Predicting Disability in Progressive Supranuclear Palsy Using Bedside Frontal-Lobe Signs.

BACKGROUND: Frontal lobe signs in progressive supranuclear palsy (PSP) are prevalent and occur early in the disease. Although they are recognized in clinical practice, studies are needed to systematically investigate them for an in-depth understanding of the neurological substrate and their potential prognostic implications in the disease. OBJECTIVES: To study the predictive role of frontal lobe signs in PSP, as well as to describe their neuropsychological and anatomical correlations. METHODS: Nine recognized signs of frontal lobe dysfunction were assessed in 61 patients with PSP. Those signs able to predict PSP Rating Scale (PSPRS) score at baseline were selected, a survival analysis was performed and associations with neuropsychological tests and cortical thickness parameters in brain MRI were studied. RESULTS: Grasping, anosognosia and orobuccal apraxia predicted the PSPRS score independently of age, gender, clinical subtype and disease duration. The occurrence of groping in the first 4 years could be a predictor of survival. Grasping and anosognosia were associated with frontal cognitive dysfunction, whereas orobuccal apraxia and groping were related to a more widespread cognitive impairment, involving temporal-parietal areas. Presence of groping showed an extensive cortical atrophy, with predominant prefrontal, temporal and superior parietal cortical thinning. CONCLUSIONS: Grasping, groping, anosognosia and orobuccal apraxia are easily evaluable bedside clinical signs that reflect distinct stages of disease progression. Grasping, anosognosia and orobuccal apraxia predict disease disability in patients with PSP, and early onset groping could be a survival predictor.

Laparoscopic Eradication of Deep Endometriosis With Segmental Rectosigmoid Resection and Bilateral Posterior Parametrectomy With Nerve-sparing "Touchless" Technique According to the "Negrar Method".

OBJECTIVE: To demonstrate nerve-sparing laparoscopic eradication of deep endometriosis with rectal and parametrial resection based on the Negrar method [1] using the "touchless" technique. DESIGN: Stepwise video case demonstration with narration. SETTING: Tertiary level endometriosis unit. The patient was a 28 year-old nulliparous patient referred for surgery with persistent dysmenorrhea, dyspareunia, and dyschezia despite medical management (progestin-containing hormonal pills). Preoperative ultrasound demonstrated bilateral endometriomas, diffuse adenomyosis, and 35 mm × 17 mm stenosing rectal nodule. Histopathology confirmed 60% stenosis of the rectum secondary to the endometriotic nodule up to submucosal layer with margins free of endometriosis. She was discharged 7 days postoperatively with no postoperative complications. INTERVENTIONS: Laparoscopic nerve-sparing eradication of deep endometriosis with segmental rectosigmoid resection and bilateral posterior parametrectomy [2] according to the "Negrar method" with nerve-sparing "touchless" technique, sliding the nerve bundles laterocaudally, and keeping intact the visceral pelvic fascia covering them, thus without direct contact with the nerves. CONCLUSION: In our experience, based on more than 3000 of these procedures [3], this nerve-sparing procedure, based on identifying the nerves and their laterocaudad dissection, without a direct impact on their fibers but just on their fascial envelopes has proven successful in lowering the rates of postoperative dysfunctions and neural impairment related to neuro-apraxia and edema that occurs by directly affecting them [1]. Although there are no robust data to demonstrate benefit of "touchless" nerve-sparing dissection techniques, neuro-apraxia from compression of neural fibers that has been observed can be minimized [1,4,5].

Corticobasal syndrome mimicking Foix-Chavany-Marie syndrome with suggested 4-repeat tauopathy by tau PET.

