Objective: To assert pathophysiology in spinocerebellar ataxia type 12 (SCA12) extends way beyond cerebellar or spinal pathology. To further sensitise scientific community about consistent nigro-striatal dysfunction in SCA 12 that may contribute in phenotypical presentation and therapeutic target.

Background: Spinocerebellar ataxia type 12 is rare autosomal dominant cerebellar disorder. Pathogenesis is caused by expanded repeats of CAG/CTG in open frame of the gene PPP2R2B on chromosome 5q32. Neuroimaging has shown mild to moderate cerebral and cerebellar atrophy. Taken in to consideration the diverse phenotype in conjunction with Parkinsonism, imprecise pathogenicity, mild cerebellar atrophy and neuronal inclusion bodies in substantia niagra we applied Dopamine Transporter imaging in 10 patients to appreciate archetype of neurodegeneration in SCA12.

Method: 15 genetically confirmed and clinically symptomatic patients of SCA12 with more than 43 repeats were subjected to TRODAT scan. All of 15 patients were clinically examined and characterised for motor and non-motor features with TETRAS, MOCA, SARA. HDRS scales.

Results: All of 15 patients presented with tremor of varied intensity. 6 patients rendered Parkinsonism as dominating feature. Illustration of TRODAT scan showed reduced presynaptic dopamine tracer reuptake in all 15 patients with posterior putamen being most affected. 7 patients showed mild depletion of DAT tracers, 2 patients showed severe depletion and rest of the patients exhibited moderate depletion. Anterrior to posterior gradient for degree of TRODAT uptake was maintained in majority of patients. Severity of motor and non motor symptoms were not in agreement with amount of DAT depletion in straitum. Asymmetric presynaptic DAT depletion was concommitant with asymmetric presentation of disease.

Conclusion: Patients with SCA 12 consistently showed abnormal dopamine transporter binding. Severity of Nigro-Striatal degeneration did not influence clinical manifestation of Parkinsonian symptoms.  Presynaptic dopamine dysfunction reflected in all 15 patients designates SCA12 as multi axial brain disorder beyond cerebellum. As presynaptic depletion of DAT corresponds with loss of nigro-striatal dopaminergic neuron, Levodopa can be tried in patients with SCA 12

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MDS Abstracts - https://www.mdsabstracts.org/abstract/dopamine-dysfunction-in-nigro-striatal-pathway-multi-axial-pathology-in-sca-12/