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Brain Communications 2022The Gerstmann syndrome is a constellation of neurological deficits that include agraphia, acalculia, left-right discrimination and finger agnosia. Despite a growing...
The Gerstmann syndrome is a constellation of neurological deficits that include agraphia, acalculia, left-right discrimination and finger agnosia. Despite a growing interest in this clinical phenomenon, there remains controversy regarding the specific neuroanatomic substrates involved. Advancements in data-driven, computational modelling provides an opportunity to create a unified cortical model with greater anatomic precision based on underlying structural and functional connectivity across complex cognitive domains. A literature search was conducted for healthy task-based functional MRI and PET studies for the four cognitive domains underlying Gerstmann's tetrad using the electronic databases PubMed, Medline, and BrainMap Sleuth (2.4). Coordinate-based, meta-analytic software was utilized to gather relevant regions of interest from included studies to create an activation likelihood estimation (ALE) map for each cognitive domain. Machine-learning was used to match activated regions of the ALE to the corresponding parcel from the cortical parcellation scheme previously published under the Human Connectome Project (HCP). Diffusion spectrum imaging-based tractography was performed to determine the structural connectivity between relevant parcels in each domain on 51 healthy subjects from the HCP database. Ultimately 102 functional MRI studies met our inclusion criteria. A frontoparietal network was found to be involved in the four cognitive domains: calculation, writing, finger gnosis, and left-right orientation. There were three parcels in the left hemisphere, where the ALE of at least three cognitive domains were found to be overlapping, specifically the anterior intraparietal area, area 7 postcentral (7PC) and the medial intraparietal sulcus. These parcels surround the anteromedial portion of the intraparietal sulcus. Area 7PC was found to be involved in all four domains. These regions were extensively connected in the intraparietal sulcus, as well as with a number of surrounding large-scale brain networks involved in higher-order functions. We present a tractographic model of the four neural networks involved in the functions which are impaired in Gerstmann syndrome. We identified a 'Gerstmann Core' of extensively connected functional regions where at least three of the four networks overlap. These results provide clinically actionable and precise anatomic information which may help guide clinical translation in this region, such as during resective brain surgery in or near the intraparietal sulcus, and provides an empiric basis for future study.
PubMed: 35706977
DOI: 10.1093/braincomms/fcac140 -
Journal of Alzheimer's Disease : JAD 2022The established causative mutations in the APP, PSEN1, and PSEN2 can explain less than 1%,Alzheimer's disease (AD) patients. Of the identified variants, the PSEN2...
BACKGROUND
The established causative mutations in the APP, PSEN1, and PSEN2 can explain less than 1%,Alzheimer's disease (AD) patients. Of the identified variants, the PSEN2 mutations are even less common.
OBJECTIVE
With the genetic study from the dementia cohort of Peking Union Medical College Hospital (PUMCH), we aim to illustrate the PSEN2 mutation spectrum and novel functionally validated mutations in Chinese AD patients.
METHODS
702 AD participants, aged 30-85, were identified in PUMCH dementia cohort. They all received history inquiry, physical examination, biochemical test, cognitive evaluation, brain CT/MRI, and next-generation DNA sequencing. Functional analysis was achieved by transfection of the HEK293 cells with plasmids harboring the wild-type PSEN2 or candidate mutations.
RESULTS
Nine PSEN2 rare variants were found, including two reported (M239T, R62C) and seven novel variants (N141S, I368F, L396I, G117X, I146T, S147N, H220Y). The HEK293 cells transfected with the PSEN2 N141S, M239T, I368F plasmids showed higher Aβ42 and Aβ42/Aβ40 levels relative to the wild-type PSEN2. The PSEN2 L396I, G117X, S147N, H220Y, and R62C did not alter Aβ42, Aβ40 levels, or Aβ42/Aβ40 ratio. 1.9%,(13/702) subjects harbored rare PSEN2 variants. 0.4%,(3/702) subjects carried pathogenic/likely pathogenic PSEN2 mutations. The three subjects with the functionally validated PSEN2 mutations were all familial early-onset AD patients. The common symptoms included amnesia and mental symptom. Additionally, the M239T mutation carrier presented with dressing apraxia, visuospatial agraphia, dyscalculia and visual mislocalization.
CONCLUSION
The PSEN2 N141S, M239T, and I368F are functionally validated mutations.