BACKGROUND: Corticobasal syndrome (CBS) is a neurodegenerative disease diagnosed based on clinical manifestations such as asymmetrical parkinsonism, limb apraxia, and speech and language impairment. The background pathology of CBS is commonly a variety of proteinopathies, but association with cerebrovascular disease has also been reported. Foix-Chavany-Marie syndrome (FCMS) is a rare neurological disorder characterized by facio-pharyngo-glossal diplegia with automatic-voluntary movement dissociation presenting with bilateral paresis of the facial, lingual, pharyngeal and masticatory muscles. FCMS is commonly attributable to stroke. Transactive response DNA binding protein of 43 kD (TDP-43) proteinopathy is also known as the pathological background of FCMS, while the pathological background of the majority of CBS cases consists of diverse tauopathies instead of TDP-43 proteinopathy. In this report, we describe a case mimicking FCMS that was finally diagnosed as CBS with suggested 4-repeat tauopathy. CASE PRESENTATION: A 68-year-old female started experiencing difficulty speaking followed by difficulty writing, and especially texting, several years before her visit. Her impairment had been gradually worsening, and she came to our hospital. On neurological examination, she demonstrated the facial apraxia, frontal lobe dysfunction, and upper motor neuron signs. She presented some characteristics suggestive of FCMS. Her symptoms exhibited rapid progression and myoclonus, parkinsonism, and left-side dominant cortical sensory deficit occurred, resulting in the fulfillment of diagnostic criteria for CBS after 9 months. Tau PET imaging displayed notable ligand uptake in the brainstem, subthalamic nuclei, basal ganglia, and bilateral subcortical frontal lobe, suggesting that her pathological background was 4-repeat tauopathy. As a result of her progressive dysphagia, she became unable to eat and passed away after 12 months. CONCLUSION: We hereby present an atypical case of CBS showing clinical features mimicking FCMS at first presentation. TDP-43 proteinopathy was suspected based on the clinical symptoms in the early stages of the disease; however, the clinical course and imaging findings including tau PET suggested that her pathological background was 4-repeat tauopathy.

Is Shadowing Behavior Caused by Body Representation Disorders and Apraxia?

Shadowing is a person-following behavior, commonly observed in dementia (e.g., Alzheimer's disease). It may be caused by neuropsychological impairments associated with posterior brain lesions, as Kudo et al. described it in a patient with posterior cortical atrophy and no frontal signs. These authors have suggested that shadowing may arise from the combination of visuospatial impairments, aphasia, apraxia, and prosopagnosia. However, how these symptoms may contribute to shadowing remains unclear. It is suggested that the combination of visuospatial impairments, body representation disorders, and apraxia, may result in complete loss of spatial representations and hence, shadowing behavior.

Association of Circumscribed Subcortical Gray and White Matter Lesions With Apraxic Deficits in Patients With Left Hemisphere Stroke.

BACKGROUND AND OBJECTIVES: Apraxia is commonly attributed to left hemisphere (LH) lesions of the cortical fronto-temporo-parietal praxis networks or white matter lesions causing disconnections between cortical nodes. By contrast, the contribution of lesions to the subcortical gray matter, that is, basal ganglia or thalamus, to apraxic deficits remains controversial. Here, we investigate whether damage to these subcortical gray matter structures (i.e., caudate nucleus, putamen, globus pallidus, and thalamus) or the adjacent white matter tracts was associated with apraxic deficits. METHODS: We identified patients with distinct subcortical lesions with and without apraxia from a large retrospective sample of subacute LH ischemic stroke patients (n = 194). To test which subcortical structures (caudate nucleus, putamen, globus pallidus, thalamus, and adjacent white matter tracts), when lesioned, contributed to apraxic deficits, we statistically compared the proportion of lesioned voxels within subcortical gray and white matter structures between the apraxic and nonapraxic patients. RESULTS: Of the 194 stroke patients screened, 39 (median age = 65 years, range 30-82 years; median time poststroke at the apraxia assessment = 7 days, range 1-44 days) had lesions confined to subcortical regions (gray and white matter). Eleven patients showed apraxic deficits when imitating gestures or pantomiming object use. Region-wise statistical lesion comparison (controlled for lesion size) revealed a more significant proportion of damage ('lesion load') in the caudate nucleus in apraxic stroke patients (mean difference = 6.9%, 95% CI 0.4-13.3, p = 0.038, η p 2 = 0.11). By contrast, apraxic patients had lower lesion load in the globus pallidus (mean difference = 9.9%, 95% CI 0.1-19.8, p = 0.048, η p 2 = 0.10), whereas the lesion load in other subcortical structures (putamen, thalamus, and adjacent white matter tracts) did not differ significantly between the apraxic and nonapraxic patients. DISCUSSION: These findings provide new insights into the subcortical anatomy of apraxia after LH stroke, suggesting a specific contribution of caudate nucleus lesions to apraxic deficits.

