UNASSIGNED: The tremor characteristics of patients with spinocerebellar ataxia 12 (SCA12) are often likened to those in patients with essential tremor (ET); however, data are sparse, and videotaped tremor examinations are rare.
UNASSIGNED: A 37-year-old woman with progressive hand and head tremors underwent genetic testing after conventional diagnostics failed to explain her symptoms. A PPP2R2B variation confirmed spinocerebellar ataxia type 12 (SCA12), a condition not previously considered because classical cerebellar signs were absent. The tremor characteristics of this patient differed in numerous respects from those seen in patients with ET.
UNASSIGNED: Although often likened to ET, under careful scrutiny, the tremor characteristics observed in this patient with SCA12 were inconsistent with those typically seen in ET. Such discrepancies highlight the necessity of careful phenotyping for tremor disorders, particularly in familial cases. Recognizing the specific tremor phenomenology of SCA12 and distinguishing it from ET is crucial to avoid misdiagnosis and to guide appropriate management and familial counseling.
UNASSIGNED: This report characterizes in detail an early-stage SCA12 patient initially misdiagnosed as essential tremor, underscoring the importance of nuanced clinical assessment and genetic testing in atypical tremor cases. Similar patients should be meticulously phenotyped to prevent misclassification and enhance our understanding of tremor pathophysiology.

Spinocerebellar ataxia type 12 (SCA12) is a rare SCA subtype with unclear clinical and imaging features. Also, the radiological changes in prodromal and early stages remain unknown.
Ten symptomatic and two pre-symptomatic cases from three Chinese pedigrees received clinical assessments and imaging studies including routine magnetic resonance imaging (MRI), diffusion kurtosis imaging (DKI), and positron emission tomography (PET) using 18F-flurodeoxyglucose (FDG) to investigate glucose metabolism in brain and 18F-vesicle monoamine transporter 2 (VMAT2) to inspect the integrity of the dopaminergic neuron. Seventy-two healthy individuals were recruited as controls in the quantitative FDG-PET analysis. Imaging parameters were compared between symptomatic and presymptomatic cases with different disease durations.
Patients displayed prominent action tremor, moderate ataxia, and subtle parkinsonism with poor levodopa-response. MRI showed extensive but heterogeneous cerebral atrophy, which was most evident in the frontoparietal lobes. Cerebellar atrophy was apparent in later stages. DKI detected impaired fibers in the cerebellar peduncles. In both symptomatic and pre-symptomatic cases, PET-CT showed an earlier FDG decline than atrophic changes in multiple regions, and the frontoparietal lobes were the earliest and most severe. However, the VMAT2 density were normal in the putamen and caudate nucleus of most cases (7/8).
We first found that hypometabolism in the cerebral cortex, but not cerebellum, is an early and prominent change in SCA12. The integrity of presynaptic dopaminergic neurons remains largely spared during the whole disease process.