Severe Speech Impairments Research Articles

Anesthetic Considerations for Angelman Syndrome: Case Series and Review of the Literature.

BackgroundAngelman syndrome is a rare neurodevelopmental disorder characterized by intellectual disability, severe speech impairment, ataxia, seizures, happy demeanor, distinctive craniofacial features, high vagal tone, and gamma-amino butyric acid receptor abnormalities. The aim of this report is to review our experience of patients with Angelman syndrome undergoing anesthetic management.MethodsWe retrospectively reviewed perioperative course of patients with Angelman syndrome who underwent procedures under anesthesia from 2000 to 2016.ResultsSix patients with Angelman syndrome underwent 18 procedures; 14 performed under general anesthesia, and 4 with monitored anesthetic care, many for minor procedures (e.g., dental and diagnostic). Five patients had profound developmental delay and were nonverbal and 4 of them had epilepsy. The perioperative courses were uncomplicated except a 2 year-old girl having an intraoperative bronchospasm, a 16 year-old girl requiring flumazenil administration, and 28 year-old man who was electively intubated with a videolaryngoscope because of airway management concerns. No patients were documented as having postoperative pain.ConclusionsAngelman syndrome patients often require anesthesia for relatively innocuous procedures, and their speech impairment and happy demeanor can confound postoperative pain assessment. Patients can have atypical responses to benzodiazepines. Craniofacial abnormalities can complicate airway management. Although not encountered in this series, anesthesiologists need to be aware that Angelman syndrome patients have developed malignant bradydysrhythmias while anesthetized.

An Active RBSE Framework to Generate Optimal Stimulus Sequences in a BCI for Spelling.

A class of brain computer interfaces (BCIs) employs noninvasive recordings of electroencephalography (EEG) signals to enable users with severe speech and motor impairments to interact with their environment and social network. For example, EEG based BCIs for typing popularly utilize event related potentials (ERPs) for inference. Presentation paradigm design in current ERP-based letter by letter typing BCIs typically query the user with an arbitrary subset characters. However, the typing accuracy and also typing speed can potentially be enhanced with more informed subset selection and flash assignment. In this manuscript, we introduce the active recursive Bayesian state estimation (active-RBSE) framework for inference and sequence optimization. Prior to presentation in each iteration, rather than showing a subset of randomly selected characters, the developed framework optimally selects a subset based on a query function. Selected queries are made adaptively specialized for users during each intent detection. Through a simulation-based study, we assess the effect of active-RBSE on the performance of a language-model assisted typing BCI in terms of typing speed and accuracy. To provide a baseline for comparison, we also utilize standard presentation paradigms namely, row and column matrix presentation paradigm and also random rapid serial visual presentation paradigms. The results show that utilization of active-RBSE can enhance the online performance of the system, both in terms of typing accuracy and speed. Moreover, we conduct real time experiments with human participants to study the human-in-the-loop effect on the performance of the proposed active-RBSE framework and consistent with the simulation results, the results of these experiments show improvement both in typing speed and accuracy.

Unbalanced translocation affecting the long arms of chromosomes 10 and 22 causes complex syndromes with very severe neuro-developmental delay, speech impairment, autistic behavior and epilepsy

Unbalanced translocation affecting the long arms of chromosomes 10 and 22 causes complex syndromes with very severe neuro-developmental delay, speech impairment, autistic behavior and epilepsy

Novel Unbalanced Translocations Affecting the Long Arms of Chromosomes 10 and 22 Cause Complex Syndromes with Very Severe Neurodevelopmental Delay, Speech Impairment, Autistic Behavior, and Epilepsy

