A 61-year-old woman with depression and migraines presented with positionally-induced dizziness and episodes of mild imbalance associated with photophobia, phonophobia, and nausea. Her neurologic and ocular-motor exams were normal, except very mild downbeat nystagmus (DBN) with fixation removed. Her presentation was felt to be most consistent with vestibular migraine.
Two years after her initial visit, lithium was initiated for refractory depression. She developed oscillopsia weeks later: examination revealed significant spontaneous DBN even with fixation. Bedside and video head-impulse-tests were normal, she had no ataxia, and MRI Brain was normal. Her worsening was thought to be due to lithium, which was discontinued.
Her symptoms improved by 50%, but she had persistent DBN and oscillopsia. Laboratory evaluation for nutritional, inflammatory, and autoimmune causes of cerebellar dysfunction were unrevealing. She was prescribed 4-aminopyridine (4-AP) which significantly improved her oscillopsia.
Three years later she developed mild-moderate gait ataxia. Recently available whole-exome sequencing revealed GAA repeat expansion within one copy of the FGF14 gene, consistent with spinocerebellar ataxia 27B (SCA27B).
The mild DBN with fixation removed on initial exam likely represented the harbinger of neurodegenerative cerebellar ataxia from SCA27B. Lithium is a well-known cause of DBN, but when taken in short duration as with this patient, lasting effects (i.e., persistent DBN) were unexpected. In the 2 years since the description of the FGF14 genetic mutation, SCA27B has emerged as the most common etiology of idiopathic DBN. Interestingly, these patients’ oscillopsia and balance tend to respond favorably to 4-AP.
Take-home-points include: 1) The importance of revisiting working diagnoses when uncertainty exists (i.e., persistence of DBN after lithium cessation), 2) Consider prescribing 4-AP for DBN and/or cerebellar ataxia, and 3) Consider SCA27B in all patients with DBN (especially with a favorable 4-AP response).