Neuroimaging biomarkers and CSF sTREM2 levels in Alzheimer's disease: a longitudinal study.

Understanding the exact pathophysiological mechanisms underlying the involvement of triggering receptor expressed on myeloid cells 2 (TREM2) related microglia activation is crucial for the development of clinical trials targeting microglia activation at different stages of Alzheimer's disease (AD). Given the contradictory findings in the literature, it is imperative to investigate the longitudinal alterations in cerebrospinal fluid (CSF) soluble TREM2 (sTREM2) levels as a marker for microglia activation, and its potential association with AD biomarkers, in order to address the current knowledge gap. In this study, we aimed to assess the longitudinal changes in CSF sTREM2 levels within the framework of the A/T/N classification system for AD biomarkers and to explore potential associations with AD pathological features, including the presence of amyloid-beta (Aß) plaques and tau aggregates. The baseline and longitudinal (any available follow-up visit) CSF sTREM2 levels and processed tau-PET and Aß-PET data of 1001 subjects were recruited from the ADNI database. The participants were classified into four groups based on the A/T/N framework: A+ /TN+ , A+ /TN- , A- /TN+ , and A- /TN- . Linear regression analyses were conducted to assess the relationship between CSF sTREM2 with cognitive performance, tau and Aß-PET adjusting for age, gender, education, and APOE ε4 status. Based on our analysis there was a significant difference in baseline and rate of change of CSF sTREM2 between ATN groups. While there was no association between baseline CSF sTREM2 and cognitive performance (ADNI-mem), we found that the rate of change of CSF sTREM2 is significantly associated with cognitive performance in the entire cohort but not the ATN groups. We found that the baseline CSF sTREM2 is significantly associated with baseline tau-PET and Aß-PET rate of change only in the A+ /TN+ group. A significant association was found between the rate of change of CSF sTREM2 and the tau- and Aß-PET rate of change only in the A+ /TN- group. Our study suggests that the TREM2-related microglia activation and their relations with AD markers and cognitive performance vary the in presence or absence of Aß and tau pathology. Furthermore, our findings revealed that a faster increase in the level of CSF sTREM2 might attenuate future Aß plaque formation and tau aggregate accumulation only in the presence of Aß pathology.

Disruption in functional networks mediated tau spreading in Alzheimer's disease.

Alzheimer's disease may be conceptualized as a 'disconnection syndrome', characterized by the breakdown of neural connectivity within the brain as a result of amyloid-beta plaques, tau neurofibrillary tangles and other factors leading to progressive degeneration and shrinkage of neurons, along with synaptic dysfunction. It has been suggested that misfolded tau proteins spread through functional connections (known as 'prion-like' properties of tau). However, the local effect of tau spreading on the synaptic function and communication between regions is not well understood. I aimed to investigate how the spreading of tau aggregates through connections can locally influence functional connectivity. In total, the imaging data of 211 participants including 117 amyloid-beta-negative non-demented and 94 amyloid-beta-positive non-demented participants were recruited from the Alzheimer's Disease Neuroimaging Initiative. Furthermore, normative resting-state functional MRI connectomes were used to model tau spreading through functional connections, and functional MRI of the included participants was used to determine the effect of tau spreading on functional connectivity. I found that lower functional connectivity to tau epicentres is associated with tau spreading through functional connections in both amyloid-beta-negative and amyloid-beta-positive participants. Also, amyloid-beta-PET in tau epicentres mediated the association of tau spreading and functional connectivity to epicentres suggesting a partial mediating effect of amyloid-beta deposition in tau epicentres on the local effect of tau spreading on functional connectivity. My findings provide strong support for the notion that tau spreading through connection is locally associated with disrupted functional connectivity between tau epicentre and non-epicentre regions independent of amyloid-beta pathology. Also, I defined several groups based on the relationship between tau spreading and functional disconnection, which provides quantitative assessment to investigate susceptibility or resilience to functional disconnection related to tau spreading. I showed that amyloid-beta, other copathologies and the apolipoprotein E epsilon 4 allele can be a leading factor towards vulnerability to tau relative functional disconnection.

