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International Journal of Molecular... Oct 2023Amyotrophic lateral sclerosis is a devastating neurodegenerative disease characterized by the gradual loss of motor neurons in the brain and spinal cord, leading to... (Review)
Review
Amyotrophic lateral sclerosis is a devastating neurodegenerative disease characterized by the gradual loss of motor neurons in the brain and spinal cord, leading to progressive motor function decline. Unfortunately, there is no effective treatment, and its increasing prevalence is linked to an aging population, improved diagnostics, heightened awareness, and changing lifestyles. In the gastrointestinal system, the gut microbiota plays a vital role in producing metabolites, neurotransmitters, and immune molecules. Short-chain fatty acids, of interest for their potential health benefits, are influenced by a fiber- and plant-based diet, promoting a diverse and balanced gut microbiome. These fatty acids impact the body by binding to receptors on enteroendocrine cells, influencing hormones like glucagon-like peptide-1 and peptide YY, which regulate appetite and insulin sensitivity. Furthermore, these fatty acids impact the blood-brain barrier, neurotransmitter levels, and neurotrophic factors, and directly stimulate vagal afferent nerves, affecting gut-brain communication. The vagus nerve is a crucial link between the gut and the brain, transmitting signals related to appetite, inflammation, and various processes. Dysregulation of this pathway can contribute to conditions like obesity and irritable bowel syndrome. Emerging evidence suggests the complex interplay among these fatty acids, the gut microbiota, and environmental factors influences neurodegenerative processes via interconnected pathways, including immune function, anti-inflammation, gut barrier, and energy metabolism. Embracing a balanced, fiber-rich diet may foster a diverse gut microbiome, potentially impacting neurodegenerative disease risk. Comprehensive understanding requires further research into interventions targeting the gut microbiome and fatty acid production and their potential therapeutic role in neurodegeneration.
Topics: Humans; Aged; Gastrointestinal Microbiome; Amyotrophic Lateral Sclerosis; Neurodegenerative Diseases; Brain; Fatty Acids, Volatile; Fatty Acids
PubMed: 37894774
DOI: 10.3390/ijms242015094 -
Frontiers in Neuroscience 2023Spinal cord injury (SCI) is a catastrophic condition with few therapeutic options. Astaxanthin (AST), a natural nutritional supplement with powerful antioxidant...
Spinal cord injury (SCI) is a catastrophic condition with few therapeutic options. Astaxanthin (AST), a natural nutritional supplement with powerful antioxidant activities, is finding its new application in the field of SCI. Here, we performed a systematic review to assess the neurological roles of AST in rats following SCI, and assessed the potential for clinical translation. Searches were conducted on PubMed, Embase, Cochrane Library, the Web of Science, China National Knowledge Infrastructure, WanFang data, Vip Journal Integration Platform, and SinoMed databases. Animal studies that evaluated the neurobiological roles of AST in a rat model of SCI were included. A total of 10 articles were included; most of them had moderate-to-high methodological quality, while the overall quality of evidence was not high. Generally, the meta-analyses revealed that rats treated with AST exhibited an increased Basso, Beattie, and Bresnahan (BBB) score compared with the controls, and the weighted mean differences (WMDs) between those two groups showed a gradual upward trend from days 7 (six studies, n = 88, WMD = 2.85, 95% CI = 1.83 to 3.87, < 0.00001) to days 28 (five studies, n = 76, WMD = 6.42, 95% CI = 4.29 to 8.55, < 0.00001) after treatment. AST treatment was associated with improved outcomes in spared white matter area, motor neuron survival, and SOD and MDA levels. Subgroup analyses indicated there were differences in the improvement of BBB scores between distinct injury types. The trial sequential analysis then firmly proved that AST could facilitate the locomotor recovery of rats following SCI. In addition, this review suggested that AST could modulate oxidative stress, neuroinflammation, neuron loss, and autophagy multiple signaling pathways for treating SCI. Collectively, with a protective effect, good safety, and a systematic action mechanism, AST is a promising candidate for future clinical trials of SCI. Nonetheless, in light of the limitations of the included studies, larger and high-quality studies are needed for verification.
