Citations

Purpose: Functional speech disorders (FSDs), a subtype of functional neurological disorders, are distinguishable from neurogenic motor speech disorders based on their clinical features, clinical course, and response to treatment. However, their differential diagnosis and management can be challenging. FSDs are not well understood, but growing evidence suggests a biopsychosocial basis distinct from structural lesions that cause neurogenic motor speech disorders. Method and Results: Following an overview of FSDs, four patients are described to illustrate the range of clinical manifestations, biopsychosocial contexts, and responses to treatment of FSDs. The path to differential diagnosis is discussed, with particular attention to positive features that led to the FSD diagnosis. Approaches to education, counseling, and management are discussed. Conclusions: This case series demonstrates that FSDs can present with a variety of manifestations including dysfluencies, articulation errors, dysphonia, rate and prosodic abnormalities, and combinations of disruptions in speech subsystems. FSDs may present in the context of known recent or remote physical or psychosocial trauma or, as in many cases, in the absence of an identifiable triggering event. FSDs are recognizable by positive clinical features and should not be considered a diagnosis of exclusion. With appropriate identification, counseling, and treatment, FSDs may resolve, sometimes rapidly; in some cases, treatment may be prolonged or ineffective.

The objective of this study was to characterize network-level changes in nonfluent/agrammatic Primary Progressive Aphasia (agPPA) and Primary Progressive Apraxia of Speech (PPAOS) with graph theory (GT) measures derived from scalp electroencephalography (EEG) recordings. EEGs of 15 agPPA and 7 PPAOS patients were collected during relaxed wakefulness with eyes closed (21 electrodes, 10–20 positions, 256 Hz sampling rate, 1–200 Hz bandpass filter). Eight artifact-free, non-overlapping 1024-point epochs were selected. Via Brainwave software, GT weighted connectivity and minimum spanning tree (MST) measures were calculated for theta and upper and lower alpha frequency bands. Differences in GT and MST measures between agPPA and PPAOS were assessed with Wilcoxon rank-sum tests. Of greatest interest, Spearman correlations were computed between behavioral and network measures in all frequency bands across all patients. There were no statistically significant differences in GT or MST measures between agPPA and PPAOS. There were significant correlations between several network and behavioral variables. The correlations demonstrate a relationship between reduced global efficiency and clinical symptom severity (e.g., parkinsonism, AOS). This preliminary, exploratory study demonstrates potential for EEG GT measures to quantify network changes associated with degenerative speech–language disorders.

This study compared orofacial muscle strength between normal and dysarthric speakers and across types of dysarthria, and examined correlations between strength and dysarthria severity. Participants included 79 speakers with flaccid, spastic, mixed spastic–flaccid, ataxic, or hypokinetic dysarthria and 33 healthy controls. Maximum pressure generation (Pmax) by the tongue, lips, and cheeks represented strength. Pmax was lower for speakers with mixed spastic–flaccid dysarthria for all tongue and lip measures, as well as for speakers with flaccid or spastic dysarthria for anterior tongue elevation and lip compression. Anterior tongue elevation and cheek compression tended to be lower than normal for the hypokinetic group. Pmax did not differ significantly between controls and speakers with ataxic dysarthria on any measure. Correlations were generally weak between dysarthria severity and orofacial weakness but were stronger in the dysarthria groups with more prominent orofacial weakness. The results generally support predictions that orofacial weakness accompanies flaccid and/or spastic dysarthria but not ataxic dysarthria. The findings support including type of dysarthria as a variable of interest when examining orofacial weakness in motor speech disorders.

AbstractBackgroundThe apolipoprotein ε4 (APOE4) allele is the most common and well established risk factor for typical late‐onset amnestic Alzheimer’s dementia. Less is known about the role of APOE in patients with atypical clinical presentations of AD, with studies often disagreeing on APOE4 frequencies in these cohorts. We aimed to assess relationships between APOE genotype and age, amyloid‐beta (Aβ) deposition and clinical phenotype in Alzheimer’s disease.Method138 atypical AD patients (57 posterior cortical atrophy and 81 logopenic aphasia) were recruited by the Neurodegenerative Research Group at Mayo Clinic, and underwent APOE testing and Pittsburgh Compound B PET. 318 typical AD patients with APOE genotype and known onset age were identified from ADNI (121 had Aβ‐PET). Aβ‐PET was quantified using the centiloid scale. Logistic regression was used to estimate the proportion of APOE4 carriers by onset age and clinical group. Linear regression was used to estimate mean Aβ centiloid by age, APOE4 status, and clinical group in patients who were Aβ‐positive (centiloid≥19).ResultThe overall frequency of APOE4 carriers was lower in atypical AD (52%) compared to typical AD (66%), particularly for ε4ε4 homozygotes (9% vs 20%). APOE4 frequency increased with age in atypical AD, but showed a bell‐shaped curve in typical AD where highest frequencies were observed between 65‐70 years (Figure). Typical AD showed higher APOE4 frequencies than atypical AD only between the ages of 57 and 69 years. Aβ centiloid was higher in atypical AD compared to typical AD by approximately 16 centiloid units, but did not differ according to APOE4 status (Figure). Aβ centiloid stayed relatively flat with increasing age for both carriers and non‐carriers in atypical AD, but declines with increasing age in typical AD. Relationships between APOE4 and age, as well as centiloid, did not differ between the two atypical AD phenotypes.ConclusionAPOE4 frequency differs between atypical and typical AD but is highly dependent upon age, with higher APOE4 frequency in typical AD only observed between 57 and 69 years. The findings highlight the importance of age and clinical phenotype in understanding the effects of APOE genotype in Alzheimer’s disease.

