RESUMO
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.
Assuntos
Distúrbios da Fala , Humanos , Distúrbios da Fala/genética , Criança , Predisposição Genética para Doença/genética , Apraxias/genética , Fatores de Transcrição Forkhead/genética , Masculino , FemininoRESUMO
Speech disorders are associated with different degrees of functional and structural abnormalities. However, the abnormalities associated with specific disorders, and the common abnormalities shown by all disorders, remain unclear. Herein, a meta-analysis was conducted to integrate the results of 70 studies that compared 1843 speech disorder patients (dysarthria, dysphonia, stuttering, and aphasia) to 1950 healthy controls in terms of brain activity, functional connectivity, gray matter, and white matter fractional anisotropy. The analysis revealed that compared to controls, the dysarthria group showed higher activity in the left superior temporal gyrus and lower activity in the left postcentral gyrus. The dysphonia group had higher activity in the right precentral and postcentral gyrus. The stuttering group had higher activity in the right inferior frontal gyrus and lower activity in the left inferior frontal gyrus. The aphasia group showed lower activity in the bilateral anterior cingulate gyrus and left superior frontal gyrus. Across the four disorders, there were concurrent lower activity, gray matter, and fractional anisotropy in motor and auditory cortices, and stronger connectivity between the default mode network and frontoparietal network. These findings enhance our understanding of the neural basis of speech disorders, potentially aiding clinical diagnosis and intervention.
Assuntos
Afasia , Córtex Auditivo , Disfonia , Gagueira , Humanos , Disartria , Funções Verossimilhança , Distúrbios da FalaRESUMO
OBJECTIVES: Speech and language impairments are core features of the neurodevelopmental genetic condition Kleefstra syndrome. Communication has not been systematically examined to guide intervention recommendations. We define the speech, language and cognitive phenotypic spectrum in a large cohort of individuals with Kleefstra syndrome. METHOD: 103 individuals with Kleefstra syndrome (40 males, median age 9.5 years, range 1-43 years) with pathogenic variants (52 9q34.3 deletions, 50 intragenic variants, 1 balanced translocation) were included. Speech, language and non-verbal communication were assessed. Cognitive, health and neurodevelopmental data were obtained. RESULTS: The cognitive spectrum ranged from average intelligence (12/79, 15%) to severe intellectual disability (12/79, 15%). Language ability also ranged from average intelligence (10/90, 11%) to severe intellectual disability (53/90, 59%). Speech disorders occurred in 48/49 (98%) verbal individuals and even occurred alongside average language and cognition. Developmental regression occurred in 11/80 (14%) individuals across motor, language and psychosocial domains. Communication aids, such as sign and speech-generating devices, were crucial for 61/103 (59%) individuals including those who were minimally verbal, had a speech disorder or following regression. CONCLUSIONS: The speech, language and cognitive profile of Kleefstra syndrome is broad, ranging from severe impairment to average ability. Genotype and age do not explain the phenotypic variability. Early access to communication aids may improve communication and quality of life.
Assuntos
Deleção Cromossômica , Cromossomos Humanos Par 9 , Cognição , Anormalidades Craniofaciais , Deficiência Intelectual , Fenótipo , Humanos , Masculino , Deficiência Intelectual/genética , Deficiência Intelectual/fisiopatologia , Criança , Adolescente , Feminino , Adulto , Pré-Escolar , Cromossomos Humanos Par 9/genética , Adulto Jovem , Lactente , Anormalidades Craniofaciais/genética , Anormalidades Craniofaciais/fisiopatologia , Fala , Distúrbios da Fala/genética , Distúrbios da Fala/fisiopatologia , Idioma , Inteligência/genética , Transtornos da Linguagem/genética , Transtornos da Linguagem/fisiopatologia , Cardiopatias CongênitasRESUMO
Cerebral creatine deficiency syndromes (CCDS) are inherited metabolic phenotypes of creatine synthesis and transport. There are two enzyme deficiencies, guanidinoacetate methyltransferase (GAMT), encoded by GAMT and arginine-glycine amidinotransferase (AGAT), encoded by GATM, which are involved in the synthesis of creatine. After synthesis, creatine is taken up by a sodium-dependent membrane bound creatine transporter (CRTR), encoded by SLC6A8, into all organs. Creatine uptake is very important especially in high energy demanding organs such as the brain, and muscle. To classify the pathogenicity of variants in GAMT, GATM, and SLC6A8, we developed the CCDS Variant Curation Expert Panel (VCEP) in 2018, supported by The Clinical Genome Resource (ClinGen), a National Institutes of Health (NIH)-funded resource. We developed disease-specific variant classification guidelines for GAMT-, GATM-, and SLC6A8-related CCDS, adapted from the American College of Medical Genetics/Association of Molecular Pathology (ACMG/AMP) variant interpretation guidelines. We applied specific variant classification guidelines to 30 pilot variants in each of the three genes that have variants associated with CCDS. Our CCDS VCEP was approved by the ClinGen Sequence Variant Interpretation Working Group (SVI WG) and Clinical Domain Oversight Committee in July 2022. We curated 181 variants including 72 variants in GAMT, 45 variants in GATM, and 64 variants in SLC6A8 and submitted these classifications to ClinVar, a public variant database supported by the National Center for Biotechnology Information. Missense variants were the most common variant type in all three genes. We submitted 32 new variants and reclassified 34 variants with conflicting interpretations. We report specific phenotype (PP4) using a points system based on the urine and plasma guanidinoacetate and creatine levels, brain magnetic resonance spectroscopy (MRS) creatine level, and enzyme activity or creatine uptake in fibroblasts ranging from PP4, PP4_Moderate and PP4_Strong. Our CCDS VCEP is one of the first panels applying disease specific variant classification algorithms for an X-linked disease. The availability of these guidelines and classifications can guide molecular genetics and genomic laboratories and health care providers to assess the molecular diagnosis of individuals with a CCDS phenotype.
