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Evaluating patients with neuropathy is common, especially in elderly patients with comorbidities. Neuropathy can often be a manifestation of systemic diseases, cancer, or drug-induced toxicity; thus, the differential diagnosis is challenging. The mechanism of nerve damage can vary significantly, affecting the patient's therapeutic management. We describe a 66-year-old woman who presented with subacute and progressively worsening motor weakness of the lower extremities with bilateral numbness and tingling after a recent respiratory tract infection. Her medical history included diabetes mellitus and Sezary syndrome in the context of cutaneous T-cell lymphoma. This case emphasizes the significance of a detailed evaluation and considering clinical signs and electrophysiologic findings in patients with neuropathy and a history of hematologic malignancy. Early recognition and management can be crucial in shaping the clinical course of the disease.
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Doenças do Sistema Nervoso Periférico , Síndrome de Sézary , Humanos , Feminino , Idoso , Síndrome de Sézary/complicações , Síndrome de Sézary/diagnóstico , Doenças do Sistema Nervoso Periférico/diagnóstico , Doenças do Sistema Nervoso Periférico/etiologia , Raciocínio Clínico , Progressão da Doença , Neoplasias Cutâneas/complicações , Neoplasias Cutâneas/diagnósticoRESUMO
Background: Among the currently approved antiobesity medications, the glucagon-like-peptide-1 receptor-agonists (GLP-1 RAs) liraglutide and semaglutide, and the dual glucose-dependent-insulinotropic-polypeptide (GIP)/GLP-1 RA tirzepatide have been suggested to reduce cardiovascular-risk in overweight or obesity without diabetes. Objectives: The objective of this study was to evaluate the cardio- and neuroprotective potential of these novel agents in the nondiabetic overweight/obese adult population. Data sources and methods: A systematic review and meta-analysis of randomized-controlled clinical trials (RCTs) was performed to estimate the risk of major adverse cardiovascular events (MACE), all-cause and cardiovascular mortality in overweight or obese adults without diabetes treated with GLP-1 or GIP/GLP-1 RAs (vs placebo). Secondary outcomes included the risk of myocardial infarction (MI) and stroke. Results: Sixteen RCTs (13 and 3 on GLP-1 RAs and tirzepatide, respectively) comprising 28,168 participants were included. GLP-1 or GIP/GLP-1 RAs reduced MACE (odds ratio (OR): 0.79; 95% confidence interval (CI): 0.71-0.89; p < 0.01; I 2 = 0) and all-cause mortality (OR: 0.80; 95% CI: 0.70-0.92; p < 0.01; I 2 = 0), while there was a trend toward lower cardiovascular-mortality (OR: 0.84; 95% CI: 0.71-1.01; p = 0.06; I 2 = 0%) compared to placebo. Additionally, GLP-1 or GIP/GLP-1 RAs reduced the odds of MI (OR: 0.72; 95% CI: 0.61-0.86; p < 0.01; I 2 = 0%) and nonfatal-MI (OR: 0.72; 95% CI: 0.61-0.85; p < 0.01; I 2 = 0%); while no associations between antiobesity treatment and fatal-MI, stroke, nonfatal, or fatal stroke were uncovered. Conclusion: GLP-1 and GIP/GLP-1 RAs reduce cardiovascular-risk and all-cause mortality in overweight or obese adults without diabetes. Additionally, GLP-1 RAs and GIP/GLP-1 RAs attenuate the risk of MI. Since data on stroke are still limited, future RCTs are warranted to evaluate the neuroprotective potential of these novel antiobesity agents. Trial registration: PROSPERO CRD42024515966.
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Background: Arthritis, particularly osteoarthritis (OA), is a common synovial condition observed in individuals with multiple sclerosis (MS). Despite its high prevalence and significant impact on the quality of life of MS individuals, there is a gap in the current literature regarding the prevalence of OA in this population and its relation to MS pathology. This systematic review and meta-analysis aimed to estimate the prevalence of OA in the MS population and explore potential associations with demographic and MS-specific characteristics. Methods: Adhering to PRISMA guidelines, a systematic search of the MEDLINE PubMed, Scopus and Google Scholar databases was conducted. Results: Fifteen studies were included in the systematic review and meta-analysis. The aggregated prevalence of OA in the MS population was 27% (95% CI: 15-40%), with substantial heterogeneity (I2 = 99.9%). Sensitivity analysis, excluding one study, showed a prevalence of 21% (95% CI: 16-28%). The risk ratio of OA in MS versus controls was 1.07 (95% CI: 0.84-1.37), indicating no significant difference. Meta-regression revealed no associations between OA prevalence and age or disease duration in MS patients. Conclusions: This study reports a 21-27% prevalence of OA in people with MS. Understanding the implications of OA in pain and mobility domains, as well as the challenges in distinguishing OA symptoms from MS manifestations, underscores the need for further research to elucidate the pathophysiological mechanisms and interactions between these conditions. Additional studies are warranted to enhance clinical management and improve outcomes for individuals with MS and co-existing OA.
