Asleep or awake motor mapping for resection of perirolandic glioma in the nondominant hemisphere? Development and validation of a multimodal score to tailor the surgical strategy.

OBJECTIVE: Resection of glioma in the nondominant hemisphere involving the motor areas and pathways requires the use of brain-mapping techniques to spare essential sites subserving motor control. No clear indications are available for performing motor mapping under either awake or asleep conditions or for the best mapping paradigm (e.g., resting or active, high-frequency [HF] or low-frequency [LF] stimulation) that provides the best oncological and functional outcomes when tailored to the clinical context. This work aimed to identify clinical and imaging factors that influence surgical strategy (asleep motor mapping vs awake motor mapping) and that are associated with the best functional and oncological outcomes and to design a "motor mapping score" for guiding tumor resection in this area. METHODS: The authors evaluated a retrospective series of patients with nondominant-hemisphere glioma-located or infiltrating within 2 cm anteriorly or posteriorly to the central sulcus and affecting the primary motor cortex, its fibers, and/or the praxis network-who underwent operations with asleep (HF monopolar probe) or awake (LF and HF probes) motor mapping. Clinical and imaging variables were used to design a motor mapping score. A prospective series of patients was used to validate this motor mapping score. RESULTS: One hundred thirty-five patients were retrospectively analyzed: 69 underwent operations with asleep (HF stimulation) motor mapping, and 66 underwent awake (LF and HF stimulation and praxis task evaluation) motor mapping. Previous motor (strength) deficit, previous treatment (surgery/radiotherapy), tumor volume > 30 cm3, and tumor involvement of the praxis network (on MRI) were identified and used to design the mapping score. Motor deficit, previous treatment, and location within or close to the central sulcus favor use of asleep motor mapping; large tumor volume and involvement of the praxis network favor use of awake motor mapping. The motor mapping score was validated in a prospective series of 52 patients-35 underwent operations with awake motor mapping and 17 with asleep motor mapping on the basis of the score indications-who had a low rate of postoperative motor-praxis deficit (3%) and a high extent of resection (median 97%; complete resection in > 70% of patients). CONCLUSIONS: Extensive resection of tumor involving the eloquent areas for motor control is feasible, and when an appropriate mapping strategy is applied, the incidence of postoperative motor-praxis deficit is low. Asleep (HF stimulation) motor mapping is preferable for lesions close to or involving the central sulcus and/or in patients with preoperative strength deficit and/or history of previous treatment. When a patient has no motor deficit or previous treatment and has a lesion (> 30 cm3) involving the praxis network, awake mapping is preferable.

Anticipatory and Reactive Grip Force Control in Patients with Alzheimer's Disease: A Pilot Study.

BACKGROUND: Alzheimer's disease (AD) affects several cognitive functions and causes altered motor function. Fine motor deficits during object manipulation are evident in other neurological conditions, but have not been assessed in dementia patients yet. OBJECTIVE: Investigate reactive and anticipatory grip force control in response to unexpected and expected load force perturbation in AD. METHODS: Reactive and anticipatory grip force was investigated using a grip-device with force sensors. In this pilot study, fifteen AD patients and fourteen healthy controls performed a catching task. They held the device with one hand while a sandbag was dropped into an attached receptacle either by the experimenter or by the participant. RESULTS: In contrast to studies of other neurological conditions, the majority of AD patients exerted lower static grip force levels than controls. Interestingly, patients who were slow in the Luria's three-step test produced normal grip forces. The timing and magnitude of reactive grip force control were largely preserved in patients. In contrast, timing and extent of anticipatory grip forces were impaired in patients, although anticipatory control was generally preserved. These deficits were correlated with decreasing Mini-Mental State Examination scores. Apraxia scores, assessed by pantomime of tool-use, did not correlate with performance in the catching task. CONCLUSION: We interpreted the decreased grip force in AD in the context of loss of strength and lethargy, typical for patients with AD. The lower static grip force during object manipulation may emerge as a potential biomarker for early stages of AD, but more studies with larger sample sizes are necessary.

Neural Changes Induced by a Speech Motor Treatment in Childhood Apraxia of Speech: A Case Series.

