Parallels between bipolar disorder and ATP1A3-related diseases: a window into the investigation of lithium for alternating hemiplegia of childhood

Alternating hemiplegia of childhood (AHC) shares many aspects with the psychiatric condition, bipolar disorder. AHC is a heterogeneous genetic disorder that can manifest in various fashions but will usually involve paroxysmal neuropsychiatric symptoms that are precipitated by environmental events or stressors, superimposed over developmental abnormalities of various severities. It occurs as a consequence of a variety of mutations of the alpha3 subunit of the sodium pump (ATP1A3). Treatment is generally symptomatic with flunarizine a nonselective calcium channel blocker, but other approaches have been attempted. Nonetheless, given the inadequate response of most patients, there continues to be a significant unmet need for adequate treatment approaches. Bipolar disorder, a severe psychiatric illness, also manifests with paroxysmal neuropsychiatric symptoms that are precipitated by environmental events or stressors. It is also characterized by significant dysfunction of the sodium pump. Lithium is an effective intervention for bipolar disorder and has never been utilized in AHC. Both bipolar disorder and AHC are associated with sodium pump dysfunction and increased intracellular sodium concentration. Both conditions respond to calcium channel blockers and the ketogenic diet. Lithium trials in AHC are warranted.