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Applied Neuropsychology. Adult 2024Verbal and oral apraxia are two possible consequences of stroke. It seems that there are not sufficient studies regarding the frequency of these disorders. This study...
Verbal and oral apraxia are two possible consequences of stroke. It seems that there are not sufficient studies regarding the frequency of these disorders. This study aimed to evaluate the frequency of Verbal and oral apraxia. In addition, the relationship between apraxia and some variables such as age, gender, and education, as well as the relationship between types of apraxia with each other, and damaged areas of the brain in apraxia of the oral system in Persian-speaking patients with stroke were studied. In this descriptive-analytical study, 42 patients participated using the convenient sampling method. Verbal and oral apraxia were assessed using the oral and verbal apraxia tasks for adults test. Data were analyzed using independent t-test, Chi-square, and Fisher's exact test. The frequency of patients with oral apraxia was 35.7%, those with verbal apraxia was 2.3%, and the combination of both verbal and oral apraxia was 4.7%. People with apraxia were significantly older than those without apraxia. There was not any significant relationship between apraxia and gender, apraxia and education, and oral apraxia with verbal apraxia ( < 0.05). The present study's findings showed the high frequency of post-stroke apraxia and the high rate of its incidence with age.
Topics: Adult; Humans; Apraxias; Stroke; Brain; Risk Factors
PubMed: 34726969
DOI: 10.1080/23279095.2021.1993225 -
Frontiers in Aging Neuroscience 2023Ataxia with oculomotor apraxia type 1 (AOA1) is a progressive neurodegenerative disorder characterized by a gradual loss of coordination of hand movements, speech, and...
Ataxia with oculomotor apraxia type 1 (AOA1) is a progressive neurodegenerative disorder characterized by a gradual loss of coordination of hand movements, speech, and eye movements. AOA1 is caused by an inactivation mutation in the gene. APTX resolves abortive DNA ligation intermediates. APTX deficiency may lead to the accumulation of 5'-AMP termini, especially in the mitochondrial genome. The consequences of APTX deficiency includes impaired mitochondrial function, increased DNA single-strand breaks, elevated reactive oxygen species production, and altered mitochondrial morphology. All of these processes can cause misplacement of nuclear and mitochondrial DNA, which can activate innate immune sensors to elicit an inflammatory response. This study explores the impact of APTX knockout in microglial cells, the immune cells of the brain. RNA-seq analysis revealed significant differences in the transcriptomes of wild-type and APTX knockout cells, especially in response to viral infections and innate immune pathways. Specifically, genes and proteins involved in the cGAS-STING and RIG-I/MAVS pathways were downregulated in APTX knockout cells, which suggests an impaired immune response to cytosolic DNA and RNA. The clinical relevance of these findings was supported by analyzing publicly available RNA-seq data from AOA1 patient cell lines. Comparisons between APTX-deficient patient cells and healthy control cells also revealed altered immune responses and dysregulated DNA- and RNA-sensing pathways in the patient cells. Overall, this study highlights the critical role of APTX in regulating innate immunity, particularly in DNA- and RNA-sensing pathways. Our findings contribute to a better understanding of the underlying molecular mechanisms of AOA1 pathology and highlights potential therapeutic targets for this disease.
PubMed: 38161589
DOI: 10.3389/fnagi.2023.1290681 -
Brain : a Journal of Neurology Jan 2024Despite human's praxis abilities are unique among primates, comparative observations suggest that these cognitive motor skills could have emerged from exploitation and...
