Neuroplasticity and Motor Rehabilitation in Multiple Sclerosis: A Systematic Review on MRI Markers of Functional and Structural Changes

Background: Motor rehabilitation is routinely used in clinical practice as an effective method to reduce progressive disability gain in multiple sclerosis (MS), but rehabilitation approaches are typically unstandardized, and only few studies have investigated the impact of rehabilitation on brain neuroplasticity.Objective: To summarize and critically analyze studies applying MRI markers of functional connectivity and structural changes to assess the effect of motor rehabilitation on brain neuroplasticity in MS.Methods: Literature search was performed using PubMed and EMBASE, selecting studies having as a subject motor rehabilitation and advanced MRI techniques investigating neuroplasticity in adult patients affected by MS.Results: Seventeen out of 798 papers were selected, of which 5 applied structural MRI (4 diffusion tensor imaging, 1 volumetric measurements), 7 applied functional fMRI (5 task-related fMRI, 2 resting-state fMRI) whereas the remaining 5 applied both structural and functional imaging.Discussion: The considerable data heterogeneity and the small sample sizes characterizing the studies limit interpretation and generalization of the results. Overall, motor rehabilitation promotes clinical improvement, paralleled by positive adaptive brain changes, whose features and extent depend upon different variables, including the type of rehabilitation approach. MRI markers of functional and structural connectivity should be implemented in studies testing the efficacy of motor rehabilitation. They allow for a better understanding of neuroplastic mechanisms underlying rehabilitation-mediated clinical achievements, facilitating the identification of rehabilitation strategies tailored to patients' needs and abilities.

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Viscoelastometric Testing to Assess Hemostasis of COVID-19: A Systematic Review

Journal of Clinical Medicine ◽

10.3390/jcm10081740 ◽

2021 ◽

Vol 10 (8) ◽

pp. 1740

Author(s):

Marion Bareille ◽

Michaël Hardy ◽

Jonathan Douxfils ◽

Stéphanie Roullet ◽

Dominique Lasne ◽

...

Keyword(s):

Systematic Review ◽

Mechanical Strength ◽

Small Sample ◽

The Common ◽

Small Sample Sizes ◽

Definition Of ◽

Reported Data ◽

Prophylactic Anticoagulation ◽

The Impact ◽

Heparin Neutralization

Infection by SARS-CoV-2 is associated with a high risk of thrombosis. The laboratory documentation of hypercoagulability and impaired fibrinolysis remains a challenge. Our aim was to assess the potential usefulness of viscoelastometric testing (VET) to predict thrombotic events in COVID-19 patients according to the literature. We also (i) analyzed the impact of anticoagulation and the methods used to neutralize heparin, (ii) analyzed whether maximal clot mechanical strength brings more information than Clauss fibrinogen, and (iii) critically scrutinized the diagnosis of hypofibrinolysis. We performed a systematic search in PubMed and Scopus databases until December 31st, 2020. VET methods and parameters, and patients’ features and outcomes were extracted. VET was performed for 1063 patients (893 intensive care unit (ICU) and 170 non-ICU, 44 studies). There was extensive heterogeneity concerning study design, VET device used (ROTEM, TEG, Quantra and ClotPro) and reagents (with non-systematic use of heparin neutralization), timing of assay, and definition of hypercoagulable state. Notably, only 4 out of 25 studies using ROTEM reported data with heparinase (HEPTEM). The common findings were increased clot mechanical strength mainly due to excessive fibrinogen component and impaired to absent fibrinolysis, more conspicuous in the presence of an added plasminogen activator. Only 4 studies out of the 16 that addressed the point found an association of VETs with thrombotic events. So-called functional fibrinogen assessed by VETs showed a variable correlation with Clauss fibrinogen. Abnormal VET pattern, often evidenced despite standard prophylactic anticoagulation, tended to normalize after increased dosing. VET studies reported heterogeneity, and small sample sizes do not support an association between the poorly defined prothrombotic phenotype of COVID-19 and thrombotic events.

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Estimation of annual probabilities of changing disability levels in Australians with relapsing-remitting multiple sclerosis

Multiple Sclerosis Journal ◽

10.1177/1352458518806103 ◽

2018 ◽

Vol 25 (13) ◽

pp. 1800-1808 ◽

Cited By ~ 2

Author(s):

Hasnat Ahmad ◽

Ingrid van der Mei ◽

Bruce V Taylor ◽

Robyn M Lucas ◽

Anne-Louise Ponsonby ◽

...

