Speech apraxia and oral apraxia: association or dissociation? A multivariate lesion-symptom mapping study in acute stroke patients.

The anatomical relationship between speech apraxia (SA) and oral apraxia (OA) is still unclear. To shed light on this matter we studied 137 patients with acute ischaemic left-hemisphere stroke and performed support vector regression-based, multivariate lesion-symptom mapping. Thirty-three patients presented with either SA or OA. These two symptoms mostly co-occurred (n = 28), except for few patients with isolated SA (n = 2) or OA (n = 3). All patient with either SA or OA presented with aphasia (p < 0.001) and these symptoms were highly associated with apraxia (p < 0.001). Co-occurring SA and OA were predominantly associated with insular lesions, while the insula was completely spared in the five patients with isolated SA or OA. Isolated SA occurred in case of frontal lesions (prefrontal gyrus and superior longitudinal fasciculus), while isolated OA occurred in case of either temporoparietal or striatocapsular lesions. Our study supports the notion of a predominant, but not exclusive, role of the insula in verbal and non-verbal oral praxis, and indicates that frontal regions may contribute exclusively to verbal oral praxis, while temporoparietal and striatocapsular regions contribute to non-verbal oral praxis. However, since tests for SA and OA so far intrinsically also investigate aphasia and apraxia, refined tests are warranted.

The Precentral Insular Cortical Network for Speech Articulation.

Apraxia of speech is a motor disorder characterized by the impaired ability to coordinate the sequential articulatory movements necessary to produce speech. The critical cortical area(s) involved in speech apraxia remain controversial because many of the previously reported cases had additional aphasic impairments, preventing localization of the specific cortical circuit necessary for the somatomotor execution of speech. Four patients with "pure speech apraxia" (i.e., who had no aphasic and orofacial motor impairments) are reported here. The critical lesion in all four patients involved, in the left hemisphere, the precentral gyrus of the insula (gyrus brevis III) and, to a lesser extent, the nearby areas with which it is strongly connected: the adjacent subcentral opercular cortex (part of secondary somatosensory cortex) and the most inferior part of the central sulcus where the orofacial musculature is represented. There was no damage to rostrally adjacent Broca's area in the inferior frontal gyrus. The present study demonstrates the critical circuit for the coordination of complex articulatory movements prior to and during the execution of the motor speech plans. Importantly, this specific cortical circuit is different from those that relate to the cognitive aspects of language production (e.g., Broca's area on the inferior frontal gyrus).

Amyotrophic lateral sclerosis with speech apraxia, predominant upper motor neuron signs, and prominent iron accumulation in the frontal operculum and precentral gyrus.

Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disease; transactivation response DNA-binding protein of 43 kDa (TDP-43) and iron accumulation are supposed to play a crucial role in the pathomechanism of the disease. Here, we report an unusual case of a patient with ALS who presented with speech apraxia as an initial symptom and upper motor neuron deficiencies. In the early clinical stages, single-photon emission computed tomography visualized focal hypoperfusion of the right frontal operculum, and magnetic resonance imaging identified a hypointense area along the frontal lobe on T2-weighted images. Neuropathological examination revealed that neuronophagia of Betz cells, gliosis, appearance of phosphorylated TDP-43 (p-TDP-43)-positive glial and neuronal inclusions, and prominent iron accumulation were frequently visible in the precentral gyrus. TDP-43 pathology and focal iron accumulation were also visible in the frontal operculum, but only a mild neuronal loss and a few p-TDP-43-positive neuronal and glial inclusions were found in the hypoglossal nucleus of the medulla oblongata and anterior horn of the spinal cord. Immunoblot analysis revealed an atypical band pattern for ALS. In our case, abnormal TDP-43 and iron accumulation might possibly have caused neurodegeneration of the frontal operculum, in tandem or independently; it might then have spread into the primary motor area. Our results suggest a causative association between TDP-43 and iron accumulation in the pathomechanisms of ALS presenting with upper motor neuron signs.

Missense variants in the chromatin remodeler CHD1 are associated with neurodevelopmental disability.

