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Scientific Reports May 2024Multiple sclerosis (MS) is a common autoimmune neurological disease affecting patients' motor, sensory, and visual performance. Stem Cell Transplantation (SCT) is a... (Meta-Analysis)
Meta-Analysis
Multiple sclerosis (MS) is a common autoimmune neurological disease affecting patients' motor, sensory, and visual performance. Stem Cell Transplantation (SCT) is a medical intervention where a patient is infused with healthy stem cells with the purpose of resetting their immune system. SCT shows remyelinating and immunomodulatory functions in MS patients, representing a potential therapeutic option. We conducted this systematic review and meta-analysis that included randomized control trials (RCTs) of SCT in MS patients to investigate its clinical efficacy and safety, excluding observational and non-English studies. After systematically searching PubMed, Web of Science, Scopus, and Cochrane Library until January 7, 2024, nine RCTs, including 422 patients, were eligible. We assessed the risk of bias (ROB) in these RCTs using Cochrane ROB Tool 1. Data were synthesized using Review Manager version 5.4 and OpenMeta Analyst software. We also conducted subgroup and sensitivity analyses. SCT significantly improved patients expanded disability status scale after 2 months (N = 39, MD = - 0.57, 95% CI [- 1.08, - 0.06], p = 0.03). SCT also reduced brain lesion volume (N = 136, MD = - 7.05, 95% CI [- 10.69, - 3.4], p = 0.0002). The effect on EDSS at 6 and 12 months, timed 25-foot walk (T25-FW), and brain lesions number was nonsignificant. Significant adverse events (AEs) included local reactions at MSCs infusion site (N = 25, RR = 2.55, 95% CI [1.08, 6.03], p = 0.034) and hematological disorders in patients received immunosuppression and autologous hematopoietic SCT (AHSCT) (N = 16, RR = 2.33, 95% CI [1.23, 4.39], p = 0.009). SCT can improve the disability of MS patients and reduce their brain lesion volume. The transplantation was generally safe and tolerated, with no mortality or significant serious AEs, except for infusion site reactions after mesenchymal SCT and hematological AEs after AHSCT. However, generalizing our results is limited by the sparse number of RCTs conducted on AHSCT. Our protocol was registered on PROSPERO with a registration number: CRD42022324141.
Topics: Humans; Multiple Sclerosis; Randomized Controlled Trials as Topic; Stem Cell Transplantation; Treatment Outcome
PubMed: 38822024
DOI: 10.1038/s41598-024-62726-4 -
Reviews in Medical Virology Nov 2023A number of different neurological complications have been reported following vaccination against the coronavirus disease 2019 (COVID-19). Electroencephalogram (EEG) is... (Review)
Review
A number of different neurological complications have been reported following vaccination against the coronavirus disease 2019 (COVID-19). Electroencephalogram (EEG) is one of the modalities used to evaluate the neurological complications of diseases. The aim of the present study was to identify the EEG changes in participants vaccinated against COVID-19. PubMed, Scopus, Web of Science, medRxiv, and Google Scholar were searched up to 1 September 2022, with terms related to COVID-19 vaccines, EEG, neurological signs/symptoms, or neurological disorders. All case reports and case series were included if the participants had received at least one dose of a COVID-19 vaccine and a post vaccination EEG report was also reported. We used the Joanna Briggs Institute (JBI) Critical Appraisal Checklist for case reports and case series to appraise the methodological quality of the included studies. Thirty-one studies were included, which were comprised of 24 case reports and seven case series and a total of 36 participants. Generalised slowing and non-convulsive focal status epilepticus were the most common EEG findings post-COVID-19 vaccination. The most frequent symptoms were headache, fatigue, generalised weakness, and vomiting. In addition, the most common signs were encephalopathy, post-ictal phases, and confusion. Encephalitis, acute disseminated encephalomyelitis, and post-vaccinal encephalopathy were the most commonly diagnosed adverse events. Furthermore, most of the imaging studies appeared normal. The EEG reports mainly showed background slowing and epileptiform discharges, encephalitis, encephalopathies, and demyelinating disorders. Future studies with larger samples and more vaccine types may help to further unravel the potential neurological effects of COVID-19 vaccinations on recipients.
