We describe two cases of Marchiafava-Bignami disease which have been treated with amantadine and discuss a potential mechanism.

Several reports have described the use of amantadine in the management of Marchiafava-Bignami disease (MBD); however, its role is unclear and there are no known mechanisms.

Case 1. A 38 year-old woman with excessive wine drinking presented with agitation, impaired speech, and minimally conscious state. MRI revealed lesions in the splenium and genu. After a diagnosis of MBD she was treated with IV thiamin, multivitamins, and amantadine 100mg BID for two weeks. She recovered to near baseline after three weeks.

Case 2: A 54 year-old woman with years of heavy alcohol use presented with sudden bradyphrenia, acalculia, disinhibited behavior, weakness and urinary incontinence. MRI revealed a large anterior callosal lesion. Two months after initial recovery from MBD she noted that consuming “energy drinks” resulted in a transient near-complete resolution of her residual behavioral, fatigue, and language symptoms.  As amantadine could potentially mimic this effect, 100 mg BID was trialed with noted improvement. A further escalation to 200 mg TID was trialed, resulting in significant improvement in language and behavioral symptoms.

A treatment approach for MBD is not established. In addition to our cases, two other reports have described the use of amantadine in MBD. The mechanism of amantadine's role in MBD is unknown. It is possible that the dopaminergic effect of amantadine leads to an improved recovery and function in dopamine mediated pathways, including mesocortical and mesolimbic pathways, in the initial recovery as well as improved speech, behavior, and fatigue months after initial recovery. Support for this theory comes from studies in TBI where amantadine has shown increases in prefrontal cortical metabolic activity and a possible increase in striatal D2 dopamine–receptor availability.