Cognitive performance and magnetic resonance imaging in people with multiple sclerosis: A systematic review and meta-analysis.

BACKGROUND: Several studies have shown the different relationships between cognitive functions and structural magnetic resonance imaging (MRI) measurements in people with multiple sclerosis (pwMS). However, there is an ongoing debate regarding the magnitude of correlation between MRI measurements and specific cognitive function tests. This systematic review and meta-analysis aimed to synthesize the most consistent correlations between MRI measurements and cognitive function in pwMS. METHODS: PubMed/MEDLINE, Embase, Scopus, and Web of Science databases were systematically searched up to February 2023, to find relevant data. The search utilized syntax and medical subject headings (MeSH) relevant to cognitive performance tests and MRI measurements in pwMS. The R software version 4.3.3 with random effect models was used to estimate the pooled effect sizes. RESULTS: 13,559 studies were reviewed, of which 136 were included. The meta-analyses showed that thalamic volume had the most significant correlations with Symbol Digit Modalities Test (SDMT) r = 0.47 (95 % CI: 0.39 to 0.56, p < 0.001, I2 = 88 %), Brief Visual Memory Test-Revised-Total Recall (BVMT-TR) r = 0.51 (95 % CI: 0.36 to 0.66, p < 0.001, I2 = 81 %), California Verbal Learning Test-II-Total Recall (CVLT-TR) r = 0.47 (95 % CI: 0.34 to 0.59, p < 0.001, I2 = 69 %,), and Delis-Kaplan Executive Function System (DKEFS) r = 0.48 (95 % CI: 0.34 to 0.63, p < 0.001, I2 = 22 %,). CONCLUSION: We conclude that thalamic volume exhibits highest relationships with information processing speed (IPS), visuospatial learning-memory, verbal learning-memory, and executive function in pwMS. A comprehensive understanding of the intricacies of the mechanisms underpinning this association requires additional research.

Global prevalence and incidence of Young Onset Parkinson's disease: A systematic review and meta-analysis.

BACKGROUND: There is a lack of enough evidence regarding the epidemiology of Young-onset Parkinson's disease (YOPD) which is needed by clinicians and healthcare policymakers. AIM: Herein, in this systematic review and meta-analysis, we aimed to estimate the global prevalence and incidence rates of YOPD. METHODS: We searched the literature in PubMed, Scopus, and Web of Science in May 2022. We included retrospective, prospective, cross-sectional observational population-based studies that reported the prevalence or incidence of PD in individuals younger than 40 years with known diagnostic criteria. RESULTS: After two-step screening, 50 studies were eligible to be included in our study. The age-standardized prevalence of YOPD was 10.2 per 100,000 persons globally while it was 14.7 per 100,000 population in European countries. Age-standardized prevalence estimates for 5-year age bands showed that the YOPD prevalence estimates varied from 6.1 per 100,000 population in the group aged 20-24 to 16.1 per 100,000 population in the group aged 35-39. Also, the age-standardized incidence of YOPD was 1.3 per 100,000 person-years population worldwide and 1.2 per 100,000 person-years in the European population. CONCLUSION: Based on this systematic review and meta-analysis, the overall prevalence of YOPD is 10.2 per 100,000 population, although estimates of the prevalence and incidence in low-income countries remain scarce. To improve monitoring and certain diagnoses of YOPD, healthcare providers and policymakers should be aware that much more effective tools are required.

Behavioral and dysexecutive variant of Alzheimer's disease: Insights from structural and molecular imaging studies.

Frontal variant Alzheimer's disease (AD) manifests with either behavioral or dysexecutive syndromes. Recent efforts to gain a deeper understanding of this phenotype have led to a re-conceptualization of frontal AD. Behavioral (bAD) and dysexecutive (dAD) phenotypes could be considered subtypes, as suggested by both clinical and neuroimaging studies. In this review, we focused on imaging studies to highlight specific brain patterns in these two uncommon clinical AD phenotypes. Although studies did not compare directly these two variants, a common epicenter located in the frontal cortex could be inferred. On the contrary, 18F-FDG-PET findings suggested differing metabolic patterns, with bAD showing specific involvement of frontal regions and dAD exhibiting widespread alterations. Structural MRI findings confirmed this pattern, suggesting that degeneration might involve neural circuits associated with behavioral control in bAD and attentional networks in dAD. Furthermore, molecular imaging has identified different neocortical tau distribution in bAD and dAD patients compared to typical AD patients, although the distribution is remarkably heterogeneous. In contrast, Aß deposition patterns are less differentiated between these atypical variants and typical AD. Although preliminary, these findings underscore the complexity of AD frontal phenotypes and suggest that they represent distinct entities. Further research is essential to refine our understanding of the pathophysiological mechanisms in frontal AD.

