Clinical characteristics, cerebellar MR spectroscopy and response to 3,4-diaminopyridine in spinocerebellar ataxia 27B: the Sheffield Ataxia Centre experience

Abstract Background The clinical and genetic heterogeneity of hereditary ataxias presents a significant diagnostic challenge, particularly in sporadic adult-onset cases. Spinocerebellar ataxia type 27B (SCA27B) is caused by an intronic GAA·TTC repeat expansion in the fibroblast growth factor 14 (F GF14 ) gene and is inherited in an autosomal dominant manner, although with reduced penetrance. This novel ataxia is emerging as a frequent yet underdiagnosed cause of late-onset often sporadic cerebellar ataxia. Method In this study, we describe our experience in clinical presentation, neuroimaging characteristics (including MR spectroscopy of the cerebellum), tremor analysis, and therapeutic response to 3,4-diaminopyridine in a cohort of 50 patients with SCA27B. Results The mean age at onset was 61.8 years. Episodic symptoms were reported in 28% of cases, while downbeat nystagmus and oscillopsia were observed in 50% and 28% individuals , respectively. Tremor was also present in 22% of patients. Tremor analysis demonstrated bilateral, intermediate-frequency (~ 6 Hz) tremor with both action and resting components, occasionally involving, apart from arms, the lower limbs and head. MRI findings revealed involvement of the superior cerebellar peduncle, and MR spectroscopy of the cerebellum (MRS) demonstrated a progressive decline in NAA/Cr area ratios in the cerebellar hemisphere over time. Notably, treatment with 3,4-diaminopyridine was associated with subjective symptom improvement in most patients and objective stabilization and/or improvement on MRS. Conclusion Our findings expand the clinical, neuroimaging and tremor phenotype of SCA27B and support the use of 3,4-diaminopyridine as a potentially effective therapy.