Isolated abnormalities in terminal regions of chromosomes 10q and 22q were formerly described in patients affected by neuropsychological impairment, abnormal facies, and heterogeneous structural abnormalities of the body. Chromosomes 10q and 22q harbor important genes that play a major role in CNS development, like DOCK1 and SHANK3, and in overall body growth, like FGFR2 and HTRA1. By using clinical, neuroradiological, neurophysiological, and genetic assessment, we studied 3 siblings affected by 2 different forms of very severe neuropsychological impairment with structural physical abnormalities, epilepsy, and body overgrowth. The genetic analysis revealed 2 different unbalanced translocations t(10;22)(q26.13;q13.32) of genetic material between the long arms of chromosomes 10 and 22, deriving from a maternal balanced translocation. Consequences of the unbalanced translocation were the simultaneous partial monosomy of 10q26.13 to 10qter and partial trisomy of 22q13.32 to 22qter in 2 patients and the simultaneous trisomy distal q10 and monosomy distal q22 in 1 patient, respectively. To the best of our knowledge, we here describe for the first time a causal association between an unbalanced translocation t(10;22) affecting the long arms of both chromosomes 10 and 22 and a very severe neurodevelopmental delay in 3 siblings.

Mobile communication jacket for people with severe speech impairment

Purpose: Cerebral palsy is a movement disorder caused by damage to motor control areas of the developing brain during early childhood. Motor disorders can also affect the ability to produce clear speech and to communicate. The aim of this study was to develop and to test a prototype of an assistive tool with an embedded mobile communication device to support patients with severe speech impairments.Methods: A prototype was developed by equipping a cycling jacket with a display, a small keyboard, a LED and an alarm system, all controlled by a microcontroller. Functionality of the prototype was tested in six participants (aged 7–20 years) with cerebral palsy and global developmental disorder and three healthy persons. A patient questionnaire consisting of seven items was used as an evaluation tool.Results: A working prototype of the communication jacket was developed and tested. The questionnaire elicited positive responses from participants. Improvements to correct revealed weaknesses were proposed. Enhancements like voice output of pre-selected phrases and enlarged display were implemented.Conclusions: Integration in a jacket makes the system mobile and continuously available to the user. The communication jacket may be of great benefit to patients with motor and speech impairments.Implications for RehabilitationThe communication jacket developed can be easily used by people with movement and speech impairment.All technical components are integrated in a garment and do not have to be held with the hands or transported separately.The system is adaptable to individual use. Both expected and unexpected events can be dealt with, which contributes to the quality of life and self-fulfilment.

Unbalanced Translocation Affecting the Long Arms of Chromosome 10 and 22 Causes Complex Syndromes with Very Severe Neurodevelopmental Delay, Speech Impairment, Autistic Behavior, and Epilepsy

Unbalanced Translocation Affecting the Long Arms of Chromosome 10 and 22 Causes Complex Syndromes with Very Severe Neurodevelopmental Delay, Speech Impairment, Autistic Behavior, and Epilepsy

Heterozygous HNRNPU variants cause early onset epilepsy and severe intellectual disability.

Pathogenic variants in genes encoding subunits of the spliceosome are the cause of several human diseases, such as neurodegenerative diseases. The RNA splicing process is facilitated by the spliceosome, a large RNA-protein complex consisting of small nuclear ribonucleoproteins (snRNPs), and many other proteins, such as heterogeneous nuclear ribonucleoproteins (hnRNPs). The HNRNPU gene (OMIM *602869) encodes the heterogeneous nuclear ribonucleoprotein U, which plays a crucial role in mammalian development. HNRNPU is expressed in the fetal brain and adult heart, kidney, liver, brain, and cerebellum. Microdeletions in the 1q44 region encompassing HNRNPU have been described in patients with intellectual disability (ID) and other clinical features, such as seizures, corpus callosum abnormalities (CCA), and microcephaly. Recently, pathogenic HNRNPU variants were identified in large ID and epileptic encephalopathy cohorts. In this study, we provide detailed clinical information of five novels and review two of the previously published individuals with (likely) pathogenic de novo variants in the HNRNPU gene including three non-sense and two missense variants, one small intragenic deletion, and one duplication. The phenotype in individuals with variants in HNRNPU is characterized by early onset seizures (6/7), severe ID (6/6), severe speech impairment (6/6), hypotonia (6/7), and central nervous system (CNS) (5/6), cardiac (4/6), and renal abnormalities (3/4). In this study, we broaden the clinical and mutational HNRNPU-associated spectrum, and demonstrate that heterozygous HNRNPU variants cause epilepsy, severe ID with striking speech impairment and variable CNS, cardiac, and renal anomalies.