PubMed: 37881327
DOI: 10.3389/fnins.2023.1255755 -
Neurological Sciences : Official... Feb 2024This systematic review and meta-analysis aimed to determine the frequency and correlates of fatigue in patients with amyotrophic lateral sclerosis (ALS). (Meta-Analysis)
Meta-Analysis Review
OBJECTIVES
This systematic review and meta-analysis aimed to determine the frequency and correlates of fatigue in patients with amyotrophic lateral sclerosis (ALS).
METHODS
Three databases were searched up to 2nd May 2023 to identify studies reporting fatigue frequency in ALS. Studies included had to identify ALS patients through one of ALS diagnostic criteria and measure fatigue by a validated tool with a specific cut-off value. Meta-analysis was conducted using RStudio's "meta" package with a random-effects model. Subgroup analyses and meta-regression explored the relationship between fatigue frequency in ALS and different covariates.
RESULTS
Eleven studies, compromising 1072 patients, met the inclusion criteria and were included in our analysis. The pooled frequency of fatigue across all studies was 48% (95% CI = 40% to 57%). Our subgroup analysis based on the ALSFRS-R revealed a higher frequency of fatigue in studies with lower scores (< 30) compared to those with higher scores (≥ 30), with a pooled frequency of 62% (95% CI = 43% to 79%) and 43% (95% CI = 37% to 49%), respectively. Also, the meta-regression analysis showed a significant negative association between fatigue and ALSFRS-R mean (P = 0.02). The included studies reported an association between fatigue and lower functional status and poorer quality of life in patients with ALS.
CONCLUSION
Our findings suggest that fatigue is prevalent in almost half of ALS patients and is associated with lower functional status and poorer quality of life, highlighting the importance of assessing and managing fatigue in ALS patients.
Topics: Humans; Amyotrophic Lateral Sclerosis; Prevalence; Quality of Life; Fatigue
PubMed: 37837507
DOI: 10.1007/s10072-023-07119-7 -
Brain Sciences Aug 2023Social cognition has a broad theoretical definition, which includes the ability to mentalise, i.e., recognise and infer mental states to explain and predict another's... (Review)
Review
Social cognition has a broad theoretical definition, which includes the ability to mentalise, i.e., recognise and infer mental states to explain and predict another's behaviour. There is growing recognition of the clinical, diagnostic, and prognostic value of assessing a person's ability to perform social cognitive tasks, particularly aspects of theory of mind, such as mentalising. One such measure of mentalising is the 'Reading the Mind in the Eyes' test (RMET). This systematic review and meta-analysis consider performance on the RMET, applied to people with neurodegenerative conditions in matched control studies, since its publication in 2001. Overall, this review includes 22 papers with data from N = 800 participants with neurodegenerative conditions: Alzheimer's disease, = 31; Parkinson's disease, = 221; Lewy body dementia, = 33; motor neuron disease, = 218; Huntington's disease = 80; multiple sclerosis, = 217; and N = 601 matched typical controls. Our meta-analyses show that deficits in mentalising, as measured by the RMET, are consistently reported across neurodegenerative conditions, with participants in both early and late disease stages being affected. Social cognition is an emerging field of cognitive neuroscience requiring specific and sensitive measurement across each subdomain. Adult-based meta-normative data feature, for which future groups or individuals could be compared against, and hypotheses relating to the source of these mentalising deficits are further discussed. This review was registered with PROSPERO (CRD42020182874).
PubMed: 37759869
DOI: 10.3390/brainsci13091268 -
Journal of Translational Medicine Sep 2023Cell-based strategies focusing on replacement or protection of dopaminergic neurons have been considered as a potential approach to treat Parkinson's disease (PD) for... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Cell-based strategies focusing on replacement or protection of dopaminergic neurons have been considered as a potential approach to treat Parkinson's disease (PD) for decades. However, despite promising preclinical results, clinical trials on cell-therapy for PD reported mixed outcomes and a thorough synthesis of these findings is lacking. We performed a systematic review and meta-analysis to evaluate cell-therapy for PD patients.
