Multiple System Atrophy With Predominant Striatonigral Degeneration and TAR DNA-Binding Protein of 43 kDa Pathology: An Unusual Variant of Multiple System Atrophy.

Background: The pathological hallmark in MSA is oligodendrocytic glial cytoplasmic inclusions (GCIs) containing α-synuclein, in addition to neuronal loss and astrogliosis especially involving the striatonigral and olivopontocerebellar systems. Rarely, TAR DNA-binding protein of 43 kDa (TDP-43), a component of ubiquitinated inclusions observed mainly in amyotrophic lateral sclerosis and frontotemporal lobar degeneration has been demonstrated in cases of MSA and, more recently, was shown to colocalize with α-synuclein pathology in GCIs in 2 patients.

Methods: A 66-year-old woman presented with a syndrome characterized by spasticity, dysautonomia, bulbar dysfunction, and parkinsonism. Symptoms progressed until her death at age 74. Neuropathological evaluation was performed at the New York Brain Bank at Columbia University.

Results: On gross examination, there was striking severe volume loss of the left striatum compared to mild involvement of the right striatum. Microscopically, neuronal loss and gliosis of the putamen and globus pallidus were severe on the left side, in contrast to mild involvement on the right side. Immunohistochemistry for α-synuclein revealed widespread GCIs. The sections subjected to TDP-43 antibodies showed a few GCIs with definite nucleocytoplasmic translocation of the labeling within the lenticular nucleus and within the paracentral cortex.

Conclusions: This report adds to the evidence that TDP-43 and α-synuclein colocalize in GCIs. Whether this coexistence contributes to the pathogenesis of a subset of MSA patients or is an age-related process is not known. More cases with these peculiar pathological hallmarks might help determine whether TDP-43 contributes to neurodegeneration in a subset of patients with MSA.