Topics: Alzheimer Disease; Amyloid beta-Protein Precursor; HEK293 Cells; Humans; Mutation; Presenilin-2
PubMed: 35491795
DOI: 10.3233/JAD-220194 -
Neurology May 2022Most primary progressive aphasia (PPA) literature is based on English language users. Linguistic features that vary from English, such as logographic writing systems,...
BACKGROUND AND OBJECTIVES
Most primary progressive aphasia (PPA) literature is based on English language users. Linguistic features that vary from English, such as logographic writing systems, are underinvestigated. The current study characterized the dysgraphia phenotypes of patients with PPA who write in Chinese and investigated their diagnostic utility in classifying PPA variants.
METHODS
This study recruited 40 participants with PPA and 20 cognitively normal participants from San Francisco, Hong Kong, and Taiwan. We measured dictation accuracy using the Chinese Language Assessment for PPA (CLAP) 60-character orthographic dictation test and examined the occurrence of various writing errors across the study groups. We also performed voxel-based morphometry analysis to identify the gray matter regions correlated with dictation accuracy and prevalence of writing errors.
RESULTS
All PPA groups produced significantly less accurate writing responses than the control group and no significant differences in dictation accuracy were noted among the PPA variants. With a cut score of 36 out of 60 in the CLAP orthographic dictation task, the test achieved sensitivity and specificity of 90% and 95% in identifying Chinese participants with PPA vs controls. In addition to a character frequency effect, dictation accuracy was affected by homophone density and the number of strokes in semantic variant PPA and logopenic variant PPA groups. Dictation accuracy was correlated with volumetric changes over left ventral temporal cortices, regions known to be critical for orthographic long-term memory. Individuals with semantic variant PPA frequently presented with phonologically plausible errors at lexical level, patients with logopenic variant PPA showed higher preponderance towards visual and stroke errors, and patients with nonfluent/agrammatic variant PPA commonly exhibited compound word and radical errors. The prevalence of phonologically plausible, visual, and compound word errors was negatively correlated with cortical volume over the bilateral temporal regions, left temporo-occipital area, and bilateral orbitofrontal gyri, respectively.
DISCUSSION
The findings demonstrate the potential role of the orthographic dictation task as a screening tool and PPA classification indicator in Chinese language users. Each PPA variant had specific Chinese dysgraphia phenotypes that vary from those previously reported in English-speaking patients with PPA, highlighting the importance of language diversity in PPA.
Topics: Agraphia; Aphasia, Primary Progressive; China; Humans; Language; Phenotype; Primary Progressive Nonfluent Aphasia
PubMed: 35410909
DOI: 10.1212/WNL.0000000000200350 -
PloS One 2022Adults with specific learning disabilities (e.g., dyslexia, dysgraphia, and dyscalculia) reveal limitations in daily functioning in various life domains. Following...
Adults with specific learning disabilities (e.g., dyslexia, dysgraphia, and dyscalculia) reveal limitations in daily functioning in various life domains. Following previous evidence of deficient executive functions and unique sensory patterns in this population, this study examined how relationships between these two domains are expressed in daily functioning. Participants included 55 adults with specific learning disabilities and 55 controls matched by age, gender, socioeconomic status, and education. Participants completed a sociodemographic questionnaire, the Behavioral Rating Inventory of Executive Functions-adult version, and the Adolescent/Adult Sensory Profile. Results indicated significant relationships between executive functions (per the Behavioral Rating Inventory of Executive Functions-adult version) and sensory patterns (per the Adolescent/Adult Sensory Profile) as reflected in daily functioning. The low sensory registration pattern predicted 12% to 16% of the variance in the behavioral regulation index, metacognitive index, and general executive composite scores and was a significant predictor of specific executive function abilities. Results indicated that the difficulties of adults with specific learning disabilities in using executive function abilities efficiently might be tied to a high sensory threshold and passive self-regulation strategies. A deeper understanding of this population's sensory-executive mechanisms may improve evaluation and intervention processes. This understanding can consequently increase executive abilities for improved daily functioning and life satisfaction.
Topics: Adolescent; Adult; Executive Function; Humans; Learning Disabilities; Surveys and Questionnaires
PubMed: 35390062
DOI: 10.1371/journal.pone.0266385 -
CoDAS 2022We present the case report of a 61-year-old male participant with chronic conduction aphasia and deep agraphia after ischemic stroke who received training on writing...
