-
Transplantation and Cellular Therapy Jun 2022Chimeric antigen receptor (CAR) T cell therapy is a novel therapy for patients with relapsed or refractory hematologic malignancies. Most CAR T cell therapy recipients... (Review)
Review
Clinical Presentation, Risk Factors, and Outcomes of Immune Effector Cell-Associated Neurotoxicity Syndrome Following Chimeric Antigen Receptor T Cell Therapy: A Systematic Review.
Chimeric antigen receptor (CAR) T cell therapy is a novel therapy for patients with relapsed or refractory hematologic malignancies. Most CAR T cell therapy recipients will experience clinical features of the immune effector cell-associated neurotoxicity syndrome (ICANS), a potentially life-threatening condition. Here we describe the clinical, biological, and radiological findings associated with ICANS in adults with hematologic malignancies treated with CAR T cell therapy, as well as the acute and long-term outcomes of ICANS. A literature search of Ovid Medline, Embase, PubMed, Scopus, Web of Science Core Collection, Cochrane Library, and Google Scholar was conducted from each database's inception through February 1, 2022, using search terms reflecting CAR T cell therapy and ICANS. We included studies that enrolled adults (age ≥18 years) who received CAR T cell therapy as management for hematologic malignancies and reported the clinical presentation, predictors, and/or acute or long-term outcomes of ICANS. Two reviewers independently extracted data following the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analysis) reporting guidelines. Quality was assessed using the Joanna Briggs Institute critical appraisal tool for cohort studies. Of the 2928 studies screened, 23 observational studies (10 prospective, 11 retrospective, 1 mixed design, and 1 cross-sectional) with a total of 1666 participants met our eligibility criteria and were included in our review. The most common hematologic malignancies were diffuse large B cell lymphoma, acute lymphocytic leukemia, non-Hodgkin lymphoma, and chronic lymphocytic leukemia. ICANS onset was most often associated with the presence and severity of cytokine release syndrome, as well as with C-reactive protein and ferritin levels. Aphasia was the most common ICANS-related symptom reported, although the neurologic manifestations of ICANS were highly variable. Neuroimaging studies (magnetic resonance imaging or computed tomography) were often normal in cases of ICANS; however, electroencephalography often showed generalized background slowing, abnormal rhythmic, and periodic discharge patterns. The pooled mean (± SD) onset of ICANS was 6.4 ± 3.2 days, with a pooled mean duration of 8.3 ± 10.5 days. Two of the 23 studies (9%) reported 5 ICANS-related deaths among 233 participants. A subset of patients experienced persistent neurocognitive complaints at ≥1-year after CAR T cell therapy. The clinical presentation, onset, severity, long-term sequelae, and grading system of ICANS are variable. Future studies should consider using a consensus grading/reporting scale that would permit cross-trial comparisons of the safety profile of various CAR T cell products and enable the development of interventions to mitigate or manage these neurotoxicities. © 2022 American Society for Transplantation and Cellular Therapy. Published by Elsevier Inc. This systematic review was conducted according to a published protocol (PROSPERO CRD42020207864) and followed the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) and Synthesis without Meta-Analysis (SWiM) in systematic review reporting guidelines (Supplementary Table S1) [15,16].
Topics: Adult; Cell- and Tissue-Based Therapy; Cross-Sectional Studies; Hematologic Neoplasms; Humans; Immunotherapy, Adoptive; Neurotoxicity Syndromes; Prospective Studies; Receptors, Chimeric Antigen; Retrospective Studies; Risk Factors
PubMed: 35288347
DOI: 10.1016/j.jtct.2022.03.006 -
Asian Spine Journal Oct 2022In this systematic review and meta-analysis, we aim to thoroughly describe and objectively compare the efficacy of anterior cervical plate (ACP) and stand-alone cage...
Thorough Comparative Analysis of Stand-Alone Cage and Anterior Cervical Plate for Anterior Cervical Discectomy and Fusion in the Treatment of Cervical Degenerative Disease: A Systematic Review and Meta-analysis.