BACKGROUND: The list of Mendelian disorders of the epigenetic machinery has expanded rapidly during the last 5 years. A few missense variants in the chromatin remodeler CHD1 have been found in several large-scale sequencing efforts focused on uncovering the genetic aetiology of autism. OBJECTIVES: To explore whether variants in CHD1 are associated with a human phenotype. METHODS: We used GeneMatcher to identify other physicians caring for patients with variants in CHD1. We also explored the epigenetic consequences of one of these variants in cultured fibroblasts. RESULTS: Here we describe six CHD1 heterozygous missense variants in a cohort of patients with autism, speech apraxia, developmental delay and facial dysmorphic features. Importantly, three of these variants occurred de novo. We also report on a subject with a de novo deletion covering a large fraction of the CHD1 gene without any obvious neurological phenotype. Finally, we demonstrate increased levels of the closed chromatin modification H3K27me3 in fibroblasts from a subject carrying a de novo variant in CHD1. CONCLUSIONS: Our results suggest that variants in CHD1 can lead to diverse phenotypic outcomes; however, the neurodevelopmental phenotype appears to be limited to patients with missense variants, which is compatible with a dominant negative mechanism of disease.

A new MAPT deletion in a case of speech apraxia leading to corticobasal syndrome.

Speech apraxia is a disorder of speech motor planning/programming leading to slow rate, articulatory distortion, and distorted sound substitutions. We describe the clinical profile evolution of a patient presenting with slowly progressive isolated speech apraxia that eventually led to the diagnosis of corticobasal syndrome (CBS), supporting the evidence that this rare speech disorder can be the first presentation of CBS. Moreover, we found a novel variant in MAPT gene, which is hypothesized to be disease-causing mutation. These results underscore the importance of genetic analysis - particularly in selected atypical cases - for in vivo understanding of possible pathophysiological disease process.

APOE ε4 influences ß-amyloid deposition in primary progressive aphasia and speech apraxia.

BACKGROUND: Apolipoprotein E ε4 (APOE ε4) is a risk factor for ß-amyloid deposition in Alzheimer's disease dementia. Its influence on ß-amyloid deposition in speech and language disorders, including primary progressive aphasia (PPA), is unclear. METHODS: One hundred thirty subjects with PPA or progressive speech apraxia underwent APOE genotyping and Pittsburgh compound B (PiB) PET scanning. The relationship between APOE ε4 and PiB status, as well as severity and regional distribution of PiB, was assessed. RESULTS: Forty-five subjects had an APOE ε4 allele and 60 subjects were PiB-positive. The odds ratio for a subject with APOE ε4 being PiB-positive compared with a subject without APOE ε4 being PiB-positive was 10.2 (95% confidence interval, 4.4-25.5; P < .0001). The APOE ε4 allele did not influence regional PiB distribution or severity. CONCLUSION: APOE ε4 increases the risk of ß-amyloid deposition in PPA and progressive speech apraxia but does not influence regional ß-amyloid distribution or severity.

Depression and Apathy across Different Variants of Progressive Supranuclear Palsy.

BACKGROUND: Apathy and depression commonly occur in patients with progressive supranuclear palsy (PSP)-Richardson's syndrome variant; depression often requiring treatment. Little is known, however, about apathy and depression among other PSP variants. METHODS: We prospectively studied 97 newly diagnosed PSP patients. All were classified into a PSP variant using the 2017 Movement Disorder Society-PSP criteria and administered the Geriatric Depression and Apathy Evaluation Scales. Differences in apathy and depression frequency and severity across six variants, and secondarily across PSP-Richardson's syndrome, PSP-Cortical and PSP-Subcortical, were analyzed using ANCOVA and linear regression adjusting for disease severity. RESULTS: Depression (55%) was more common than apathy (12%). PSP-Speech/Language (PSP-SL) variant had the lowest depression frequency (13%) and lower depression scores than the other variants. No differences in apathy frequency/severity were identified. CONCLUSION: PSP-SL patients may have less depression compared to PSP-Richardson's syndrome and other PSP variants.

A Two-Base Pair Deletion in IQ Repeats in ASPM Underlies Microcephaly in a Pakistani Family.