Topics: Humans; Brain Diseases; COVID-19; COVID-19 Vaccines; Electroencephalography; Encephalitis; Vaccination; Case Reports as Topic
PubMed: 37807809
DOI: 10.1002/rmv.2484 -
Magnetic Resonance Imaging Dec 2023Multiple sclerosis (MS), namely the phenotype of the relapsing-remitting form, is the most common white matter disease and is mostly characterized by demyelination and... (Review)
Review
Multiple sclerosis (MS), namely the phenotype of the relapsing-remitting form, is the most common white matter disease and is mostly characterized by demyelination and inflammation, which lead to neurodegeneration and cognitive decline. Its diagnosis and monitoring are performed through conventional structural MRI, in which T2-hyperintense lesions can be identified, but this technique lacks sensitivity and specificity, mainly in detecting damage to normal appearing tissues. Models of diffusion-weighted MRI such as diffusion-tensor imaging (DTI) and neurite orientation dispersion and density imaging (NODDI) allow to uncover microstructural abnormalities that occur in MS, mainly in normal appearing tissues such as the normal appearing white matter (NAWM), which allows to overcome limitations of conventional MRI. DTI is the standard method used for modelling this kind of data, but it has limitations, which can be tackled by using more complex diffusion models, such as NODDI, which provides additional information on morphological properties of tissues. Although there are several studies in MS using both diffusion models, there is no formal assessment that summarizes the findings of both methods in lesioned and normal appearing tissues, and whether one is more advantageous than the other. Hence, this systematic review aims to identify what microstructural abnormalities are seen in lesions and/or NAWM in relapsing-remitting MS while using two different approaches to modelling diffusion data, namely DTI and NODDI, and if one of them is more appropriate than the other or if they are complementary to each other. The search was performed using PubMed, which was last searched on November 2022, and aimed at finding studies that either utilized both DTI and NODDI in the same dataset, or only one of the methods. Eleven articles were included in this review, which included cohorts with a relatively low sample size (total number of patients = 254, total number of healthy controls = 240), and patients with a moderate disease duration, all with relapsing-remitting MS. Overall, studies found decreased fractional anisotropy (FA), neurite density index (NDI) and orientation dispersion index (ODI), and increased mean, axial and radial diffusivities (MD, AD and RD, respectively) in lesions, when compared to contralateral NAWM and healthy controls' white matter. Compared to healthy controls' white matter, NAWM showed lower FA and NDI and higher MD, AD, RD, and ODI. Results from the included articles confirm that there is active demyelination and inflammation in both lesions and NAWM, as well as loss in neurites, and that structural damage is not confined to focal lesions, which is in concordance with histological findings and results from other imaging techniques. Furthermore, NODDI is suggested to have higher sensitivity and specificity, as seen by inspecting imaging results, compared to DTI, while still being clinically feasible. The use of biomarkers derived from such advanced diffusion models in clinical practice could imply a better understanding of treatment efficacy and disease progression, without relying on the manifestation of clinical symptoms, such as relapses.
Topics: Humans; Multiple Sclerosis; Diffusion Tensor Imaging; Diffusion Magnetic Resonance Imaging; White Matter; Brain; Neurites; Image Processing, Computer-Assisted
PubMed: 37775062
DOI: 10.1016/j.mri.2023.09.010 -
Multiple Sclerosis and Related Disorders Dec 2023This systematic review and meta-analysis summarize the efficacy and safety of Tocilizumab (TCZ) in treating NMOSD and investigates the factors that affect its efficacy.... (Meta-Analysis)
Meta-Analysis
This systematic review and meta-analysis summarize the efficacy and safety of Tocilizumab (TCZ) in treating NMOSD and investigates the factors that affect its efficacy. TCZ is the first monoclonal antibody against the IL-6 receptor for treating NMOSD, and its efficacy and safety vary in different studies. We collected English-language research literature until January 1, 2023, by searching databases such as PubMed, MEDLINE, Embase, Cochrane Library, and clinicaltrials.gov, and identified 9 studies involving 153 patients (139 female and 14 male) that met our inclusion criteria. In these studies, the average ARR ratio and EDSS score reduction values in the TCZ treatment group were -1.34 (95 % CI, -1.60 to -1.09) and -0.81 (95 % CI, -1.04 to -0.58), respectively. Based on the data we have collected, compared to the AQP4-IgG negative NMOSD patients, TCZ demonstrates a more pronounced effectiveness in AQP4-IgG positive NMOSD patients. The study also found that the effectiveness of TCZ in reducing NMOSD patients' ARR ratio was related to gender, race, and TCZ dosage, while the effectiveness of reducing EDSS score was not related to these factors. Among the 153 patients receiving TCZ treatment, 101 (66 %) experienced mild adverse reactions, and one patient experienced a severe adverse reaction (facial cellulitis). The comprehensive data indicate that TCZ treatment can reduce the frequency of NMOSD relapses, improve patients' neurological function, and have good safety. The effectiveness of TCZ in reducing NMOSD patients' ARR ratio is related to multiple factors.