Despite human's praxis abilities are unique among primates, comparative observations suggest that these cognitive motor skills could have emerged from exploitation and adaptation of phylogenetically older building blocks, namely the parieto-frontal networks subserving prehension and manipulation. Within this framework, investigating to which extent praxis and prehension-manipulation overlap and diverge within parieto-frontal circuits could help in understanding how human cognition shapes hand actions. This issue has never been investigated by combining lesion mapping and direct electrophysiological approaches in neurosurgical patients. To this purpose, 79 right-handed left-brain tumour patient candidates for awake neurosurgery were selected based on inclusion criteria. First, a lesion mapping was performed in the early postoperative phase to localize the regions associated with an impairment in praxis (imitation of meaningless and meaningful intransitive gestures) and visuo-guided prehension (reaching-to-grasping) abilities. Then, lesion results were anatomically matched with intraoperatively identified cortical and white matter regions, whose direct electrical stimulation impaired the Hand Manipulation Task. The lesion mapping analysis showed that prehension and praxis impairments occurring in the early postoperative phase were associated with specific parietal sectors. Dorso-mesial parietal resections, including the superior parietal lobe and precuneus, affected prehension performance, while resections involving rostral intraparietal and inferior parietal areas affected praxis abilities (covariate clusters, 5000 permutations, cluster-level family-wise error correction P < 0.05). The dorsal bank of the rostral intraparietal sulcus was associated with both prehension and praxis (overlap of non-covariate clusters). Within praxis results, while resection involving inferior parietal areas affected mainly the imitation of meaningful gestures, resection involving intraparietal areas affected both meaningless and meaningful gesture imitation. In parallel, the intraoperative electrical stimulation of the rostral intraparietal and the adjacent inferior parietal lobe with their surrounding white matter during the hand manipulation task evoked different motor impairments, i.e. the arrest and clumsy patterns, respectively. When integrating lesion mapping and intraoperative stimulation results, it emerges that imitation of praxis gestures first depends on the integrity of parietal areas within the dorso-ventral stream. Among these areas, the rostral intraparietal and the inferior parietal area play distinct roles in praxis and sensorimotor process controlling manipulation. Due to its visuo-motor 'attitude', the rostral intraparietal sulcus, putative human homologue of monkey anterior intraparietal, might enable the visuo-motor conversion of the observed gesture (direct pathway). Moreover, its functional interaction with the adjacent, phylogenetic more recent, inferior parietal areas might contribute to integrate the semantic-conceptual knowledge (indirect pathway) within the sensorimotor workflow, contributing to the cognitive upgrade of hand actions.
Topics: Humans; Psychomotor Performance; Phylogeny; Cerebral Cortex; Parietal Lobe; Cognition; Brain Mapping; Magnetic Resonance Imaging; Gestures
PubMed: 37715997
DOI: 10.1093/brain/awad316 -
Journal of Speech, Language, and... May 2024The purposes of this review article were to provide an introduction to and "bird's-eye" overview of the current evidence base for treatment of childhood apraxia of...
PURPOSE
The purposes of this review article were to provide an introduction to and "bird's-eye" overview of the current evidence base for treatment of childhood apraxia of speech (CAS), identify some gaps and trends in this rapidly growing literature, and formulate some future research directions, in order to advance the evidence base and clinical practice for children with CAS.
METHOD
Following a brief introduction outlining important concepts, a narrative review of the CAS treatment literature is provided, and trends and future directions are identified based on this review. The review is organized around four fundamental treatment research questions: (a) "Does Treatment X work?", (b) "Does Treatment X work better than Treatment Y?", (c) "For whom does Treatment X work?", and (d) "What does 'work' mean, anyway?"
RESULTS
A wide range of CAS treatments with varying degrees of evidence for efficacy exists. Research is beginning to emerge that compares different treatments and seeks to determine optimal treatment parameters. Few studies to date have explored child-level predictors of treatment response, and the evidence base currently is limited in scope with respect to populations and outcomes studied.
CONCLUSIONS
A growing evidence base supports the efficacy of a number of treatments for CAS. However, many important gaps in the literature were identified that warrant redoubled and sustained research attention. Research is beginning to emerge that addresses treatment optimization, comparison, candidacy, and outcomes. Suggestions for future research are offered, and the concept of a hypothesized pathway was applied to CAS to illustrate how components of an intervention can effect change in a clinical goal and can help guide development and refinement of treatments for children with CAS.
PubMed: 38768073
DOI: 10.1044/2024_JSLHR-23-00233 -
American Journal of Speech-language... Aug 2023This exploratory study aimed to characterize motor speech impairments in a small sample of children with epilepsy, both with and without a known seizure etiology. A...
PURPOSE
This exploratory study aimed to characterize motor speech impairments in a small sample of children with epilepsy, both with and without a known seizure etiology. A secondary aim was to evaluate the validity of the Profile for Childhood Apraxia of speech and Dysarthria (ProCAD), a newly developed tool for differential diagnosis of childhood apraxia of speech and dysarthria.
METHOD
Thirteen children with seizure disorders completed a comprehensive speech and language assessment. Three expert speech-language pathologists rated the presence of auditory-perceptual features of motor speech impairment using the ProCAD. Motor speech features, diagnoses, and standardized test scores were compared between children with a known seizure etiology and children with idiopathic epilepsy.
RESULTS
Nine of the 13 children exhibited motor speech impairment; dysarthria was the most common diagnosis. Most children (11/13) exhibited language impairment. Group comparisons showed that children with a known seizure etiology had more atypical motor speech features and lower language scores than children with idiopathic seizures.
CONCLUSION
These preliminary findings suggest a high rate of motor speech impairment among children with epilepsy.
