Does lithium balance the neuronal bilateral asymmetries in cluster headache?

Pupil size was measured using a pupillograph, and an asymmetric responsiveness to tyramine, instilled bilaterally, was observed in asymptomatic cluster headache patients. Relatives of cluster headache patients showed an anisocoric mydriasis to tyramine, too. This asymmetry was caused by a less marked mydriatic response of one side which, in the cluster headache sufferers, corresponds to the symptomatic side. After three months of treatment with lithium carbonate (900 mg/die), a bilateral decrease of pupil size was noted, possibly due to a reduced sympathergic tone. After six months of continued treatment an unknown mechanism, likely adaptive in nature, attenuated the effect of lithium on pupil size. Lithium also induced a symmetric response to tyramine by increasing tyramine mydriasis on the symptomatic pupil while reducing it on the asymptomatic pupil. It is postulated that lithium improves cluster headache by correcting abnormal bilateral asymmetries in central neuronal systems which regulate autonomic function and pain sensitivity of the structures involved in the cluster attack.