Topics: Humans; Male; Female; Neuromyelitis Optica; Antibodies, Monoclonal, Humanized; Disability Evaluation; Immunoglobulin G; Aquaporin 4
PubMed: 37866020
DOI: 10.1016/j.msard.2023.105062 -
Clinical NeuropharmacologyFatigue is a chronic and debilitating symptom of many long-term neurological conditions (LTNCs). Although methylphenidate provides some promise in alleviating fatigue in... (Meta-Analysis)
Meta-Analysis
OBJECTIVE
Fatigue is a chronic and debilitating symptom of many long-term neurological conditions (LTNCs). Although methylphenidate provides some promise in alleviating fatigue in other clinical groups, little work has explored its potential utility within LTNCs. The current systematic review and meta-analysis evaluates the utility of methylphenidate for symptoms of fatigue in LTNCs.
METHODS
Five databases (PsycINFO, MEDLINE, Embase, Scopus, and Cochrane Library) were searched for relevant articles from their inception to February 2022. A purpose-developed evaluation tool was used to assess each study's research quality (QuEST:F).
RESULTS
Of the 1698 articles identified, 11 articles were included within this review (n = 370). Meta-analytical findings reported an overall significant benefit of methylphenidate for symptoms of fatigue across a mixed neurological sample ( g = -0.44; 95% confidence interval, -0.77 to -0.11). Subgroup analyses identified a significantly greater benefit ( P < 0.001) of methylphenidate for fatigue in LTNCs with static pathogenic trajectories (eg, traumatic brain injury) (number needed to treat = 2.5) compared with progressive conditions (eg, multiple sclerosis) (number needed to treat = 40.2).
CONCLUSIONS
Methylphenidate may pose an effective intervention for the treatment of fatigue in a number of LTNCs. Nonetheless, given the quality of the current evidence base, there exists a clear need for further robust assessment of the utility of methylphenidate-with a focus on subgroup-specific variability.
Topics: Humans; Methylphenidate; Neoplasms; Fatigue; Multiple Sclerosis; Central Nervous System Stimulants
PubMed: 37962311
DOI: 10.1097/WNF.0000000000000572 -
JAMA Network Open Oct 2023Hyponatremia and the syndrome of inappropriate secretion of antidiuretic hormone (SIADH) are associated with significant mortality and morbidity. The effectiveness and...
IMPORTANCE
Hyponatremia and the syndrome of inappropriate secretion of antidiuretic hormone (SIADH) are associated with significant mortality and morbidity. The effectiveness and safety of oral urea for SIADH are still debated.
OBJECTIVE
To evaluate the efficacy and safety of urea for the treatment of SIADH.
EVIDENCE REVIEW
A systematic search of Medline and Embase was conducted for controlled and uncontrolled studies of urea for SIADH in adult patients. The primary outcome was serum sodium concentration after treatment. Secondary outcomes included the proportion of patients with osmotic demyelination syndrome (ODS), intracranial pressure, and resource use such as length of stay.
FINDINGS
Twenty-three studies involving 537 patients with SIADH were included, of which 462 were treated with urea. The pooled mean baseline serum sodium was 125.0 mmol/L (95% CI, 122.6-127.5 mmol/L). The median treatment duration with oral urea was 5 days. Urea increased serum sodium concentration by a mean of 9.6 mmol/L (95% CI, 7.5-11.7 mmol/L). The mean increase in serum sodium after 24 hours was 4.9 mmol/L (95% CI, 0.5-9.3 mmol/L). Adverse events were few, mainly consisting of distaste or dysgeusia, and no case of ODS was reported. Resource use was too infrequently reported to be synthesized.
CONCLUSIONS AND RELEVANCE
In this systematic review of the use of urea in SIADH and despite the lack of randomized clinical trials, lower-quality evidence was identified that suggests that urea may be an effective, safe, and inexpensive treatment modality that warrants further exploration.