We report a case series of children with childhood apraxia of speech, by describing behavioral and white matter microstructural changes following 2 different treatment approaches.Five children with childhood apraxia of speech were assigned to a motor speech treatment (PROMPT) and 5 to a language, nonspeech oral motor treatment. Speech assessment and brain MRI were performed pre- and post-treatment. The ventral (tongue/larynx) and dorsal (lips) corticobulbar tracts were reconstructed in each subject. Mean fractional anisotropy and mean diffusivity were extracted. The hand corticospinal tract was assessed as a control pathway. In both groups speech improvements paralleled changes in the left ventral corticobulbar tract fractional anisotropy. The PROMPT treated group also showed fractional anisotropy increase and mean diffusivity decrease in the left dorsal corticobulbar tract. No changes were detected in the hand tract. Our results may provide preliminary support to the possible neurobiologic effect of a multimodal speech motor treatment in childhood apraxia of speech.

FDG-PET patterns associated with ideomotor apraxia and imitation apraxia in patients with corticobasal syndrome.

INTRODUCTION: Apraxia is a core clinical feature of corticobasal syndrome (CBS). Among the subtypes of apraxia, ideomotor and imitation apraxia are frequently found in CBS. However, little is known about the brain networks that are characteristic of each apraxia subtype or their clinical implication. In this study, we used 18F-fluorodeoxyglucose positron emission tomography (FDG-PET) to explore the specific patterns of glucose hypometabolism that are characteristic of apraxia subtypes by focusing on ideomotor and imitation apraxia. METHODS: We compared the areas of glucose hypometabolism in the brains of 52 patients with CBS and 13 healthy controls, both as a whole and according to apraxia subtypes. In addition, we investigated the relationship between the apraxia subtypes and the clinical phenotype of CBS. RESULTS: In patients with CBS, common hypometabolism was observed in the frontal gyrus, precentral gyrus and caudate regardless of apraxia subtypes. In particular, ideomotor apraxia was associated with hypometabolism in the angular gyrus, while imitation apraxia was associated with hypometabolism in the posterior part including the postcentral gyrus, precuneus, and posterior cingulate gyrus. Patients who showed both ideomotor and imitation apraxia were more likely to show the typical features of CBS and progressive supranuclear palsy compared with patients showing only one type of apraxia. CONCLUSION: Group comparison analysis using FDG-PET revealed distinct pathways of ideomotor and imitation apraxia in CBS. These findings add to our understanding of the brain networks underlying apraxia in association with the clinical features of CBS.

Clinical Features and Prognostic Factors of Pediatric Glioblastoma: Report of 38 Cases.

OBJECTIVE: To better characterize children with glioblastoma, assess outcomes, and identify prognostic factors associated with overall survival and progression-free survival in a relatively large cohort from a single institution. METHODS: For this retrospective review, 38 pediatric patients with a diagnosis of glioblastoma who were treated at The First Affiliated Hospital of Zhengzhou University between January 2015 and January 2020 were selected. Clinical and pathological characteristics, imaging, treatment, and survival variables were compared. RESULTS: There were 24 boys and 14 girls with a median age of 11.5 years (range, 3-18 years). All patients underwent surgery, with gross total resection in 16 and subtotal resection in 22. Of patients, 18 received radiation combined with chemotherapy, 6 received radiation or chemotherapy alone, and 14 did not receive any adjuvant therapy. Contrast-enhanced magnetic resonance imaging of 21 patients showed rim enhancement, while heterogeneous enhancement was shown on imaging of the other 17 patients. Tumors were observed in hemispheric locations in 19 cases and in central locations in the others. Median overall survival was 10.5 months with a median progression-free survival of 6 months. Extent of resection, adjuvant therapy, and original site of tumor were identified as independent predictors for progression-free survival and overall survival on multivariate analysis. There were significant differences in prognosis among different enhancement characteristics; patients with rim-enhancing tumors had a better prognosis. CONCLUSIONS: Pediatric glioblastoma carries a dismal prognosis. Maximum safe resection followed by adjuvant radiation with chemotherapy is considered standard treatment. Better outcomes are associated with hemispheric tumor locations and rim enhancement on magnetic resonance imaging.

