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Pharmaceuticals (Basel, Switzerland) May 2024Immunotherapy with chimeric antigen receptor T (CAR-T) cell therapies has brought substantial improvement in clinical outcomes in patients with relapsed/refractory B... (Review)
Review
Immunotherapy with chimeric antigen receptor T (CAR-T) cell therapies has brought substantial improvement in clinical outcomes in patients with relapsed/refractory B cell neoplasms. However, complications such as cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS) limit the therapeutic efficacy of this treatment approach. ICANS can have a broad range of clinical manifestations, while various scoring systems have been developed for its grading. Cognitive decline is prevalent in CAR-T therapy recipients including impaired attention, difficulty in item naming, and writing, agraphia, and executive dysfunction. In this review, we aim to present the diagnostic methods and tests that have been used for the recognition of cognitive impairment in these patients. Moreover, up-to-date data about the duration of cognitive impairment symptoms after the infusion are presented. More research on the risk factors, pathogenesis, preventive measures, and therapy of neurocognitive impairment is crucial for better outcomes for our patients.
PubMed: 38794161
DOI: 10.3390/ph17050591 -
Frontiers in Neuroinformatics 2022Parkinson's disease dysgraphia (PDYS), one of the earliest signs of Parkinson's disease (PD), has been researched as a promising biomarker of PD and as the target of a...
Parkinson's disease dysgraphia (PDYS), one of the earliest signs of Parkinson's disease (PD), has been researched as a promising biomarker of PD and as the target of a noninvasive and inexpensive approach to monitoring the progress of the disease. However, although several approaches to supportive PDYS diagnosis have been proposed (mainly based on handcrafted features (HF) extracted from online handwriting or the utilization of deep neural networks), it remains unclear which approach provides the highest discrimination power and how these approaches can be transferred between different datasets and languages. This study aims to compare classification performance based on two types of features: features automatically extracted by a pretrained convolutional neural network (CNN) and HF designed by human experts. Both approaches are evaluated on a multilingual dataset collected from 143 PD patients and 151 healthy controls in the Czech Republic, United States, Colombia, and Hungary. The subjects performed the spiral drawing task (SDT; a language-independent task) and the sentence writing task (SWT; a language-dependent task). Models based on logistic regression and gradient boosting were trained in several scenarios, specifically single language (SL), leave one language out (LOLO), and all languages combined (ALC). We found that the HF slightly outperformed the CNN-extracted features in all considered evaluation scenarios for the SWT. In detail, the following balanced accuracy (BACC) scores were achieved: SL-0.65 (HF), 0.58 (CNN); LOLO-0.65 (HF), 0.57 (CNN); and ALC-0.69 (HF), 0.66 (CNN). However, in the case of the SDT, features extracted by a CNN provided competitive results: SL-0.66 (HF), 0.62 (CNN); LOLO-0.56 (HF), 0.54 (CNN); and ALC-0.60 (HF), 0.60 (CNN). In summary, regarding the SWT, the HF outperformed the CNN-extracted features over 6% (mean BACC of 0.66 for HF, and 0.60 for CNN). In the case of the SDT, both feature sets provided almost identical classification performance (mean BACC of 0.60 for HF, and 0.58 for CNN).
PubMed: 35722168
DOI: 10.3389/fninf.2022.877139 -
Journal of Family Medicine and Primary... Aug 2023Specific learning disability (SLD) is a cognitive neurobiological disorder caused by atypical brain functioning. SLD is recognized when the individual's achievement in...
BACKGROUND
Specific learning disability (SLD) is a cognitive neurobiological disorder caused by atypical brain functioning. SLD is recognized when the individual's achievement in school is below that expected for age, schooling, and level of intelligence. Screening millions of students with SLD by health personnel is a logistical impossibility. Awareness and knowledge about learning disorders among schoolteachers may play a major role in the early identification and management of children with these disorders. Therefore, the assessment of teachers' knowledge and perceptions about learning disabilities (LDs) is relevant.
METHOD
A school-based cross-sectional study was conducted among teachers in government/government-aided and private schools in Vellore, India. The participants were selected by a simple random sampling method. There was a total of 80 teachers included in the study. Data capture was done using a questionnaire. A Chi-square test was done to test the association and the odds ratio test helped determine the strength of the association. A value of <0.05 was considered to be statistically significant.