Topics: Child; Humans; Dysarthria; Speech; Speech Disorders; Apraxias; Epilepsy; Phenotype; Seizures
PubMed: 36827527
DOI: 10.1044/2022_AJSLP-22-00176 -
Neuropediatrics Dec 2023Childhood apraxia of speech (CAS) is a pediatric motor speech disorder. The genetic etiology of this complex neurological condition is not yet well understood, although...
Childhood apraxia of speech (CAS) is a pediatric motor speech disorder. The genetic etiology of this complex neurological condition is not yet well understood, although some genes have been linked to it. We describe the case of a boy with a severe and persistent motor speech disorder, consistent with CAS, and a coexisting language impairment.Whole exome sequencing in our case revealed a and splicing mutation in the gene.
Topics: Male; Child; Humans; Speech; Apraxias; Speech Disorders; Mutation; Exome Sequencing; Membrane Proteins; Tumor Suppressor Proteins
PubMed: 37549685
DOI: 10.1055/s-0043-1771033 -
Clinical Nuclear Medicine Feb 2024Corticobasal syndrome (CBS) is a neurodegeneration characterized by asymmetric parkinsonism, dystonia, myoclonus, and apraxia. In the early stage, CBS presents with...
BACKGROUND
Corticobasal syndrome (CBS) is a neurodegeneration characterized by asymmetric parkinsonism, dystonia, myoclonus, and apraxia. In the early stage, CBS presents with asymmetric parkinsonism and cortical symptoms (apraxia and alien hand), and neuroimaging finding is often vague, making early clinical differentiation from idiopathic Parkinson disease (IPD) challenging. This study was performed to delineate the specific patterns of cortical hypoperfusion, dopamine transporter (DAT) uptake using dual-phase FP-CIT PET in discriminating between CBS and IPD at early stage.
PATIENTS AND METHODS
The study enrolled clinically diagnosed CBS (n = 11) and IPD (n = 22) patients (age and sex matched). All participants underwent dual-phase 18 F-FP-CIT PET, and regional SUV ratio (SUVR) was obtained by semiquantitative analysis. The early perfusion imaging and DAT imaging were compared between groups.
RESULTS
The regional SUVRs (early phase) of the frontal lobe, thalamus, cingulate, and caudate were significantly lower in patients with CBS, whereas the SUVR of occipital lobe was lower in the IPD group. The CBS group exhibited more prominent asymmetry than the IPD group, particularly in the perirolandic area, superior frontal gyrus, and anterior parietal lobe in early phase PET. Striatal DAT uptake (delayed phase) revealed that the caudate showed lower SUVR and prominent asymmetry in the CBS group, and the caudate-to-putamen ratio (CP ratio) was significantly lower in CBS patients ( P < 0.001). Among the parameters (early and delayed), the CP ratio in DAT exhibited the most powerful discriminative power from receiver operating characteristic curve comparison (area under curve = 0.983).
CONCLUSIONS
This study demonstrated that the dual-phase FP-CIT PET is useful in differentiating CBS and IPD in the early stage of the disease, and a lower CP ratio of DAT imaging is highly informative for distinguishing between corticobasal degeneration and IPD.
Topics: Humans; Corticobasal Degeneration; Parkinson Disease; Parkinsonian Disorders; Tropanes; Positron-Emission Tomography; Dopamine Plasma Membrane Transport Proteins; Apraxias; Early Diagnosis
PubMed: 38015725
DOI: 10.1097/RLU.0000000000004979 -
BMC Neurology Oct 2023Creutzfeldt-Jakob disease (CJD) is a rapidly progressive and ultimately fatal neurodegenerative condition caused by prions. The clinical symptoms of CJD vary with its...
BACKGROUND
Creutzfeldt-Jakob disease (CJD) is a rapidly progressive and ultimately fatal neurodegenerative condition caused by prions. The clinical symptoms of CJD vary with its subtype, and may include dementia, visual hallucinations, myoclonus, ataxia, (extra)pyramidal signs and akinetic mutism. In the early course of disease however, several clinical symptoms of CJD may mimic those of co-existing morbidities.
CASE PRESENTATION
We report a male in his 60s with a history of situs inversus totalis and Churg Strauss syndrome, who presented with speech fluency disturbances, neuropsychiatric symptoms and allodynia, a few months after becoming a widower. Initially presumed a bereavement disorder along with a flare-up of Churg Strauss, his symptoms gradually worsened with apraxia, myoclonic jerks and eventually, akinetic mutism. MRI revealed hyperintensities at the caudate nucleus and thalami, while the cerebrospinal fluid was positive for the 14-3-3 protein and the real-time quick test, making the diagnosis of CJD highly probable. This case illustrates the complexities that may arise in diagnosing CJD when pre-existing multimorbidity may cloud the clinical presentation. We also discuss the potential mechanisms underlying the co-occurrence of three rare conditions (situs inversus totalis, Churg Strauss syndrome, CJD) in one patient, taking into consideration the possibility of coincidence as well as common underlying factors.