The Outcomes of Remote Administration of Combined Aphasia and Apraxia of Speech Treatment: A Single-Subject Experimental Design Study.

PURPOSE: This study was designed to examine the outcomes of Combined Aphasia and Apraxia of Speech Treatment (CAAST) administered remotely in terms of acquisition and generalization effects and to compare these effects to previous in-person CAAST studies and Response Elaboration Training (RET)/Modified-Response Elaboration Training (M-RET) benchmarks. METHOD: Multiple probe designs across participants and behaviors were employed with three speakers with chronic aphasia and apraxia of speech. Correct information units (CIUs) were the primary outcome measure to measure changes in language production. Percent consonants correct (PCC) was used as the secondary outcome measure to evaluate changes in speech sound accuracy. Production of CIUs was compared with existing benchmarks from Bunker et al.'s (2019) meta-analysis of previous RET/M-RET studies. In addition, both CIUs and PCC were compared with the most recent CAAST in-person studies. RESULTS: All participants demonstrated substantial increases in CIUs for treated and untreated picture sets, comparable to outcomes of in-person CAAST administration. These language changes were maintained at posttreatment intervals for all participants. PCC also improved for all participants, with gains in articulatory accuracy being maintained posttreatment. CONCLUSIONS: Improvements in CIU production and PCC for all three participants were in keeping with results from Wambaugh et al. (2017). These findings provide additional support for the efficacy of CAAST and indicate that remote administration may be a viable alternative to in-person application. SUPPLEMENTAL MATERIAL: https://doi.org/10.23641/asha.23418635.

A Selective Hand Posture Apraxia in an Individual With Posterior Cortical Atrophy and Probable Corticobasal Syndrome.

A selective impairment for making hand postures that are required to use specific tools has rarely been reported in individuals with acquired brain injury, and such an impairment has not been documented at all in individuals with degenerative disorders. We describe an individual with posterior cortical atrophy and probable corticobasal syndrome who was unable to use tools because of an inability to make the proper hand posture required for each tool. This individual was, however, able to use the tools properly once her hand postures were corrected, and her ability to manipulate the tools (ie, timing, arm posture, and amplitude) was intact. Also, she had no difficulty with a test of her manipulation knowledge. Areas of hypoperfusion observed by single-photon emission computerized tomography included the anterior intraparietal sulcus in the left parietal lobe, which is an area that has been proposed to control hand postures. This selective impairment might be explained by the reasoning-based hypothesis for apraxia, which attributes hand posture errors in the absence of manipulation errors to dysfunction in one of the three independent pathways that subserve tool use, rather than the manipulation-based hypothesis for apraxia, which attributes hand posture errors to impaired manipulation knowledge. This is the first case with a degenerative disorder that revealed a selective impairment for making hand postures for tool use, which might be explained mainly by apraxia of hand postures along with visuospatial dysfunction (simultanagnosia) and/or sensory disturbance.

Sensory Integration Deficits in Neurodegenerative Diseases: Implications for Apraxia.

OBJECTIVE: Apraxia is the inability to perform voluntary, skilled movements following brain lesions, in the absence of sensory integration deficits. Yet, patients with neurodegenerative diseases (ND) may have sensory integration deficits, so we tested the associations and dissociations between apraxia and sensory integration. METHODS: A total of 44 patients with ND and 20 healthy controls underwent extensive testing of sensory integration (i.e., localization of tactile, visual, and proprioceptive stimuli; agraphesthesia; astereognosis) and apraxia (i.e., finger dexterity, imitation, tool use). RESULTS: The results showed (i) that patients with Alzheimer's disease, corticobasal syndrome, or posterior cortical atrophy were impaired on both dimensions; (ii) An association between both dimensions; (iii) that when sensory integration was controlled for, the frequency of apraxia decreased dramatically in some clinical subgroups. CONCLUSION: In a non-negligible portion of patients, the hypothesis of a disruption of sensory integration can be more parsimonious than the hypothesis of apraxia in case of impaired skilled gestures. Clinicians and researchers are advised to integrate sensory integration measures along with their evaluation of apraxia.

