithium patients were incapacitated by the condition for 1 month less per year of disease compared with no treatment.

This benefit was also not outweighed by adverse events, which were mild and manageable, and in line with those expected with lithium therapy.

“This is the first drug demonstrating this level of evidence”, Isabelle Arnulf (Pitié-Salpêtrière University Hospital, Paris, France) and colleagues point out in Neurology.

Over an average follow-up of 21.8 months, 36.6% of 71 patients treated with lithium 500–1600 mg/day became free of KLS episodes, compared with just 3.4% of patients in a non-lithium group, comprising 49 patients receiving no treatment and five receiving the contraceptive pill for menstruation-associated KLS episodes and five receiving valproate due to contraindication to lithium. This was despite the lithium treatment group having more severe disease prior to treatment.

The remaining patients receiving lithium experienced, on average, 2.6 fewer episodes per year and episodes were an average of 7.6 days shorter than before treatment. The longest episode was 18.1 days shorter, on average, and the time spent incapacitated by the disease decreased by 36.9 days per year of treatment.

Compared with no treatment, lithium was associated with significantly greater decreases in the average episode duration, the longest episode duration, time spent incapacitated and the frequency of episodes per year.

The researchers note that side effects, reported by half of the patients taking lithium, included tremor, increased thirst, diarrhoea and subclinical hypothyroidism. All events were mild and only five patients stopped treatment due to side effects.

Alongside the reductions in symptoms, evidence of a clinical effect of lithium was seen in the presence of mini-episodes, occurring in 9.8% of lithium-treated patients and lasting a maximum of 24 hours. Also, 13 patients had an immediate relapse when lithium was forgotten on two successive evenings and a further nine relapsed when their lithium levels fell below 0.8 mmol/L.

Arnulf et al believe that lithium’s mechanism of action in KLS likely differs from that in bipolar disorder. They suggest that it may restore the blood–brain barrier, the permeability of which can be increased by KLS episodes, thereby preventing deleterious antibodies from entering the central nervous system (CNS). Alternatively, lithium may prevent recurrent inflammation in the CNS, they add.

In a related editorial, Geert Mayer, from Hephata Klinik in Schwalmstadt, Germany, says the findings are “an important contribution towards the solution of the dilemma to find the right medication, among a diffuse spectrum of medications, for the rare disease KLS.”

By Lucy Piper

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