Bile acid profile associated with CSF and PET biomarkers in Alzheimer's disease.

BACKGROUND: Recent studies have shown that gut microbiota can affect the development of Alzheimer's disease (AD) through various mechanisms. Bile acids (BAs), which are the final byproducts of cholesterol metabolism created through both the human body and gut microbiome, appear to be influenced by gut microbiota and may impact AD pathological characteristics such as the accumulation of tau and amyloid-ß. We aimed to investigate the associations between various serum BAs and CSF biomarkers (including Aß, total tau, and p-tau). Additionally, we sought to examine the longitudinal changes in brain Aß and tau through PET imaging in relation to BAs profile. METHODS: The data of 828 subjects including 491 diagnosed with mild cognitive impairment (MCI), 119 patients diagnosed with AD, and 267 cognitively normal (CN) participants were obtained from ADNI. The baseline and longitudinal [18F] florbetapir and [18F] flortaucipir PET standard uptake value ratios (SUVR) measures were obtained to assess the accumulation of tau and Aß. Moreover, baseline levels of serum BAs and CSF Aß1-42, tau, and p-tau were used. RESULTS: After FDR correction we observed that five BAs level and relevant calculated ratios were associated with CSF p-tau and tau, three with CSF Aß1-42. Furthermore, three BAs level and relevant calculated ratios were associated with the tau-PET rate of change, and two with the Aß rate of change. CONCLUSION: The findings from our study suggest a correlation between altered profiles of BAs and CSF and imaging biomarkers associated with AD. These results provide supporting evidence for the link between the gut microbiome and the pathological features of AD.

Progranulin and neuropathological features of Alzheimer's disease: longitudinal study.

BACKGROUND: Progranulin is an anti-inflammatory protein that plays an essential role in the synapse function and the maintenance of neurons in the central nervous system (CNS). It has been shown that the CSF level of progranulin increases in Alzheimer's disease (AD) patients and is associated with the deposition of amyloid-beta (Aß) and tau in the brain tissue. In this study, we aimed to assess the longitudinal changes in cerebrospinal fluid (CSF) progranulin levels during different pathophysiological stages of AD and investigate associated AD pathologic features. METHODS: We obtained the CSF and neuroimaging data of 1001 subjects from the ADNI database. The participants were classified into four groups based on the A/T/N framework: A + /TN + , A + /TN-, A-/TN + , and A-/TN-. RESULTS: Based on our analysis there was a significant difference in CSF progranulin (P = 0.001) between ATN groups. Further ANOVA analysis revealed that there was no significant difference in the rate of change of CSF-progranulin ATN groups. We found that the rate of change of CSF progranulin was associated with baseline Aß-PET only in the A-/TN + group. A significant association was found between the rate of change of CSF progranulin and the Aß-PET rate of change only in A-/TN + CONCLUSION: Our findings revealed that an increase in CSF progranulin over time is associated with faster formation of Aß plaques in patients with only tau pathology based on the A/T/N classification (suspected non-Alzheimer's pathology). Together, our findings showed that the role of progranulin-related microglial activity on AD pathology can be stage-dependent, complicated, and more prominent in non-AD pathologic changes. Thus, there is a need for further studies to consider progranulin-based therapies for AD treatment.

Stent-assistant versus non-stent-assistant coiling for ruptured and unruptured intracranial aneurysms: A meta-analysis and systematic review.