Aims: Autosomal recessive primary microcephaly (MCPH) is a clinically rare and genetically highly heterogeneous developmental disorder. Biallelic variants in the abnormal spindle-like microcephaly-associated (ASPM) gene account for 40% to 68% of all MCPH cases. This study was designed to elucidate the genetic basis of MCPH in an extended family. To highlight recurrent mutations useful in implementing genetic testing programs, we further aimed to carry out a descriptive review of the reported ASPM mutations. Materials and Methods: A large inbred kindred with seven affected members was investigated, and detailed clinical and behavioral assessments were carried out. Single nucleotide polymorphism (SNP)-based homozygosity mapping and exome sequencing were performed. Results: Affected individuals had characteristic features, including small head, receding forehead, mild to moderate intellectual disability, developmental delay, short stature, apraxia, and behavioral anomalies. We mapped the disease gene locus and detected a rare frameshift deletion c.6854_6855del (p.(Leu2285GlnfsTer32)) in exon 18 of ASPM. A total of 215 mutations in ASPM have been reported in at least 453 families, nearly 50% of which are of Pakistani origin. These mutations can be classified as recurrent, founder or private in Pakistani and other populations. Conclusion: SNP-based homozygosity mapping and exome sequencing are essential in delineating the genetically distinct microcephaly types. The highlighted recurrent mutations in ASPM could be useful in implementing genetic testing programs for MCPH.

Intragenic CNTN4 copy number variants associated with a spectrum of neurobehavioral phenotypes.

Deletions and duplications involving the CNTN4 gene, which encodes for the contactin 4 protein, have been reported in children with autism spectrum disorder (ASD) and other neurodevelopmental phenotypes. In this study, we performed clinical and genetic characterization of three individuals from unrelated families with copy number variants (CNV) (one deletion and two duplications) within CNTN4. The patients exhibited cognitive delay (3/3), growth restriction (3/3), motor delay (2/3), and febrile seizure/epilepsy (2/3). In contrast to previous reports, all probands presented with speech apraxia or delay with no diagnosis of ASD. Parental studies for the proband with the deletion and one of the 2 probands with the duplication revealed paternal origin of the CNTN4 CNV. Interestingly, previously documented CNV involving this gene were mostly inherited from unaffected fathers, raising questions regarding reduced penetrance and potential parent-of-origin effect. Our findings are compared with previously reported patients and patients in the DECIPHER database. The speech impairment in the three probands suggests a role for CNTN4 in language development. We discuss potential factors contributing to phenotypic heterogeneity and reduced penetrance and attempt to find possible genotype-phenotype correlation. Larger cohorts are needed for comprehensive and unbiased phenotyping and molecular characterization that may lead to better understanding of the underlying mechanisms of reduced penetrance, variable expressivity, and potential parent-of-origin effect of copy number variants encompassing CNTN4.

Speech and Language Presentations of FTLD-TDP Type B Neuropathology.

Four right-handed patients who presented with an isolated impairment of speech or language had transactive response DNA-binding protein of 43 kDa (TDP-43) type B pathology. Comportment and pyramidal motor function were preserved at presentation. Three of the cases developed axial rigidity and oculomotor findings late in their course with no additional pyramidal or lower motor neuron impairments. However, in all 4 cases, postmortem examination disclosed some degree of upper and lower motor neuron disease (MND) pathology in motor cortex, brainstem, and spinal cord. Although TDP-43 type B pathology is commonly associated with MND and behavioral variant frontotemporal dementia, it is less recognized as a pathologic correlate of primary progressive aphasia and/or apraxia of speech as the presenting syndrome. These cases, taken together, contribute to the growing heterogeneity in clinical presentations associated with TDP pathology. Additionally, 2 cases demonstrated left anterior temporal lobe atrophy but without word comprehension impairments, shedding light on the relevance of the left temporal tip for single-word comprehension.

Cerebellar mutism syndrome.