Limb Apraxias: The Influence of Higher Order Perceptual and Semantic Deficits in Motor Recovery After Stroke.

Stroke is a leading cause of disability worldwide. Limb apraxia is a group of higher order motor disorders associated with greater disability and dependence after stroke. Original neuropsychology studies distinguished separate brain pathways involved in perception and action, known as the dual stream hypothesis. This framework has allowed a better understanding of the deficits identified in Limb Apraxia. In this review, we propose a hierarchical organization of this disorder, in which a distinction can be made between several visuomotor pathways that lead to purposeful actions. Based on this, executive apraxias (such as limb kinetic apraxia) cause deficits in executing fine motor hand skills, and intermediate apraxias (such as optic ataxia and tactile apraxia) cause deficits in reaching to grasp and manipulating objects in space. These disorders usually affect the contralesional limb. A further set of disorders collectively known as limb apraxias include deficits in gesture imitation, pantomime, gesture recognition, and object use. These deficits are due to deficits in integrating perceptual and semantic information to generate complex movements. Limb apraxias are usually caused by left-hemisphere lesions in right-handed stroke patients, affecting both limbs. The anterior- to posterior-axis of brain areas are disrupted depending on the increasing involvement of perceptual and semantic processes with each condition. Lower-level executive apraxias are linked to lesions in the frontal lobe and the basal ganglia, while intermediate apraxias are linked to lesions in dorso-dorsal subdivisions of the dorsal fronto-parietal networks. Limb apraxias can be caused by lesions in both dorsal and ventral subdivisions including the ventro-dorsal stream and a third visuomotor pathway, involved in body schema and social cognition. Rehabilitation of these disorders with behavioral therapies has aimed to either restore perceptuo-semantic deficits or compensate to overcome these deficits. Further studies are required to better stratify patients, using modern neurophysiology and neuroimaging techniques, to provide targeted and personalized therapies for these disorders in the future.

Hearing outcomes in children with congenital cytomegalovirus infection: From management controversies to lack of parents' knowledge.

OBJECTIVES: Congenital cytomegalovirus (cCMV) is the leading nongenetic cause of sensorineural hearing loss (HL). However, there are no universally accepted approaches to diagnosis, follow-up and treatment. The aim of this study was to evaluate the main characteristics of cCMV-infected children, focusing on their management and long-term hearing outcomes. METHODS: This retrospective study included all children with cCMV infection who were referred to a third-level referral audiologic center for a 6-year hearing follow-up. The main information collected from the medical records included gestational age, birth weight, trimester of maternal seroconversion, hearing status at birth and after 6 years, hearing fluctuations, treatment with oral valganciclovir (within the first month of life and for 6 months), use of hearing devices, presence of speech-language delay, motor delay, cognitive delay and balance disorders, awareness of cCMV among parents, and parents' engagement in behaviors that could increase the risk of CMV infection during pregnancy. RESULTS: A total of 141 children with cCMV infection (72 males and 69 females; mean gestational age: 37+3 weeks; mean birth weight: 2893 g) were assessed. Overall, 48 children (34.0%) had a diagnosis of speech-language delay, 32 (22.7%) of sensorineural HL (59.4% bilaterally; 50% of profound degree), 18 (12.8%) of motor delay, 16 (11.3%) of balance disorders, and 6 (4.3%) of cognitive delay. Among children with HL, 8 (25.0%) were fitted with hearing aids (5 unilaterally and 3 bilaterally), and 5 (15.6%) had undergone cochlear implantation (1 unilaterally and 4 bilaterally), while a bimodal hearing solution was adopted for 2 (6.3%) patients. Compared to children with asymptomatic cCMV infection, symptomatic children had a higher prevalence of neurological and auditory sequelae (P < 0.01) and bilateral (P = 0.003) and severe-to-profound HL (P = 0.004). Overall, 23 children (16.3%) received oral valganciclovir, and only one of them experienced hearing deterioration. Only 14.9% of mothers and 5% of fathers were aware that cCMV could cause progressive or late-onset HL, and 87.9% of parents (248/282) had engaged in behaviors that increased the risk of CMV infection during pregnancy. CONCLUSION: This study confirmed the importance of performing a long audiological follow-up in children diagnosed with cCMV infection due to the possible late-onset, progressive and fluctuating nature of HL. Moreover, the study highlighted many current controversies in preventive (poor prenatal education), diagnostic (routine maternal serological screening) and therapeutic (valganciclovir administered to asymptomatic children) approaches to cCMV infection. More efforts should be made to improve prevention strategies and raise awareness of cCMV infection risks among the population.