In this systematic review and meta-analysis, we aim to thoroughly describe and objectively compare the efficacy of anterior cervical plate (ACP) and stand-alone cage (SAC). Although recognized as an effective procedure for cervical degenerative disease (CDD), a debate between the methods of anterior cervical discectomy and fusion exists. ACP provides stability to the fusion construct; however, some complications have been reported, such as dysphagia, adjacent disc disease, and soft tissue injury. To overcome these complications, a SAC was later introduced. A systematic search was conducted on the basis of PRISMA (preferred reporting items for systematic reviews and meta-analyses) guidelines to identify relevant studies through PubMed, Google Scholar, and Cochrane database. A total of 14 studies (960 patients) were included in the meta-analysis. Twenty outcomes were clinically and radiologically compared between the two procedures. ACP and SAC were comparable in terms of dysphasia rate, loss of segmental angle, loss of disc height, the Odom criteria, Robinson's criteria, hospital stay, Japanese Orthopaedic Association score, Neck Disability Index, Visual Analog Scale, and fusion time. However, SAC was superior in terms of shorter operation time, less blood loss, lower dysphagia rate, and lower rate of adjacent level disease, whereas ACP was advantageous in terms of lower subsidence rate, better maintenance of the cervical global and segmental angles and disc height, and higher fusion rate. Both procedures can be used in patients with CDD, although it might be more beneficial to choose ACP in patients with multi-level pathologies, wherein better mechanical stability is provided. However, SAC may be more beneficial to use in patients with comorbidities, anemia, or swelling problems because it offers lower complication rates.
PubMed: 35263831
DOI: 10.31616/asj.2021.0123 -
Frontiers in Neuroscience 2021Melodic intonation therapy (MIT) is a melodic musical training method that could be combined with language rehabilitation. However, some of the existing literature...
Melodic intonation therapy (MIT) is a melodic musical training method that could be combined with language rehabilitation. However, some of the existing literature focuses on theoretical mechanism research, while others only focus on clinical behavioral evidence. Few clinical experimental studies can combine the two for behavioral and mechanism analysis. This review aimed at systematizing recent results from studies that have delved explicitly into the MIT effect on non-fluent aphasia by their study design properties, summarizing the findings, and identifying knowledge gaps for future work. MIT clinical trials and case studies were retrieved and teased out the results to explore the validity and relevance of these results. These studies focused on MIT intervention for patients with non-fluent aphasia in stroke recovery period. After retrieving 128 MIT-related articles, 39 valid RCT studies and case reports were provided for analysis. Our summary shows that behavioral measurements at MIT are excessive and provide insufficient evidence of MRI imaging structure. This proves that MIT still needs many MRI studies to determine its clinical evidence and intervention targets. The strengthening of large-scale clinical evidence of imaging observations will result in the clear neural circuit prompts and prediction models proposed for the MIT treatment and its prognosis.
PubMed: 35153655
DOI: 10.3389/fnins.2021.753356 -
Nature Protocols Mar 2022Low-intensity transcranial electrical stimulation (tES), including alternating or direct current stimulation, applies weak electrical stimulation to modulate the... (Review)
Review
Low-intensity transcranial electrical stimulation (tES), including alternating or direct current stimulation, applies weak electrical stimulation to modulate the activity of brain circuits. Integration of tES with concurrent functional MRI (fMRI) allows for the mapping of neural activity during neuromodulation, supporting causal studies of both brain function and tES effects. Methodological aspects of tES-fMRI studies underpin the results, and reporting them in appropriate detail is required for reproducibility and interpretability. Despite the growing number of published reports, there are no consensus-based checklists for disclosing methodological details of concurrent tES-fMRI studies. The objective of this work was to develop a consensus-based checklist of reporting standards for concurrent tES-fMRI studies to support methodological rigor, transparency and reproducibility (ContES checklist). A two-phase Delphi consensus process was conducted by a steering committee (SC) of 13 members and 49 expert panelists through the International Network of the tES-fMRI Consortium. The process began with a circulation of a preliminary checklist of essential items and additional recommendations, developed by the SC on the basis of a systematic review of 57 concurrent tES-fMRI studies. Contributors were then invited to suggest revisions or additions to the initial checklist. After the revision phase, contributors rated the importance of the 17 essential items and 42 additional recommendations in the final checklist. The state of methodological transparency within the 57 reviewed concurrent tES-fMRI studies was then assessed by using the checklist. Experts refined the checklist through the revision and rating phases, leading to a checklist with three categories of essential items and additional recommendations: (i) technological factors, (ii) safety and noise tests and (iii) methodological factors. The level of reporting of checklist items varied among the 57 concurrent tES-fMRI papers, ranging from 24% to 76%. On average, 53% of checklist items were reported in a given article. In conclusion, use of the ContES checklist is expected to enhance the methodological reporting quality of future concurrent tES-fMRI studies and increase methodological transparency and reproducibility.