Clinical, imaging features and follow-up study of schizencephaly in 35 children

Objective To summarize the correlation between clinical manifestations and imaging characteristics of schizencephaly in order to provide a basis for the diagnosis and prognosis. Methods Thirty-five outpatients with schizencephaly diagnosed at Department of Pediatric Neurology of Henan Provincial People′s Hospital from January 2009 to May 2015 were retrospectively selected, and they were divided into different groups (patients with unilateral lesions or bilateral lesions) according to their cranial magnetic resonance imaging (MRI) features.The clinical manifestations were compared between different groups. Results Of 35 patients, 19 (54.3%) patients were male and 16 (45.7%) patients were female.Twenty-four patients were found with unilateral lesions(68.6%), including 16 cases (66.7%) with hemiparesis and 8 cases(33.3%) with no motor impairment.Mental retardation was observed in 8 patients (33.3%) and 6 patients (25.0%) showed speech impairment.Eleven patients were found the bilateral lesions (31.4%), including 5 patients (45.4%) with tetraparesis, 4 patients (36.4%) with hemiparesis, and 2 patients (18.2%) with no motor impairment.Mental retardation was observed in 9 patients (81.8%) and 9 patients (81.8%) showed speech impairment.There were significant differences in motor impairment, mental retardation and speech impairment between the unilateral lesion group and bilateral lesion group (Z=-2.40, P=0.002; χ2=7.09, P=0.012; χ2=9.94; P=0.003). Epileptic seizure occurred in 18 patients (51.4%). Binary Logistic regression analysis indicated that cortical dysplasia beyond the cleft and open-lip lesions were the major risk factors for seizures (OR=4.44, 2.73; P=0.005, 0.029). Imaging characteristics: there were closed-lip lesions in 10 patients (28.6%), open-lip lesions in 21 patients (60.0%) and open/closed-lip lesions in 4 patients (11.4%). Anatomic localization of all clefts was found in the frontal lobes in 19 patients (54.3%), in frontoparietal lobes in 11 patients (31.4%), in pa-rietal lobes in 2 patients (5.7%), and in occipital lobes in 3 patients (8.6%). After 1-6-year follow-up, 12 patients treated with antiepileptic drug were seizure - free (all with unilateral lesions), and 6 patients had refractory epilepsy (3 patients with bilateral lesions). Conclusions Schizencephaly is a rare structural disorder of cerebral cortical development.Those with bilateral lesions are usually manifested with severe motor, speech impairment and mental retardation and their prognosis is poor.Schizencephaly patients complicated with cortical dysplasia beyond the cleft or open-lip lesions are more easily attacked by seizures.MRI plays an important role in the diagnosis and prognosis judgment of schizencephaly. Key words: Schizencephaly; Epilepsy; Hemiplegia; Prognosis

Language Sampling for Preschoolers With Severe Speech Impairments.

The purposes of this investigation were to determine if measures such as mean length of utterance (MLU) and percentage of comprehensible words can be derived reliably from language samples of children with severe speech impairments and if such measures correlate with tools that measure constructs assumed to be related. Language samples of 15 preschoolers with severe speech impairments (but receptive language within normal limits) were transcribed independently by 2 transcribers. Nonparametric statistics were used to determine which measures, if any, could be transcribed reliably and to determine if correlations existed between language sample measures and standardized measures of speech, language, and cognition. Reliable measures were extracted from the majority of the language samples, including MLU in words, mean number of syllables per utterance, and percentage of comprehensible words. Language sample comprehensibility measures were correlated with a single word comprehensibility task. Also, language sample MLUs and mean length of the participants' 3 longest sentences from the MacArthur-Bates Communicative Development Inventory (Fenson et al., 2006) were correlated. Language sampling, given certain modifications, may be used for some 3-to 5-year-old children with normal receptive language who have severe speech impairments to provide reliable expressive language and comprehensibility information.