RESULTS
The majority of the teachers (70%) had adequate general knowledge regarding LDs. When analyzed separately, 82.5% of government/aided teachers and only 57.5% of teachers were having adequate general knowledge regarding LDs. There was a significant association between the type of school and general knowledge regarding LDs. Government/aided teachers had better general knowledge regarding LDs and dyslexia than private teachers.
CONCLUSIONS
Among 80 teachers, 70% (56) of them had adequate general knowledge regarding LDs. When analyzed separately, 82.5% (33) of government/aided teachers and only 57.5% (23) teachers were having adequate general knowledge regarding LDs. The government/aided schoolteachers had significantly higher levels of knowledge in most domains of the general knowledge section as compared to private schoolteachers. If teachers are having adequate knowledge regarding LDs, it will significantly increase the chances of children with LDs getting detected early and undergoing the treatment they require. Teacher education programs and workshops are needed to be conducted at regular intervals to improve the knowledge regarding SLDs among teachers.
PubMed: 37767410
DOI: 10.4103/jfmpc.jfmpc_2018_22 -
JMIR Serious Games May 2021Specific learning difficulties (SpLD) include several disorders such as dyslexia, dyscalculia, and dysgraphia, and the children with these SpLD receive special...
BACKGROUND
Specific learning difficulties (SpLD) include several disorders such as dyslexia, dyscalculia, and dysgraphia, and the children with these SpLD receive special education. However, the studies and the educational material so far focus mainly on one specific disorder.
OBJECTIVE
This study's primary goal is to develop comprehensive training material for different types of SpLD, with five serious games addressing different aspects of the SpLD. The second focus is measuring the impact of adaptive difficulty level adjustment in the children's and their educators' usability and technology acceptance perception. Receiving feedback from the children and their educators, and refining the games according to their suggestions have also been essential in this two-phase study.
METHODS
A total of 10 SpLD educators and 23 children with different types of SpLD tested the prototypes of the five serious games (ie, Word game, Memory game, Category game, Space game, and Math game), gave detailed feedback, answered the System Usability Scale and Technology Acceptance Model (TAM) questionnaires, and applied think-aloud protocols during game play.
RESULTS
The games' standard and adaptive versions were analyzed in terms of average playtime and the number of false answers. Detailed analyses of the interviews, with word clouds and player performances, were also provided. The TAM questionnaires' average and mean values and box plots of each data acquisition session for the children and the educators were also reported via System Usability Scale and TAM questionnaires. The TAM results of the educators had an average of 8.41 (SD 0.87) out of 10 in the first interview and an average of 8.71 (SD 0.64) out of 10 in the second interview. The children had an average of 9.07 (SD 0.56) out of 10 in the first interview.
CONCLUSIONS
Both the educators and the children with SpLD enjoyed playing the games, gave positive feedback, and suggested new ways for improvement. The results showed that these games provide thorough training material for different types of SpLD with personalized and tailored difficulty systems. The final version of the proposed games will become a part of the special education centers' supplementary curriculum and training materials, making new enhancements and improvements possible in the future.
PubMed: 34057415
DOI: 10.2196/25997 -
Children (Basel, Switzerland) May 2023In Switzerland, psychomotor therapy (PMT) is a standard treatment for children with graphomotor impairments, but scientific evidence of its effectiveness is rare. To...
In Switzerland, psychomotor therapy (PMT) is a standard treatment for children with graphomotor impairments, but scientific evidence of its effectiveness is rare. To investigate the effectiveness of PMT, we conducted a randomised field trial (RFT). The sample consisted of 121 first and second graders with graphomotor impairments, some of whom met the criteria of developmental coordination disorder, while the remaining suffered from developmental dysgraphia. The treatments lasted over 5 months. Handwriting fluency and consistency were measured five times on a digitising tablet. All participating children completed a self-concept interview, and a standardised fine motor performance test twice. Psychomotor therapy significantly improved the fine motor skills of the therapy group compared to those of the waiting group. However, there was no evidence that the treated children improved more than the waiting children in terms of their graphomotor skills such as frequency, automaticity, and consistency of forming letters. Finally, the children of the therapy group showed partial improvements in their handwriting self-concept, while those of the waiting group children remained stable. This short-term RFT demonstrated the effectiveness of PMT in terms of fine motor skills and some aspects of the handwriting self-concept but showed no effects on handwriting fluency and consistency.
PubMed: 37371196
DOI: 10.3390/children10060964 -
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 -
Cureus Jun 2021Gerstmann syndrome is a neurobehavioral syndrome characterized by four cardinal symptoms: acalculia, agraphia, finger-toe agnosia, and dysgraphia. The syndrome is caused...
