Progression of Nonfluent Primary Progressive Aphasia and Primary Progressive Apraxia of Speech into Corticobasal Syndrome
Danna Garcia-Guaqueta1, Hugo Botha1, Rene Utianski1, Joseph Duffy1, Heather Clark1, Austin Goodrich2, Mary Machulda3, Jennifer Whitwell4, Keith Josephs1
1Department of Neurology, 2Department of Quantitative Health Sciences, 3Department of Psychiatry and Psychology, 4Department of Radiology, Mayo Clinic
Objective:
This study aimed to examine the evolution of nonfluent variant primary progressive aphasia (nfvPPA) and primary progressive apraxia of speech (PPAOS) into corticobasal syndrome (CBS).
Background:
Patients with nfvPPA and PPAOS can develop features of CBS, although it is unclear how commonly or early this occurs and whether they evolve to meet diagnostic criteria for probable CBS.
Design/Methods:
We conducted a retrospective longitudinal study in 140 patients with nfvPPA or PPAOS who completed at least one visit where neurological and speech/language evaluations were performed (total of 329 visits). We applied the consensus criteria for possible and probable CBS at every visit, evaluating the presence of limb rigidity or akinesia, dystonia, myoclonus, limb apraxia, nonverbal oral apraxia (NVOA), and alien limb phenomenon. Given the strong association of NVOA with apraxia of speech, we also assessed a modified CBS criteria whereby we excluded NVOA as a criterion for CBS. The frequency of every CBS feature by year from disease onset was also assessed.
Results:
Patients were followed on average 5.2 years from symptom onset (range: 0.4-15.9). Asymmetric akinesia, NVOA, and limb apraxia were the most common CBS features, while dystonia, myoclonus, and alien limb phenomenon were rare. 101 patients progressed to possible CBS and 4 to probable CBS. Using the modified criteria, 82 progressed to possible CBS and 4 to probable CBS. Patients with nfvPPA progressed to CBS earlier than those with PPAOS (p-value = 0.046) which was driven by limb apraxia that appeared earlier in nfvPPA (p-value = 0.0041). Both groups, however, had a similar proportion of progressors by the end of the follow-up period.
Conclusions:
Patients with nfvPPA and PPAOS frequently develop CBS features, although they rarely meet probable criteria even after long follow-up. Those with nfvPPA show a faster trajectory to CBS than those with PPAOS although PPAOS catches up later.