Topics: Adult; Humans; Urea; Inappropriate ADH Syndrome; Vasopressins; Demyelinating Diseases; Sodium
PubMed: 37902751
DOI: 10.1001/jamanetworkopen.2023.40313 -
Neurological Sciences : Official... Sep 2023Gait imbalance is one of the frequent complications in subjects with multiple sclerosis (MS). Fampridine (4-aminopyridine) is a potassium-channel blocker that is... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Gait imbalance is one of the frequent complications in subjects with multiple sclerosis (MS). Fampridine (4-aminopyridine) is a potassium-channel blocker that is administered for gait imbalance in MS. Different studies showed the effects of fampridine on gait status based on various tests in subjects with MS. Some showed significant improvement after treatment, and others did not. So, we designed this systematic review, and meta-analysis to estimate the pooled effects of fampridine on gait status in patients with MS.
METHODS
The main goal is the evaluation of times of different gait test pre and post fampridine treatment. Two independent expert researchers conducted a systematic and comprehensive search in PubMed, Scopus, EMBASE, Web of Science, and Google Scholar and also gray literature, including references of the references and conference abstracts. The search was done on September 16, 2022. Before-after studies trials reporting scores of the walking tests. We extracted data regarding the total number of participants, first author, publication year, country of origin, mean age, Expanded Disability Status Scale (EDSS), and the results of walking tests.
RESULTS
The literature search revealed 1963 studies; after deleting duplicates, 1098 studies remained. Seventy-seven full texts were evaluated. Finally, 18 studies were included for meta-analysis, while most of them were not placebo-controlled trials. The most frequent country of origin was Germany, and the mean age and EDSS ranged between 44 and 56 years and 4 and 6, respectively. The studies were published between 2013 and 2019. The pooled standardized mean difference (SMD) (after-before) of the MS Walking Scale (MSWS-12) was - 1.97 (95%CI: - 1.7, - 1.03) (I = 93.1%, P < 0.001). The pooled SMD (after-before) of the six-minute walk test (6MWT) was 0.49 (95%CI: 0.22, - 0.76) (I = 0%, P = 0.7). The pooled SMD (after-before) of T Timed 25-Foot Walk (T25FW) was - 0.99(95%CI: - 1.52, - 0.47) (I = 97.5%, P < 0.001).
CONCLUSION
This systematic review and meta-analysis show that fampridine improves gait imbalance in patients with MS.
Topics: Humans; Adult; Middle Aged; Multiple Sclerosis; Treatment Outcome; 4-Aminopyridine; Potassium Channel Blockers; Gait; Walking
PubMed: 37055710
DOI: 10.1007/s10072-023-06795-9 -
Neurological Sciences : Official... Nov 2023Neuromyelitis optica spectrum disorder (NMOSD) is an autoimmune astrocytopathy with evidence of neuroinflammation and demyelination that affects the central nervous... (Review)
Review
The temporal relationship of paraneoplastic aquaporin-4-IgG seropositive neuromyelitis optica spectrum disorder (NMOSD) and breast cancer: a systematic review and meta-analysis.
OBJECTIVE
Neuromyelitis optica spectrum disorder (NMOSD) is an autoimmune astrocytopathy with evidence of neuroinflammation and demyelination that affects the central nervous system and is mediated by aquaporin-4 (AQP4) immunoglobulin (IgG). AQP4-IgG may also be present in paraneoplastic syndromes secondary to malignancy such as breast cancer.
METHODS
A systematic review and meta-analysis of the literature were completed using PubMed, Scopus, and ScienceDirect databases (CRD42022352109).
RESULTS
A total of 12 publications, which included 19 cases, met the inclusion criteria and were assessed in both the qualitative and quantitative synthesis. The mean age was 51.26 years (SD: 13.12, SEM: 3.01), and 100% of the cases were reported in women. Speech abnormalities and symptoms of myelopathy were the most observed neurological manifestations. MRI often revealed longitudinally extensive transverse myelitis (LETM) involving the cervical spine. Three of 19 (15.9%) cases were diagnosed with NMOSD and breast cancer within the same month. Five of 19 (26.1%) cases had a diagnosis of breast cancer preceding that of NMOSD. Eight of 19 (42.1%) cases were diagnosed with breast cancer after NMOSD. The median time of breast cancer diagnosis was 1.0 months (range 216 months) after NMOSD.
