Primary progressive aphasia and motor neuron disease: A review.

Background: This study aims at reviewing, within the framework of motor neuron disease-frontotemporal degeneration (MND-FTD)-spectrum disorders, evidence on the co-occurrence between primary progressive aphasia (PPA) and MND in order to profile such a complex at pathological, genetic and clinical levels. Methods: This review was pre-registered (osf.io/ds8m4) and performed in accordance with the 2020 PRISMA guidelines. Case reports/series and group studies were included if addressing (1) progressive non-fluent aphasia (PNFA) or semantic dementia (SD) with MND or (2) MND patients with co-morbid PNFA/SD. Results: Out of 546 initial records, 56 studies were included. As to case reports/series (N = 35), which included 61 PPA-MND patients, the following findings yielded: (1) PNFA is more frequent than SD in PPA-MND; (2) in PPA-MND, the most prevalent motor phenotypes are amyotrophic lateral sclerosis and predominant-upper MND, with bulbar involvement being ubiquitous; (3) extrapyramidal features are moderately frequent in PPA-MND; (4) PPA-MND patients usually display frontotemporal, left-greater-than-right involvement; (5) TDP-43-B is the typical pathological substrate of PPA-MND; (6) TBK1 mutations represent the most frequent genetic risk factors for PPA-MND.As to group studies, including 121 patients, proportional meta-analytic procedures revealed that: (1) the lifetime prevalence of MND in PPA is 6%; (2) PPA occurs in 19% of patients with co-morbid MND and FTD; (3) MND is more frequent in PNFA (10%) than in SD patients (3%). Discussion: Insights herewith delivered into the clinical, neuropathological and genetic features of PPA-MND patients prompt further investigations aimed at improving clinical practice within the MND-FTD spectrum.

Neural Correlates of Esophageal Speech: An fMRI Pilot Study.

OBJECTIVES: The esophageal speech is one of the possible alaryngeal voices resulting after total laryngectomy. Its production is made by the regurgitation of the air coming from the esophagus, sonorized through the passage from the walls of the upper esophageal sphincter. The neural correlates of this voice have never been investigated, while the neural control of laryngeal voice has been already documented by different studies. METHODS: Four patients using esophageal speech after total laryngectomy and four healthy controls underwent functional magnetic resonance imaging. The fMRI experiment was carried out using a "Block Design Paradigm." RESULTS: Comparison of the phonation task in the two groups revealed higher brain activities in the cingulate gyrus, the cerebellum and the medulla as well as lower brain activities in the precentral gyrus, the inferior and middle frontal gyrus and the superior temporal gyrus in the laryngectomized group. CONCLUSIONS: The findings in this pilot study provide insight into neural phonation control in laryngectomized patients with esophageal speech. The imaging results demonstrated that in patients with esophageal speech, altered brain activities can be observed. The adaptive changes in the brain following laryngectomy reflect the changes in the body and in the voice modality. In addition, this pilot study establishes that a blocked design fMRI is sensitive enough to define a neural network associated with esophageal voice and lays the foundation for further studies in this field.