Keyword(s):

Multiple Sclerosis ◽

Transition Probabilities ◽

Age At Onset ◽

Small Sample ◽

Severe Disability ◽

Economic Evaluations ◽

Combining Data ◽

Relapsing Remitting ◽

Mild Disability ◽

Small Sample Sizes

Background: Transition probabilities are the engine within many health economics decision models. However, the probabilities of progression of disability due to multiple sclerosis (MS) have not previously been estimated in Australia. Objectives: To estimate annual probabilities of changing disability levels in Australians with relapsing-remitting MS (RRMS). Methods: Combining data from Ausimmune/Ausimmune Longitudinal (2003–2011) and Tasmanian MS Longitudinal (2002–2005) studies ( n = 330), annual transition probabilities were obtained between no/mild (Expanded Disability Status Scale (EDSS) levels 0–3.5), moderate (EDSS 4–6.0) and severe (EDSS 6.5–9.5) disability. Results: From no/mild disability, 6.4% (95% confidence interval (CI): 4.7–8.4) and 0.1% (0.0–0.2) progressed to moderate and severe disability annually, respectively. From moderate disability, 6.9% (1.0–11.4) improved (to no/mild state) and 2.6% (1.1–4.5) worsened. From severe disability, 0.0% improved to moderate and no/mild disability. Male sex, age at onset, longer disease duration, not using immunotherapies greater than 3 months and a history of relapse were related to higher probabilities of worsening. Conclusion: We have estimated probabilities of changing disability levels in Australians with RRMS. Probabilities differed between various subgroups, but due to small sample sizes, results should be interpreted with caution. Our findings will be helpful in predicting long-term disease outcomes and in health economic evaluations of MS.

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Cannabis and breastfeeding

Paediatrics & Child Health ◽

10.1093/pch/pxaa037 ◽

2020 ◽

Vol 25 (Supplement_1) ◽

pp. S26-S28 ◽

Cited By ~ 1

Author(s):

Lisa Graves

Keyword(s):

Health Care Providers ◽

Small Sample ◽

Adverse Outcomes ◽

Care Providers ◽

High Quality ◽

High Quality Evidence ◽

Small Sample Sizes ◽

The Impact ◽

Quality Evidence

Abstract Cannabis is one of the most commonly used substances in Canada with 15% of Canadians reporting use in 2019. There is emerging evidence that cannabis is linked to an impact on the developing brain in utero and adverse outcomes in infants, children, and adolescents. The impact of cannabis during breastfeeding has been limited by studies with small sample sizes, follow-up limited to 1 year and the challenge of separating prenatal exposure from that during breastfeeding. In the absence of high-quality evidence, health care providers need to continue to engage women in conversation about the potential concerns related to breastfeeding and cannabis use.

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Connectivity changes in major depressive disorder after rTMS: a review of functional and structural connectivity data

Epidemiology and Psychiatric Sciences ◽

10.1017/s2045796021000482 ◽

2021 ◽

Vol 30 ◽

Author(s):

G. Schiena ◽

G. Franco ◽

A. Boscutti ◽

G. Delvecchio ◽

E. Maggioni ◽

...

Keyword(s):

Diffusion Tensor ◽

Repetitive Transcranial Magnetic Stimulation ◽

Small Sample Size ◽

Structural Connectivity ◽

Unipolar Depression ◽

Brain Regions ◽

Small Sample ◽

Anterior Cingulate ◽

Antidepressant Effect ◽

Dorsolateral Prefrontal

Abstract Aims In the search for effective therapeutic strategies for depression, repetitive transcranial magnetic stimulation (rTMS) emerged as a non-invasive, promising treatment. This is because the antidepressant effect of rTMS might be related to neuronal plasticity mechanisms possibly reverting connectivity alterations often observed in depression. Therefore, in this review, we aimed at providing an overview of the findings reported by studies investigating functional and structural connectivity changes after rTMS in depression. Methods A bibliographic search was conducted on PubMed, including studies that used unilateral, excitatory (⩾10 Hz) rTMS treatment targeted on the left dorsolateral prefrontal cortex (DLPFC) in unipolar depressed patients. Results The majority of the results showed significant TMS-induced changes in functional connectivity (FC) between areas important for emotion regulation, including the DLPFC and the subgenual anterior cingulate cortex, and among regions that are part of the major resting-state networks, such as the Default Mode Network, the Salience Networks and the Central Executive Network. Finally, in diffusion tensor imaging studies, it has been reported that rTMS appeared to increase fractional anisotropy in the frontal lobe. Limitations The small sample size, the heterogeneity of the rTMS stimulation parameters, the concomitant use of psychotropic drugs might have limited the generalisability of the results. Conclusions Overall, rTMS treatment induces structural and FC changes in brain regions and networks implicated in the pathogenesis of unipolar depression. However, whether these changes underlie the antidepressant effect of rTMS still needs to be clarified.