Assuntos
Amidinotransferases , Amidinotransferases/deficiência , Erros Inatos do Metabolismo dos Aminoácidos , Creatina , Creatina/deficiência , Guanidinoacetato N-Metiltransferase , Deficiência Intelectual , Transtornos do Desenvolvimento da Linguagem , Transtornos dos Movimentos/congênito , Proteínas do Tecido Nervoso , Proteínas da Membrana Plasmática de Transporte de Neurotransmissores , Proteínas da Membrana Plasmática de Transporte de Neurotransmissores/deficiência , Distúrbios da Fala , Humanos , Guanidinoacetato N-Metiltransferase/deficiência , Guanidinoacetato N-Metiltransferase/genética , Creatina/metabolismo , Proteínas da Membrana Plasmática de Transporte de Neurotransmissores/genética , Amidinotransferases/genética , Amidinotransferases/metabolismo , Deficiência Intelectual Ligada ao Cromossomo X/genética , Deficiência Intelectual Ligada ao Cromossomo X/diagnóstico , Mutação , Encefalopatias Metabólicas Congênitas/genética , Encefalopatias Metabólicas Congênitas/diagnóstico , Fenótipo , Curadoria de Dados , Deficiências do DesenvolvimentoRESUMO
Childhood apraxia of speech (CAS), the prototypic severe childhood speech disorder, is characterized by motor programming and planning deficits. Genetic factors make substantive contributions to CAS aetiology, with a monogenic pathogenic variant identified in a third of cases, implicating around 20 single genes to date. Here we aimed to identify molecular causation in 70 unrelated probands ascertained with CAS. We performed trio genome sequencing. Our bioinformatic analysis examined single nucleotide, indel, copy number, structural and short tandem repeat variants. We prioritised appropriate variants arising de novo or inherited that were expected to be damaging based on in silico predictions. We identified high confidence variants in 18/70 (26%) probands, almost doubling the current number of candidate genes for CAS. Three of the 18 variants affected SETBP1, SETD1A and DDX3X, thus confirming their roles in CAS, while the remaining 15 occurred in genes not previously associated with this disorder. Fifteen variants arose de novo and three were inherited. We provide further novel insights into the biology of child speech disorder, highlighting the roles of chromatin organization and gene regulation in CAS, and confirm that genes involved in CAS are co-expressed during brain development. Our findings confirm a diagnostic yield comparable to, or even higher, than other neurodevelopmental disorders with substantial de novo variant burden. Data also support the increasingly recognised overlaps between genes conferring risk for a range of neurodevelopmental disorders. Understanding the aetiological basis of CAS is critical to end the diagnostic odyssey and ensure affected individuals are poised for precision medicine trials.
Assuntos
Apraxias , Distúrbios da Fala , Criança , Humanos , Distúrbios da Fala/genética , Apraxias/genética , Mapeamento Cromossômico , Causalidade , Encéfalo , Histona-Lisina N-MetiltransferaseRESUMO
Biallelic pathogenic variations in the zinc finger protein 142 (ZNF142) gene are associated with neurodevelopmental disorder with impaired speech and hyperkinetic movements (NEDISHM). This disorder is characterized by developmental delay, intellectual disability, speech delay, and movement disorders such as dystonia, tremor, ataxia, and chorea. Here, we report a patient who exhibited common neurological features and rarely reported brain MRI findings. Exome sequencing identified a novel biallelic variant in ZNF142 (c.3528_3529delTG; p.C1176fs*5 (NM_001105537.4)). NEDISHM was first described by Khan et al. (2019) and has been reported in 39 patients to date. Furthermore, upon reviewing our in-house data covering 750 individuals, we identified three different pathogenic ZNF142 variants. It appears that the frequency of ZNF142 alleles is not as low as initially thought, suggesting that this gene should be included in new generation sequencing panels for similar clinical scenarios. Our goal is to compile and expand upon the clinical features observed in NEDISHM, providing novel insights and presenting a new variant to the literature. We also aim to demonstrate that ZNF142 pathogenic variants should be considered in neurodevelopmental diseases.
