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Eye and Brain 2024This review delineates the ocular motor disturbances across a spectrum of neurodegenerative disorders, including Alzheimer's Disease (AD) and related disorders (ADRD),... (Review)
Review
This review delineates the ocular motor disturbances across a spectrum of neurodegenerative disorders, including Alzheimer's Disease (AD) and related disorders (ADRD), Parkinson's Disease (PD), atypical parkinsonism, and others, leveraging advancements in eye-tracking technology for enhanced diagnostic precision. We delve into the different classes of eye movements, their clinical assessment, and specific abnormalities manifesting in these diseases, highlighting the nuanced differences and shared patterns. For instance, AD and ADRD are characterized by increased saccadic latencies and instability in fixation, while PD features saccadic hypometria and mild smooth pursuit impairments. Atypical parkinsonism, notably Progressive Supranuclear Palsy (PSP) and Corticobasal Syndrome (CBS), presents with distinct ocular motor signatures such as vertical supranuclear gaze palsy and saccadic apraxia, respectively. Our review underscores the diagnostic value of eye movement analysis in differentiating between these disorders and also posits the existence of underlying common pathological mechanisms. We discuss how eye movements have potential as biomarkers for neurodegenerative diseases but also some of the existing limitations.
PubMed: 38617403
DOI: 10.2147/EB.S384769 -
International Journal of Language &... Jul 2023'Speech sound disorder' is an umbrella term that encompasses dysarthria, articulation disorders, childhood apraxia of speech and phonological disorders. However,... (Review)
Review
BACKGROUND
'Speech sound disorder' is an umbrella term that encompasses dysarthria, articulation disorders, childhood apraxia of speech and phonological disorders. However, differential diagnosis between these disorders is a persistent challenge in speech pathology, as many diagnostic procedures use symptom clusters instead of identifying an origin of breakdown in the speech and language system.
AIMS
This article reviews typical and disordered speech through the lens of two well-developed models of production-one focused on phonological encoding and one focused on speech motor planning. We illustrate potential breakdown locations within these models that may relate to childhood apraxia of speech and phonological disorders.
MAIN CONTRIBUTION
This paper presents an overview of an approach to conceptualisation of speech sound disorders that is grounded in current models of speech production and emphasises consideration of underlying processes. The paper also sketches a research agenda for the development of valid, reliable and clinically feasible assessment protocols for children with speech sound disorders.
CONCLUSION
The process-oriented approach outlined here is in the early stages of development but holds promise for developing a more detailed and comprehensive understanding of, and assessment protocols for speech sound disorders that go beyond broad diagnostic labels based on error analysis. Directions for future research are discussed.
WHAT THIS PAPER ADDS
What is already known on the subject Speech sound disorders (SSD) are heterogeneous, and there is agreement that some children have a phonological impairment (phonological disorders, PD) whereas others have an impairment of speech motor planning (childhood apraxia of speech, CAS). There is also recognition that speech production involves multiple processes, and several approaches to the assessment and diagnosis of SSD have been proposed. What this paper adds to existing knowledge This paper provides a more detailed conceptualisation of potential impairments in children with SSD that is grounded in current models of speech production and encourages greater consideration of underlying processes. The paper illustrates this approach and provides guidance for further development. One consequence of this perspective is the notion that broad diagnostic category labels (PD, CAS) may each comprise different subtypes or profiles depending on the processes that are affected. What are the potential or actual clinical implications of this work? Although the approach is in the early stages of development and no comprehensive validated set of tasks and measures is available to assess all processes, clinicians may find the conceptualisation of different underlying processes and the notion of potential subtypes within PD and CAS informative when evaluating SSD. In addition, this perspective discourages either/or thinking (PD or CAS) and instead encourages consideration of the possibility that children may have different combinations of impairments at different processing stages.