The prehistory of speech and language is revealed in brain damage.

The aim of this paper is to develop further the idea that symptoms that emerge in speech and language processing following brain damage can make a contribution to discussions of the early evolution of language. These diverse impairments are called aphasia, and this paper proposes that the recovery of a non-fluent aphasia syndrome following stroke could provide insights into the course of the pre-history of human language evolution. The observable symptoms emerge during recovery, crucially enabled by (dis)inhibition in parallel with a range of impairments in action processing (apraxias), including apraxia of speech. They are underpinned by changes in cortical and subcortical status following brain damage. It is proposed that the observed recovery mimics ontogenic and phylogenic processes in human speech and language. The arguments put forward provide insights tending to support the motor-gestural model of speech and language evolution. This article is part of the theme issue 'Reconstructing prehistoric languages'.

Effectiveness of a Functional Rehabilitation Program for Upper Limb Apraxia in Poststroke Patients: A Randomized Controlled Trial.

OBJECTIVE: To analyze the effectiveness of a home-based restorative and compensatory upper limb apraxia (ULA) rehabilitation program. DESIGN: Randomized controlled trial. SETTING: Neurology Unit of San Cecilio Hospital and 2 private and specialized health care centers. PARTICIPANTS: Community dwelling participants (N=38) between the ages of 25 and 95 years old (sex ratio, 1:1) with unilateral mild-to-moderate poststroke lesions (time of evolution since stroke, 12.03±8.98mo) and secondary ULA. INTERVENTIONS: Participants were randomly assigned to an 8-week combined ULA functional rehabilitation group (n=19) 3 days per week for 30 minutes or to a traditional health care education protocol group (n=19) once a month for 8 weeks. Both interventions were conducted at home. MAIN OUTCOME MEASURES: Sociodemographic and clinical data, Barthel Index (primary outcome), Lawton and Brody Scale, observation and scoring activities of daily living, the De Renzi tests for ideational and ideomotor apraxia and imitating gestures test, recognition of gestures, test for upper limb apraxia , and stroke-specific quality of life scale were assessed at 3 time points: baseline, posttreatment (8wk), and follow-up (8wk). RESULTS: There were statistically significant differences among the groups regarding ideomotor apraxia, imitating gestures, global recognition of gestures, intransitive gestures, and comprehension of gesture production (P<.05) in favor of the experimental group. However, no statistically significant differences were found between the groups regarding functionality or quality of life (P>.05). Regarding the within-group effect, statistically significant differences were found in all neuropsychological outcomes at posttreatment and follow-up (P<.05). CONCLUSION: A functional rehabilitation program was found to be superior to a traditional health care education program and resulted in improvements in neuropsychological functioning in ULA poststroke. Conventional education showed an insufficient effect on apraxia recovery. Further studies with larger sample sizes are needed to determine the effect of rehabilitation strategies on functionality and quality of life of poststroke ULA patients.

Altered Inferior Parietal Functional Connectivity is Correlated with Praxis and Social Skill Performance in Children with Autism Spectrum Disorder.

Children with autism spectrum disorder (ASD) have difficulties perceiving and producing skilled gestures, or praxis. The inferior parietal lobule (IPL) is crucial to praxis acquisition and expression, yet how IPL connectivity contributes to autism-associated impairments in praxis as well as social-communicative skill remains unclear. Using resting-state functional magnetic resonance imaging, we applied independent component analysis to test how IPL connectivity relates to praxis and social-communicative skills in children with and without ASD. Across all children (with/without ASD), praxis positively correlated with connectivity of left posterior-IPL with the left dorsal premotor cortex and with the bilateral posterior/medial parietal cortex. Praxis also correlated with connectivity of right central-IPL connectivity with the left intraparietal sulcus and medial parietal lobe. Further, in children with ASD, poorer praxis and social-communicative skills both correlated with weaker right central-IPL connectivity with the left cerebellum, posterior cingulate, and right dorsal premotor cortex. Our findings suggest that IPL connectivity is linked to praxis development, that contributions arise bilaterally, and that right IPL connectivity is associated with impaired praxis and social-communicative skills in autism. The findings underscore the potential impact of IPL connectivity and impaired skill acquisition on the development of a range of social-communicative and motor functions during childhood, including autism-associated impairments.