GNB5 mutation causes a novel neuropsychiatric disorder featuring attention deficit hyperactivity disorder, severely impaired language development and normal cognition.

BackgroundNeuropsychiatric disorders are common forms of disability in humans. Despite recent progress in deciphering the genetics of these disorders, their phenotypic complexity continues to be a major challenge. Mendelian neuropsychiatric disorders are rare but their study has the potential to unravel novel mechanisms that are relevant to their complex counterparts.ResultsIn an extended consanguineous family, we identified a novel neuropsychiatric phenotype characterized by severe speech impairment, variable expressivity of attention deficit hyperactivity disorder (ADHD), and motor delay. We identified the disease locus through linkage analysis on 15q21.2, and exome sequencing revealed a novel missense variant in GNB5. GNB5 encodes an atypical β subunit of the heterotrimeric GTP-binding proteins (Gβ5). Gβ5 is enriched in the central nervous system where it forms constitutive complexes with members of the regulator of G protein signaling family of proteins to modulate neurotransmitter signaling that affects a number of neurobehavioral outcomes. Here, we show that the S81L mutant form of Gβ5 has significantly impaired activity in terminating responses that are elicited by dopamine.ConclusionsWe demonstrate that these deficits originate from the impaired expression of the mutant Gβ5 protein, resulting in the decreased ability to stabilize regulator of G protein signaling complexes. Our data suggest that this novel neuropsychiatric phenotype is the human equivalent of Gnb5 deficiency in mice, which manifest motor deficits and hyperactivity, and highlight a critical role of Gβ5 in normal behavior as well as language and motor development in humans.Electronic supplementary materialThe online version of this article (doi:10.1186/s13059-016-1061-6) contains supplementary material, which is available to authorized users.

From Cortical and Subcortical Grey Matter Abnormalities to Neurobehavioral Phenotype of Angelman Syndrome: A Voxel-Based Morphometry Study.

Angelman syndrome (AS) is a rare neurogenetic disorder due to loss of expression of maternal ubiquitin-protein ligase E3A (UBE3A) gene. It is characterized by severe developmental delay, speech impairment, movement or balance disorder and typical behavioral uniqueness. Affected individuals show normal magnetic resonance imaging (MRI) findings, although mild dysmyelination may be observed. In this study, we adopted a quantitative MRI analysis with voxel-based morphometry (FSL-VBM) method to investigate disease-related changes in the cortical/subcortical grey matter (GM) structures. Since 2006 to 2013 twenty-six AS patients were assessed by our multidisciplinary team. From those, sixteen AS children with confirmed maternal 15q11-q13 deletions (mean age 7.7 ± 3.6 years) and twenty-one age-matched controls were recruited. The developmental delay and motor dysfunction were assessed using Bayley III and Gross Motor Function Measure (GMFM). Principal component analysis (PCA) was applied to the clinical and neuropsychological datasets. High-resolution T1-weighted images were acquired and FSL-VBM approach was applied to investigate differences in the local GM volume and to correlate clinical and neuropsychological changes in the regional distribution of GM. We found bilateral GM volume loss in AS compared to control children in the striatum, limbic structures, insular and orbitofrontal cortices. Voxel-wise correlation analysis with the principal components of the PCA output revealed a strong relationship with GM volume in the superior parietal lobule and precuneus on the left hemisphere. The anatomical distribution of cortical/subcortical GM changes plausibly related to several clinical features of the disease and may provide an important morphological underpinning for clinical and neurobehavioral symptoms in children with AS.