PubMed: 37483105
DOI: 10.1111/1460-6984.12934 -
Molecular Psychiatry May 2024Severe speech disorders lead to poor literacy, reduced academic attainment and negative psychosocial outcomes. As early as the 1950s, the familial nature of speech... (Review)
Review
Severe speech disorders lead to poor literacy, reduced academic attainment and negative psychosocial outcomes. As early as the 1950s, the familial nature of speech disorders was recognized, implying a genetic basis; but the molecular genetic basis remained unknown. In 2001, investigation of a large three generational family with severe speech disorder, known as childhood apraxia of speech (CAS), revealed the first causative gene; FOXP2. A long hiatus then followed for CAS candidate genes, but in the past three years, genetic analysis of cohorts ascertained for CAS have revealed over 30 causative genes. A total of 36 pathogenic variants have been identified from 122 cases across 3 cohorts in this nascent field. All genes identified have been in coding regions to date, with no apparent benefit at this stage for WGS over WES in identifying monogenic conditions associated with CAS. Hence current findings suggest a remarkable one in three children have a genetic variant that explains their CAS, with significant genetic heterogeneity emerging. Around half of the candidate genes identified are currently supported by medium (6 genes) to strong (9 genes) evidence supporting the association between the gene and CAS. Despite genetic heterogeneity; many implicated proteins functionally converge on pathways involved in chromatin modification or transcriptional regulation, opening the door to precision diagnosis and therapies. Most of the new candidate genes for CAS are associated with previously described neurodevelopmental conditions that include intellectual disability, autism and epilepsy; broadening the phenotypic spectrum to a distinctly milder presentation defined by primary speech disorder in the setting of normal intellect. Insights into the genetic bases of CAS, a severe, rare speech disorder, are yet to translate to understanding the heritability of more common, typically milder forms of speech or language impairment such as stuttering or phonological disorder. These disorders likely follow complex inheritance with polygenic contributions in many cases, rather than the monogenic patterns that underly one-third of patients with CAS. Clinical genetic testing for should now be implemented for individuals with CAS, given its high diagnostic rate, which parallels many other neurodevelopmental disorders where this testing is already standard of care. The shared mechanisms implicated by gene discovery for CAS highlight potential new targets for future precision therapies.
Topics: Humans; Speech Disorders; Child; Genetic Predisposition to Disease; Apraxias; Forkhead Transcription Factors; Male; Female
PubMed: 38366112
DOI: 10.1038/s41380-024-02409-8 -
Journal of Chemical Neuroanatomy Nov 2023The aim of the present article is to preserve, in English translation, two historical communications on aphasia and the pathophysiology of language by the neurobiologist... (Review)
Review
Neurobiological and pathophysiological concepts of Christfried Jakob (1866-1956) on language and aphasia: An English translation of two communications [1910,1932] and a modern perspective.
The aim of the present article is to preserve, in English translation, two historical communications on aphasia and the pathophysiology of language by the neurobiologist Christfried Jakob (1866-1956) of Buenos Aires, and to place them in a modern perspective. The morphofunctional basis of human language and its pathology occupied Jakob's mind over three decades. His synthetic conclusions were based on the neuropathological examination of dozens of aphasic cases from the Hospital de Las Mercedes and the National Women's Psychiatric Hospital between 1906 and 1936. Special mention is made of the role of the cerebellum, the thalamus, and their connections with the cerebral cortex, and the language network. Current research and imaging studies support and elaborate that which Jacob presented so many years ago; many of his analyses and ideas are informative and remain relevant today.
Topics: Female; Humans; Cerebral Cortex; Aphasia; Cerebellum; Language
PubMed: 37717828
DOI: 10.1016/j.jchemneu.2023.102341 -
Journal of Neurology, Neurosurgery, and... Mar 2024Primary progressive aphasia (PPA) defines a group of neurodegenerative disorders characterised by language decline. Three PPA variants correlate with distinct underlying...