Topics: Checklist; Consensus; Magnetic Resonance Imaging; Reproducibility of Results; Transcranial Direct Current Stimulation
PubMed: 35121855
DOI: 10.1038/s41596-021-00664-5 -
Archives of Rehabilitation Research and... Dec 2021To determine the aims, participants, and outcomes of training communication partners of Chinese-speaking persons with aphasia (PWA). (Review)
Review
OBJECTIVE
To determine the aims, participants, and outcomes of training communication partners of Chinese-speaking persons with aphasia (PWA).
DATA SOURCES
Sixty search terms related to communication partner training (CPT) in Chinese characters were searched in 8 electronic databases (published 1991-2020).
STUDY SELECTION
Journal articles written in Chinese that primarily target the Chinese audience and university theses were selected for review. Studies involving CPT and training to enable communication partner to deliver language tasks were included, but reports without PWA or direct training of communication partners were excluded. A final corpus of 37 articles, representing publications of group studies, case studies, qualitative studies, and opinion articles, were selected for full review.
DATA EXTRACTION
For all articles, 2 reviewers independently reviewed abstracts, excluding those without PWA or those that did not involve training of communication partners. One reviewer extracted descriptive data of participants with aphasia, communication partners, intervention details of the intervention (purpose, amount, setting, description), outcome measures, results, and clinical guidelines. A second reviewer performed accuracy verifications.
DATA SYNTHESIS
Quality of reviewed articles were classified using the American Academy of Neurology levels of evidence. The current review suggested an evidence base of low to medium quality supporting 2 intervention groups: (1) training partners to deliver therapy tasks and (2) training to improve communication between PWA and their communication partners. There was a higher proportion of persons with acute and subacute aphasia involved in these investigations, suggesting evidence on treatment efficacy of CPT in the acute stage.
CONCLUSIONS
Additional high-quality research with a better methodological quality, for example, randomized controlled trials or experimental design, are required to strengthen the current evidence of CPT. This systematic review suggests that the inclusion of studies published in languages other than English may influence the findings of mainstream reviews relating to aphasia.
PubMed: 34977535
DOI: 10.1016/j.arrct.2021.100152 -
Neuroscience and Biobehavioral Reviews Jan 2022Language assessment in post-comatose patients is difficult due to their limited behavioral repertoire; yet associated language deficits might lead to an underestimation... (Review)
Review
Language assessment in post-comatose patients is difficult due to their limited behavioral repertoire; yet associated language deficits might lead to an underestimation of consciousness levels in unresponsive wakefulness syndrome (UWS) or minimally conscious state (MCS; -/+) diagnoses. We present a systematic review of studies from 2002 assessing residual language abilities with neuroimaging, electrophysiological or behavioral measures in patients with severe brain injury. Eighty-five articles including a total of 2278 patients were assessed for quality. The median percentages of patients showing residual implicit language abilities (i.e., cortical responses to specific words/sentences) were 33 % for UWS, 50 % for MCS- and 78 % for MCS + patients, whereas explicit language abilities (i.e., command-following using brain-computer interfaces) were reported in 20 % of UWS, 33 % of MCS- and 50 % of MCS + patients. Cortical responses to verbal stimuli increased along with consciousness levels and the progressive recovery of consciousness after a coma was paralleled by the reappearance of both implicit and explicit language processing. This review highlights the importance of language assessment in patients with disorders of consciousness.
Topics: Consciousness; Consciousness Disorders; Humans; Language; Persistent Vegetative State; Wakefulness
PubMed: 34864003
DOI: 10.1016/j.neubiorev.2021.12.001 -
Stroke Mar 2022Optimizing speech and language therapy (SLT) regimens for maximal aphasia recovery is a clinical research priority. We examined associations between SLT intensity... (Meta-Analysis)
Meta-Analysis
BACKGROUND AND PURPOSE
Optimizing speech and language therapy (SLT) regimens for maximal aphasia recovery is a clinical research priority. We examined associations between SLT intensity (hours/week), dosage (total hours), frequency (days/week), duration (weeks), delivery (face to face, computer supported, individual tailoring, and home practice), content, and language outcomes for people with aphasia.
