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The evolution of parkinsonism in primary progressive apraxia of speech: A 6-year longitudinal study

      Highlights

      • Primary progressive apraxia of speech (PPAOS) is a degenerative syndrome characterized by an isolated motor speech disorder.
      • PPAOS patients develop parkinsonism and evolve into a Parkinson-plus disorder over the disease course.
      • PPAOS evolves into a Parkinson plus syndrome combining clinical features of PSP and corticobasal syndrome (CBS).

      Abstract

      Introduction

      Primary progressive apraxia of speech (PPAOS) is a neurodegenerative syndrome in which patients present with an isolated motor speech disorder. Some PPAOS patients develop parkinsonism and other features of progressive supranuclear palsy (PSP) and/or corticobasal syndrome (CBS) over time. We aimed to assess the evolution of parkinsonian characteristics in PPAOS patients who had been followed yearly for at least six years.

      Methods

      From a large cohort of 46 PPAOS patients, eight were followed yearly for > 6-years in multiple NIH-funded grants. Parkinsonian and other features, including bradykinesia, tremor, rigidity, postural instability, apraxia, ocular motor function and cognition were assessed at each visit, and research criteria applied for PSP and CBS diagnosis. Neurological, speech-language test scores, and [18F]fluorodeoxyglucose PET (FDG-PET) and MRI midbrain volumes were assessed.

      Results

      A Parkinson's plus syndrome developed in all eight patients (100%). Bradykinesia was the earliest feature, followed by rigidity and postural instability. Tremor was not a significant feature. Parkinsonism, limb apraxia and ocular motor impairment tended to develop four-to-five years after onset with some patients having slight asymmetric parkinsonism. Six patients (75%) met research criteria for probable PSP, although only one for PSP-Richardson's syndrome; three patients met criteria for possible CBS. Slightly asymmetric, left-sided, hypometabolism was observed on FDG-PET, not matching asymmetry of Parkinsonism. Midbrain hypometabolism was absent-minimal. Three patients had progressive midbrain volumes in the PSP-Richardson's syndrome range.

      Conclusions

      A Parkinson's plus syndrome may inevitably develop in PPAOS supporting PPAOS as an early presentation of a Parkinson's plus disorder.

      Keywords

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