AbstractBackgroundIndividuals with Primary Progressive Apraxia of Speech (PPAOS) have AOS as the initial and predominant symptom. Many develop aphasia and/or dysarthria later in the disease course. Past research has shown that patients with neurodegenerative AOS experience reduced participation in communication that is further exacerbated by co‐occurring language deficits. Previous studies suggest measures of disease severity do not necessarily correlate with measures of participation restrictions. The aim of this study was to describe changes in communication limitations in these patients over a one‐year interval, measured by 1) the patient via the Communicative Participation Item Bank (CPIB) and 2) the speech‐language pathologist via ASHA's Functional Communication Measures (FCMs) and an adapted Motor Speech Disorder (MSD) severity rating and determine if there are significant changes in these and other objective speech and language measures (e.g. Western Aphasia Battery‐Revised Aphasia Quotient, Apraxia of Speech Rating Scale‐3).MethodSeventeen patients (10 male) with progressive AOS were seen for a second visit approximately one year following the first visit. The measures collected at each visit were statistically compared. Correlations were calculated between the participation ratings and other clinical assessment measures at each visit and qualitatively compared.ResultThere were statistically significant differences in AOS and aphasia severity between visits. There were significant changes in clinical assessments, MSD severity rating, and all ASHA FCMs between visits, but not the CPIB. Comparison of correlations suggest the relationships among clinical and participation measures may change over time.ConclusionThe findings of this study support the use of patient reported outcome measures, like the CPIB, as they may better reflect the patient experience and associated changes in day‐to‐day functioning when other measures may simply index the progression of the disease.

AbstractBackgroundThe Neurodegenerative Research Group (NRG) at Mayo clinic has followed patients with degenerative speech and/or language disorders for over a decade. In this presentation I will present data from this cohort to inform a broader discussion about the importance of apraxia of speech (AOS) and its subtypes, heterogeneity within the agrammatic PPA variant, and perils of mixed phenotypes.MethodWe reviewed the NRG database to identify patients who initially presented with isolated (PPAOS), AOS in conjunction with agrammatic aphasia (AOS‐PAA), isolated agrammatic aphasia (PAA), and patients who had PAA or AOS overlapping with another degenerative diagnosis. Data from the following clinical instruments were abstracted: WAB AQ (aphasia severity), UPDRS III (parkinsonism), WAB Praxis (ideomotor apraxia), and the MoCA (cognitive ability). We assessed the effect of baseline diagnosis and AOS subtype on these outcomes over time using Bayesian linear mixed effects models. We qualitatively reviewed longitudinal diagnostic trajectories. Preliminary analyses were done on available autopsy data.ResultPAA was associated with greater aphasia at baseline and more rapid decline; PPAOS was associated with normal language at baseline and slow decline; and PAA‐AOS with intermediate baseline aphasia and decline. However, for those with AOS longitudinal decline differed based on AOS subtype: prosodic PPAOS was associated with the slowest decline and phonetic PAA‐AOS with the fastest. Some patients met criteria for non‐PPA disorders during follow up. However, compared to patients who met criteria for these disorders at enrollment, the speech/language‐first patients remained qualitatively distinct, and neither resembled the cases that were mixed at onset. Preliminary autopsy data suggests that AOS is predictive of tau and that the specific tauopathy may be related to the initial syndrome and AOS subtype.ConclusionThe differences between PAA, PAA‐AOS and PPAOS suggest that these disorders should not be lumped. In fact, the longitudinal trajectories are sufficiently different that doing so would add noise to observational and interventional studies. Instead, more detailed phenotyping, including AOS subtype, can aid prognostication and may improve prediction of the underlying pathology. Finally, caution should be exercised when considering PPAOS and PPA patients for other FTLD diagnostic categories.