The debate on apraxia and the supplementary motor area in the twentieth century.

Hand function and apraxia are equally relevant to neurosurgeons: as a symptom, as well as through the functional anatomy of "praxis" which underlies the dexterity needed for neurosurgical practice. The supplementary motor area is crucial for its understanding. Historically, Hugo Liepmann dominated the apraxia debate at the beginning of the twentieth century, a debate that has remained influential until today. Kurt Goldstein, a contemporary of Liepmann, is regularly mentioned as the first to have described the alien hand syndrome in 1909. Wilder Penfield was a key figure in exploring the role of the fronto-mesial cortex in human motor control and coined the term "supplementary motor area". It was Goldstein who not only contributed substantially to the apraxia debate more than 100 years ago; he also established the link between the dysfunction of the fronto-mesial cortex and abnormal higher motor control in humans.

Speech and language development in children with 49,XXXXY syndrome.

49,XXXXY is the rarest X and Y chromosomal variation and is frequently characterized by expressive and receptive language dysfunction, low muscle tonus, and intellectual deficits. Due to the low incidence of this disorder, comprehensive studies analyzing the specific aspects of the speech and language phenotype in these boys have been uncommon. This is the first in-depth investigation of the speech and language profiles in a large cohort of boys with 49,XXXXY. Based on the clinical judgment of speech and language pathologists, there was an increased incidence (91.8%) of Childhood Apraxia of Speech (CAS), which has not been previously described in this disorder. In preschool boys, some significant differences were demonstrated between boys who received early hormonal treatment (n = 16) and untreated boys (n = 4) on the language scales (p = .047) on the Bayley Scales of Infants and Toddlers, as well as significant differences between treated (n = 13) and untreated boys (n = 8) on the Expressive One Word Picture Vocabulary Test (p = .008). No significant differences between treatment groups were found in school age children, however, treated groups demonstrated less discrepancies between expressive and receptive language. More research and larger samples are needed to determine the extent of the impact of testosterone treatment on boys with 49,XXXXY. This study identifies CAS as a potential explanation for the significant expressive language dysfunction and subsequent behavioral dysfunction. These findings may assist in facilitating more targeted treatment and improved outcomes for boys with 49,XXXXY.

Examining speech motor planning difficulties in apraxia of speech and aphasia via the sequential production of phonetically similar words.

This study investigated the underlying nature of apraxia of speech (AOS) by testing two competing hypotheses. The Reduced Buffer Capacity Hypothesis argues that people with AOS can plan speech only one syllable at a time Rogers and Storkel [1999. Planning speech one syllable at a time: The reduced buffer capacity hypothesis in apraxia of speech. Aphasiology, 13(9-11), 793-805. https://doi.org/10.1080/026870399401885]. The Program Retrieval Deficit Hypothesis states that selecting a motor programme is difficult in face of competition from other simultaneously activated programmes Mailend and Maas [2013. Speech motor programming in apraxia of speech: Evidence from a delayed picture-word interference task. American Journal of Speech-Language Pathology, 22(2), S380-S396. https://doi.org/10.1044/1058-0360(2013/12-0101)]. Speakers with AOS and aphasia, aphasia without AOS, and unimpaired controls were asked to prepare and hold a two-word utterance until a go-signal prompted a spoken response. Phonetic similarity between target words was manipulated. Speakers with AOS had longer reaction times in conditions with two similar words compared to two identical words. The Control and the Aphasia group did not show this effect. These results suggest that speakers with AOS need additional processing time to retrieve target words when multiple motor programmes are simultaneously activated.

Complex Movement Disorders in Ataxia with Oculomotor Apraxia Type 1: Beyond the Cerebellar Syndrome.