Cerebellar mutism most commonly, but not exclusively, develops in children after surgery for midline cerebellar or intraventricular tumors in the posterior fossa, typically medulloblastoma. Cerebellar mutism syndrome (CMS) comprises a complex set of neurologic and neurocognitive signs and symptoms, the cardinal and central component of which is an initially profound but usually reversible speech disorder. As such, CMS is currently recognized as an extreme form of the so-called cerebellar cognitive affective syndrome (Schmahmann syndrome). The putative cause of CMS is a substantial surgical injury to the proximal components of the bilateral efferent cerebellar pathways, disrupting cerebellar input to the supratentorial brain. The resultant cerebellocerebral diaschisis may lead to supratentorial cortical perfusion depression with frontal predominance. The speech disorder is, therefore, likely an apraxia. As our understanding of the mechanism and the clinical spectrum of CMS evolves, clinically useful preoperative risk stratification schemes, adjustments to surgical strategies and techniques, and possible early therapeutic-rehabilitative measures are being sought and developed to reduce the burden of this severe and particularly handicapping chronic morbidity on affected individuals and their families.

L'apport critique de l'évaluation de la communication dans le diagnostic précoce de l'apraxie primaire progressive de la parole.

Primary progressive apraxia of speech (PPAoS) is a neurodegenerative syndrome characterized by speech apraxia at its onset; as it progresses, it often evolves into total mutism. Even though this syndrome is increasingly recognized, its early differential diagnostic is still complex. The objective of this study was to illustrate why a fine evaluation of speech and language is essential for the differential diagnosis of PPAoS. This longitudinal case study presents the progression of a PPAoS patient over a period of 5 years. Periodic neurological and speech-language assessments were carried out to follow the progression of neurological, memory, language and speech symptoms. The different diagnostic labels established over time were also reported. The evolution of the patient's communication profile was characterized by a preservation of language components and episodic memory, in parallel with a progressive deterioration of speech which gradually reduced intelligibility, and was associated with signs of spasticity, resulting in a complete anarthria. This case study sheds light upon the evolution of a patient with PPAoS. A better understanding of the clinical profile and progression of PPAoS is necessary in order to improve early diagnosis and adequate care for these patients.

Acquired epileptic opercular syndrome related to a heterozygous deleterious substitution in GRIN2A.

Epileptic encephalopathies with continuous spike-and-waves during sleep (CSWS) are characterized by cognitive or language impairment, and are occasionally associated with pathogenic variants of the GRIN2A gene. In these disorders, speech dysfunction could be either related to cerebral dysfunction caused by the GRIN2A deleterious variant or intense interictal epileptic activity. Here, we present a patient with apraxia of speech, clearly linked to severity of epilepsy, carrying a GRIN2A variant. A 6-year-old boy developed acute regression of expressive language following epileptic seizures, leading to complete mutism, at which time EEG revealed CSWS. MEG showed bilateral superior parietal and opercular independent CSWS onsets and PET with fluorodeoxyglucose demonstrated significant increase in relative glucose metabolism in bilateral superior parietal regions. Corticosteroids induced a regression of CSWS together with impressive improvement in speech abilities. This case supports the hypothesis of a triggering role for epileptic discharges in speech deterioration observed in children carrying a deleterious variant of GRIN2A. When classic antiepileptic drugs fail to control epileptic activity, corticosteroids should be considered. Multimodal functional neuroimaging suggests a role for opercular and superior parietal areas in acquired epileptic opercular syndrome. [Published with video sequences on www.epilepticdisorders.com].

Apraxia de fala Infantil em quadros com comorbidades / Apraxia de fala Infantil com comorbidades / Childhood apraxia of speech in cases with comorbidities

Introdução: O conhecimento sobre aquisição fonológica é balizador para a prática clínica na avaliação de transtornos fonológicos. Objetivo: Realizar revisão sistemática das publicações científicas sobre aquisição fonológica consonantal do Português Brasileiro (PB) por crianças com desenvolvimento linguístico típico. Metodologia: Foram selecionados descritores que atendiam à pergunta de pesquisa "qual a idade de aquisição fonológica consonantal típica de crianças falantes monolíngues do Português Brasileiro (PB)?" nas bases de dados Bireme, Pubmed, Scopus, Web of Science, Portal Periódicos Capes e Google Acadêmico, e literatura cinzenta. Critério de inclusão foi tratar-se de aquisição fonológica consonantal do PB por crianças. Excluíram-se estudos sobre aquisição de: vogais e/ou ditongos, domínios linguísticos que não fossem fonologia, segunda língua ou bilíngue, outra língua que não o PB, leitura, escrita, soletração, língua de sinais, também pesquisas somente com análise fonética, com dados de fala de crianças com alterações de fala, texto escrito, e linguagem não natural. Foram considerados os tipos de estudo, objetivos e indicadores de aquisição. Os estudos selecionados foram analisados via Iniciativa STROBE e Sistema GRADE. Resultados: Dos 1.381 estudos obtidos, selecionou-se 33. A aquisição fonológica consonantal foi identificada entre as idades um ano e quatro meses a sete anos, dependendo do fonema ou classe dos fonemas, apresentando grande variação entre indivíduos. A definição sobre aquisição convergiu para a frequência de 75% a 85% de produções corretas da consoante ou estrutura silábica. Conclusão: Constatou-se que a aquisição fonológica consonantal apresenta ampla variação entre indivíduos e entre diferentes consoantes e destas nas diversas estruturas silábicas.