We present the case report of a 61-year-old male participant with chronic conduction aphasia and deep agraphia after ischemic stroke who received training on writing under dictation associated with transcranial direct current stimulation. The treatment consisted of five 50-minute dictation sessions with the application of 2 mA of anodal transcranial direct current stimulation for 20 minutes over the left occipitotemporal cortex. The participant improved his written production of pseudowords and regular low-frequency words, via the phonological route, in addition to a small improvement in the production of irregular words, via the lexical route. After training, there was also a small improvement in writing for untrained stimuli, suggesting generalization. In the assessment carried out 5 months after the end of the treatment, the benefit was maintained for stimuli processed via the phonological route. The results are promising given the severity and chronicity of the case and suggest that transcranial direct current stimulation associated with writing therapy represents a possible clinical alternative for patients with deep agraphia.
Topics: Agraphia; Aphasia; Humans; Male; Middle Aged; Stroke; Transcranial Direct Current Stimulation; Writing
PubMed: 35137891
DOI: 10.1590/2317-1782/20212020319 -
Journal of Learning Disabilities 2022This article presents the application of the interactive dynamic literacy (IDL) model (Kim, 2020b) toward understanding difficulties in learning to read and write....
This article presents the application of the interactive dynamic literacy (IDL) model (Kim, 2020b) toward understanding difficulties in learning to read and write. According to the IDL model, reading and writing are part of communicative acts that draw on largely shared processes and skills as well as unique processes and skills. As such, reading and writing are dissociable but interdependent systems that have hierarchical, interactive, and dynamic relations. These key tenets of the IDL model are applied to the disruption of reading and writing development to explain co-occurrence of reading-writing difficulties using a single framework. The following hypotheses are presented: (a) co-occurrence between word reading and spelling and handwriting difficulties; (b) co-occurrence of dyslexia with written composition difficulties; (c) co-occurrence between reading comprehension and written composition difficulties; (d) co-occurrence of language difficulties with reading difficulties and writing difficulties; (e) co-occurrence of reading, writing, and language difficulties with weak domain-general skills or executive functions such as working memory and attentional control (including attention-deficit/ hyperactivity disorder [ADHD]); and (f) multiple pathways for reading and writing difficulties. Implications are discussed.
Topics: Agraphia; Dyslexia; Humans; Literacy; Reading; Writing
PubMed: 35001719
DOI: 10.1177/00222194211060868 -
International Journal of School &... 2021Dysgraphia, a specific learning disability, impairs legible and automatic letter production by hand, which can interfere with written composing. The goal of the current...
Dysgraphia, a specific learning disability, impairs legible and automatic letter production by hand, which can interfere with written composing. The goal of the current study was not to investigate effective methods for teaching self-regulated writing to students with dysgraphia, but rather to investigate their self that is involved in their self-regulated writing. Students with dysgraphia in grades 4 to 9 (17 males; 3 females, =139.44 months, =12.15) composed six personal narratives about themselves and their relationships to others. Five indicators of self/self-others, informed by Theory of Mind (Frith & Frith, 2010), were coded in the six personal narratives. They also completed normed measures of self-regulation of attention and of written composing. Correlations identified which coded indicators of self/self-others and which measures of attention regulation were significantly related to the same written composing measure to be used as predictors in multiple regressions. Results showed that coded quality of Text Organization (Self Schema in Personal Story) for "My Life Before the School Years" as first predictor AND either Focused or Switching Attention as second predictor jointly accounted for significant variance and each predictor explained unique variance in writing fluency (timed composing). Implications of findings for educational practice and future research are discussed.
PubMed: 34925970
DOI: 10.1080/21683603.2020.1721384 -
BMJ Case Reports Dec 2021A 69-year-old man was presented to our emergency department with acute onset of hemianopsia, aphasia and dizziness. He reported that while he was sitting in front of his...