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BACKGROUND AND OBJECTIVES: Limited data exist on the safety of IV thrombolysis (IVT) for acute ischemic stroke (AIS) after dabigatran reversal with idarucizumab. We sought to evaluate the safety and efficacy of idarucizumab pretreatment in patients with AIS receiving IVT. METHODS: A national registry-based study evaluated the safety and efficacy of IVT in this specific subgroup. We also conducted a systematic review and meta-analysis of cohort studies and case series, aiming to document the pooled rates of (1) symptomatic intracranial hemorrhage (sICH), (2) any intracranial hemorrhage, (3) 3-month mortality, and (4) the proportion of excellent (modified Rankin Scale [mRS] scores 0-1) and (5) good (mRS scores 0-2) functional outcome at 3 months among patients with AIS, who received IVT after dabigatran reversal with idarucizumab. Moreover, we sought to compare these outcomes between IVT-treated patients after dabigatran reversal with idarucizumab and IVT-treated patients without dabigatran pretreatment. RESULTS: Thirteen cohorts including our nation-wide registry-based cohort and 1 case series comprising 553 patients with AIS (mean age: 75 years; male sex: 65%; median baseline NIH Stroke Scale score: 11 points) receiving idarucizumab before IVT were included in this meta-analysis. The pooled rate of sICH after IVT after idarucizumab administration was 4% (95% CI 1-9; I2 = 26%), while the pooled rates of any intracranial hemorrhage and 3-month mortality were 10% (95% CI 5-16; I2 = 24%) and 18% (95% CI 10-27; I2 = 0%), respectively. The pooled rates of excellent and good functional outcomes at 3 months were 56% (95% CI 27-83; I2 = 69%) and 70% (95% CI 57-81; I2 = 40%), respectively. The risk of sICH (risk ratio [RR] 1.86; 95% CI 0.91-3.80; I2 = 0%), any intracranial hemorrhage (RR 1.76; 95% CI 0.99-3.11; I2 = 8%), and 3-month mortality (RR 1.50; 95% CI 0.91-2.48; I2 = 0%) did not differ between patients with AIS receiving IVT with and without idarucizumab. Moreover, idarucizumab administration was associated with higher likelihood of achieving a 3-month good functional outcome (RR 1.35; 95% CI 1.11-1.65; I2 = 27%). DISCUSSION: IVT for AIS after dabigatran reversal with idarucizumab seems to be safe and effective in observational studies with limited number of patients. Randomized-controlled clinical trials are warranted to provide robust evidence on the safety and efficacy of IVT in this specific AIS subgroup.
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Anticorpos Monoclonais Humanizados , Antitrombinas , Dabigatrana , AVC Isquêmico , Sistema de Registros , Terapia Trombolítica , Idoso , Feminino , Humanos , Masculino , Anticorpos Monoclonais Humanizados/administração & dosagem , Anticorpos Monoclonais Humanizados/efeitos adversos , Antitrombinas/administração & dosagem , Antitrombinas/efeitos adversos , Dabigatrana/administração & dosagem , Dabigatrana/efeitos adversos , Dabigatrana/antagonistas & inibidores , Hemorragias Intracranianas/induzido quimicamente , Hemorragias Intracranianas/tratamento farmacológico , Hemorragias Intracranianas/epidemiologia , AVC Isquêmico/tratamento farmacológico , Terapia Trombolítica/efeitos adversos , Terapia Trombolítica/métodos , Resultado do TratamentoRESUMO
INTRODUCTION: Sexual dysfunction (SD) is a common symptom that affects 40-90% of patients with multiple sclerosis (MS). Previous studies have highlighted the negative impact of sexual dysfunction in the mental health status and overall quality of life in patients with MS. METHODS: The aim of this study was to examine the effects of transcutaneous tibial nerve stimulation (TTNS) in the primary SD symptoms in patients with MS. A total of 40 participants were randomized (1:1 ratio) to either TTNS or Sham group and received three 20 min sessions over the course of two months. Pre and post intervention SD was evaluated using the Multiple Sclerosis Intimacy Questionnaire (MISQ-15). RESULTS: Statistically significant improvements in the aspects of primary sexual dysfunction were observed in the TTNS group pre-post intervention (specifically erectile function (for males)/vaginal lubrication (for females) (p < .001), orgasm quality and satisfaction for both male and female patients (p < .001), sexual desire (p < .05) and bladder related symptomatology (p < .005). In the sham group pre-post intervention, the only observed improvement was in the sexual desire aspect (p < .05). Post intervention the groups significantly differed erectile function/vaginal lubrication and orgasm quality and satisfaction (p < .05). CONCLUSIONS: Our findings underline the efficacy of TTNS in improving primary SD symptoms as well as bladder problems in both male and female patients with MS. TTNS demonstrated significant improvement in the following domains: erectile function, vaginal lubrication, orgasm quality, satisfaction, bladder-related symptoms, and sexual desire.