CONCLUSIONS
The diagnosis of breast cancer most often occurs after the onset of the paraneoplastic NMOSD symptoms. However, a wide time range for the diagnosis of breast cancer was observed both before and after the onset of neurological symptoms. Older women with a new diagnosis of NMOSD should be considered for frequent breast cancer screening.
PubMed: 37453952
DOI: 10.1007/s10072-023-06952-0 -
Calcified Tissue International Mar 2024People with multiple sclerosis (MS) have a higher prevalence of osteoporosis, falls and fractures. Guidelines for MS populations targeting the management of... (Review)
Review
People with multiple sclerosis (MS) have a higher prevalence of osteoporosis, falls and fractures. Guidelines for MS populations targeting the management of osteoporosis, fracture and falls risk may help reduce the burden of musculoskeletal disease in this population. We aimed to systematically review current guidelines regarding osteoporosis prevention, screening, diagnosis and management in people with MS. In accordance with the Preferred Reporting Items for Systematic Reviews and Meta-analysis (PRISMA) guidelines, a systematic review of scientific databases (MEDLINE, CINAHL, Embase and Scopus) was performed (n = 208). In addition, websites from MS organisations and societies were screened for clinical guidelines (n = 28). Following duplicate removal, screening and exclusions (n = 230), in total six guidelines were included in this review. Three of the identified guidelines were specific to managing osteoporosis in MS, while two linked vitamin D to bone health and one was focused on the effect of acute glucocorticoid use for MS exacerbations on bone health. All guidelines were found to contain inadequate recommendations for osteoporosis screening, management and treatment in people with MS given the evidence of higher prevalence of osteoporosis at an earlier age and compounding risk factors in this population. Early diagnosis and treatment of osteoporosis in people with MS is necessary as fractures lead to significant morbidity and mortality. Development of structured clinical guidelines directed at specific healthcare services will ensure screening, appropriate management, and care of bone health in people with MS.
Topics: Humans; Accidental Falls; Bone Density; Multiple Sclerosis; Osteoporosis; Fractures, Bone
PubMed: 38015240
DOI: 10.1007/s00223-023-01159-z -
Annals of Medicine Dec 2023To appraise whether plasma exchange (PLEX) effectively improves visual function for acute optic neuritis (ON) in neuromyelitis optica (NMO) or neuromyelitis optica... (Review)
Review
OBJECTIVES
To appraise whether plasma exchange (PLEX) effectively improves visual function for acute optic neuritis (ON) in neuromyelitis optica (NMO) or neuromyelitis optica spectrum disorder (NMOSD).
METHODS AND ANALYSIS
We searched Medline, Embase, Cochrane Library, ProQuest Central, and Web of Science to identify relevant articles published between 2006 and 2020.Eligible studies were in English and evaluated visual outcomes for people with acute ON in NMO or NMOSD treated with PLEX. They also had adequate pre- and posttreatment data. Excluded were studies with 1 or 2 case reports, or incomplete data.
RESULTS
Twelve studies were qualitatively synthesized (1 RCT; 1 controlled NRSI; 10 observational studies). Five before-and-after observational studies were used for quantitative synthesis. The PLEX in the 5 studies (3 to 7 cycles over 2 to 3 weeks) was performed as second-line or adjunctive therapy for acute ON in NMO/NMOSD.The qualitative synthesis revealed that visual-acuity recovery occurred between one day and 6 months after the first PLEX cycle completion. Thirty-two of 48 participants in the 5 quantitative-synthesis studies received PLEX. Relative to pre-PLEX values, visual-acuity improvements were nonsignificant at these post-PLEX time points: 1 day (SMD 0.611; 95% CI -0.620 to 1.842); 2 weeks (SMD 0.0214; 95% CI -1.250 to 1.293); 3 months (SMD 1.014; 95% CI -0.954 to 2.982); and 6 months (SMD 0.450; 95% CI -2.643 to 3.543).
CONCLUSIONS
There were inadequate data to determine whether PLEX effectively treats acute ON in NMO/NMOSD.
Topics: Humans; Plasma Exchange; Neuromyelitis Optica; Optic Neuritis; Outcome Assessment, Health Care
PubMed: 37387119
DOI: 10.1080/07853890.2023.2227422