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Real-world data evaluating immunotherapy markers and checkpoint inhibitor response among GI cancers in a large community-based oncology network.

Journal of Clinical Oncology ◽

10.1200/jco.2021.39.3_suppl.113 ◽

2021 ◽

Vol 39 (3_suppl) ◽

pp. 113-113

Author(s):

Carissa Jones ◽

Rebecca Lachs ◽

Emma Sturgill ◽

Amanda Misch ◽

Caressa Lietman ◽

...

Keyword(s):

Checkpoint Inhibitor ◽

Small Sample ◽

Tumor Type ◽

Real World Data ◽

Loss To Follow Up ◽

Kaplan Meier ◽

Gi Cancers ◽

Small Sample Sizes ◽

Line Of Therapy ◽

The Impact

113 Background: Checkpoint inhibitor (CPI) therapies have shown prolonged survival in patients (pts) with microsatellite instability (MSI). Tumor mutation burden (TMB) has also been associated with benefit from CPIs, with pembrolizumab recently approved for solid tumors with a TMB of ≥10 muts/mb. However, the validity of a tissue-agnostic approach has been debated given the high degree of TMB variation across tumor types. We sought to evaluate the impact of TMB and MSI on CPI response in pts with advanced gastrointestinal (GI) cancers who received NGS profiling. Methods: Patients within the Sarah Cannon network with GI cancer and comprehensive next generation sequencing (NGS) data were identified through Genospace, Sarah Cannon’s clinico-genomic analytics platform. Microsatellite (MS) status [high (MSI-H) vs. stable (MSS)] was defined by NGS. TMB-high (TMB-H) was defined as ≥10 muts/mb. Kaplan-Meier estimates were used to examine time to treatment failure (TTF), defined as the time from therapy start to start of next therapy, death, or loss to follow-up. Results: We identified 5,788 pts with GI cancers who received NGS, of which 48% (N=3,603) had colorectal cancer (CRC). MS status was evaluated on 4,219 (66%) NGS reports, TMB on 2,922 (46%) reports, and both on 2,863 (45%) reports. MSI-H and TMB-H co-occurred on 127 reports (4%), MSS/TMB-H occurred on 312 reports (11%), and MSS/TMB-Low (TMB-L) occurred on 2,424 reports (85%). No reports were MSI-H/TMB-L. Overall, 580 pts (14%) received CPI therapy (N=52 MSI-H/TMB-H, N=41 MSS/TMB-H, N=215 MSS/TMB-L). Independent of line of therapy or tumor type, TTF was significantly shorter for CPI vs. non-CPI therapies [median TTF (mTTF)=151 vs. 238 days, respectively, p=3.4x10-9]. As expected, MSI-H was also associated with longer CPI TTF compared to MSS (mTTF=727 vs. 124 days, p=3.1x10-11). Due to small sample sizes, further analyses were focused on pts with CRC (Table). TMB-H was independently associated with longer CPI TTF compared to TMB-L (Table, p=9.2x10-10). Similarly, the co-occurrence of MSI-H/TMB-H was also associated with longer CPI TTF (Table). However, there was no difference in CPI TTF for MSS/TMB-H and MSS/TMB-L (Table, p=0.45). All pts who received non-CPI therapies, regardless of MS/TMB group, had longer TTF than MSS/TMB-H and MSS/TMB-L pts who received CPI (Table). mTTF [days (N)] for pts with CRC by biomarker. Conclusions: Despite recent tissue-agnostic approvals, TMB does not appear to be a good biomarker of CPI response in pts with CRC. Rather, time to CPI failure is associated with the co-occurrence of TMB-H with MSI-H. Continued research is needed to identify better biomarkers of response to immunotherapy in GI cancers. [Table: see text]

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The impact of the 30 most cited articles on hip arthroscopy: what is the subject matter?

Journal of Hip Preservation Surgery ◽

10.1093/jhps/hnz067 ◽

2020 ◽

Vol 7 (1) ◽

pp. 14-21

Author(s):

Alexander von Glinski ◽

Emre Yilmaz ◽

Ryan Goodmanson ◽

Clifford Pierre ◽

Sven Frieler ◽

...