METHODS
Databases including MEDLINE and Embase were searched (inception to September 2015). Published, unpublished, and emerging trials including SLT and ≥10 individual participant data on aphasia, language outcomes, and time post-onset were selected. Patient-level data on stroke, language, SLT, and trial risk of bias were independently extracted. Outcome measurement scores were standardized. A statistical inferencing, one-stage, random effects, network meta-analysis approach filtered individual participant data into an optimal model examining SLT regimen for overall language, auditory comprehension, naming, and functional communication pre-post intervention gains, adjusting for a priori-defined covariates (age, sex, time poststroke, and baseline aphasia severity), reporting estimates of mean change scores (95% CI).
RESULTS
Data from 959 individual participant data (25 trials) were included. Greatest gains in overall language and comprehension were associated with >20 to 50 hours SLT dosage (18.37 [10.58-26.16] Western Aphasia Battery-Aphasia Quotient; 5.23 [1.51-8.95] Aachen Aphasia Test-Token Test). Greatest clinical overall language, functional communication, and comprehension gains were associated with 2 to 4 and 9+ SLT hours/week. Greatest clinical gains were associated with frequent SLT for overall language, functional communication (3-5+ days/week), and comprehension (4-5 days/week). Evidence of comprehension gains was absent for SLT ≤20 hours, <3 hours/week, and ≤3 days/week. Mixed receptive-expressive therapy, functionally tailored, with prescribed home practice was associated with the greatest overall gains. Relative variance was <30%. Risk of trial bias was low to moderate; low for meta-biases.
CONCLUSIONS
Greatest language recovery was associated with frequent, functionally tailored, receptive-expressive SLT, with prescribed home practice at a greater intensity and duration than reports of usual clinical services internationally. These exploratory findings suggest critical therapeutic ranges, informing hypothesis-testing trials and tailoring of clinical services. Registration: URL: https://www.crd.york.ac.uk/PROSPERO/; Unique identifier: CRD42018110947.
Topics: Aphasia; Humans; Language Therapy; Network Meta-Analysis; Stroke; Stroke Rehabilitation
PubMed: 34847708
DOI: 10.1161/STROKEAHA.121.035216 -
Clinical Microbiology and Infection :... May 2022Lyme neuroborreliosis (LNB) presenting with encephalitis is rare and scarcely described. (Review)
Review
BACKGROUND
Lyme neuroborreliosis (LNB) presenting with encephalitis is rare and scarcely described.
OBJECTIVES
To describe the available literature on LNB encephalitis and to characterize this patient group through a Scandinavian retrospective cohort study.
DATA SOURCES
Medline, Embase, Scopus, Cochrane library.
STUDY ELIGIBILITY CRITERIA
There was no discrimination on study type, time of publication or language.
PARTICIPANTS
Review: All articles with definite LNB and confirmed/possible encephalitis.
COHORT
LNB cohorts from Denmark, Sweden and Norway 1990-2019 were screened for patients with encephalitis.
METHODS
Review: Adhering to PRISMA guidelines; two authors extracted reviews and assessed quality of studies.
COHORT
Data on demography, symptoms, cerebrospinal fluid findings, differential diagnostic examinations, treatment, residual symptoms, 1-year mortality were registered.
RESULTS
Review: 2330 articles screened on title/abstract, 281 full texts, yielding 42 articles (case reports/series or cohort studies), including 45 patients from 18 countries spanning 35 years. Altered mental status ranged from personality changes and confusion to unconsciousness. Common focal symptoms were hemiparesis, ataxia and dysarthria; seven patients had seizures. Median time from symptom onset to hospital was 2 weeks (IQR 2-90 days). Of 38 patients with available follow-up after median 12 months (IQR 5-13), 32 had fully or partially recovered, two had died.