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Mielite , Neuromielite Óptica , Neoplasias da Medula Espinal , Humanos , Neuromielite Óptica/diagnóstico , Neuromielite Óptica/diagnóstico por imagem , Diagnóstico Diferencial , Feminino , Neoplasias da Medula Espinal/diagnóstico , Mielite/diagnóstico , Mielite/diagnóstico por imagem , Imageamento por Ressonância Magnética , AdultoRESUMO
Background/Objectives: Myelin oligodendrocyte glycoprotein (MOG) is exclusively expressed in the central nervous system (CNS) and is found on the outer surface of oligodendrocytes. Antibodies to MOG are associated with CNS demyelination, whereas peripheral nervous system (PNS) demyelination is seldom reported to be related to MOG-IgG. Methods: The database of patients seen in our neurological academic center was searched for MOG-IgG seropositivity and concomitant demyelinating polyneuropathy. For the purpose of the review, in March 2024, we searched for case reports and case series in the following databases: PubMed, Scopus, Cochrane, and ScienceDirect. Inclusion criteria were MOG-IgG seropositivity and demyelinating polyneuropathy. Exclusion criteria were type of publication other than case reports and case series, unconfirmed diagnosis of demyelinating polyneuropathy, and other diseases causing demyelination in either the CNS or PNS. Critical appraisal of the selected case reports and case series was realized by JBI. Results: Four new cases were identified with MOG-IgG and confirmed demyelinating polyneuropathy. This review identified 22 cases that have been published since 2018. Clinical, imaging, neurophysiological, and immunological characteristics, as well as treatment options and outcomes are presented and compared to those of other cases with combined central and peripheral demyelination (CCPD). Conclusions: The pathogenetic mechanism is unclear; thus, different hypotheses are discussed. New case reporting and large cohort studies will help further the exploration of the underlying mechanism and guide more effective therapeutic interventions.
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Background: Neuronal nicotinic acetylcholine receptors (nAChRs) are abundant in the central nervous system (CNS), playing critical roles in brain function. Antigenicity of nAChRs has been well demonstrated with antibodies to ganglionic AChR subtypes (i.e., subunit α3 of α3ß4-nAChR) and muscle AChR autoantibodies, thus making nAChRs candidate autoantigens in autoimmune CNS disorders. Antibodies to several membrane receptors, like NMDAR, have been identified in autoimmune encephalitis syndromes (AES), but many AES patients have yet to be unidentified for autoantibodies. This study aimed to develop of a cell-based assay (CBA) that selectively detects potentially pathogenic antibodies to subunits of the major nAChR subtypes (α4ß2- and α7-nAChRs) and its use for the identification of such antibodies in "orphan" AES cases. Methods: The study involved screening of sera derived from 1752 patients from Greece, Turkey and Italy, who requested testing for AES-associated antibodies, and from 1203 "control" patients with other neuropsychiatric diseases, from the same countries or from Germany. A sensitive live-CBA with α4ß2-or α7-nAChR-transfected cells was developed to detect antibodies against extracellular domains of nAChR major subunits. Flow cytometry (FACS) was performed to confirm the CBA findings and indirect immunohistochemistry (IHC) to investigate serum autoantibodies' binding to rat brain tissue. Results: Three patients were found to be positive for serum antibodies against nAChR α4 subunit by CBA and the presence of the specific antibodies was quantitatively confirmed by FACS. We detected specific binding of patient-derived serum anti-nAChR α4 subunit antibodies to rat cerebellum and hippocampus tissue. No serum antibodies bound to the α7-nAChR-transfected or control-transfected cells, and no control serum antibodies bound to the transfected cells. All patients positive for serum anti-nAChRs α4 subunit antibodies were negative for other AES-associated antibodies. All three of the anti-nAChR α4 subunit serum antibody-positive patients fall into the AES spectrum, with one having Rasmussen encephalitis, another autoimmune meningoencephalomyelitis and another being diagnosed with possible autoimmune encephalitis. Conclusion: This study lends credence to the hypothesis that the major nAChR subunits are autoimmune targets in some cases of AES and establishes a sensitive live-CBA for the identification of such patients.