METHODS
We systematically identified all clinical trials investigating cell- or tissue-based therapies for PD published before July 2023. Out of those, studies reporting transplantation of homogenous cells (containing one cell type) were included in meta-analysis. The mean difference or standardized mean difference in quantitative neurological scale scores before and after cell-therapy was analyzed to evaluate treatment effects.
RESULTS
The systematic literature search revealed 106 articles. Eleven studies reporting data from 11 independent trials (210 patients) were eligible for meta-analysis. Disease severity and motor function evaluation indicated beneficial effects of homogenous cell-therapy in the 'off' state at 3-, 6-, 12-, or 24-month follow-ups, and for motor function even after 36 months. Most of the patients were levodopa responders (61.6-100% in different follow-ups). Cell-therapy was also effective in improving the daily living activities in the 'off' state of PD patients. Cells from diverse sources were used and multiple transplantation modes were applied. Autografts did not improve functional outcomes, while allografts exhibited beneficial effects. Encouragingly, both transplantation into basal ganglia and to areas outside the basal ganglia were effective to reduce disease severity. Some trials reported adverse events potentially related to the surgical procedure. One confirmed and four possible cases of graft-induced dyskinesia were reported in two trials included in this meta-analysis.
CONCLUSIONS
This meta-analysis provides preliminary evidence for the beneficial effects of homogenous cell-therapy for PD, potentially to the levodopa responders. Allogeneic cells were superior to autologous cells, and the effective transplantation sites are not limited to the basal ganglia. PROSPERO registration number: CRD42022369760.
Topics: Humans; Parkinson Disease; Levodopa; Transplantation, Autologous; Transplantation, Homologous; Allogeneic Cells
PubMed: 37679754
DOI: 10.1186/s12967-023-04484-x -
Cureus Aug 2023Being one of the most prevalent progressive neurodegenerative disorders (falling second only to Alzheimer's disease) with a clinical pattern affecting millions of lives... (Review)
Review
Being one of the most prevalent progressive neurodegenerative disorders (falling second only to Alzheimer's disease) with a clinical pattern affecting millions of lives all over the world, Parkinson's disease (PD) has never failed to attract a formidable interest from the vast majority of neurologists and researchers worldwide. This review article will analyze the pathophysiology, etiology, genetics, and pathological stages of Parkinson's disease with their corresponding clinical sequels. A review article was conducted using research databases including PubMed, PubMed Central, Springer, and Elsevier. The research articles reviewed using databases were written in English, German, Japanese, and Chinese and published within the preceding 50 years. Based on the article's findings, we concluded that Parkinson's disease is a progressive disorder with a variety of motor and non-motor symptoms that are influenced by a cascade of pathological neuronal abnormalities such as Lewy neurites and Lewy bodies that gradually build up with an eventual consequence of neurodegeneration of dopamine-secreting neurons. Multiple genetic mutations, pathophysiological events, and environmental factors act as the foundation to initiate that cascade.
PubMed: 37664277
DOI: 10.7759/cureus.44353 -
Journal of Neurology Dec 2023Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease characterized by the degeneration of both upper and lower motoneurons, leading to motor and... (Review)
Review
Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease characterized by the degeneration of both upper and lower motoneurons, leading to motor and non-motor symptoms. Recent evidence suggests that ALS is indeed a multisystem disorder, associated with cognitive impairment, dysautonomia, pain and fatigue, excess of secretions, and sensory symptoms. To evaluate whether sensory neuropathy could broaden its spectrum, we systematically reviewed its presence and characteristics in ALS, extracting data on epidemiological, clinical, neurophysiological, neuropathological, and genetic features. Sensory neuropathy can be found in up to 20% of ALS patients, affecting both large and small fibers, although there is a great heterogeneity related to different techniques used for its detection (electromyography vs skin biopsy vs nerve biopsy). Moreover, the association between CIDP-like neuropathy and ALS needs to be better explored, although it could be interpreted as part of the neuroinflammatory process in the latter disease. Sensory neuropathy in ALS may be associated with a spinal onset and might be more frequent in SOD1 patients. Moreover, it seems mutually exclusive with cognitive impairment. No associations with sex and other genetic mutation were observed. All these data in the literature reveal the importance of actively looking for sensory neuropathy in ALS patients, and suggest including sensory neuropathy among ALS non-motor features, as it may explain sensory symptoms frequently reported throughout the course of the disease. Its early identification could help avoid diagnostic delays and improve patients' treatment and quality of life.