Background: Several different endovascular and non-invasive treatment methods are suggested for the various types of intracranial aneurysms including simple, balloon-assisted, and stent-assisted coiling (SAC). Previous studies investigated the safety and efficacy of SAC versus non-stent-assisted coiling (non-SAC) but the results were controversial. We aim to perform a systematic review and meta-analysis to compare the efficacy and safety of SAC with non-SAC technique in stratifying by the ruptured and unruptured aneurysms. Methods: PubMed, Scopus, Web of Science, and Cochrane Central Register of Controlled Trials were searched in April 2022 for studies investigated the efficacy and safety of SAC versus non-SAC. Results: Overall, 26 studies entered into our qualitative and quantitative synthesis. We found that there was overall lower recurrence rate in SAC versus non-SAC significant (RR: 0.43, 95%CI: 0.33, 0.53). Furthermore, the comparisons were significant in unruptured (RR: 0.63, 95%CI: 0.40, 0.86), ruptured (RR: 0.29, 95%CI), and combination aneurysms (RR: 0.42, 95%CI: 0.30, 0.54). Also, we found higher risk of intraprocedural rupture for SAC versus non-SAC in unruptured aneurysms (RR: 1.40, 95%CI: 1.31, 1.50). Investigating hemorrhagic events risk showed that there was significant difference in ruptured (RR: 1.73, 95%CI: 1.12, 2.34) and combination aneurysms (RR: 0.60, 95%CI: 0.37, 0.82). There was no significant difference in immediate occlusion rate, complete occlusion, and risk of ischemic events in our analysis. Conclusion: Overall, our findings demonstrated that SAC may have higher efficacy in term of recurrence rate, but also may have a higher risk of complications in the treatment of intracranial aneurysms. As there are several factors affecting the outcomes and safety of these interventions, further RCTs controlled for multiple factors are required better guide the neurointerventionists choose the best strategy.

MRI features and disability in multiple sclerosis: A systematic review and meta-analysis.

BACKGROUND: In this systematic review and meta-analysis, we aimed to investigate the correlation between disability in patients with Multiple sclerosis (MS) measured by the Expanded Disability Status Scale (EDSS) and brain Magnetic Resonance Imaging (MRI) features to provide reliable results on which characteristics in the MRI can predict disability and prognosis of the disease. METHODS: A systematic literature search was performed using three databases including PubMed, Scopus, and Web of Science. The selected peer-reviewed studies must report a correlation between EDSS scores and MRI features. The correlation coefficients of included studies were converted to the Fisher's z scale, and the results were pooled. RESULTS: Overall, 105 studies A total of 16,613 patients with MS entered our study. We found no significant correlation between total brain volume and EDSS assessment (95 % CI: -0.37 to 0.08; z-score: -0.15). We examined the potential correlation between the volume of T1 and T2 lesions and the level of disability. A positive significant correlation was found (95 % CI: 0.19 to 0.43; z-score: 0.31), (95 % CI: 0.17 to 0.33; z-score: 0.25). We observed a significant correlation between white matter volume and EDSS score in patients with MS (95 % CI: -0.37 to -0.03; z-score: -0.21). Moreover, there was a significant negative correlation between gray matter volume and disability (95 % CI: -0.025 to -0.07; z-score: -0.16). CONCLUSION: In conclusion, this systematic review and meta-analysis revealed that disability in patients with MS is linked to extensive changes in different brain regions, encompassing gray and white matter, as well as T1 and T2 weighted MRI lesions.

T1 and T2 weighted lesions and cognition in multiple Sclerosis: A systematic review and meta-analysis.