Assuntos
Alelos , Transtornos do Neurodesenvolvimento , Criança , Humanos , Masculino , Proteínas de Ligação a DNA/genética , Sequenciamento do Exoma , Predisposição Genética para Doença , Hipercinese/genética , Deficiência Intelectual/genética , Deficiência Intelectual/patologia , Mutação/genética , Transtornos do Neurodesenvolvimento/genética , Transtornos do Neurodesenvolvimento/patologia , Fenótipo , Distúrbios da Fala/genética , Distúrbios da Fala/patologia , Fatores de Transcrição/genéticaRESUMO
Hypokinetic dysarthria (HD) is a difficult-to-treat symptom affecting quality of life in patients with Parkinson's disease (PD). Levodopa may partially alleviate some symptoms of HD in PD, but the neural correlates of these effects are not fully understood. The aim of our study was to identify neural mechanisms by which levodopa affects articulation and prosody in patients with PD. Altogether 20 PD patients participated in a task fMRI study (overt sentence reading). Using a single dose of levodopa after an overnight withdrawal of dopaminergic medication, levodopa-induced BOLD signal changes within the articulatory pathway (in regions of interest; ROIs) were studied. We also correlated levodopa-induced BOLD signal changes with the changes in acoustic parameters of speech. We observed no significant changes in acoustic parameters due to acute levodopa administration. After levodopa administration as compared to the OFF dopaminergic condition, patients showed task-induced BOLD signal decreases in the left ventral thalamus (p = 0.0033). The changes in thalamic activation were associated with changes in pitch variation (R = 0.67, p = 0.006), while the changes in caudate nucleus activation were related to changes in the second formant variability which evaluates precise articulation (R = 0.70, p = 0.003). The results are in line with the notion that levodopa does not have a major impact on HD in PD, but it may induce neural changes within the basal ganglia circuitries that are related to changes in speech prosody and articulation.
Assuntos
Levodopa , Doença de Parkinson , Humanos , Levodopa/efeitos adversos , Doença de Parkinson/complicações , Doença de Parkinson/diagnóstico por imagem , Doença de Parkinson/tratamento farmacológico , Fala/fisiologia , Imageamento por Ressonância Magnética/métodos , Qualidade de Vida , Distúrbios da Fala/diagnóstico por imagem , Distúrbios da Fala/etiologia , Disartria/etiologia , Disartria/complicações , Antiparkinsonianos/efeitos adversosRESUMO
Auditory selective attention forms an important foundation of children's learning by enabling the prioritisation and encoding of relevant stimuli. It may also influence reading development, which relies on metalinguistic skills including the awareness of the sound structure of spoken language. Reports of attentional impairments and speech perception difficulties in noisy environments in dyslexic readers are also suggestive of the putative contribution of auditory attention to reading development. To date, it is unclear whether non-speech selective attention and its underlying neural mechanisms are impaired in children with dyslexia and to which extent these deficits relate to individual reading and speech perception abilities in suboptimal listening conditions. In this EEG study, we assessed non-speech sustained auditory selective attention in 106 7-to-12-year-old children with and without dyslexia. Children attended to one of two tone streams, detecting occasional sequence repeats in the attended stream, and performed a speech-in-speech perception task. Results show that when children directed their attention to one stream, inter-trial-phase-coherence at the attended rate increased in fronto-central sites; this, in turn, was associated with better target detection. Behavioural and neural indices of attention did not systematically differ as a function of dyslexia diagnosis. However, behavioural indices of attention did explain individual differences in reading fluency and speech-in-speech perception abilities: both these skills were impaired in dyslexic readers. Taken together, our results show that children with dyslexia do not show group-level auditory attention deficits but these deficits may represent a risk for developing reading impairments and problems with speech perception in complex acoustic environments. RESEARCH HIGHLIGHTS: Non-speech sustained auditory selective attention modulates EEG phase coherence in children with/without dyslexia Children with dyslexia show difficulties in speech-in-speech perception Attention relates to dyslexic readers' speech-in-speech perception and reading skills Dyslexia diagnosis is not linked to behavioural/EEG indices of auditory attention.
Assuntos
Dislexia , Percepção da Fala , Criança , Humanos , Leitura , Som , Fala , Distúrbios da Fala , FonéticaRESUMO
Human speech and language are among the most complex motor and cognitive abilities. The discovery of a mutation in the transcription factor FOXP2 in KE family members with speech disturbances has been a landmark example of the genetic control of vocal communication in humans. Cellular mechanisms underlying this control have remained unclear. By leveraging FOXP2 mutation/deletion mouse models, we found that the KE family FOXP2R553H mutation directly disables intracellular dynein-dynactin 'protein motors' in the striatum by induction of a disruptive high level of dynactin1 that impairs TrkB endosome trafficking, microtubule dynamics, dendritic outgrowth and electrophysiological activity in striatal neurons alongside vocalization deficits. Dynactin1 knockdown in mice carrying FOXP2R553H mutations rescued these cellular abnormalities and improved vocalization. We suggest that FOXP2 controls vocal circuit formation by regulating protein motor homeostasis in striatal neurons, and that its disruption could contribute to the pathophysiology of FOXP2 mutation/deletion-associated speech disorders.