Background: Ataxia with oculomotor apraxia (AOA1) is characterized by early-onset progressive cerebellar ataxia with peripheral neuropathy, oculomotor apraxia and hypoalbuminemia and hypercholesterolemia. Case Report: A 23-year-old previously healthy woman presented with slowly-progressive gait impairment since the age of six years. Neurological examination revealed profound areflexia, chorea, generalized dystonia and oculomotor apraxia. Brain MRI revealed mild cerebellar atrophy and needle EMG showed axonal sensorimotor neuropathy. Whole exome sequencing revealed a mutation in the aprataxin gene. Discussion: AOA1 can present with choreoathetosis mixed with dystonic features, resembling ataxia-telangiectasia. This case is instructive since mixed and complex movement disorders is not very common in AOA1. Highlights: Ataxia with oculomotor apraxia type 1 (AOA1) is characterized by early-onset ataxia and oculomotor apraxia caused by variants in the APTX gene.Ataxia is usually not the sole movement abnormality in AOA1.Hyperkinetic movement disorders, especially chorea and dystonia, may occur.Mixed and complex movement disorders is not very common in AOA1.Patients with early-onset ataxia associated with mixed movement disorders should also be investigated for AOA1.

The evolution of parkinsonism in primary progressive apraxia of speech: A 6-year longitudinal study.

INTRODUCTION: Primary progressive apraxia of speech (PPAOS) is a neurodegenerative syndrome in which patients present with an isolated motor speech disorder. Some PPAOS patients develop parkinsonism and other features of progressive supranuclear palsy (PSP) and/or corticobasal syndrome (CBS) over time. We aimed to assess the evolution of parkinsonian characteristics in PPAOS patients who had been followed yearly for at least six years. METHODS: From a large cohort of 46 PPAOS patients, eight were followed yearly for > 6-years in multiple NIH-funded grants. Parkinsonian and other features, including bradykinesia, tremor, rigidity, postural instability, apraxia, ocular motor function and cognition were assessed at each visit, and research criteria applied for PSP and CBS diagnosis. Neurological, speech-language test scores, and [18F]fluorodeoxyglucose PET (FDG-PET) and MRI midbrain volumes were assessed. RESULTS: A Parkinson's plus syndrome developed in all eight patients (100%). Bradykinesia was the earliest feature, followed by rigidity and postural instability. Tremor was not a significant feature. Parkinsonism, limb apraxia and ocular motor impairment tended to develop four-to-five years after onset with some patients having slight asymmetric parkinsonism. Six patients (75%) met research criteria for probable PSP, although only one for PSP-Richardson's syndrome; three patients met criteria for possible CBS. Slightly asymmetric, left-sided, hypometabolism was observed on FDG-PET, not matching asymmetry of Parkinsonism. Midbrain hypometabolism was absent-minimal. Three patients had progressive midbrain volumes in the PSP-Richardson's syndrome range. CONCLUSIONS: A Parkinson's plus syndrome may inevitably develop in PPAOS supporting PPAOS as an early presentation of a Parkinson's plus disorder.

Asymmetric Bálint's syndrome with multimodal agnosia, bilateral agraphesthesia, and ineffective kinesthetic reading due to subcortical hemorrhage in the left parieto-occipito-temporal area.

We report a patient with asymmetric Bálint's syndrome (predominantly right-sided oculomotor apraxia and simultanagnosia and optic ataxia for the right hemispace), and multimodal agnosia (apperceptive visual agnosia and bilateral associative tactile agnosia) with accompanying right hemianopia, bilateral agraphesthesia, hemispatial neglect, global alexia with unavailable kinesthetic reading, and lexical agraphia for kanji (Japanese morphograms), after hemorrhage in the left parieto-occipito-temporal area. The coexistence of tactile agnosia, bilateral agraphesthesia, and ineffective kinesthetic reading suggests that tactile-kinesthetic information can be interrupted because of damage to the fiber connection from the parietal lobe to the occipito-temporal area, leading to these tactually related cognitive impairments.

Dressing Apraxia as Initial Manifestation of Creutzfeldt-Jakob Disease.