BACKGROUND: Considering the different results regarding the correlation between Magnetic Resonance Imaging (MRI) structural measures and cognitive dysfunction in patients with MS, we aimed to perform a systematic review and meta-analysis study to investigate the correlation between T1 and T2 weighted lesions and cognitive scores to find the most robust MRI markers for cognitive function in MS population. METHODS: The literature of this paper was identified through a comprehensive search of electronic datasets including PubMed, Scopus, Web of Science, and Embase in February 2022. Studies that reported the correlation between cognitive status and T1 and T2 weighted lesions in MS patients were selected. RESULTS: 21 studies with a total of 3771 MS patients with mean ages ranging from 30 to 57 years were entered into our study. Our analysis revealed that the volume of T1 lesions was significantly correlated with Symbol Digit Modality test (SDMT) (r: -0.30, 95 %CI: -0.59, -0.01) and Paced Auditory Serial-Addition Task (PASAT) scores (r: -0.23, 95 %CI: -0.36, -0.10). We investigated the correlation between T2 lesions and cognitive scores. The pooled estimates of z scores were significant for SDMT (r: -0.27, 95 %CI: -0.51, -0.03) and PASAT (r: -0.27, 95 %CI: -0.41, -0.13). CONCLUSION: In conclusion, our systematic review and meta-analysis study provides strong evidence of the correlation between T1 and T2 lesions and cognitive function in MS patients. Further research is needed to explore the potential mechanisms underlying this relationship and to develop targeted interventions to improve cognitive outcomes in MS patients.

sTREM2 is associated with attenuated tau aggregate accumulation in the presence of amyloid-ß pathology.

Triggering Receptor Expressed on Myeloid Cell 2 (TREM2) plays a crucial role in the transition of microglia from a state of homeostasis to a state associated with the disease. Mutations in TREM2 are strongly linked with a higher risk of developing neurodegenerative diseases, including Alzheimer's disease. There have been contradictory findings regarding the potential detrimental or protective effects of microglial activation and TREM2-related microglial responses in Alzheimer's disease. Although previous studies reported increased CSF soluble TREM2 (sTREM2) in different clinical stages of Alzheimer's disease, the exact association between Alzheimer's disease hallmarks such as amyloid-beta and tau pathology remains unclear. In the present study, I aimed to investigate the association between TREM2-related microglial responses and tau accumulation in the presence and absence of amyloid-beta pathology in order to give a better view of the role of microglial activation in Alzheimer's disease development. Imaging data of 178 non-demented participants including 107 amyloid-beta-negative participants, 71 amyloid-beta-positive were recruited from Alzheimer's disease Neuroimaging Initiative. The CSF sTREM2 was used as an in vivo indicator of microglial responses associated with TREM2. Furthermore, I used longitudinal tau-PET and resting-state functional MRI connectomes in order to investigate the association of TREM2-related microglial activation and tau spreading through functional connections. A higher level of sTREM2 was associated with slower tau aggregate accumulation in non-demented amyloid-beta-positive. Furthermore, measuring the tau spreading through inter-connected regions using functional MRI connectomes confirms that the TREM2-related microglial activity might be a protective factor against tau pathology in brain tissue. These findings demonstrate that in individuals with initial amyloid-beta abnormalities, TREM2-related microglial activation is linked to reduced regional accumulation of tau aggregates and also, spreading across inter-connected brain regions, as evaluated through functional MRI connectomes during the early stages of Alzheimer's disease.

Cerebrospinal fluid biomarkers profile in scans without evidence of dopaminergic deficits (SWEDD).

Background: A small proportion of patients with clinical parkinsonism have normal transporter-single photon emission computed tomography (DaTSPECT) which is commonly defined as scans without evidence of dopaminergic deficits (SWEDD). A better understanding of SWEDD can improve the current therapeutic options and appropriate disease monitoring. Aim: We aimed to assess CSF biomarkers levels including α-synuclein (α-syn), amyloid ßeta (Aß1-42), total tau (t-tau), and phosphorylated tau (p-tau) in SWEDD and investigate the longitudinal alteration in the CSF profile. Methods: In total, 406 early-stage PD, 58 SWEDD, and 187 healthy controls (HCs) were entered into our study from PPMI. We compared the level of CSF biomarkers at baseline, six months, one year, and two years. Furthermore, the longitudinal alteration of CSF biomarkers was explored in each group using linear mixed models. Results: There was no significant difference in the level of CSF α-syn Aß1-42, t-tau, and p-tau between HCs and SWEDD at different time points. Investigating the level of CSF α-syn in PD and SWEDD showed a significant difference at one (p = 0.016) and two years (p = 0.006). Also, we observed a significant difference in the level of CSF Aß1-42 between SWEDD and PD at one year (p = 0.012). Moreover, there was a significant difference in the level of CSF t-tau between SWEDD and PD subjects at one (p = 0.013) and two years (p = 0.017). Furthermore, there was a significant difference in the level of CSF p-tau between SWEDD and PD groups at two years visits (p = 0.030). Longitudinal analysis showed a significant decrease after one (p = 0.029) and two years (p = 0.002) from baseline in the level of CSF α-syn only in the PD group. Also, we observed that the level of CSF Aß1-42 significantly increased after one year in SWEDD (p = 0.031) and decreased after two years from baseline in PD subjects (p = 0.005). Moreover, there was a significant increase in the level of CSF t-tau after two years (p = 0.036) and CSF p-tau after six months from baseline in SWEDD subjects (p = 0.011). Conclusion: This finding suggests a faster neurodegeneration process in PD patients compared to SWEDD at least based on these biomarkers. Future studies with longer follow-up duration and more sample sizes are necessary to validate our results.

