Sporadic amyotrophic lateral sclerosis: clinical and biological changes under treatment with Valproic acid and Lithium carbonate

A study has evaluated the ability of Lithium carbonate and Valproate cotreatment to modify the survival rate and functional score of patients with definite sporadic amyotrophic lateral sclerosis ( ALS ).

The clinical response of 18 enrolled patients was compared to the evolution of 31 out-patients with amyotrophic lateral sclerosis, carefully paired by age, gender, evolution rate and time of the disease, who never received treatment with Lithium and/or Valproate.

The ALS functional rating scale, revised version ( ALSFRS-R ), was applied at baseline, 1 month, and every 4 months until the outcome ( death or an adverse event ).

Biochemical markers, such as Cu/Zn superoxide dismutase and glutathione peroxidase activity, and reduced glutathione were assayed in plasma samples obtained at the baseline visit and after 5 and 9 months of treatment.

The results showed that Lithium and Valproate cotreatment significantly increased survival ( p=0.016 ), and this treatment also exerted neuroprotection in patients because all three markers reached levels that were not significantly different from the matched samples of healthy donors.

The trial stopped after 21 months, when the sample was reduced to under two-thirds, due to the late adverse events of the treatment.
The results call for large randomized clinical trials with the dual association, but at low doses to avoid adverse events. ( Xagena )

Boll MC et al, J Neurol Sci 2014;340:103-108


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