Debunking the Puzzle of Eyelid Apraxia: The Muscle of Riolan Hypothesis.

PURPOSE: Apraxia of eyelid opening (AEO) has been defined by the presence of an intermittent nonparalytic bilateral loss of the volitional ability to open the eyes or to maintain the eyelids in a sustained elevated position. It is not known whether the condition represents an apraxia, a dystonia, or a freezing phenomenon, and several different nomenclatorial terms have been suggested for this condition including the so-called AEO (scAEO), blepahrocolysis, focal eyelid dystonia, and so on. The primary goal of this review is to attempt to clarify the pathogenetic mechanisms underlying scAEO as a clinical phenomenon. This review also addresses the issue of whether scAEO is part of the spectrum of blepharospasm (BSP) which includes BSP, dystonic blinks and other dystonic eyelid conditions, or whether it is a separate phenomenologically heterogeneous disease with clinical features that merely overlap with BSP. METHODS: A literature review was conducted in PubMed, MEDLINE, PubMed Central (PMC), NCBI Bookshelf, and Embase for several related keywords including the terms "apraxia of eyelid opening," "pretarsal blepharospasm," "blepharocolysis," "eyelid freezing," "eyelid akinesia," "levator inhibition," "blepharospasm-plus," as well as "blepharospasm." The clinical findings in patients with scAEO who fulfilled the classic diagnostic criteria of the disease that were originally set by Lepore and Duvoisin were included, while patients with isolated blepharospasm or dystonic blinks (DB) were excluded. In addition, electromyographic (EMG) studies in patients with scAEO were reviewed in detail with special emphasis on studies that performed synchronous EMG recordings both from the levator muscle (LPS) and the pretarsal orbicularis oculi muscle (OO). RESULTS: The apraxia designation is clearly a misnomer. Although scAEO behaves clinically as a hypotonic freezing phenomenon, it also shares several cardinal features with focal dystonias. The authors broadly categorized the EMG data into 3 different patterns. The first pattern (n = 26/94 [27.6%]) was predominantly associated with involuntary discharges in the OO muscle and has been termed pretarsal blepharospasm (ptBSP). The commonest pattern was pattern no. 2 (n = 53/94 [56.38%]), which was characterized by involuntary discharges in the OO muscle, together with a disturbed reciprocal innervation of the antagonist levator muscle and is dubbed disturbed reciprocal innervation (DRI). This EMG pattern is difficult to discern from the first pattern. Pattern no. 3 (n = 15/94 [15.9%]) is characterized by an isolated levator palpebrae inhibition (ILPI). This levator silence was observed alone without EMG evidence of contractions in the pretarsal orbicularis or a disturbed reciprocal relation of both muscles. CONCLUSION: EMG evidence shows that the great majority (84%) of patients show a dystonic pattern, whereas ILPI (16%) does not fit the dystonic spectrum. The authors propose that a spasmodic contraction of the muscle of Riolan may be the etiological basis for levator inhibition in patients with ILPI. If this is true, all the 3 EMG patterns observed in scAEO patients (ptBSP, DRI, and ILPI) would represent an atypical form of BSP. The authors suggest coining the terms Riolan muscle BSP ( rmBSP ) for ILPI, and the term atypical focal eyelid dystonia ( AFED ) instead of the term scAEO, as both terms holistically encompass both the clinical and EMG data and concur with the authors' theorem.

Evaluation of the Dementia Apraxia Test in Parkinson's Disease Patients.