Assuntos
Corpo Estriado , Fala , Humanos , Camundongos , Animais , Fala/fisiologia , Corpo Estriado/metabolismo , Neurônios/metabolismo , Neostriado/metabolismo , Distúrbios da Fala , Mutação/genética , Fatores de Transcrição Forkhead/genética , Fatores de Transcrição Forkhead/metabolismo , Vocalização Animal/fisiologiaRESUMO
Automatic speech assessments have the potential to dramatically improve ALS clinical practice and facilitate patient stratification for ALS clinical trials. Acoustic speech analysis has demonstrated the ability to capture a variety of relevant speech motor impairments, but implementation has been hindered by both the nature of lab-based assessments (requiring travel and time for patients) and also by the opacity of some acoustic feature analysis methods. These challenges and others have obscured the ability to distinguish different ALS disease stages/severities. Validation of automated acoustic analysis tools could enable detection of early signs of ALS, and these tools could be deployed to screen and monitor patients without requiring clinic visits. Here, we sought to determine whether acoustic features gathered using an automated assessment app could detect ALS as well as different levels of speech impairment severity resulting from ALS. Speech samples (readings of a standardized, 99-word passage) from 119 ALS patients with varying degrees of disease severity as well as 22 neurologically healthy participants were analyzed, and 53 acoustic features were extracted. Patients were stratified into early and late stages of disease (ALS-early/ALS-E and ALS-late/ALS-L) based on the ALS Functional Ratings Scale-Revised bulbar score (FRS-bulb) (median [interquartile range] of FRS-bulbar scores: 11[3]). The data were analyzed using a sparse Bayesian logistic regression classifier. It was determined that the current relatively small set of acoustic features could distinguish between ALS and controls well (area under receiver-operating characteristic curve/AUROC = 0.85), that the ALS-E patients could be separated well from control participants (AUROC = 0.78), and that ALS-E and ALS-L patients could be reasonably separated (AUROC = 0.70). These results highlight the potential for automated acoustic analyses to detect and stratify ALS.
Assuntos
Esclerose Lateral Amiotrófica , Humanos , Esclerose Lateral Amiotrófica/diagnóstico , Teorema de Bayes , Fala , Distúrbios da Fala/diagnóstico , Curva ROCRESUMO
BACKGROUND: Heterozygous disruptions of FOXP2 were the first identified molecular cause for severe speech disorder: childhood apraxia of speech (CAS), and yet few cases have been reported, limiting knowledge of the condition. METHODS: Here we phenotyped 28 individuals from 17 families with pathogenic FOXP2-only variants (12 loss-of-function, five missense variants; 14 males; aged 2 to 62 years). Health and development (cognitive, motor, social domains) were examined, including speech and language outcomes with the first cross-linguistic analysis of English and German. RESULTS: Speech disorders were prevalent (23/25, 92%) and CAS was most common (22/25, 88%), with similar speech presentations across English and German. Speech was still impaired in adulthood, and some speech sounds (eg, 'th', 'r', 'ch', 'j') were never acquired. Language impairments (21/25, 84%) ranged from mild to severe. Comorbidities included feeding difficulties in infancy (10/26, 38%), fine (13/26, 50%) and gross (13/26, 50%) motor impairment, anxiety (5/27, 19%), depression (6/27, 22%) and sleep disturbance (10/24, 42%). Physical features were common (22/27, 81%) but with no consistent pattern. Cognition ranged from average to mildly impaired and was incongruent with language ability; for example, seven participants with severe language disorder had average non-verbal cognition. CONCLUSIONS: Although we identify an increased prevalence of conditions like anxiety, depression and sleep disturbance, we confirm that the consequences of FOXP2 dysfunction remain relatively specific to speech disorder, as compared with other recently identified monogenic conditions associated with CAS. Thus, our findings reinforce that FOXP2 provides a valuable entry point for examining the neurobiological bases of speech disorder.