Multiple sclerosis and ulcerative colitis: A systematic review and meta-analysis.

Background: Comorbidity is a current area of interest in multiple sclerosis (MS) and is essential for multidisciplinary management. Although recent studies suggest that patients with MS have an elevated risk of developing inflammatory bowel diseases (IBD), this systematic review and meta-analysis aimed to estimate the overall risk of developing ulcerative colitis (UC), specifically in patients with MS. Methods: In 2021, a comprehensive literature search was performed on PubMed, Scopus, Embase, and Web of Science to identify studies investigating the association between UC and MS. The selected papers were utilized to estimate the associations, risk ratios (RRs), and a 95% confidence interval (CI). Results: The analysis revealed a slightly elevated risk of UC incidence in patients with MS compared to controls, but this finding was not statistically significant (RR: 1.27 [95% CI: 0.96-1.67]). In contrast, the study found that patients with UC have a significantly higher risk of developing MS than controls (RR: 1.66 [95% CI: 1.15-2.40]). Conclusion: Our findings highlight that the presence of UC increases the risk of developing MS by more than 50%, whereas the presence of MS does not increase the risk of UC occurrence. These results underscore the importance of considering the potential development of UC in the clinical management and early diagnosis of patients with MS, as it may contribute to better therapeutic outcomes.

Efficacy and safety of rituximab in multiple sclerosis: a systematic review and meta-analysis.

OBJECTIVE: We aimed to synthesize all available observational studies and clinical trials of rituximab to estimate the safety and efficacy of this monoclonal antibody in people with multiple sclerosis (MS). METHODS: The four databases including PubMed, Scopus, Embase, and Web of Science were comprehensively searched in April 2022. We defined PICO as follows. Problem or study population (P): patients with MS; intervention (I): Rituximab; comparison (C): none; outcome (O): efficacy and safety. RESULTS: After two-step screening, a total of 27 studies entered into our qualitative and quantitative synthesis. Our analysis showed a significant decrease in EDSS score in all patients with MS after treatment (SMD: - 0.44, 95% CI - 0.85, - 0.03). In addition, the ARR was reduced after using rituximab compared to the pre-treatment period (SMD: - 0.65, 95% CI - 1.55, 0.24) but it was not significant. The most common side effect after rituximab with a pooled prevalence of 28.63% (95% CI 16.61%, 42.33%). Furthermore, the pooled prevalence of infection was 24% in patients with MS (95% CI 13%, 36%). In the end, the pooled prevalence of malignancies after rituximab treatment was 0.39% (95% CI 0.02%, 1.03%). CONCLUSION: Our findings illustrated an acceptable safety for this treatment. However, further studies with randomized design, long follow-up, and large sample sizes are needed to confirm the safety and efficacy of rituximab in patients with MS.

Functional and structural lesion network mapping in neurological and psychiatric disorders: a systematic review.