INTRODUCTION: Ideomotor apraxia, a disorder of skilled movements affecting limbs and/or face, can be seen in patients with Parkinson's disease (PD), yet tests of apraxia in PD are rare. The aim of this project was to evaluate the psychometric properties and validity of the Dementia Apraxia Test (DATE) in a PD sample. METHODS: 118 PD patients were included. Besides DATE performance, motor and non-motor burden, cognition, and activity of daily living (ADL) function were assessed. Patients were classified as cognitively impaired (n = 41) or non-cognitively impaired (n = 77). RESULTS: Interrater reliability of the DATE (sub-)scores between video ratings and on-site ratings by the investigator was good (0.81 ≤ rk ≤ 0.87). Items were mostly easy to perform, especially the buccofacial apraxia items, which had also low discriminatory power. DATE scores were associated with cognition and ADL function. DATE performance was confounded by motor impairment and patients' age; however, when analysed for both cognitive groups separately, the correlation between DATE and motor performance was not significant. DISCUSSION/CONCLUSION: The DATE seems to be an objective and predominantly valid apraxia screening tool for PD patients, with a few items needing revision. Due to the potential effect of motor impairment and age, standardized scores adjusting for these confounders are needed.

Cross-Sectional and Longitudinal Assessment of Behavior in Primary Progressive Apraxia of Speech and Agrammatic Aphasia.

INTRODUCTION: Progressive agrammatic aphasia (PAA) can be associated with abnormal behaviors; however, it is unknown whether behaviors occur and/or are different in patients with primary progressive apraxia of speech (PPAOS). We aimed to compare baseline and longitudinal behavioral symptomatology between PPAOS, patients with PAA, and patients with both apraxia of speech and PAA (AOS-PAA). METHODS: We recruited 89 patients for this study, 40 with PPAOS, 11 with PAA, and 38 with AOS-PAA. Behavioral disturbances were evaluated using the frontal behavior inventory (FBI) which was also split into negative behaviors and disinhibition, and the 20-item behavioral assessment scale (20-BAS). Data analysis was performed using linear regression and linear mixed models. RESULTS: Of the 89 patients in the study, 54% were women and the mean age at onset was 68 years. All patients, regardless of diagnosis, endorsed at least one symptom on the FBI at baseline, most frequently verbal apraxia (100%), logopenia (95.6%), irritability (55.9%), and apathy (42.6%). On the 20-BAS, 47.6% of the patients endorsed at least one symptom, most commonly "crying more easily" (19.5%) and personality change (18.3%). PPAOS was the least behaviorally affected group, with differences between PPAOS and AOS-PAA mainly driven by negative behaviors as opposed to disinhibition for PPAOS and PAA. The behavioral metrics showed average sensitivity and specificity to distinguish between groups. Behavioral disturbances worsened over time although rate of behavioral change across groups was similar. CONCLUSION: Behavioral disturbances are more common and severe in patients with agrammatic aphasia with or without AOS compared to patients with isolated apraxia of speech.

Role of Diffusion Tensor Tractography in Diagnosis of Limb-Kinetic Apraxia in Stroke Patients: A Mini-Narrative Review.

Limb-kinetic apraxia (LKA) is an execution disorder of movements caused by an injury to the secondary motor area (the supplementary motor area and premotor cortex) with preservation of an intact corticospinal tract (CST). A precise diagnosis of LKA is often limited because it is made based on the clinical observation of movement characteristics with confirmation of the CST state, and no specific clinical assessment tools for LKA have been developed. Diffusion tensor tractography (DTT) enables a three-dimensional estimation of the neural tracts related to LKA, such as the CST and corticofugal tract from the secondary motor area. This article reviewed 5 DTT-based studies on LKA-related neural tracts in stroke patients. These studies suggest that DTT could be a useful diagnostic tool for LKA along with previous diagnostic tools, such as brain magnetic resonance imaging and transcranial magnetic stimulation. In particular, DTT for the affected corticofugal tract can provide useful evidence for diagnosing LKA when clinicians cannot observe the movement characteristics because of severe weakness after a severe injury to the affected CST. Furthermore, a reviewed study suggested that LKA might be related to the unaffected neural tracts for motor function when the affected neural tracts were severely injured. This review summarizes the role of DTT in the diagnosis of LKA in stroke patients.

Ataxia with Ocular Apraxia Type 1 (AOA1) (APTX, W279* Mutation): Neurological, Neuropsychological, and Molecular Outlining of a Heterogenous Phenotype in Four Colombian Siblings.