Assuntos
Apraxias , Transtornos da Linguagem , Masculino , Humanos , Criança , Distúrbios da Fala/genética , Transtornos da Linguagem/epidemiologia , Transtornos da Linguagem/genética , Fala , Apraxias/genética , Mutação de Sentido Incorreto/genética , Fatores de Transcrição Forkhead/genéticaRESUMO
Perturbation of the excitation/inhibition (E/I) balance leads to neurodevelopmental diseases including to autism spectrum disorders, intellectual disability, and epilepsy. Loss-of-function mutations in the DYRK1A gene, located on human chromosome 21 (Hsa21,) lead to an intellectual disability syndrome associated with microcephaly, epilepsy, and autistic troubles. Overexpression of DYRK1A, on the other hand, has been linked with learning and memory defects observed in people with Down syndrome (DS). Dyrk1a is expressed in both glutamatergic and GABAergic neurons, but its impact on each neuronal population has not yet been elucidated. Here we investigated the impact of Dyrk1a gene copy number variation in glutamatergic neurons using a conditional knockout allele of Dyrk1a crossed with the Tg(Camk2-Cre)4Gsc transgenic mouse. We explored this genetic modification in homozygotes, heterozygotes and combined with the Dp(16Lipi-Zbtb21)1Yey trisomic mouse model to unravel the consequence of Dyrk1a dosage from 0 to 3, to understand its role in normal physiology, and in MRD7 and DS. Overall, Dyrk1a dosage in postnatal glutamatergic neurons did not impact locomotor activity, working memory or epileptic susceptibility, but revealed that Dyrk1a is involved in long-term explicit memory. Molecular analyses pointed at a deregulation of transcriptional activity through immediate early genes and a role of DYRK1A at the glutamatergic post-synapse by deregulating and interacting with key post-synaptic proteins implicated in mechanism leading to long-term enhanced synaptic plasticity. Altogether, our work gives important information to understand the action of DYRK1A inhibitors and have a better therapeutic approach.
Assuntos
Transtorno Autístico/genética , Transtornos Cognitivos/genética , Síndrome de Down/genética , Dosagem de Genes , Ácido Glutâmico/metabolismo , Deficiência Intelectual/genética , Neurônios/metabolismo , Distúrbios da Fala/genética , Animais , Encéfalo/patologia , Proteína Quinase Tipo 2 Dependente de Cálcio-Calmodulina/metabolismo , Transtornos Cognitivos/complicações , Modelos Animais de Doenças , Síndrome de Down/complicações , Regulação da Expressão Gênica , Humanos , Camundongos , Camundongos Transgênicos , Proteômica/métodos , Transmissão Sináptica/genética , Transcrição GênicaRESUMO
In this study, a computer-driven, phoneme-agnostic method was explored for assessing speech disorders (SDs) in children, bypassing traditional labor-intensive phonetic transcription. Using the SpeechMark® automatic syllabic cluster (SC) analysis, which detects sequences of acoustic features that characterize well-formed syllables, 1952 American English utterances of 60 preschoolers were analyzed [16 with speech disorder present (SD-P) and 44 with speech disorder not present (SD-NP)] from two dialectal areas. A four-factor regression analysis evaluated the robustness of seven automated measures produced by SpeechMark® and their interactions. SCs significantly predicted SD status (p < 0.001). A secondary analysis using a generalized linear model with a negative binomial distribution evaluated the number of SCs produced by the groups. Results highlighted that children with SD-P produced fewer well-formed clusters [incidence rate ratio (IRR) = 0.8116, p ≤ 0.0137]. The interaction between speech group and age indicated that the effect of age on syllable count was more pronounced in children with SD-P (IRR = 1.0451, p = 0.0251), suggesting that even small changes in age can have a significant effect on SCs. In conclusion, speech status significantly influences the degree to which preschool children produce acoustically well-formed SCs, suggesting the potential for SCs to be speech biomarkers for SD in preschoolers.
Assuntos
Fonética , Acústica da Fala , Distúrbios da Fala , Medida da Produção da Fala , Humanos , Pré-Escolar , Masculino , Feminino , Medida da Produção da Fala/métodos , Distúrbios da Fala/fisiopatologia , Distúrbios da Fala/diagnóstico , Criança , Linguagem Infantil , Fatores EtáriosRESUMO
INTRODUCTION: Fistula formation and velopharyngeal insufficiency (VPI) are complications of cleft palate repair that often require surgical correction. The goal of the present study was to examine a single institution's experience with cleft palate repair with respect to fistula formation and need for surgery to correct velopharyngeal dysfunction. METHODS: Institutional review board approval was obtained. Patient demographics and operative details over a 10-year period were collected. Primary outcomes measured were development of fistula and need for surgery to correct VPI. Chi-square tests and independent t tests were utilized to determine significance (0.05). RESULTS: Following exclusion of patients without enough information for analysis, 242 patients were included in the study. Fistulas were reported in 21.5% of patients, and surgery to correct velopharyngeal dysfunction was needed in 10.7% of patients. Two-stage palate repair was associated with need for surgery to correct VPI (P = 0.014). Furlow palatoplasty was associated with decreased rate of fistula formation (P = 0.002) and decreased need for surgery to correct VPI (P = 0.014). CONCLUSION: This study reiterates much of the literature regarding differing cleft palate repair techniques. A 2-stage palate repair is often touted as having less growth restriction, but the present study suggests this may yield an increased need for surgery to correct VPI. Prior studies of Furlow palatoplasty have demonstrated an association with higher rates of fistula formation. The present study demonstrated a decreased rate of fistula formation with the Furlow technique, which may be due to the use of the Children's Hospital of Philadelphia modification. This study suggests clinically superior outcomes of the Furlow palatoplasty over other techniques.