Keyword(s):

Surgical Treatment ◽

Hip Arthroscopy ◽

Randomized Clinical Trials ◽

Technical Note ◽

Small Sample ◽

Level Of Evidence ◽

Thomson Reuters ◽

Treatment Indications ◽

Small Sample Sizes ◽

The Impact

Abstract The purpose of this study was to identify the 30 most cited articles on hip arthroscopy and discuss their influence on recent surgical treatment. Due to advancements in hip arthroscopy, there is a widening spectrum of diagnostic and treatment indications. The purpose of this study was to identify the 30 most cited articles on hip arthroscopy and discuss their influence on contemporary surgical treatment. The Thomson Reuters Web of Science was used to identify the 30 most cited studies on hip arthroscopy between 1900 and 2018. These 30 articles generated 6152 citations with an average of 205.07 citations per item. Number of citations ranged from 146 to 461. Twenty-five out of the 30 papers were clinical cohort studies with a level of evidence between III and IV, encompassing 4348 patients. Four studies were reviewed (one including a technical note) and one a case report. We were able to identify the 30 most cited articles in the field of hip arthroscopy. Most articles were reported in high-impact journals, but reported small sample sizes in a retrospective setting. Prospective multi-arm cohort trials or randomized clinical trials represent opportunities for future studies.

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Repeated Intrathecal Triamcinolone Acetonide Administration in Progressive Multiple Sclerosis: A Review

Multiple Sclerosis International ◽

10.1155/2011/219049 ◽

2011 ◽

Vol 2011 ◽

pp. 1-8 ◽

Cited By ~ 1

Author(s):

Mazen Abu-Mugheisib ◽

Reiner Benecke ◽

Uwe K. Zettl

Keyword(s):

Multiple Sclerosis ◽

Triamcinolone Acetonide ◽

Progressive Multiple Sclerosis ◽

Intrathecal Administration ◽

Small Sample ◽

Walking Distance ◽

Advantages And Disadvantages ◽

Therapy Option ◽

Small Sample Sizes ◽

Selection Of

At the present time, anti-inflammatory, immunomodulatory, or immunosuppressive treatments of multiple sclerosis (MS) are mainly effective in the early phases of the disease but are of less advantage in progressive phases. Current therapeutic strategies of both primary and secondary progressive MS are rare. One alternative may be intrathecal application of triamcinolone acetonide (TCA). Number of papers deal with advantages and disadvantages of intrathecal administration in MS. Former trials lacked detailed selection of MS patients, with small sample sizes, low steroid dosages, and only a small number of intrathecal administration of short acting steroids. The present paper summarizes recent trials performed following a different treatment regime. They were conducted in patients with progressive MS suffering mainly from spinal symptoms and documented a significant improvement of EDSS and walking distance (WD). Intrathecal TCA administration is a proposal to take into account as one therapy option in patients with a progressive clinical course and predominantly spinal symptoms.

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The scale of it all: postcanine tooth size, the taxon-level effect, and the universality of Gould's scaling law

Paleobiology ◽

10.1666/08089.1 ◽

2010 ◽

Vol 36 (2) ◽

pp. 188-203 ◽

Cited By ~ 19

Author(s):

Lynn E. Copes ◽

Gary T. Schwartz

Keyword(s):

Body Mass ◽

Scaling Law ◽

Small Sample ◽

Tooth Size ◽

Mathematical Methods ◽

Scaling Relationship ◽

Small Sample Sizes ◽

Relationship Of ◽

The Impact ◽

Level Effect

In a seminal paper in 1975, Gould proposed that postcanine occlusal area (PCOA) should scale metabolically (0.75) with body mass across mammals. By regressing PCOA against skull length in a small sample of large-bodied herbivorous mammals, Gould provided some marginal support for this hypothesis, which he then extrapolated as a universal scaling law for Mammalia. Since then, many studies have sought to confirm this scaling relationship within a single order and have found equivocal support for Gould's assertion. In part, this may be related to the use of proxies for both PCOA and body mass, small sample sizes, or the influence of a “taxon-level effect,” rendering Gould's scaling “universal” problematic.Our goal was to test the universality of Gould's prediction and the impact of the taxon-level effect on regressions of tooth size on body mass in a large extant mammalian sample (683 species spanning 14 orders). We tested for the presence of two types of taxon-level effect that may influence the acceptance or rejection of hypothesized scaling coefficients. The hypotheses of both metabolic and isometric scaling can be rejected in Mammalia, but not in all sub-groups therein. The level of data aggregation also influences the interpretation of the scaling relationship. Because the scaling relationship of tooth size to body mass is highly dependent on both the taxonomic level of analysis and the mathematical methods used to organize the data, paleontologists attempting to retrodict body mass from fossilized dental remains must be aware of the effect that sample composition may have on their results.