Gerstmann syndrome is a neurobehavioral syndrome characterized by four cardinal symptoms: acalculia, agraphia, finger-toe agnosia, and dysgraphia. The syndrome is caused primarily by lesions at the confluence of parietal, temporal, and occipital lobes, but also can involve the middle frontal lobe of the dominant hemisphere. Documented inciting lesions include stroke, tumor, hemorrhage, arteriovenous malformations, and seizures. A meningeal solitary fibrous tumor (SFT)/hemangiopericytoma (HPC) is a diagnostic challenge due to its resemblance to more common brain tumors like meningioma, with histopathology being the definitive diagnostic test. A 37-year-old male presented to our tertiary center with blurred vision, "not being himself," and "acting funny" for three weeks. On exam, he was found to have a right inferior quadrantanopia, grade II papilledema and demonstrated all four symptoms of Gerstmann syndrome - inability to perform simple calculations (acalculia), or identify his fingers (finger agnosia), could not distinguish his left side from the right (left-right disorientation), nor write out his name (agraphia). Brain imaging showed an extra-axial, highly vascularized 7.6-cm mass compressing the left parietal lobe. He underwent a complete resection of the mass. Postoperatively, he had gradual improvement with complete resolution of agraphia, acalculia, finger agnosia, and left-right disorientation within a week status post-resection. Tumor pathology indicated hemangiopericytoma/solitary fibrous tumor. This case enunciates the enigmatic tetrad of Gerstmann syndrome. Though classically described as a sequela of stroke, the mass effect of the tumor on the parietal lobe may produce the symptoms, which can resolve following resection.
PubMed: 34327089
DOI: 10.7759/cureus.15863 -
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 -
Children (Basel, Switzerland) Feb 2023The purpose of this study was to analyze the relationship between the quality and speed of handwriting and the process characteristics of the handwriting of children in...
The purpose of this study was to analyze the relationship between the quality and speed of handwriting and the process characteristics of the handwriting of children in the second grade of elementary school considered as a function of age and gender. A sample of 57 children (mean age 7.25 years, SD 0.43) participated in the study. The Concise Assessment Method for Children's Handwriting (BHK) was used to assess the quality and speed of handwriting. The characteristics of the process of handwriting were assessed using MovAlyzeR software. The handwriting of boys showed a significantly greater number of strokes and slanted more to the right than the handwriting of girls. Handwriting quality and speed significantly correlated with several process characteristics: the number of strokes, reaction time, duration, relative pen-down duration, average pen pressure, vertical size, horizontal size, road length, and average absolute velocity. This research contributes to the construction of normative values in the process characteristics of the handwriting of elementary school children and provides a promising step towards the early identification of difficulties that can lead to dysgraphia, thus preventing later difficulties in handwriting.
PubMed: 36980003
DOI: 10.3390/children10030445 -
Frontiers in Neurology 2021Micrographia, one element of the dysgraphia of Parkinson's disease (PD), may be classified according to the presence or absence of a decremental pattern. The...
Micrographia, one element of the dysgraphia of Parkinson's disease (PD), may be classified according to the presence or absence of a decremental pattern. The decremental form, progressive micrographia, is an expression of the sequence effect seen generally in bradykinesia. Its responsiveness to levodopa has not been evaluated kinematically. Aim of this study is to investigate the difference in levodopa response for progressive and non-progressive micrographia. Twenty-four PD patients and 24 age-matched repeatedly wrote the letter e on a computerized digital tablet. PD patients performed the task two times, in a defined off state and again after levodopa. Scripts were classified as progressive micrographia (PD) or non-progressive micrographia (PD) depending on whether a 10% decrement was seen between the first and final characters of a line of lettering. While levodopa produced a similar response on the MDS-UPDRS motor scale for the two groups, the effect on the two types of micrographia was different. While writing speed improved significantly in both groups after levodopa, the responses were over twofold greater for PD Moreover, the decremental features of PD-in size, speed, and pen-pressure-were largely unaltered by a levodopa dose. Progressive micrographia is less responsive to levodopa. Our findings agree with research showing that the sequence effect of bradykinesia is relatively resistant to medication. Yet we did not find a weaker overall levodopa motor benefit. Caution is needed in the interpretation of such micrographia measurements for estimating drug responses.
PubMed: 34046005
DOI: 10.3389/fneur.2021.665112