Background: The traditional approach to studying the neurobiological mechanisms of brain disorders and localizing brain function involves identifying brain abnormalities and comparing them to matched controls. This method has been instrumental in clinical neurology, providing insight into the functional roles of different brain regions. However, it becomes challenging when lesions in diverse regions produce similar symptoms. To address this, researchers have begun mapping brain lesions to functional or structural networks, a process known as lesion network mapping (LNM). This approach seeks to identify common brain circuits associated with lesions in various areas. In this review, we focus on recent studies that have utilized LNM to map neurological and psychiatric symptoms, shedding light on how this method enhances our understanding of brain network functions. Methods: We conducted a systematic search of four databases: PubMed, Scopus, and Web of Science, using the term "Lesion network mapping." Our focus was on observational studies that applied lesion network mapping in the context of neurological and psychiatric disorders. Results: Following our screening process, we included 52 studies, comprising a total of 6,814 subjects, in our systematic review. These studies, which utilized functional connectivity, revealed several regions and network overlaps across various movement and psychiatric disorders. For instance, the cerebellum was found to be part of a common network for conditions such as essential tremor relief, parkinsonism, Holmes tremor, freezing of gait, cervical dystonia, infantile spasms, and tics. Additionally, the thalamus was identified as part of a common network for essential tremor relief, Holmes tremor, and executive function deficits. The dorsal attention network was significantly associated with fall risk in elderly individuals and parkinsonism. Conclusion: LNM has proven to be a powerful tool in localizing a broad range of neuropsychiatric, behavioral, and movement disorders. It holds promise in identifying new treatment targets through symptom mapping. Nonetheless, the validity of these approaches should be confirmed by more comprehensive prospective studies.

Risk of myocardial infarction in Parkinson's disease: A systematic review and meta-analysis.

BACKGROUND AND PURPOSE: Previous studies investigating cardiovascular disorders in patients with Parkinson's disease (PD) showed heterogeneous results regarding whether there is a higher or lower risk of myocardial infarction (MI) in these patients compared to the general population. Because of the inconsistency in findings, herein the aim was to perform a systematic review and meta-analysis to investigate the risk of MI in patients with PD. METHODS: A comprehensive literature search was performed using four databases, PubMed, Web of Science, Scopus and Embase, in June 2022. Peer-reviewed observational studies comprising case-controls, cohort, cross-sectional and longitudinal studies that reported MI in the PD population were included. RESULTS: After the screening, 20 studies with a total of 80,441 patients with PD and 802,857 controls were included in our qualitative and quantitative synthesis. The pooled estimated odds ratio for MI in PD patients compared to controls was 0.80 (95% confidence interval [CI] 0.56-1.05) which indicates that there is no association. The pooled prevalence of MI was 5% (95% CI 3%-7%) with a range of 1%-20% amongst patients with PD. The men (6%, 95% CI 1%-13%) and women (6%, 95% CI 1%-14%, Q = 29.27, I2 = 98.50%, p < 0.001) had similar MI prevalence. CONCLUSION: This comprehensive systematic review and meta-analysis provide compelling evidence that PD is associated with a reduced risk of MI. Whilst the exact mechanism underlying this association remains to be fully elucidated, it is clear that certain risk factors for cardiac events appear to be less present in PD patients, which may serve as a protective factor. However, given the reports of increased risk for cerebrovascular events in PD patients, it is possible that the major risk factors for MI and cardiovascular accidents in this population differ. These findings have important implications for clinical management and further research in this area is warranted.

Safety and efficacy of cladribine in multiple sclerosis: a systematic review and meta-analysis.