Speech effects of Hawley and vacuum-formed retainers by acoustic analysis: A single-center randomized controlled trial

To investigate the effects of alteration on speech articulation of adult patients between Hawley retainers and vacuum-formed retainers by an objective acoustic analysis of vowels and voiceless fricatives. Twenty adults, aged 19.0-29.0 years, who had just finished active orthodontic treatment were included in this study. They were divided into a Hawley retainer group and a vacuum-formed retainer group by sortation randomization method. The assessment of speech sounds was performed objectively using acoustic analysis before and after retainer application at the following time points: before wearing (T0), immediately after wearing (T1), and at 24 hours (T2), 1 week (T3), 1 month (T4), and 3 months (T5). The production of /з:/, /i:/, /f/, /θ/, /s/, and /∫/ sounds for the Hawley retainer group and /i:/, /θ/, /s/, and /∫/ sounds for the vacuum-formed retainer group showed severe speech impairment according to acoustic analysis (P < .05). A comparison of the Hawley retainer group with the vacuum-formed retainer group revealed that the performance of /i:/, /f/, and /s/ sounds were significantly different (P < .05). Although sound distortion could be found in both the Hawley retainer group and the vacuum-formed retainer group, changes in articulation were more obvious in the Hawley retainer group.

A novel homozygous splice site mutation in NALCN identified in siblings with cachexia, strabismus, severe intellectual disability, epilepsy and abnormal respiratory rhythm

We studied three siblings, born to consanguineous parents who presented with severe intellectual disability, cachexia, strabismus, seizures and episodes of abnormal respiratory rhythm. Whole exome sequencing led to identification of a novel homozygous splice site mutation, IVS29-1G > A in the NALCN gene, that resulted in aberrant transcript in the patients. NALCN encodes a voltage-independent cation channel, involved in regulation of neuronal excitability. Three homozygous mutations in the NALCN gene were previously identified in only eight patients with severe hypotonia, speech impairment, cognitive delay, constipation and Infantile–Neuroaxonal-dystrophy- like symptoms. Our patients broaden the clinical spectrum associated with recessive mutations in NALCN, featuring also disrupted respiratory rhythm mimicking homozygous Nalcn knockout mice.

REHABILITATION OF PATIENTS WITH SPEECH DISORDERS OCCURRING FROM POSTERIOR CORTICAL LESIONS

Актуальность. Накопившиеся в последнее время научные данные о механизмах компенсации у больных с последствиями нарушения мозгового кровообращения позволяют пересмотреть традиционные методики восстановления афазии.

Soliciting BCI user experience feedback from people with severe speech and physical impairments

Brain–computer interface (BCI) researchers have shown increasing interest in soliciting user experience (UX) feedback, but the severe speech and physical impairments (SSPI) of potential users create barriers to effective implementation with existing feedback instruments. This article describes augmentative and alternative communication (AAC)-based techniques for obtaining feedback from this population, and presents results from administration of a modified questionnaire to 12 individuals with SSPI after trials with a BCI spelling system. The proposed techniques facilitated successful questionnaire completion and provision of narrative feedback for all participants. Questionnaire administration required less than 5 minutes and minimal effort from participants. Results indicated that individual users may have very different reactions to the same system, and that ratings of workload and comfort provide important information not available through objective performance measures. People with SSPI are critical stakeholders in the future development of BCI, and appropriate adaptation of feedback questionnaires and administration techniques allows them to participate in shaping this assistive technology.

Prevalence of Creatine Deficiency Syndromes in Children With Nonsyndromic Autism.

Creatine deficiency may play a role in the neurobiology of autism and may represent a treatable cause of autism. The goal of the study was to ascertain the prevalence of creatine deficiency syndromes (CDSs) in children with autism spectrum disorder (ASD). In a prospective multicenter study, 443 children were investigated after a confirmed diagnosis of ASD. Random spot urine screening for creatine metabolites (creatine, guanidinoacetate, creatinine, and arginine) with liquid chromatography-tandem mass spectrometry and second-tier testing with high-performance liquid chromatography methodology was followed by recall testing in 24-hour urines and confirmatory testing by Sanger-based DNA sequencing of GAMT, GATM, and SLC6A8 genes. Additional diagnostic tests included plasma creatine metabolites and in vivo brain proton magnetic resonance spectroscopy. The creatine metabolites in spot urine in the autism group were compared with 128 healthy controls controlled for age. In 443 subjects with ASD investigated for CDS, we had 0 events (event: 0, 95% confidence interval 0-0.0068), therefore with 95% confidence the prevalence of CDS is <7 in 1000 children with ASD. The autism and control groups did not vary in terms of creatine metabolites (P > .0125) in urine. Our study revealed a very low prevalence of CDS in children with nonsyndromic ASD and no obvious association between creatine metabolites and autism. Unlike our study population, we expect more frequent CDS among children with severe developmental delay, speech impairment, seizures, and movement disorders in addition to impairments in social communication, restricted interests, and repetitive behaviors.