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Diffusion tensor magnetic resonance imaging in very early onset pediatric multiple sclerosis

Multiple Sclerosis Journal ◽

10.1177/1352458515596600 ◽

2015 ◽

Vol 22 (5) ◽

pp. 620-627 ◽

Cited By ~ 9

Author(s):

MA Rocca ◽

M Sonkin ◽

M Copetti ◽

E Pagani ◽

DL Arnold ◽

...

Keyword(s):

Magnetic Resonance Imaging ◽

Multiple Sclerosis ◽

Magnetic Resonance ◽

Structural Integrity ◽

Linear Models ◽

Diffusion Tensor ◽

Mean Diffusivity ◽

Lesion Volume ◽

Resonance Imaging ◽

The Impact

Objectives: Active myelination during childhood may influence the impact of multiple sclerosis (MS) on brain structural integrity. We studied normal-appearing white matter (NAWM) in children with MS onset before age 12 years using diffusion tensor (DT) magnetic resonance imaging (MRI). Methods: DT MRI scans were obtained from 22 MS children with their first attack before age 12 years, and 31 healthy controls from two referral centers. Using probabilistic tractography, brain tissue integrity within interhemispheric, intrahemispheric, and projection tracts was compared between patients and site-matched controls. The impact of disease and age at MRI on tract NAWM fractional anisotropy (FA) and mean diffusivity (MD) values was evaluated using linear models. Results: Compared to controls, pediatric MS patients had reduced FA and increased MD of the bilateral superior longitudinal fasciculus and corpus callosum (CC), without center-by-group interaction. CC NAWM average FA was correlated with brain T2 lesion volume. In controls, the majority of the tracts analyzed showed a significant increase of FA and decrease of MD with age. Such a linear correlation was lost in patients. Conclusions: In very young pediatric MS patients, DT MRI abnormalities affect brain WM tracts differentially, and are only partially correlated with focal WM lesions. Impaired maturation of WM tracts with age may be an additional factor contributing to these findings.

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Structural and Functional Connectivity Substrates of Cognitive Impairment in Multiple Sclerosis

Frontiers in Neurology ◽

10.3389/fneur.2021.671894 ◽

2021 ◽

Vol 12 ◽

Author(s):

Jian Zhang ◽

Rosa Cortese ◽

Nicola De Stefano ◽

Antonio Giorgio

Keyword(s):

Multiple Sclerosis ◽

Cognitive Impairment ◽

Functional Connectivity ◽

Diffusion Tensor ◽

Structural Connectivity ◽

Diffusion Kurtosis Imaging ◽

High Angular Resolution ◽

Diffusion Spectrum Imaging ◽

Analysis Methods ◽

Scan Time

Cognitive impairment (CI) occurs in 43 to 70% of multiple sclerosis (MS) patients at both early and later disease stages. Cognitive domains typically involved in MS include attention, information processing speed, memory, and executive control. The growing use of advanced magnetic resonance imaging (MRI) techniques is furthering our understanding on the altered structural connectivity (SC) and functional connectivity (FC) substrates of CI in MS. Regarding SC, different diffusion tensor imaging (DTI) measures (e.g., fractional anisotropy, diffusivities) along tractography-derived white matter (WM) tracts showed relevance toward CI. Novel diffusion MRI techniques, including diffusion kurtosis imaging, diffusion spectrum imaging, high angular resolution diffusion imaging, and neurite orientation dispersion and density imaging, showed more pathological specificity compared to the traditional DTI but require longer scan time and mathematical complexities for their interpretation. As for FC, task-based functional MRI (fMRI) has been traditionally used in MS to brain mapping the neural activity during various cognitive tasks. Analysis methods of resting fMRI (seed-based, independent component analysis, graph analysis) have been applied to uncover the functional substrates of CI in MS by revealing adaptive or maladaptive mechanisms of functional reorganization. The relevance for CI in MS of SC–FC relationships, reflecting common pathogenic mechanisms in WM and gray matter, has been recently explored by novel MRI analysis methods. This review summarizes recent advances on MRI techniques of SC and FC and their potential to provide a deeper understanding of the pathological substrates of CI in MS.

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