Topics: Humans; Amyotrophic Lateral Sclerosis; Neurodegenerative Diseases; Quality of Life; Motor Neurons; Electromyography
PubMed: 37610446
DOI: 10.1007/s00415-023-11954-1 -
Neurological Sciences : Official... Dec 2023Amyotrophic lateral sclerosis (ALS) is a rare and fatal neurodegenerative disease that can overlap with pregnancy, but little is known about its clinical... (Review)
Review
OBJECTIVES
Amyotrophic lateral sclerosis (ALS) is a rare and fatal neurodegenerative disease that can overlap with pregnancy, but little is known about its clinical characteristics, course, and outcomes in this context. This systematic review aimed to synthesize the current evidence on ALS overlapping with pregnancy.
METHODS
We comprehensively searched four databases on February 2, 2023, to identify case studies reporting cases of ALS overlapping with pregnancy. Joanna Brigs Institute tool was followed to assess the quality of the included studies.
RESULTS
Twenty-six articles reporting 38 cases were identified and included in our study. Out of the 38 cases, 18 were aged < 30 years. The onset of ALS was before pregnancy in 18 cases, during pregnancy in 16 cases, and directly after pregnancy in 4 cases. ALS progression course was rapid or severe in 55% of the cases during pregnancy, and this percentage reached 61% in cases with an onset of ALS before pregnancy. While ALS progression course after pregnancy was rapid or severe in 63% and stable in 37% of the cases. Most cases (95%) were able to complete the pregnancy and gave live birth. However, preterm delivery was common. For neonates, 86% were healthy without any complications.
CONCLUSION
While pregnancy with ALS is likely to survive and result in giving birth to healthy infants, it could be associated with rapid or severe progression of ALS and result in a worse prognosis, highlighting the importance of close monitoring and counselling for patients and healthcare providers.
Topics: Female; Infant, Newborn; Humans; Pregnancy; Amyotrophic Lateral Sclerosis; Neurodegenerative Diseases; Prognosis; Health Status; Databases, Factual
PubMed: 37587387
DOI: 10.1007/s10072-023-06994-4 -
Journal of Neurology Oct 2023Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disorder affecting the upper and lower motor neurons, which can lead to death from respiratory failure within... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disorder affecting the upper and lower motor neurons, which can lead to death from respiratory failure within 3-5 years after the onset of this disease. Nowadays, no drug can effectively slow down the progression of this disease. High-calorie therapy, an emerging complementary alternative treatment, has been reported in studies to prolong the survival time of patients, prevent muscle atrophy and provide a better prognosis. However, no systematic review and meta-analysis were performed to summarize the evidence of this therapy. This meta-analysis comprehensively evaluates the effectiveness and safety of high-calorie therapy for treating ALS.
METHODS
We searched the electronic databases from inception to 1 April 2023: PubMed, Embase, Web of Science, Cochrane Library, Scopus, Ovid/Medline, and ProQuest. Randomized controlled trials (RCTs) that met the inclusion criteria were performed by meta-analysis. All statistical analyses were performed in STATA software.
