Progression to corticobasal syndrome: a longitudinal study of patients with nonfluent primary progressive aphasia and primary progressive apraxia of speech

J Neurol. 2024 Jul;271(7):4168-4179. doi: 10.1007/s00415-024-12344-x. Epub 2024 Apr 7.

Abstract

Background and objectives: Nonfluent variant primary progressive aphasia (nfvPPA) and primary progressive apraxia of speech (PPAOS) can be precursors to corticobasal syndrome (CBS). Details on their progression remain unclear. We aimed to examine the clinical and neuroimaging evolution of nfvPPA and PPAOS into CBS.

Methods: We conducted a retrospective longitudinal study in 140 nfvPPA or PPAOS patients and applied the consensus criteria for possible and probable CBS for every visit, evaluating limb rigidity, akinesia, limb dystonia, myoclonus, ideomotor apraxia, alien limb phenomenon, and nonverbal oral apraxia (NVOA). Given the association of NVOA with AOS, we also modified the CBS criteria by excluding NVOA and assigned every patient to either a progressors or non-progressors group. We evaluated the frequency of every CBS feature by year from disease onset, and assessed gray and white matter volume loss using SPM12.

Results: Asymmetric akinesia, NVOA, and limb apraxia were the most common CBS features that developed; while limb dystonia, myoclonus, and alien limb were rare. Eighty-two patients progressed to possible CBS; only four to probable CBS. nfvPPA and PPAOS had a similar proportion of progressors, although nfvPPA progressed to CBS earlier (p-value = 0.046), driven by an early appearance of limb apraxia (p-value = 0.0041). The non-progressors and progressors both showed premotor/motor cortex involvement at baseline, with spread into prefrontal cortex over time.

Discussion: An important proportion of patients with nfvPPA and PPAOS progress to possible CBS, while they rarely develop features of probable CBS even after long follow-up.

Keywords: Corticobasal syndrome; Nonfluent/agrammatic variant primary progressive aphasia; Nonverbal oral apraxia; Primary progressive apraxia of speech; R01-DC10367 (PI Josephs) and R01-DC12519 (PI Whitwell); R01-DC14942 (PI Josephs).

MeSH terms

  • Aged
  • Apraxias* / diagnostic imaging
  • Apraxias* / etiology
  • Apraxias* / physiopathology
  • Disease Progression*
  • Female
  • Humans
  • Longitudinal Studies
  • Magnetic Resonance Imaging
  • Male
  • Middle Aged
  • Primary Progressive Nonfluent Aphasia* / diagnostic imaging
  • Primary Progressive Nonfluent Aphasia* / physiopathology
  • Retrospective Studies