Clinicopathological co-morbidity of progressive supranuclear palsy and amyotrophic lateral sclerosis

Abstract

Coexistence of distinct neurodegenerative diseases in single cases recently gathers greater attention. In this line, phenotypic co-occurrence of progressive supranuclear palsy (PSP) and amyotrophic lateral sclerosis (ALS) has been documented in several cases. That said, clinicopathological co-mobidity of the two diseases has remained unproven. We investigated neuropathological characteristics of two patients who clinically presented both PSP and ALS. The patients, without family history of neurological disorders, first presented with atypical parkinsonism consistent with PSP with Richardson’s syndrome or progressive gait freezing. In a few years, they developed muscle weakness with or without pseudobulbar symptoms, which was compatible with ALS. Disease duration was 5-8 years after the onset of PSP and 1-2 years after the onset of ALS. Neuropathological findings demonstrated coexistence of PSP and ALS in both cases. Immunohistochemical examination in a recent case confirmed 4-repeat tauopathy including globose type neurofibrillary tangles, tufted astrocytes, and oligodendroglial coiled bodies, as well as TAR DNA-binding protein 43 kDa pathology in association with upper and lower motor neuron degeneration. In this case, immunoblotting showed hyperphosphorylated full-length 4-repeat tau bands with 64 and 68 kDa and C-terminal fragments with 33 kDa, supporting the diagnosis of PSP and excluding other parkinsonian disorders such as corticobasal degeneration. Our cases highlight clinicopathological comorbidity of PSP and ALS in sporadic cases. The possibility of multiple proteinopathies should be considered when distinct symptoms developed in the disease course.