BACKGROUND
Primary progressive aphasia (PPA) defines a group of neurodegenerative disorders characterised by language decline. Three PPA variants correlate with distinct underlying pathologies: semantic variant PPA (svPPA) with transactive response DNA-binding protein of 43 kD (TDP-43) proteinopathy, agrammatic variant PPA (agPPA) with tau deposition and logopenic variant PPA (lvPPA) with Alzheimer's disease (AD). Our objectives were to differentiate PPA variants using clinical and neuroimaging features, assess progression and evaluate structural MRI and a novel 18-F fluorodeoxyglucose positron emission tomography (FDG-PET) image decomposition machine learning algorithm for neuropathology prediction.
METHODS
We analysed 82 autopsied patients diagnosed with PPA from 1998 to 2022. Clinical histories, language characteristics, neuropsychological results and brain imaging were reviewed. A machine learning framework using a -nearest neighbours classifier assessed FDG-PET scans from 45 patients compared with a large reference database.
RESULTS
PPA variant distribution: 35 lvPPA (80% AD), 28 agPPA (89% tauopathy) and 18 svPPA (72% frontotemporal lobar degeneration-TAR DNA-binding protein (FTLD-TDP)). Apraxia of speech was associated with 4R-tauopathy in agPPA, while pure agrammatic PPA without apraxia was linked to 3R-tauopathy. Longitudinal data revealed language dysfunction remained the predominant deficit for patients with lvPPA, agPPA evolved to corticobasal or progressive supranuclear palsy syndrome (64%) and svPPA progressed to behavioural variant frontotemporal dementia (44%). agPPA-4R-tauopathy exhibited limited pre-supplementary motor area atrophy, lvPPA-AD displayed temporal atrophy extending to the superior temporal sulcus and svPPA-FTLD-TDP had severe temporal pole atrophy. The FDG-PET-based machine learning algorithm accurately predicted clinical diagnoses and underlying pathologies.
CONCLUSIONS
Distinguishing 3R-taupathy and 4R-tauopathy in agPPA may rely on apraxia of speech presence. Additional linguistic and clinical features can aid neuropathology prediction. Our data-driven brain metabolism decomposition approach effectively predicts underlying neuropathology.
PubMed: 38514176
DOI: 10.1136/jnnp-2023-332862 -
Journal of Neural Transmission (Vienna,... Mar 2024Depression is one of the most frequent neuropsychiatric symptoms in corticobasal degeneration (CBD), a rare, sporadic, and late-onset progressive neurodegenerative... (Review)
Review
Depression is one of the most frequent neuropsychiatric symptoms in corticobasal degeneration (CBD), a rare, sporadic, and late-onset progressive neurodegenerative disorder of unknown etiology. It is clinically characterized by a levodopa-poorly responsible akinetic-rigid syndrome, apraxia, limb dystonia, cognitive, mood, behavioral, and language disorders. This 4-repeat (4R) tauopathy is morphologically featured by asymmetric frontoparietal atrophy, neuronal loss, and gliosis in cortex and subcortex including substantia nigra, ballooned/achromatic neurons with filamentous 4R tau aggregates in cortex and striatum, widespread thread-like structures, pathognomonic "astroglial plaques", "tufted astrocytes", and numerous "coiled bodies" (in astrocytes and oligodendroglia) in cerebral white matter. CBD is non-specific, as pathologically proven cases include several clinical phenotypes. Pubmed and Google Scholar were systematically analyzed until October 2023, with focus on the prevalence, clinical manifestation, neuroimaging data, and treatment options of depression in CBD. Its prevalence is about 30-40% which is more frequent than in most other atypical parkinsonian syndromes. Depression usually does not correlate with motor and other clinical parameters, suggesting different pathophysiological mechanisms. Asymmetric atrophy and hypometabolism of frontoparietal cortical areas are associated with disruption of fronto-subcortical circuits, nigrostriatal dopaminergic, and cholinergic deficiency. Since no specific neuroimaging, neuropathological, or biomarker studies of depression in CBD are available, its pathobiological mechanisms and pathogenesis are poorly understood. Antidepressive therapy may be useful, but is often poorly tolerated. Depression in CBD, like in other parkinsonian syndromes, may be related to multi-regional patterns of cerebral disturbances and complex pathogenic mechanisms that deserve further elucidation as a basis for early diagnosis and adequate treatment to improve the quality of life in this fatal disease.
