Case Report: Semantic Variant of Primary Progressive Aphasia Associated With Anti-Glial Fibrillary Acid Protein Autoantibodies

BackgroundFrontotemporal lobar degeneration is a heterogeneous disorder entailing a semantic variant of primary progressive aphasia (svPPA). A subtype of frontotemporal dementia associated with glutamate receptor subunit 3 (GluA3) antibody of the α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (AMPAR) was recently identified. Here, we describe the novelty of a svPPA associated with anti-glial fibrillary acid protein (GFAP) antibodies.MethodsTo diagnose this 68-year-old woman we conducted a clinical examination, neuropsychological testing, CSF analysis, MRI and 18F-fluorodeoxyglucose (18F-FDG) Positron Emission Tomography (PET)/computed tomography (CT) imaging.ResultsThe clinical phenotype corresponds to a svPPA based on impaired confrontation naming and single-word comprehension. In addition, we observed spared speech production, impaired object knowledge, and surface dyslexia - further supporting the diagnosis of svPPA. Additional characteristic imaging features such as anterior temporal hypometabolism in 18F-FDG PET/CT confirmed patient’s svPPA diagnosis. CSF analysis revealed signs of axonal degeneration, as both tau and phosphorylated tau proteins exceeded normal levels. Her serum showed anti-GFAP autoantibodies.ConclusionWe diagnosed a svPPA in this patient and report an association between serum anti-GFAP antibodies and svPPA never reported in the literature so far, thereby expanding the clinical spectrum of svPPA and anti-GFAP-antibody related disease. Further research is needed to elucidate the underlying immunopathology of this disease entity to ultimately improve treatment.

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Supplemental Material for The Concept of Regularization: Resolving the Problem of Surface Dyslexia in Semantic Variant Primary Progressive Aphasia Across Different Languages

Neuropsychology ◽

10.1037/neu0000611.supp ◽

2019 ◽

Keyword(s):

Primary Progressive Aphasia ◽

Progressive Aphasia ◽

Primary Progressive ◽

Semantic Variant ◽

Surface Dyslexia

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Primary Progressive Aphasia: Toward a Pathophysiological Synthesis

Current Neurology and Neuroscience Reports ◽

10.1007/s11910-021-01097-z ◽

2021 ◽

Vol 21 (3) ◽

Author(s):

Justina Ruksenaite ◽

Anna Volkmer ◽

Jessica Jiang ◽

Jeremy CS Johnson ◽

Charles R Marshall ◽

...

Keyword(s):

Care Management ◽

Primary Progressive Aphasia ◽

Disease Stage ◽

Major Step ◽

Progressive Aphasia ◽

Primary Progressive ◽

New Findings ◽

Critical Issues ◽

Semantic Variant ◽

Auditory Impairments

Abstract Purpose of Review The term primary progressive aphasia (PPA) refers to a diverse group of dementias that present with prominent and early problems with speech and language. They present considerable challenges to clinicians and researchers. Recent Findings Here, we review critical issues around diagnosis of the three major PPA variants (semantic variant PPA, nonfluent/agrammatic variant PPA, logopenic variant PPA), as well as considering ‘fragmentary’ syndromes. We next consider issues around assessing disease stage, before discussing physiological phenotyping of proteinopathies across the PPA spectrum. We also review evidence for core central auditory impairments in PPA, outline critical challenges associated with treatment, discuss pathophysiological features of each major PPA variant, and conclude with thoughts on key challenges that remain to be addressed. Summary New findings elucidating the pathophysiology of PPA represent a major step forward in our understanding of these diseases, with implications for diagnosis, care, management, and therapies.

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Breakdowns in Informativeness of Naturalistic Speech Production in Primary Progressive Aphasia

Brain Sciences ◽

10.3390/brainsci11020130 ◽

2021 ◽

Vol 11 (2) ◽

pp. 130

Author(s):

Jeanne Gallée ◽

Claire Cordella ◽

Evelina Fedorenko ◽

Daisy Hochberg ◽

Alexandra Touroutoglou ◽

...

Keyword(s):

Primary Progressive Aphasia ◽

Speech Analysis ◽

Clinical Settings ◽

Functional Communication ◽

Or Efficiency ◽

Progressive Aphasia ◽

Primary Progressive ◽

Communication Impairment ◽

Semantic Variant ◽

Lower Production

“Functional communication” refers to an individual’s ability to communicate effectively in his or her everyday environment, and thus is a paramount skill to monitor and target therapeutically in people with aphasia. However, traditional controlled-paradigm assessments commonly used in both research and clinical settings often fail to adequately capture this ability. In the current study, facets of functional communication were measured from picture-elicited speech samples from 70 individuals with mild primary progressive aphasia (PPA), including the three variants, and 31 age-matched controls. Building upon methods recently used by Berube et al. (2019), we measured the informativeness of speech by quantifying the content of each patient’s description that was relevant to a picture relative to the total amount of speech they produced. Importantly, form-based errors, such as mispronunciations of words, unusual word choices, or grammatical mistakes are not penalized in this approach. We found that the relative informativeness, or efficiency, of speech was preserved in non-fluent variant PPA patients as compared with controls, whereas the logopenic and semantic variant PPA patients produced significantly less informative output. Furthermore, reduced informativeness in the semantic variant is attributable to a lower production of content units and a propensity for self-referential tangents, whereas for the logopenic variant, a lower production of content units and relatively ”empty” speech and false starts contribute to this reduction. These findings demonstrate that functional communication impairment does not uniformly affect all the PPA variants and highlight the utility of naturalistic speech analysis for measuring the breakdown of functional communication in PPA.

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