Assuntos
Fissura Palatina , Complicações Pós-Operatórias , Insuficiência Velofaríngea , Humanos , Fissura Palatina/cirurgia , Masculino , Feminino , Insuficiência Velofaríngea/cirurgia , Insuficiência Velofaríngea/etiologia , Resultado do Tratamento , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/etiologia , Pré-Escolar , Lactente , Estudos Retrospectivos , Fístula Bucal/etiologia , Fístula Bucal/cirurgia , Procedimentos de Cirurgia Plástica/métodos , Procedimentos de Cirurgia Plástica/efeitos adversos , Criança , Seguimentos , Distúrbios da Fala/etiologia , AdolescenteRESUMO
BACKGROUND: Diadochokinetic (DDK) rate tasks are extensively used in the evaluation of speech disorders; however, it is unclear how the different types of speech stimuli affect DDK rate performance. AIMS: To investigate the effect of age, gender and type of stimuli (non-words versus real words) on the DDK rates in individuals across the lifespan and to provide normative data for Greek. Also to examine the discrimination ability of the speech DDK stimuli administered (non-words and real words) based on a dual DDK assessment protocol using a polytomous item response theory (IRT) model. METHODS & PROCEDURE: The participants were 1747 monolingual Greek speakers (376 children, aged 4-17 years; and 1371 adults, aged 18-90+ years). All participants had normal hearing acuity which allowed them to understand and follow instructions. Participants with a medical condition or a language disorder which would affect DDK rate performance were excluded from the study. The time-by-count method was used, and all participants had to repeat as accurately and fast as possible: (1) four disyllabic non-words (/'gaba/, /'taka/, /'kata/, /'baga/), (2) four disyllabic real words (/'kapa/, /'tapa/, /ka'la/, /'paka/) and (3) two trisyllabic non-words (/'pataka/, /'badaga/). All responses were recorded and the speech samples that did not include at least 5 s of correct repetitions were excluded from the analysis. OUTCOMES & RESULTS: Age affected significantly DDK rates with performance increasing gradually until approximately the age of 40 and then gradually decreasing. Gender had no effect. Overall, there was a significant advantage of disyllabic real word stimuli over disyllabic non-word stimuli and of trisyllabic non-word stimuli over disyllabic non-word stimuli on DDK rates performance. IRT analysis suggested that the data fit the polytomous model reasonably well and all DDK stimuli (real words and non-words) showed a strong relationship (loadings > 0.50) with the latent trait. CONCLUSIONS & IMPLICATIONS: The current study complements prior research which supports that age and type of stimuli significantly affect DDK rates performance. It is the first study, that testifies to the benefit of real-word stimuli over non-word stimuli on DDK rates across the lifespan in a large representative sample. The implementation of IRT analysis provides empirical evidence about the discrimination ability of the DDK stimuli administered and confirms the reliability of this dual DDK assessment protocol. These findings are valuable for clinicians who work with motor speech disorders. WHAT THIS PAPER ADDS: What is already known on this subject Age, type of stimuli (real words versus non-words) and language significantly affect DDK rates performance. Current research strongly suggests the administration of language-specific norms since language-dependent features seem to have a noteworthy effect on the DDK rates, but scarce evidence exists about the discriminatory ability of the DDK speech stimuli commonly administered. What this study adds to the existing knowledge Conflicting findings have been reported about the effect of different types of DDK speech stimuli (real words and non-words) but no study to date has evaluated their discriminatory abilities. The current study is the first to implement a polytomous IRT model to examine this issue. This is also the first study to attempt an investigation of the effect of types of stimuli (real words versus non-words) on a large representative sample across the lifespan (4-90+ years) and to provide normative data for Greek. What are the practical and clinical implications of this work? The present study offers concrete evidence about the advantage of real-word stimuli over non-word stimuli in Greek, as well as normative data for the Greek-speaking populations. Moreover, the IRT analysis testifies to the discriminatory ability of real-word and non-word stimuli affirming the reliability of the present dual DDK assessment protocol as a psychometrically sound measure of DDK ability. The above has significant value for clinicians who work with individuals with motor speech disorders as the protocol can help them with the diagnosis and differential diagnosis of motor speech disorders.