A 69-year-old man was presented to our emergency department with acute onset of hemianopsia, aphasia and dizziness. He reported that while he was sitting in front of his computer at home, he had performed a bilateral self-massage of his carotid arteries when suddenly the symptoms occurred. A neurological examination revealed a hemianopsia with a visual field loss on the right side. In addition, a mild aphasic syndrome with agraphia and a word-finding disorder (National Institutes of Health Stroke Scale (NIHSS): 3 points) was diagnosed. The initial brain CT scan with CT angiography showed neither an intracerebral haemorrhage nor a cerebral infarction. Also, no occlusion or any signs of artery dissection or a flow relevant stenosis of the brain supplying arteries were found. After excluding other contraindications, an intravenous thrombolysis with weight-adapted alteplase was performed. The symptoms of the patient significantly improved in the short-term follow-up. Three days after admission no neurological deficits remained. The MRI of the brain revealed multifocal, small, left hemispherical strokes in the middle cerebral artery territory. In general, watershed infarcts after carotid sinus self-massage follow a rare ischaemic stroke mechanism. This case emphasises the importance of a detailed anamnestic evaluation to determine the aetiological classification of ischaemic stroke as well as educating patients' (poststroke) behaviour.
Topics: Aged; Brain Ischemia; Carotid Sinus; Cerebral Infarction; Humans; Male; Massage; Stroke; United States
PubMed: 34920996
DOI: 10.1136/bcr-2021-244926 -
Sensors (Basel, Switzerland) Oct 2021Five to ten percent of school-aged children display dysgraphia, a neuro-motor disorder that causes difficulties in handwriting, which becomes a handicap in the daily...
Five to ten percent of school-aged children display dysgraphia, a neuro-motor disorder that causes difficulties in handwriting, which becomes a handicap in the daily life of these children. Yet, the diagnosis of dysgraphia remains tedious, subjective and dependent to the language besides stepping in late in the schooling. We propose a pre-diagnosis tool for dysgraphia using drawings called graphomotor tests. These tests are recorded using graphical tablets. We evaluate several machine-learning models and compare them to build this tool. A database comprising 305 children from the region of Grenoble, including 43 children with dysgraphia, has been established and diagnosed by specialists using the BHK test, which is the gold standard for the diagnosis of dysgraphia in France. We performed tests of classification by extracting, correcting and selecting features from the raw data collected with the tablets and achieved a maximum accuracy of 73% with cross-validation for three models. These promising results highlight the relevance of graphomotor tests to diagnose dysgraphia earlier and more broadly.
Topics: Agraphia; Algorithms; Child; Data Management; Handwriting; Humans; Machine Learning
PubMed: 34770333
DOI: 10.3390/s21217026 -
BMC Neurology Nov 2021Neurological manifestations of coronavirus disease 2019 (COVID-19) are increasingly recognized and include encephalopathy, although direct infection of the brain by...
BACKGROUND
Neurological manifestations of coronavirus disease 2019 (COVID-19) are increasingly recognized and include encephalopathy, although direct infection of the brain by SARS-CoV-2 remains controversial. We herein report the clinical course and cytokine profiles of a patient with severe SARS-CoV-2-related encephalopathy presenting aphasia.
CASE PRESENTATION
An 81-year-old man developed acute consciousness disturbance and status epileptics several days after SARS-CoV-2 infection. Following treatment with remdesivir and dexamethasone, his consciousness and epileptic seizures improved; however, amnestic aphasia and agraphia remained. Two months after methylprednisolone pulse and intravenous immunoglobulin, his neurological deficits improved. We found increased levels of interleukin (IL)-6, IL-8, and monocyte chemoattractant protein-1 (MCP-1), but not IL-2 and IL-10 in the serum and cerebrospinal fluid (CSF), and the levels of serum IL-6 and MCP-1 were much higher than those in the CSF. The level of IL-8 in the CSF after immunotherapy was four times higher than that before immunotherapy.
CONCLUSION
The cytokine profile of our patient was similar to that seen in severe SARS-CoV-2-related encephalopathy. We demonstrated (i) that the characteristic aphasia can occur as a focal neurological deficit associated with SARS-CoV-2-related encephalopathy, and (ii) that IL8-mediated central nervous system inflammation follows systemic inflammation in SARS-CoV-2-related encephalopathy and can persist and worsen even after immunotherapy. Monitoring IL-8 in CSF, and long-term corticosteroids may be required for treating SARS-CoV-2-related encephalopathy.
Topics: Aged, 80 and over; Aphasia; Brain Diseases; COVID-19; Humans; Interleukin-8; Male; SARS-CoV-2
PubMed: 34727881
DOI: 10.1186/s12883-021-02459-3