Natural History and Phenotypic Spectrum of GAA-FGF14 Sporadic Late-Onset Cerebellar Ataxia (SCA27B).

BACKGROUND: Heterozygous GAA expansions in the FGF14 gene have been related to autosomal dominant cerebellar ataxia (SCA27B-MIM:620174). Whether they represent a common cause of sporadic late-onset cerebellar ataxia (SLOCA) remains to be established. OBJECTIVES: To estimate the prevalence, characterize the phenotypic spectrum, identify discriminative features, and model longitudinal progression of SCA27B in a prospective cohort of SLOCA patients. METHODS: FGF14 expansions screening combined with longitudinal deep-phenotyping in a prospective cohort of 118 SLOCA patients (onset >40 years of age, no family history of cerebellar ataxia) without a definite diagnosis. RESULTS: Prevalence of SCA27B was 12.7% (15/118). Higher age of onset, higher Spinocerebellar Degeneration Functional Score, presence of vertigo, diplopia, nystagmus, orthostatic hypotension absence, and sensorimotor neuropathy were significantly associated with SCA27B. Ataxia progression was ≈0.4 points per year on the Scale for Assessment and Rating of Ataxia. CONCLUSIONS: FGF14 expansion is a major cause of SLOCA. Our natural history data will inform future FGF14 clinical trials. © 2023 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

"Phalanx sign" helps to discriminate MSA-C from idiopathic late onset cerebellar ataxia.

INTRODUCTION: Early diagnosis of MSA-C in patients with late-onset cerebellar ataxia (LOCA) may prove difficult. We therefore describe and evaluate the performance of the new "phalanx sign" (PS), that should be looked for during the nose-finger test to distinguish MSA-C from idiopathic late-onset ataxia (ILOCA). METHODS: Sensitivity, specificity, positive predictive value, negative predictive value and interrater reliability of PS were assessed in three groups: 21 MSA-C, 23 ILOCA and 20 age-matched healthy subjects. RESULTS: PS was positive for 61.9% of MSA-C patients', 4.3% of ILOCA patients' and in none of healthy subjects' evaluations. PS discriminated MSA-C from ILOCA (p < 0.001) with a sensitivity of 61.9%, a specificity of 95.7%, a positive predictive value of 92.9%, a negative predictive value of 73.3% and a substantial interrater reliability (Kappa = 0.7273). CONCLUSION: PS could be a helpful, easy and reproducible sign for the early diagnosis of MSA-C in patients with LOCA.

Progression of Nigrostriatal Denervation in Cerebellar Multiple System Atrophy: A Prospective Study.

OBJECTIVES: Nigrostriatal dopaminergic denervation (NSDD) remains poorly characterized in cerebellar multiple system atrophy (MSA-C). We aimed to study NSDD progression in MSA-C and evaluate the capacity for [123I]-FP-CIT-SPECT and parkinsonism to differentiate MSA-C from idiopathic late-onset cerebellar ataxia (ILOCA). METHODS: We included 85 patients successively referred for sporadic late-onset cerebellar ataxia (SLOCA). Every 6 months, SARA, UPDRS-III, and SDFS scores were measured, and MSA-C diagnostic criteria were searched for. Striatal/occipital dopaminergic binding ratio was evaluated every year with [123I]-FP-CIT-scintigraphy. RESULTS: After a mean follow-up of 33.8 months, 33 patients had probable MSA-C, 8 possible MSA-C, and 44 ILOCA. SARA and UPDRS-III scores worsened faster in the probable MSA-C group (p < 0.01) compared with the ILOCA group. The baseline striatal/occipital ratio was lower (2.3 vs 2.97; p < 0.01) and more decreasing among patients with probable MSA-C (p < 0.01). Weighting dysautonomia and parkinsonism and/or NSDD as additional and principal criterion, respectively, in the possible MSA-C diagnostic criteria slightly improved their specificity (81.6% vs 76.9%) and sensitivity (77.8% vs 72.2%) to predict a final diagnosis of probable MSA-C. DISCUSSION: Rapid symptom worsening and NSDD existence and progression predict MSA-C among patients with SLOCA. Parkinsonism, NSDD, and dysautonomia should be considered equivalent for possible MSA-C diagnosis.