COHORT
Thirty-five patients (median age 67 years, IQR 48-76) were included. The encephalitis prevalence was 3.3% (95% CI 2.2-4.4%) among 1019 screened LNB patients. Frequent encephalitis symptoms were confusion, personality changes, aphasia, ataxia. EEGs and neuroimaging showed encephalitis in 93.8% and 20.6%, respectively. Median delay from symptom onset to hospital was 14 days (IQR 7-34), with further 7 days (IQR 3-34) delay until targeted therapy. At follow-up (median 298 days post-treatment; IQR 113-389), 65.6% had residual symptoms. None had died.
CONCLUSIONS
This study shows that encephalitis is an uncommon, but likely overlooked clinical manifestation of LNB. As the high frequency of residual symptoms may be related to prolonged treatment delay, prompt LNB testing of patients with encephalitis in Borrelia burgdorferi-endemic areas should be considered.
Topics: Aged; Ataxia; Cohort Studies; Encephalitis; Humans; Lyme Neuroborreliosis; Retrospective Studies
PubMed: 34768019
DOI: 10.1016/j.cmi.2021.11.001 -
Frontiers in Human Neuroscience 2021In post-stroke aphasia, language tasks recruit a combination of residual regions within the canonical language network, as well as regions outside of it in the left and...
In post-stroke aphasia, language tasks recruit a combination of residual regions within the canonical language network, as well as regions outside of it in the left and right hemispheres. However, there is a lack of consensus as to how the neural resources engaged by language production and comprehension following a left hemisphere stroke differ from one another and from controls. The present meta-analysis used activation likelihood estimates to aggregate across 44 published fMRI and PET studies to characterize the functional reorganization patterns for expressive and receptive language processes in persons with chronic post-stroke aphasia (PWA). Our results in part replicate previous meta-analyses: we find that PWA activate residual regions within the left lateralized language network, regardless of task. Our results extend this work to show differential recruitment of the left and right hemispheres during language production and comprehension in PWA. First, we find that PWA engage left perilesional regions during language comprehension, and that the extent of this activation is likely driven by stimulus type and domain-general cognitive resources needed for task completion. In contrast to comprehension, language production was associated with activation of the right frontal and temporal cortices. Further analyses linked right hemisphere regions involved in motor speech planning for language production with successful naming in PWA, while unsuccessful naming was associated with the engagement of the right inferior frontal gyrus, a region often implicated in domain-general cognitive processes. While the within-group findings indicate that the engagement of the right hemisphere during language tasks in post-stroke aphasia differs for expressive vs. receptive tasks, the overall lack of major between-group differences between PWA and controls implies that PWA rely on similar cognitive-linguistic resources for language as controls. However, more studies are needed that report coordinates for PWA and controls completing the same tasks in order for future meta-analyses to characterize how aphasia affects the neural resources engaged during language, particularly for specific tasks and as a function of behavioral performance.
PubMed: 34759804
DOI: 10.3389/fnhum.2021.680933 -
Frontiers in Aging Neuroscience 2021A variety of tDCS approaches has been used to investigate the potential of tDCS to improve language outcomes, or slow down the decay of language competences caused by...
A variety of tDCS approaches has been used to investigate the potential of tDCS to improve language outcomes, or slow down the decay of language competences caused by Primary Progressive Aphasia (PPA). The employed stimulation protocols and study designs in PPA are generally speaking similar to those deployed in post-stroke aphasic populations. These two etiologies of aphasia however differ substantially in their pathophysiology, and for both conditions the optimal stimulation paradigm still needs to be established. A systematic review was done and after applying inclusion and exclusion criteria, 15 articles were analyzed focusing on differences and similarities across studies especially focusing on PPA patient characteristics (age, PPA variant, language background), tDCS stimulation protocols (intensity, frequency, combined therapy, electrode configuration) and study design as recent reviews and group outcomes for individual studies suggest tDCS is an effective tool to improve language outcomes, while methodological approach and patient characteristics are mentioned as moderators that may influence treatment effects. We found that studies of tDCS in PPA have clinical and methodological and heterogeneity regarding patient populations, stimulation protocols and study design. While positive group results are usually found irrespective of these differences, the magnitude, duration and generalization of these outcomes differ when comparing stimulation locations, and when results are stratified according to the clinical variant of PPA. We interpret the results of included studies in light of patient characteristics and methodological decisions. Further, we highlight the role neuroimaging can play in study protocols and interpreting results and make recommendations for future work.
PubMed: 34690737
DOI: 10.3389/fnagi.2021.710818