Introduction: Knowledge about phonological acquisition is a guideline for clinical practice in the assessment of phonological disorders. Objective: To perform a systematic review of scientific publications on consonant phonological acquisition of Brazilian Portuguese (PB) by children with typical linguistic development. Methods: there were selected descriptors that meet the question "what is the age of typical consonant phonological acquisition in monolingual Brazilian Portuguese (BP) speakers?" in the databases Bireme, Pubmed, Scopus, Web of Science, Portal Periódicos Capes and Google Scholar, and gray literature. The inclusion criteria were that it was a consonant phonological acquisition of BP by children. Studies on the acquisition of: vowels and/or diphthongs, linguistic domains other than phonology, second language or bilingual, language other than BP, reading, writing, spelling, sign language, as well as research with phonetic analysis, speech data of children with speech disorders, about written text, and unnatural language were excluded. The types of study, objectives and acquisition indicators were considered. The selected studies were analyzed by the STROBE Initiative and the GRADE System. Results: Of the 1,381 studies obtained, 33 were selected. Consonant phonological acquisition was identified between one year and four months to seven years, depending on the phoneme or class of phonemes and showing great variation between individuals. The definition of acquisition converged to the frequency of 75% to 85% of correct productions of the consonant or syllabic structure. Conclusion: It was found that the consonant phonological acquisition presents a wide variation in individuals and between different consonants and of these in the different syllabic structures.

Introducción: El conocimiento sobre la adquisición fonológica es una guía para la práctica clínica en la evaluación de los trastornos fonológicos. Objetivo: Realizar una revisión sistemática de publicaciones científicas sobre la adquisición fonológica consonante del portugués brasileño (PB) por parte de niños con desarrollo lingüístico típico. Metodos: Se seleccionaron descriptores que cumplieron con la pregunta "¿Cuál es la edad de adquisición fonológica consonante típica en hablantes monolingües de portugués brasileño (BP)?" en las bases de datos Bireme, Pubmed, Scopus, Web of Science, Portal Periódicos Capes y Google Acadêmico, y literatura gris. Los criterios de inclusión fueron la adquisición fonológica consonante de PA por parte de los niños. Se excluyeron los estudios sobre la adquisición de: vocales y/o diptongos, dominios lingüísticos distintos de la fonología, segunda lengua o bilingüe, distintos de BP, lectura, escritura, ortografía, lengua de signos, también investigaciones con análisis fonético. Con datos de habla de niños con trastornos del habla, texto escrito y lenguaje antinatural. Se consideraron los tipos de estudio, objetivos e indicadores de adquisición. Los estudios seleccionados fueron analizados por la Iniciativa STROBE y el Sistema GRADE. Resultados: De los 1381 estudios obtenidos, se seleccionaron 33. Se identificó adquisición fonológica consonante entre las edades de un año y cuatro meses a siete años, dependiendo del fonema o clase de fonemas y mostrando gran variación entre individuos. La definición de adquisición convergió a la frecuencia del 75% al ​​85% de producciones correctas de la estructura consonante o silábica. Conclusión: Se encontró que la adquisición fonológica consonante presenta una amplia variación entre individuos y entre diferentes consonantes y de estas en las diferentes estructuras silábicas.

A Foxp2 Mutation Implicated in Human Speech Deficits Alters Sequencing of Ultrasonic Vocalizations in Adult Male Mice.