Assuntos
Idioma , Longevidade , Criança , Adulto , Humanos , Reprodutibilidade dos Testes , Fala , Distúrbios da FalaRESUMO
BACKGROUND: Maintenance of speech outcomes following speech-language therapy (SLT) in Parkinson's disease (PD) is an unmet expectation of people with PD (PWPD) and poorly defined in SLT practice. PD Check-In, a model for supported self-managed maintenance of speech following Lee Silverman Voice Treatment (LSVT) LOUD was investigated. AIMS: To investigate the impact of the semi-structured component of PD Check-In on the adoption of self-management concepts and behaviours and the identification of facilitators, barriers and strategies for speech maintenance by PWPD over 24 months post-treatment. METHODS AND PROCEDURE: Following LSVT LOUD, 16 PWPD participated in individual PD Check-In semi-structured discussions with a SLT at 6 and 12 weeks, and 6, 12 and 24 months post treatment. A two-stage qualitative content analysis was applied: directed content analysis using categories from the theoretical framework of PD Check-In followed by inductive content analysis to identify subcategories. OUTCOMES AND RESULTS: Statements from PWPD indicated adoption of seven concepts of self-management across participants and across time. Six concepts from the theoretical framework of PD Check-In (partnerships, self-reflection, maintenance barriers and facilitators, revision of LSVT LOUD skill, goal setting and maintenance strategies), and one new category, participation, emerged from the analysis. Self-reflection, maintenance facilitators and barriers and participation were most prevalent in discussions. PWPD identified facilitators, barriers and strategies for maintenance across time points. CONCLUSIONS AND IMPLICATIONS: Statements from PWPD indicated a positive impact of SLT-supported self-management of speech using self-tailored strategies for sustainable maintenance according to their individual circumstances and needs. WHAT THIS PAPER ADDS: What is already known on this subject People with Parkinson's disease (PWPD) have expressed their need for speech-language therapy (SLT) services that are accessible for the duration of the condition and responsive to their expectation of maintaining speech following treatment. Outcomes for maintenance of the treatment effect following Lee Silverman Voice Treatment (LSVT) LOUD are variable. What this paper adds to existing knowledge This study presents the outcomes of five PD Check-In interventions delivered in semi-structured discussions between PWPD and a SLT over 24 months following LSVT LOUD for the development of self-management skills and behaviours. PWPD adopted self-management positively using self-tailored strategies for sustainable maintenance according to their individual circumstances and needs. What are the potential or actual clinical implications of this work? PWPD responded positively to the individual development of self-management skills and behaviours over time. Individuality and flexible responsivity are features of PD Check-In which resonate with PWPD and speak to SLT supported self-managed maintenance of speech as a long-term model for PD.
Assuntos
Doença de Parkinson , Autogestão , Fonoterapia , Humanos , Masculino , Feminino , Idoso , Doença de Parkinson/terapia , Doença de Parkinson/reabilitação , Pessoa de Meia-Idade , Autogestão/métodos , Fonoterapia/métodos , Treinamento da Voz , Idoso de 80 Anos ou mais , Terapia da Linguagem/métodos , Distúrbios da Fala/terapia , Distúrbios da Fala/reabilitação , Pesquisa QualitativaRESUMO
This study aims to demonstrate the feasibility of using a new wireless electroencephalography (EEG)-electromyography (EMG) wearable approach to generate characteristic EEG-EMG mixed patterns with mouth movements in order to detect distinct movement patterns for severe speech impairments. This paper describes a method for detecting mouth movement based on a new signal processing technology suitable for sensor integration and machine learning applications. This paper examines the relationship between the mouth motion and the brainwave in an effort to develop nonverbal interfacing for people who have lost the ability to communicate, such as people with paralysis. A set of experiments were conducted to assess the efficacy of the proposed method for feature selection. It was determined that the classification of mouth movements was meaningful. EEG-EMG signals were also collected during silent mouthing of phonemes. A few-shot neural network was trained to classify the phonemes from the EEG-EMG signals, yielding classification accuracy of 95%. This technique in data collection and processing bioelectrical signals for phoneme recognition proves a promising avenue for future communication aids.
Assuntos
Eletroencefalografia , Eletromiografia , Processamento de Sinais Assistido por Computador , Tecnologia sem Fio , Humanos , Eletroencefalografia/métodos , Eletroencefalografia/instrumentação , Eletromiografia/métodos , Eletromiografia/instrumentação , Tecnologia sem Fio/instrumentação , Boca/fisiopatologia , Boca/fisiologia , Adulto , Masculino , Movimento/fisiologia , Redes Neurais de Computação , Distúrbios da Fala/diagnóstico , Distúrbios da Fala/fisiopatologia , Feminino , Dispositivos Eletrônicos Vestíveis , Aprendizado de MáquinaRESUMO
Importance: Children with speech and language difficulties are at risk for learning and behavioral problems. Objective: To review the evidence on screening for speech and language delay or disorders in children 5 years or younger to inform the US Preventive Services Task Force. Data Sources: PubMed/MEDLINE, Cochrane Library, PsycInfo, ERIC, Linguistic and Language Behavior Abstracts (ProQuest), and trial registries through January 17, 2023; surveillance through November 24, 2023. Study Selection: English-language studies of screening test accuracy, trials or cohort studies comparing screening vs no screening; randomized clinical trials (RCTs) of interventions. Data Extraction and Synthesis: Dual review of abstracts, full-text articles, study quality, and data extraction; results were narratively summarized. Main Outcomes and Measures: Screening test accuracy, speech and language outcomes, school performance, function, quality of life, and harms. Results: Thirty-eight studies in 41 articles were included (N = 9006). No study evaluated the direct benefits of screening vs no screening. Twenty-one studies (n = 7489) assessed the accuracy of 23 different screening tools that varied with regard to whether they were designed to be completed by parents vs trained examiners, and to screen for global (any) language problems vs specific skills (eg, expressive language). Three studies assessing parent-reported tools for expressive language skills found consistently high sensitivity (range, 88%-93%) and specificity (range, 88%-85%). The accuracy of other screening tools varied widely. Seventeen RCTs (n = 1517) evaluated interventions for speech and language delay or disorders, although none enrolled children identified by routine screening in primary care. Two RCTs evaluating relatively intensive parental group training interventions (11 sessions) found benefit for different measures of expressive language skills, and 1 evaluating a less intensive intervention (6 sessions) found no difference between groups for any outcome. Two RCTs (n = 76) evaluating the Lidcombe Program of Early Stuttering Intervention delivered by speech-language pathologists featuring parent training found a 2.3% to 3.0% lower proportion of syllables stuttered at 9 months compared with the control group when delivered in clinic and via telehealth, respectively. Evidence on other interventions was limited. No RCTs reported on the harms of interventions. Conclusions and Relevance: No studies directly assessed the benefits and harms of screening. Some parent-reported screening tools for expressive language skills had reasonable accuracy for detecting expressive language delay. Group parent training programs for speech delay that provided at least 11 parental training sessions improved expressive language skills, and a stuttering intervention delivered by speech-language pathologists reduced stuttering frequency.