Hereditary ataxias are a group of devastating neurological disorders that affect coordination of gait and are often associated with poor coordination of hands, speech, and eye movements. Ataxia with ocular apraxia type 1 (AOA1) (OMIM: 606,350.0006) is characterized by slowly progressive symptoms of childhood-onset and pathogenic mutations in APTX; the only known cause underpinning AOA1. APTX encodes the protein aprataxin, composed of three domains sharing homology with proteins involved in DNA damage, signaling, and repair. We present four siblings from an endogamic family in a rural, isolated town of Colombia with ataxia and ocular apraxia of childhood-onset and confirmed molecular diagnosis of AOA1, homozygous for the W279* p.Trp279Ter mutation. We predicted the mutated APTX with AlphaFold to demonstrate the effects of this stop-gain mutation that deletes three beta helices encoded by amino acid 270 to 339 rescinding the C2H2-type zinc fingers (Znf) (C2H2 Znf) DNA-binding, the DNA-repair domain, and the whole 3D structure of APTX. All siblings exhibited different ages of onset (4, 6, 8, and 11 years old) and heterogeneous patterns of dysarthria (ranging from absence to mild-moderate dysarthria). Neuropsychological evaluation showed no neurocognitive impairment in three siblings, but one sibling showed temporospatial disorientation, semantic and phonologic fluency impairment, episodic memory affection, constructional apraxia, moderate anomia, low executive function, and symptoms of depression. To our knowledge, this report represents the most extensive series of siblings affected with AOA1 in Latin America, and the genetic analysis completed adds important knowledge to outline this family's disease and general complex phenotype of hereditary ataxias.

Identifying segmental and prosodic errors associated with the increasing word length effect in acquired apraxia of speech.

Purpose: Individuals with stroke-related apraxia of speech (AOS) plus aphasia tend to produce more speech errors with increasing word length. The Words of Increasing Length task (WIL) uses a 3-point scale to score word accuracy but penalises for error types that can arise either from language or motor impairment, reducing the test's sensitivity and specificity. The purpose here was to identify error types explaining variance in the WIL score, and those associated with AOS and word length.Method: Speech errors were perceptually identified on the WIL task for 51 Australian English-speaking adults with stroke-related aphasia, 25 with concomitant AOS. Multiple regression and linear mixed effects modelling were applied.Result: Variance in WIL scores was best explained with four error types: consonant additions, incorrect number of syllables, false starts and consonant substitutions/distortions. False starts were significantly associated with AOS diagnosis. Incorrect number of syllables, consonant omissions, false starts, and lexical stress errors increased in frequency for longer words and, while the interaction with diagnosis did not reach significance, the effect appeared driven by the AOS group.Conclusion: Findings provide further support for using polysyllabic word production to assess apraxic speech. The WIL task has limitations that may bias patients' performance and clinicians' perceptual evaluation. Data provide valuable information for designing a more sensitive diagnostic protocol for AOS.

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.

A molecular pathology, neurobiology, biochemical, genetic and neuroimaging study of progressive apraxia of speech.

Progressive apraxia of speech is a neurodegenerative syndrome affecting spoken communication. Molecular pathology, biochemistry, genetics, and longitudinal imaging were investigated in 32 autopsy-confirmed patients with progressive apraxia of speech who were followed over 10 years. Corticobasal degeneration and progressive supranuclear palsy (4R-tauopathies) were the most common underlying pathologies. Perceptually distinct speech characteristics, combined with age-at-onset, predicted specific 4R-tauopathy; phonetic subtype and younger age predicted corticobasal degeneration, and prosodic subtype and older age predicted progressive supranuclear palsy. Phonetic and prosodic subtypes showed differing relationships within the cortico-striato-pallido-nigro-luysial network. Biochemical analysis revealed no distinct differences in aggregated 4R-tau while tau H1 haplotype frequency (69%) was lower compared to 1000+ autopsy-confirmed 4R-tauopathies. Corticobasal degeneration patients had faster rates of decline, greater cortical degeneration, and shorter illness duration than progressive supranuclear palsy. These findings help define the pathobiology of progressive apraxia of speech and may have consequences for development of 4R-tau targeting treatment.