Topics: Humans; Corticobasal Degeneration; Cerebral Cortex; Depression; Quality of Life; Parkinsonian Disorders; Atrophy; Morbidity
PubMed: 38216704
DOI: 10.1007/s00702-023-02731-5 -
Movement Disorders Clinical Practice Mar 2024Frontal lobe signs in progressive supranuclear palsy (PSP) are prevalent and occur early in the disease. Although they are recognized in clinical practice, studies are...
BACKGROUND
Frontal lobe signs in progressive supranuclear palsy (PSP) are prevalent and occur early in the disease. Although they are recognized in clinical practice, studies are needed to systematically investigate them for an in-depth understanding of the neurological substrate and their potential prognostic implications in the disease.
OBJECTIVES
To study the predictive role of frontal lobe signs in PSP, as well as to describe their neuropsychological and anatomical correlations.
METHODS
Nine recognized signs of frontal lobe dysfunction were assessed in 61 patients with PSP. Those signs able to predict PSP Rating Scale (PSPRS) score at baseline were selected, a survival analysis was performed and associations with neuropsychological tests and cortical thickness parameters in brain MRI were studied.
RESULTS
Grasping, anosognosia and orobuccal apraxia predicted the PSPRS score independently of age, gender, clinical subtype and disease duration. The occurrence of groping in the first 4 years could be a predictor of survival. Grasping and anosognosia were associated with frontal cognitive dysfunction, whereas orobuccal apraxia and groping were related to a more widespread cognitive impairment, involving temporal-parietal areas. Presence of groping showed an extensive cortical atrophy, with predominant prefrontal, temporal and superior parietal cortical thinning.
CONCLUSIONS
Grasping, groping, anosognosia and orobuccal apraxia are easily evaluable bedside clinical signs that reflect distinct stages of disease progression. Grasping, anosognosia and orobuccal apraxia predict disease disability in patients with PSP, and early onset groping could be a survival predictor.
Topics: Humans; Supranuclear Palsy, Progressive; Frontal Lobe; Magnetic Resonance Imaging; Apraxias; Agnosia
PubMed: 38164060
DOI: 10.1002/mdc3.13958 -
Clinical Linguistics & Phonetics Oct 2023This multiple case pilot study explored how nonword imitation influences articulatory and segmental performance in children with and without speech disorder. Eight...
This multiple case pilot study explored how nonword imitation influences articulatory and segmental performance in children with and without speech disorder. Eight children, ages 4- to 8-years-old, participated, including two children with childhood apraxia of speech (CAS), four children with phonological disorder (PD), and two children with typical development (TD). Tokens included two complexity types and were presented in random order. Minimal feedback was provided and nonwords were never associated with a referent. Kinematic and transcription data were analysed to examine articulatory variability, segmental accuracy, and segmental variability in session 1 and session 5. Descriptive statistics, percent change, effect sizes, and Pearson correlations are reported. In session 1, the two participants with CAS showed high articulatory variability, low segmental accuracy, and high segmental variability compared to the participants with PD and TD. By session 5, both participants with CAS, two with PD, and one with TD showed increased articulatory variability in the lowest complexity nonword. Segmental accuracy remained low and variability remained high for the two participants with CAS in session 5, whereas several participants with PD and TD showed improved segmental performance. Articulatory and segmental variability were not significantly correlated. The results of this study suggest that motor practice with minimal feedback and no assignment of a lexical referent can instantiate positive changes to segmental performance for children without apraxia. Positive changes to segmental performance are not necessarily related to increased articulatory control; these two processing levels can show distinct and disparate learning trajectories.