CONCLUSIONS
The diagnosis of CJD may be easily missed when its clinical symptoms are obscured by those of pre-existing (rare) multimorbidity. This case highlights that when the multimorbidity has neurological manifestations, an extensive evaluation remains crucial to establish the diagnosis, minimize the risk of prion-transmission and provide appropriate guidance to patients and their caregivers.
Topics: Humans; Male; Creutzfeldt-Jakob Syndrome; Akinetic Mutism; Churg-Strauss Syndrome; Multimorbidity; Myoclonus; Situs Inversus
PubMed: 37784069
DOI: 10.1186/s12883-023-03401-5 -
Annals of Neurology Sep 2023The Scale for the Assessment and Rating of Ataxia (SARA) is the most widely applied clinical outcome assessment (COA) for genetic ataxias, but presents metrological and...
OBJECTIVE
The Scale for the Assessment and Rating of Ataxia (SARA) is the most widely applied clinical outcome assessment (COA) for genetic ataxias, but presents metrological and regulatory challenges. To facilitate trial planning, we characterize its responsiveness (including subitem-level relations to ataxia severity and patient-focused outcomes) across a large number of ataxias, and provide first natural history data for several of them.
METHODS
Subitem-level correlation and distribution-based analysis of 1,637 SARA assessments in 884 patients with autosomal recessive/early onset ataxia (370 with 2-8 longitudinal assessments) were complemented by linear mixed effects modeling to estimate progression and sample sizes.
RESULTS
Although SARA subitem responsiveness varied between ataxia severities, gait/stance showed a robust granular linear scaling across the broadest range (SARA < 25). Responsiveness was diminished by incomplete subscale use at intermediate or upper levels, nontransitions ("static periods"), and fluctuating decreases/increases. All subitems except nose-finger showed moderate-to-strong correlations to activities of daily living, indicating that metric properties-not content validity-limit SARA responsiveness. SARA captured mild-to-moderate progression in many genotypes (eg, SYNE1-ataxia: 0.55 points/yr, ataxia with oculomotor apraxia type 2: 1.14 points/yr, POLG-ataxia: 1.56 points/yr), but no change in others (autosomal recessive spastic ataxia of Charlevoix-Saguenay, COQ8A-ataxia). Whereas sensitivity to change was optimal in mild ataxia (SARA < 10), it substantially deteriorated in advanced ataxia (SARA > 25; 2.7-fold sample size). Use of a novel rank-optimized SARA without subitems finger-chase and nose-finger reduces sample sizes by 20 to 25%.
INTERPRETATION
This study comprehensively characterizes COA properties and annualized changes of the SARA across and within a large number of ataxias. It suggests specific approaches for optimizing its responsiveness that might facilitate regulatory qualification and trial design. ANN NEUROL 2023;94:470-485.
Topics: Humans; Activities of Daily Living; Ataxia; Spinocerebellar Ataxias; Cerebellar Ataxia; Upper Extremity
PubMed: 37243847
DOI: 10.1002/ana.26712 -
Biomedicines Oct 2023This was a retrospective, multicenter study that aimed to report the characteristics of type 3 Gaucher disease (GD3) patients in Spain, including the genotype,...
This was a retrospective, multicenter study that aimed to report the characteristics of type 3 Gaucher disease (GD3) patients in Spain, including the genotype, phenotype, therapeutic options, and treatment responses. A total of 19 patients with GD3 from 10 Spanish hospitals were enrolled in the study (14 men, 5 women). The median age at disease onset and diagnosis was 1 and 1.2 years, respectively, and the mean age at follow-up completion was 12.37 years (range: 1-25 years). Most patients exhibited splenomegaly (18/19) and hepatomegaly (17/19) at the time of diagnosis. The most frequent neurological abnormalities at onset were psychomotor retardation (14/19) and extrinsic muscle disorders (11/19), including oculomotor apraxia, supranuclear palsy, and strabismus. The L444P (c.1448T>C) allele was predominant, with the L444P (c.1448T>C) homozygous genotype mainly associated with visceral manifestations like hepatosplenomegaly, anemia, and thrombocytopenia. All patients received enzyme replacement therapy (ERT); other treatments included miglustat and the chaperone (ambroxol). Visceral manifestations, including hepatosplenomegaly and hematological and bone manifestations, were mostly controlled with ERT, except for kyphosis. The data from this study may help to increase the evidence base on this rare disease and contribute to improving the clinical management of GD3 patients.
PubMed: 37893235
DOI: 10.3390/biomedicines11102861