AbstractBackgroundLogopenic progressive aphasia (LPA) and posterior cortical atrophy (PCA) have distinct patterns of hypometabolism and atrophy. However, these clinical syndromes overlap: visuospatial impairment has been documented in LPA and aphasia in PCA. Rey‐Osterrieth Complex Figure – Copy (Rey‐O Copy) performance is correlated with parietal‐occipital atrophy in LPA. We explore visuospatial impairment on the Rey‐O Copy in LPA and PCA with the Mayo Older Americans Normative Studies (MOANS; which uses Meyers & Meyers criteria) and the Boston Qualitative Scoring System (BQSS). We also examine the proportion of visuospatial impairment in LPA, an under‐appreciated phenomenon, compared to PCA wherein it is fundamental.MethodPatients with LPA (n=25) or PCA (n=23) were recruited by the Neurodegenerative Research Group. Patients underwent comprehensive neuropsychological testing (including Rey‐O Copy) at baseline visit. Cut‐offs of T‐score=40 (BQSS) or scaled score=7 (MOANS) were used based on normative data. Proportions of patients with low performance were examined across LPA and PCA groups. Individual logistic regressions and AUROC analyses were then conducted to quantify differences in visuospatial impairment in LPA and PCA with both scoring systems. Identical analyses were conducted using raw scores corrected for age and sex, to avoid confounds of adjustments in normative data.ResultLPA and PCA groups were comparable on age, sex, and disease duration (LPA Median = 2.7 years, IQR=1.9‐3.5; PCA Median = 3.6 years, IQR=1.5‐4.9); p=.823). Surprisingly, 52‐72% of LPA participants demonstrated impaired performance across scoring systems, relative to 96% of the PCA group identified by both scoring systems. Odds ratios (OR) for the Rey‐O Copy MOANS (OR = 1.59; p=.008) and BQSS Copy Presence and Accuracy index (CPA; OR = 1.13, p=.002) were significant, persisting for age‐ and sex‐ controlled raw scores, suggesting the odds of a PCA diagnosis increased with decrement on Rey‐O Copy. AUROC values ranged from 0.77 to 0.88 across these indices.ConclusionA substantial number of LPA participants showed visuospatial impairment, despite initial primary language complaints. Differentiation of diagnostic groups by the Rey‐O is likely underscored by relatively uniform, profound, visuospatial impairment in PCA with more variability in LPA. However, the degree of visuospatial impairment overlaps remarkably across diagnoses.

AbstractBackgroundMagnetic resonance brainstem measurements are useful structural biomarkers in the Richardson's syndrome variant of progressive supranuclear palsy (PSP). However, it is unclear how these biomarkers differ across the phenotypic spectrum of PSP and how they relate to underlying pathology.ObjectiveThe aim of this study was to compare brainstem imaging measures across clinical variants of PSP and determine sensitivity and specificity based on pathologically diagnosed cases.MethodsA total of 153 patients with PSP who represented eight clinical variants were recruited at Mayo Clinic (Rochester, MN, USA) and underwent structural magnetic resonance imaging (MRI). Midbrain and pons area and superior and middle cerebellar peduncle width measurements were performed, and midbrain/pons ratio and Magnetic Resonance Parkinsonism Index (MRPI) were calculated. Among the 43 patients who later died, PSP pathology was confirmed in 29, whereas 14 had other pathology.ResultsBrainstem measurements varied across PSP clinical variants and were most abnormal in PSP‐Richardson's syndrome and frontal variants, followed by PSP‐corticobasal, PSP‐speech/language, and PSP‐parkinsonism variants. All these variants showed abnormalities compared with controls. The PSP‐gait freezing variant and patients with prominent corticospinal tract signs showed normal brainstem measures. Among cases with confirmed PSP pathology, the midbrain area, midbrain/pons ratio, and MRPI were all more abnormal compared to those with other pathologies, with best differentiation obtained with the MRPI (sensitivity = 83%; specificity = 85%).ConclusionsMRI brainstem measures show utility as diagnostic biomarkers across PSP clinical variants and have the potential to be useful in predicting underlying pathology. © 2021 International Parkinson and Movement Disorder Society

We describe two individuals with progressive verbal difficulty who exhibited impairment of propositional language, with relatively well-preserved auditory comprehension, naming, and repetition—a profile that is consistent with dynamic aphasia. By providing a brief review of pertinent literature and the results from our neurologic, speech and language, neuropsychological, and neuroimaging testing, this report sheds light on the infrequently reported dynamic aphasia in the context of frontotemporal dementia. Our patients’ insights into their verbal difficulty tend to support the notion that dynamic aphasia results from interference at the stage where thoughts are converted into verbal messages—that is, the thought–verbal interface.

Purpose This study compared performance on three-word fluency measures among individuals with primary progressive aphasia (PPA) and primary progressive apraxia of speech (PPAOS), and examined the relationship between word fluency and other measures of language and speech. Method This study included 106 adults with PPA and 30 adults with PPAOS. PPA participants were divided into three clinical subgroups: semantic (svPPA), logopenic (lvPPA), and nonfluent/agrammatic with or without apraxia of speech (nfPPA). Category fluency, letter fluency, and action/verb fluency tasks were administered to all participants. Results The four clinical groups performed abnormally on the word fluency measures, although not to a degree that represented high sensitivity to their PPA or PPAOS diagnosis. All PPA subgroups produced fewer words compared to individuals with PPAOS on all word fluency measures. Moderate correlations were found between word fluency and aphasia severity and naming performance in some of the clinical groups. Conclusions Word fluency measures are often challenging for individuals with PPA and PPAOS, but they are not of equal difficulty, with letter fluency being the most difficult. Differences among word fluency tests also vary to some degree as a function of the clinical group in question, with least impairment in PPAOS. However, the findings of this study do not support statistically significant differences in word fluency task performance among the PPA subgroups. Correlations suggest that word fluency performance in PPA is at least partly related to aphasia severity.