RESULTS
A total of six eligible RCTs were included in this meta-analysis, involving 370 ALS patients. The meta-analyses showed that high-calorie therapy had superiority in improving body weight (SMD = 1, 95% CI 0.36, 1.65) and BMI (SMD = 0.83, 95% CI 0.02, 1.63). With respect to safety, there was no difference between the high-calorie therapy and the control group regarding the number of adverse events (RR = 3.61, 95% CI 0.08, 162.49). However, ALSFRS-R scores (SMD = 0.34, 95% CI - 0.4, 1.08), survival rate (RR = 1.23, 95% CI 0.98, 1.55), and lipid profile (LDL: SMD = 0.21, 95% CI - 0.33, 0.75; HDL: SMD = 0.17, 95% CI - 0.37, 0.71; TC: SMD = 0.21, 95% CI - 0.33, 0.75), CRP (SMD = 0.85, 95% CI - 1.37, 3.06) showed no significant difference compared to the control groups.
CONCLUSIONS
High-calorie therapy is effective in gaining weight and BMI with few side effects. However, no significant superiority was detected in ALSFRS-R scores, survival time, lipid profile, and CRP indicator. The overall quality of the included studies is high, and the results have some credibility, but future corroboration by high-quality RCTs is also expected.
Topics: Humans; Amyotrophic Lateral Sclerosis; Lipids
PubMed: 37369861
DOI: 10.1007/s00415-023-11838-4 -
Artificial Intelligence in Medicine Aug 2023Amyotrophic Lateral Sclerosis (ALS) is a fatal neurodegenerative disorder characterised by the progressive loss of motor neurons in the brain and spinal cord. The fact... (Review)
Review
BACKGROUND
Amyotrophic Lateral Sclerosis (ALS) is a fatal neurodegenerative disorder characterised by the progressive loss of motor neurons in the brain and spinal cord. The fact that ALS's disease course is highly heterogeneous, and its determinants not fully known, combined with ALS's relatively low prevalence, renders the successful application of artificial intelligence (AI) techniques particularly arduous.
OBJECTIVE
This systematic review aims at identifying areas of agreement and unanswered questions regarding two notable applications of AI in ALS, namely the automatic, data-driven stratification of patients according to their phenotype, and the prediction of ALS progression. Differently from previous works, this review is focused on the methodological landscape of AI in ALS.
METHODS
We conducted a systematic search of the Scopus and PubMed databases, looking for studies on data-driven stratification methods based on unsupervised techniques resulting in (A) automatic group discovery or (B) a transformation of the feature space allowing patient subgroups to be identified; and for studies on internally or externally validated methods for the prediction of ALS progression. We described the selected studies according to the following characteristics, when applicable: variables used, methodology, splitting criteria and number of groups, prediction outcomes, validation schemes, and metrics.
RESULTS
Of the starting 1604 unique reports (2837 combined hits between Scopus and PubMed), 239 were selected for thorough screening, leading to the inclusion of 15 studies on patient stratification, 28 on prediction of ALS progression, and 6 on both stratification and prediction. In terms of variables used, most stratification and prediction studies included demographics and features derived from the ALSFRS or ALSFRS-R scores, which were also the main prediction targets. The most represented stratification methods were K-means, and hierarchical and expectation-maximisation clustering; while random forests, logistic regression, the Cox proportional hazard model, and various flavours of deep learning were the most widely used prediction methods. Predictive model validation was, albeit unexpectedly, quite rarely performed in absolute terms (leading to the exclusion of 78 eligible studies), with the overwhelming majority of included studies resorting to internal validation only.
CONCLUSION
This systematic review highlighted a general agreement in terms of input variable selection for both stratification and prediction of ALS progression, and in terms of prediction targets. A striking lack of validated models emerged, as well as a general difficulty in reproducing many published studies, mainly due to the absence of the corresponding parameter lists. While deep learning seems promising for prediction applications, its superiority with respect to traditional methods has not been established; there is, instead, ample room for its application in the subfield of patient stratification. Finally, an open question remains on the role of new environmental and behavioural variables collected via novel, real-time sensors.
Topics: Humans; Amyotrophic Lateral Sclerosis; Artificial Intelligence; Brain; Cluster Analysis; Databases, Factual
PubMed: 37316101
DOI: 10.1016/j.artmed.2023.102588