BACKGROUND: Previously, several studies investigated the effect of cladribine among patients with multiple sclerosis (MS) as a treatment option. Due to the contradictory results of previous studies regarding the efficacy and safety of cladribine in the MS population, we aimed to conduct a systematic review and meta-analysis by including clinical trials and observational studies in terms of having more confirmative results to make a general decision. METHODS: The three databases including PubMed, Scopus, and Web of Science were comprehensively searched in May 2022. We included the studies that investigated the efficacy and safety of cladribine in patients with MS. Eligible studies have to provide sufficient details on MS diagnosis and appropriate follow-up duration. We investigated the efficacy of cladribine with several outcomes including Expanded Disability Status Scale (EDSS) change, progression-free survival (PFS), relapse-free survival (RFS), and MRI-free activity survival (MFAS). RESULTS: After two-step reviewing, 23 studies were included in our qualitative and quantitative synthesis. The pooled SMD for EDSS before and after treatment was - 0.54 (95%CI: - 1.46, 0.39). Our analysis showed that the PFS after cladribine use is 79% (95%CI 71%, 86%). Also, 58% of patients with MS who received cladribine remained relapse-free (95%CI 31%, 83%). Furthermore, the MFAS after treatment was 60% (95%CI 36%, 81%). Our analysis showed that infection is the most common adverse event after cladribine treatment with a pooled prevalence of 10% (95%CI 4%, 18%). Moreover, the pooled prevalence of infusion-related adverse events was 9% (95%CI 4%, 15%). Also, the malignancies after cladribine were present in 0.4% of patients (95%CI 0.25%, 0.75%). CONCLUSION: Our results showed acceptable safety and efficacy for cladribine for the treatment of MS except in terms of reducing EDSS. Combination of our findings with the results of previous studies which compared cladribine to other disease-modifying therapies (DMTs), cladribine seems to be a safe and effective drug in achieving better treatment for relapsing-remitting MS (RRMS) patients.

Neurite Orientation Dispersion and Density Imaging in Multiple Sclerosis: A Systematic Review.

Diffusion-weighted imaging has been applied to investigate alterations in multiple sclerosis (MS). In the last years, advanced diffusion models were used to identify subtle changes and early lesions in MS. Among these models, neurite orientation dispersion and density imaging (NODDI) is an emerging approach, quantifying specific neurite morphology in both grey (GM) and white matter (WM) tissue and increasing the specificity of diffusion imaging. In this systematic review, we summarized the NODDI findings in MS. A search was conducted on PubMed, Scopus, and Embase, which yielded a total number of 24 eligible studies. Compared to healthy tissue, these studies identified consistent alterations in NODDI metrics involving WM (neurite density index), and GM lesions (neurite density index), or normal-appearing WM tissue (isotropic volume fraction and neurite density index). Despite some limitations, we pointed out the potential of NODDI in MS to unravel microstructural alterations. These results might pave the way to a deeper understanding of the pathophysiological mechanism of MS. EVIDENCE LEVEL: 2. TECHNICAL EFFICACY: Stage 3.

Acute disseminated encephalomyelitis (ADEM) following COVID-19 vaccination: A systematic review.

BACKGROUND: Although global vaccination against COVID-19 infection has its excellence, potential side effects are yet of concern. Several lines of evidence have proposed ADEM occurrence after SARS-CoV-2 infection. Moreover, a large number of case reports and case series have also suggested the casual association between ADEM and COVID-19 vaccination. To better understand the development of ADEM following COVID-19 vaccination and its potential association, we aimed to systematically review ADEM cases reported after COVID-19 vaccination. METHODS: We conducted a comprehensive systematic search using three databases including PubMed, Scopus, and Web of Science. Studies that reported ADEM after COVID-19 vaccination were eligible to include in our study. Observational studies, case reports, and case series which reported cases of ADEM with sufficient detail to confirm clinical diagnosis following COVID-19 vaccination were eligible to enter our study. RESULTS: Twenty studies were included in our systematic review after the abstract and full-text screening with a total of 54 cases. Among included patients, 45 (85.1 %) developed ADEM after the first dose of the COVID-19 vaccine, and seven (12.9 %) cases experienced ADEM after the second dose. The median time interval between vaccination and neurological symptoms was 14 days which ranged from 12 h to 63 days. Twelve (22.2 %) patients experienced symptoms of muscle weakness, ten (18.5 %) presented unconsciousness, nine (16.6 %) patients had urinary complaints, nine (16.6 %) had visual impairments, and five (9.2 %) experienced a seizure. After treatments, four (13.8 %) patients died. Forty-six patients had clinical improvement (85.1 %), also improvement in brain MRI was observed among 44 (81.4 %) patients. CONCLUSION: In conclusion, it is not clear that ADEM could be a potential complication of COVID-19 vaccination based on the current evidence and further studies are needed. However, this rare condition should not trigger stopping the mass vaccination programs since the only way to eradicate the current pandemic of COVID-19 is to extend the number of immunized people.