Background: Creutzfeldt-Jakob disease (CJD) is a rare prion disease characterized by rapidly progressive dementia. Case Report: A 76-year-old woman exhibited pronounced signs and symptoms of dressing apraxia for about seven weeks before the disease progressed and probable CJD was diagnosed supported by imaging and CSF findings. Discussion: Dressing apraxia as the initial manifestation of CJD has been sparsely reported. This remarkably focal syndrome should be considered with view on movement and neuropsychological disorders in early CJD.

Predictors of Arm Nonuse in Chronic Stroke: A Preliminary Investigation.

Background. Nonuse (NU) after stroke is characterized by failure to use the contralesional arm despite adequate capacity. It has been suggested that NU is a consequence of the greater effort and/or attention required to use the affected limb, but such accounts have not been directly tested, and we have poor understanding of the predictors of NU. Objective. We aimed to provide preliminary evidence regarding demographic, neuropsychological (ie, apraxia, attention/arousal, neglect), and psychological (ie, self-efficacy) factors that may influence NU in chronic stroke. Methods. Twenty chronic stroke survivors with mild to moderate sensory-motor impairment characterized by the Upper-Extremity Fugl-Meyer (UEFM) were assessed for NU with a modified version of the Actual Amount of Use Test (AAUT), which measures the disparity between amount of use in spontaneous versus forced conditions. Participants were also assessed with measures of limb apraxia, spatial neglect, attention/arousal, and self-efficacy. Using stepwise multiple regression, we determined which variables predicted AAUT NU scores. Results. Scores on the UEFM as well as attention/arousal predicted the degree of NU (P < .05). Attention/arousal predicted NU above and beyond UEFM (P < .05). Conclusions. The results are consistent with the importance of attention and engagement necessary to fully incorporate the paretic limb into daily activities. Larger-scale studies that include additional behavioral (eg, sensation, proprioception, spasticity, pain, mental health, motivation) and neuroanatomical measures (eg, lesion volume and white matter connectivity) will be important for future investigations.

Severe childhood speech disorder: Gene discovery highlights transcriptional dysregulation.

OBJECTIVE: Determining the genetic basis of speech disorders provides insight into the neurobiology of human communication. Despite intensive investigation over the past 2 decades, the etiology of most speech disorders in children remains unexplained. To test the hypothesis that speech disorders have a genetic etiology, we performed genetic analysis of children with severe speech disorder, specifically childhood apraxia of speech (CAS). METHODS: Precise phenotyping together with research genome or exome analysis were performed on children referred with a primary diagnosis of CAS. Gene coexpression and gene set enrichment analyses were conducted on high-confidence gene candidates. RESULTS: Thirty-four probands ascertained for CAS were studied. In 11/34 (32%) probands, we identified highly plausible pathogenic single nucleotide (n = 10; CDK13, EBF3, GNAO1, GNB1, DDX3X, MEIS2, POGZ, SETBP1, UPF2, ZNF142) or copy number (n = 1; 5q14.3q21.1 locus) variants in novel genes or loci for CAS. Testing of parental DNA was available for 9 probands and confirmed that the variants had arisen de novo. Eight genes encode proteins critical for regulation of gene transcription, and analyses of transcriptomic data found CAS-implicated genes were highly coexpressed in the developing human brain. CONCLUSION: We identify the likely genetic etiology in 11 patients with CAS and implicate 9 genes for the first time. We find that CAS is often a sporadic monogenic disorder, and highly genetically heterogeneous. Highly penetrant variants implicate shared pathways in broad transcriptional regulation, highlighting the key role of transcriptional regulation in normal speech development. CAS is a distinctive, socially debilitating clinical disorder, and understanding its molecular basis is the first step towards identifying precision medicine approaches.

Proactive interference apraxic agraphia: a writing and drawing disorder associated with corticobasal syndrome.

Proactive interference is when a previously performed task impairs performance on a current task. It is often associated with memory tasks and has not been reported to interfere with writing or drawing. We evaluated a left-handed man diagnosed with corticobasal syndrome who had a two-year history of progressive agraphia. On the sentence writing and clock drawing tasks, he initially wrote letters and numbers correctly but revealed an increase of movement errors as the tasks progressed. We propose the term "proactive interference apraxic agraphia" for this novel disorder. Prefrontal dysfunction may cause an impairment in disengaging from previously activated motor programs.