Development of proficient spoken language skills is disrupted by mutations of the FOXP2 transcription factor. A heterozygous missense mutation in the KE family causes speech apraxia, involving difficulty producing words with complex learned sequences of syllables. Manipulations in songbirds have helped to elucidate the role of this gene in vocal learning, but findings in non-human mammals have been limited or inconclusive. Here, we performed a systematic study of ultrasonic vocalizations (USVs) of adult male mice carrying the KE family mutation. Using novel statistical tools, we found that Foxp2 heterozygous mice did not have detectable changes in USV syllable acoustic structure, but produced shorter sequences and did not shift to more complex syntax in social contexts where wildtype animals did. Heterozygous mice also displayed a shift in the position of their rudimentary laryngeal motor cortex (LMC) layer-5 neurons. Our findings indicate that although mouse USVs are mostly innate, the underlying contributions of FoxP2 to sequencing of vocalizations are conserved with humans.

The Relationship Between Apraxia of Speech and Oral Apraxia: Association or Dissociation?

Acquired apraxia of speech (AOS) is a motor speech disorder that affects the implementation of articulatory gestures and the fluency and intelligibility of speech. Oral apraxia (OA) is an impairment of nonspeech volitional movement. Although many speakers with AOS also display difficulties with volitional nonspeech oral movements, the relationship between the 2 conditions is unclear. This study explored the relationship between speech and volitional nonspeech oral movement impairment in a sample of 50 participants with AOS. We examined levels of association and dissociation between speech and OA using a battery of nonspeech oromotor, speech, and auditory/aphasia tasks. There was evidence of a moderate positive association between the 2 impairments across participants. However, individual profiles revealed patterns of dissociation between the 2 in a few cases, with evidence of double dissociation of speech and oral apraxic impairment. We discuss the implications of these relationships for models of oral motor and speech control.

How much is a word? Predicting ease of articulation planning from apraxic speech error patterns.

BACKGROUND: According to intuitive concepts, 'ease of articulation' is influenced by factors like word length or the presence of consonant clusters in an utterance. Imaging studies of speech motor control use these factors to systematically tax the speech motor system. Evidence from apraxia of speech, a disorder supposed to result from speech motor planning impairment after lesions to speech motor centers in the left hemisphere, supports the relevance of these and other factors in disordered speech planning and the genesis of apraxic speech errors. Yet, there is no unified account of the structural properties rendering a word easy or difficult to pronounce. AIM: To model the motor planning demands of word articulation by a nonlinear regression model trained to predict the likelihood of accurate word production in apraxia of speech. METHOD: We used a tree-structure model in which vocal tract gestures are embedded in hierarchically nested prosodic domains to derive a recursive set of terms for the computation of the likelihood of accurate word production. The model was trained with accuracy data from a set of 136 words averaged over 66 samples from apraxic speakers. In a second step, the model coefficients were used to predict a test dataset of accuracy values for 96 new words, averaged over 120 samples produced by a different group of apraxic speakers. RESULTS: Accurate modeling of the first dataset was achieved in the training study (R(2)adj = .71). In the cross-validation, the test dataset was predicted with a high accuracy as well (R(2)adj = .67). The model shape, as reflected by the coefficient estimates, was consistent with current phonetic theories and with clinical evidence. In accordance with phonetic and psycholinguistic work, a strong influence of word stress on articulation errors was found. CONCLUSIONS: The proposed model provides a unified and transparent account of the motor planning requirements of word articulation.

Characteristics, Evaluation and Mechanism of Apraxia of Speech (review) / 中国康复理论与实践

@#Apraxia of speech (AOS) is a motor speech disorder presented with characteristic speech performance and related brain location.This article reviewed the characteristic speech performance of AOS and common assessments, discussed the mechanism and provided neurological bases of AOS in order to understand the relationship between speech performance and imaging.

Characteristics, Evaluation and Mechanism of Apraxia of Speech (review) / 中国康复理论与实践

Apraxia of speech (AOS) is a motor speech disorder presented with characteristic speech performance and related brain loca-tion. This article reviewed the characteristic speech performance of AOS and common assessments, discussed the mechanism and provided neurological bases of AOS in order to understand the relationship between speech performance and imaging.