Topics: Humans; Child; Child, Preschool; Speech; Pilot Projects; Speech Disorders; Apraxias; Speech Production Measurement
PubMed: 35971981
DOI: 10.1080/02699206.2022.2108724 -
European Journal of Medical Genetics Apr 2024Pathogenic variants in BRPF1 cause intellectual disability, ptosis and facial dysmorphism. Speech and language deficits have been identified as a manifestation of...
Pathogenic variants in BRPF1 cause intellectual disability, ptosis and facial dysmorphism. Speech and language deficits have been identified as a manifestation of BRPF1-related disorder but have not been systematically characterized. We provide a comprehensive delineation of speech and language abilities in BRPF1-related disorder and expand the phenotype. Speech and language, and health and medical history were assessed in 15 participants (male = 10, median age = 7 years 4 months) with 14 BRPF1 variants. Language disorders were common (11/12), and most had mild to moderate deficits across receptive, expressive, written, and social-pragmatic domains. Speech disorders were frequent (7/9), including phonological delay (6/9) and disorder (3/9), and childhood apraxia of speech (3/9). All those tested for cognitive abilities had a FSIQ ≥70 (4/4). Participants had vision impairment (13/15), fine (8/15) and gross motor delay (10/15) which often resolved in later childhood, infant feeding impairment (8/15), and infant hypotonia (9/15). We have implicated BRPF1-related disorder as causative for speech and language disorder, including childhood apraxia of speech. Adaptive behavior and cognition were strengths when compared to other monogenic neurodevelopmental chromatin-related disorders. The universal involvement of speech and language impairment is noteable, relative to the high degree of phenotypic variability in BRPF1-related disorder.
Topics: Child; Humans; Male; Adaptor Proteins, Signal Transducing; Apraxias; Bromodomain Containing Proteins; DNA-Binding Proteins; Intellectual Disability; Language Development Disorders; Phenotype; Speech; Speech Disorders; Female
PubMed: 38346666
DOI: 10.1016/j.ejmg.2024.104923 -
American Journal of Speech-language... Aug 2023Behaviorally, acquired apraxia of speech (AOS) is a multidimensional syndrome that the experienced clinician recognizes based on impaired articulation and abnormal...
PURPOSE
Behaviorally, acquired apraxia of speech (AOS) is a multidimensional syndrome that the experienced clinician recognizes based on impaired articulation and abnormal temporal prosody. We conducted this study to determine the extent to which three core features of AOS-when defined quantitatively-distinguish categorically among aphasia with no or minimal speech sound involvement, aphasia with AOS, and aphasia with phonemic paraphasia (APP).
METHOD
The study involved retrospective analysis of 195 participants with stroke-induced aphasia. We used three quantitative measures (phonemic error frequency, distortion error frequency, and word syllable duration [WSD]) to divide the sample into four participant groups according to the most likely speech diagnosis: aphasia with minimal speech sound errors, AOS, APP, and a borderline group with mixed profiles. We then conducted nonparametric comparisons across groups for which the measures were not defined and visualized all three measures in a three-dimensional graph.
RESULTS
The measures distributed as multidimensional spectra rather than discrete diagnostic entities, and there was considerable behavioral overlap among participant groups. Thirty percent of participants presented with aphasia with minimal sound production difficulties, and they were statistically indistinguishable from the APP group on distortion frequency and WSD. Distortion frequency and WSD were in a borderline region between AOS and APP for 29% of participants. Compared to all other groups, participants with AOS produced significantly more errors that affected listeners' phonemic perception.
CONCLUSIONS
The results suggest that the current AOS-APP dichotomy has limited validity. We conclude that a continuous multidimensional view of speech variation would be a constructive perspective from which to understand how the left cerebral hemisphere produces speech and that quantitative and normed speech measures should be used to inform differential diagnosis in clinical settings.
SUPPLEMENTAL MATERIAL
https://doi.org/10.23641/asha.21807609.
Topics: Humans; Speech; Retrospective Studies; Aphasia; Apraxias; Stroke
PubMed: 36603554
DOI: 10.1044/2022_AJSLP-22-00170