Assuntos
Transtornos do Desenvolvimento da Linguagem , Programas de Rastreamento , Serviços Preventivos de Saúde , Criança , Humanos , Transtornos do Desenvolvimento da Linguagem/diagnóstico , Fala , Distúrbios da Fala/diagnóstico , Distúrbios da Fala/terapia , Gagueira/etiologia , Guias de Prática Clínica como Assunto , Lactente , Pré-EscolarRESUMO
OBJECTIVES: Deep brain stimulation (DBS) of the subthalamic nucleus (STN) for Parkinson's disease (PD) has an ambiguous relation to speech. Speech impairment can be a stimulation-induced side effect, and parkinsonian dysarthria can improve with STN-DBS. Owing to the lack of an up-to-date and evidence-based approach, DBS reprogramming for speech impairment is largely blind and greatly relies on the physician's experience. In this study, we aimed to establish an evidence- and experience-based algorithm for managing speech impairment in patients with PD treated with STN-DBS. MATERIALS AND METHODS: We performed a single-center retrospective study to identify patients with STN-DBS and speech impairment. Onset of speech impairment, lead localization, and assessment of DBS-induced nature of speech impairment were collected. When DBS settings were adjusted for improving speech, the magnitude and duration of effect were collected. We also performed a systematic literature review to identify studies describing the effects of parameter adjustments aimed at improving speech impairment in patients with PD receiving STN-DBS. RESULTS: In the retrospective study, 245 of 631 patients (38.8%) with STN-DBS had significant speech impairment. The probability of sustained marked improvement upon reprogramming was generally low (27.9%). In the systematic review, 23 of 662 identified studies were included. Only two randomized controlled trials have been performed, providing evidence for interleaving-interlink stimulation only. Considerable methodologic heterogeneity precluded the conduction of a meta-analysis. CONCLUSIONS: Speech impairment in STN-DBS for PD is frequent, but high-quality evidence regarding DBS parameter adjustments is scarce, and the probability of sustained improvement is low. To improve this outcome, we propose an evidence- and experience-based approach to address speech impairment in STN-DBS that can be used in clinical practice.
Assuntos
Estimulação Encefálica Profunda , Doença de Parkinson , Núcleo Subtalâmico , Humanos , Fala , Doença de Parkinson/complicações , Doença de Parkinson/terapia , Núcleo Subtalâmico/fisiologia , Estudos Retrospectivos , Distúrbios da Fala/etiologia , Distúrbios da Fala/terapiaRESUMO
This study aimed to explore the effects of an integrated phonological awareness intervention on phonological errors and phonemic awareness among young school-age children. Three children with at least one phonological error pattern and below-average phonological awareness skills participated in a non-concurrent multiple baseline single-subject design across participants' investigation. The integrated phonological awareness intervention consisted of completing blending and segmenting activities using 20 trained words, with a dose of 70 to 100 productions of the targeted phonological error pattern for 10, 30-minute sessions. All participants showed improvement in the primary dependent variable of percent consonants correct for their targeted error pattern for trained words. Results for percent phonemes correct showed gains for both blending and segmenting for all participants. All the participants transferred targeted skills to untrained words with their error pattern and generalized blending and segmenting to consonant-vowel-consonant words that did not contain their target error pattern in a pretest/posttest. Integrated phonological awareness intervention was an effective method of simultaneously improving speech production and phonemic awareness skills for young school-age children across 5 hours of treatment. The intervention was designed to be replicable by school-based speech-language pathologists seeking to efficiently support students with phonological errors and phonological awareness deficits.