The Effects of Home-Based Literacy Activities on the Communication of Students with Severe Speech and Motor Impairments

This study examined the effects of using sensory, augmentative, and alternative communication (AAC), and supportive communication strategies on the rate and type of communication used by three students with severe speech and motor impairments (SSMI). Using a multiple baseline across behaviour design with sensory and AAC intervention phases, students were paired with a family member during shared reading activities using familiar and unfamiliar storybooks in their homes. All reading activities were video-recorded for analysis. Examination of recorded readings revealed that students demonstrated increases in their overall rates of communication. Further, these students successfully integrated communication devices into the reading process. The results suggest that students with severe disabilities can benefit from these forms of literacy strategies to increase their participation in reading tasks. Implications for research and practice are discussed.

De Novo Mutations in CHAMP1 Cause Intellectual Disability with Severe Speech Impairment

CHAMP1 encodes a protein with a function in kinetochore-microtubule attachment and in the regulation of chromosome segregation, both of which are known to be important for neurodevelopment. By trio whole-exome sequencing, we have identified de novo deleterious mutations in CHAMP1 in five unrelated individuals affected by intellectual disability with severe speech impairment, motor developmental delay, muscular hypotonia, and similar dysmorphic features including short philtrum and a tented upper and everted lover lip. In addition to two frameshift and one nonsense mutations, we found an identical nonsense mutation, c.1192C>T (p.Arg398*), in two affected individuals. All mutations, if resulting in a stable protein, are predicted to lead to the loss of the functionally important zinc-finger domains in the C terminus of the protein, which regulate CHAMP1 localization to chromosomes and the mitotic spindle, thereby providing a mechanistic understanding for their pathogenicity. We thus establish deleterious de novo mutations in CHAMP1 as a cause of intellectual disability.

A humanized version of Foxp2 does not affect ultrasonic vocalization in adult mice.

The transcription factor FOXP2 has been linked to severe speech and language impairments in humans. An analysis of the evolution of the FOXP2 gene has identified two amino acid substitutions that became fixed after the split of the human and chimpanzee lineages. Studying the functional consequences of these two substitutions in the endogenous Foxp2 gene of mice showed alterations in dopamine levels, striatal synaptic plasticity, neuronal morphology and cortico-striatal-dependent learning. In addition, ultrasonic vocalizations (USVs) of pups had a significantly lower average pitch than control littermates. To which degree adult USVs would be affected in mice carrying the 'humanized' Foxp2 variant remained unclear. In this study, we analyzed USVs of 68 adult male mice uttered during repeated courtship encounters with different females. Mice carrying the Foxp2(hum/hum) allele did not differ significantly in the number of call elements, their element structure or in their element composition from control littermates. We conclude that neither the structure nor the usage of USVs in adult mice is affected by the two amino acid substitutions that occurred in FOXP2 during human evolution. The reported effect for pup vocalization thus appears to be transient. These results are in line with accumulating evidence that mouse USVs are hardly influenced by vocal learning. Hence, the function and evolution of genes that are necessary, but not sufficient for vocal learning in humans, must be either studied at a different phenotypic level in mice or in other organisms.

Language Development of Individuals Who Require Aided Communication: Reflections on State of the Science and Future Research Directions

Language acquisition theories differ in the importance they assign to production as a learning mechanism. This review summarizes some of the theoretical issues linked to this debate and considers their implications for children with severe speech and physical impairments. The unique aspects of the language-learning contexts of these children are explored. Drawing largely on papers published within the journal Augmentative and Alternative Communication, this review summarizes features of language development that have been described over the past 3 decades and considers how these findings might illuminate our understanding of language development across both spoken and aided modalities. Implications for assessment, intervention and for further research are suggested.