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Autoanticorpos , Doenças do Sistema Nervoso Central , Neurônios , Receptores Nicotínicos , Adolescente , Adulto , Idoso , Animais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Ratos , Adulto Jovem , Autoanticorpos/imunologia , Autoanticorpos/sangue , Doenças do Sistema Nervoso Central/imunologia , Encefalite/imunologia , Neurônios/imunologia , Receptores Nicotínicos/imunologiaRESUMO
BACKGROUND: Immunogenicity of influenza and pneumococcal vaccines varies and requires further elucidation in patients with multiple sclerosis (MS) under treatment with disease-modifying therapies (DMTs). METHODS: Adult MS patients who consented with vaccination after standard-of-care consultation by their treating physicians were enrolled. All received a single dose of an inactivated quadrivalent influenza vaccine and of the 23-valent pneumococcal vaccine. A blood sample was collected before and after four weeks of vaccination for measurement of antibodies against Influenza A, B and S. pneumoniae. Patients were followed-up for adverse events and MS relapse for 12 months. RESULTS: One hundred and seventy-two patients (65.7 % female, mean age 42 ± 13 years old, mean MS duration 7.6 ± 7.2 years, 81.4 % under DMTs) were enrolled from November 2019 to March 2020. Antibody measurements were available for 151 patients. Seropositivity for anti-PPSV23 did not differ between baseline and at 4 weeks of follow-up (n = 56, 37.1 %). There was a significant increase of absolute antibody titers post-vaccination for both influenza A and B (p < 0.001). For Influenza A, seropositivity was evident for 57 (37.7 %) patients at 4 weeks compared to 19 (12.6 %) patients at baseline (pMcNemar < 0.001). For Influenza Β, 110 (72.8 %) seroconverted 4 weeks after vaccination compared to 12 (7.9 %) at baseline (pMcNemar < 0.001). Interferon and fumarate did not affect influenza seroconversion while rituximab was associated with lower titers. Mild local AEs (pain, edema) were observed in 23.8 %; no severe AE was reported. Thirty-four patients (19.8 %) had a relapse during the 12-month follow-up; none was attributed to the vaccination. CONCLUSIONS: Seroconversion in MS patients on treatment was more frequent following influenza compared to PPSV23 vaccination. Rituximab had an effect on the height of the immune response. Better immunization coverage as well as future evaluation of the breadth of immune response elicited by immunization is necessary for these patients.
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Anticorpos Antibacterianos , Anticorpos Antivirais , Vacinas contra Influenza , Influenza Humana , Esclerose Múltipla , Vacinas Pneumocócicas , Humanos , Feminino , Masculino , Adulto , Vacinas contra Influenza/imunologia , Vacinas contra Influenza/administração & dosagem , Vacinas contra Influenza/efeitos adversos , Vacinas Pneumocócicas/imunologia , Vacinas Pneumocócicas/administração & dosagem , Vacinas Pneumocócicas/efeitos adversos , Estudos Prospectivos , Esclerose Múltipla/imunologia , Esclerose Múltipla/tratamento farmacológico , Pessoa de Meia-Idade , Influenza Humana/prevenção & controle , Influenza Humana/imunologia , Anticorpos Antivirais/sangue , Anticorpos Antivirais/imunologia , Anticorpos Antibacterianos/sangue , Anticorpos Antibacterianos/imunologia , Imunogenicidade da Vacina , Vacinação/métodos , Infecções Pneumocócicas/prevenção & controle , Infecções Pneumocócicas/imunologia , Streptococcus pneumoniae/imunologia , Vírus da Influenza B/imunologiaRESUMO
INTRODUCTION: We aimed to investigate the performance of several neuroimaging markers provided by perfusion imaging of Acute Ischemic Stroke (AIS) patients with large vessel occlusion (LVO) in order to predict clinical outcomes following reperfusion treatments. METHODS: We prospectively evaluated consecutive AIS patients with LVO who were treated with reperfusion therapies, during a six-year period. In order to compare patients with good (mRS scores 0-2) and poor (mRS scores 3-6) functional outcomes, data regarding clinical characteristics, the Alberta Stroke Programme Early Computed Tomography Score (ASPECTS) based on unenhanced computed tomography (CT), CT angiography collateral status and perfusion parameters including ischemic core, hypoperfusion volume, mismatch volume between core and penumbra, Tmax > 10 s volume, CBV index and the Hypoperfusion Index Ratio (HIR) were assessed. RESULTS: A total of 84 acute stroke patients with LVO who met all the inclusion criteria were enrolled. In multivariable logistic regression models increasing age (odds ratio [OR]: 0.93; 95%CI: 0.88-0.96, p = 0.001), lower admission National Institute of Health Stroke Scale (NIHSS)-score (OR: 0.88; 95%CI: 0.80-0.95, p = 0.004), pretreatment with intravenous thrombolysis (OR: 3.83; 95%CI: 1.29-12.49, p = 0.019) and HIR (OR:0.36; 95%CI: 0.10-0.95, p = 0.042) were independent predictors of good functional outcome at 3 months. The initial univariable associations between HIR and higher likelihood for symptomatic intracranial hemorrhage (sICH) and parenchymal hematoma type 2 (PH2) were attenuated in multivariable analyses failing to reach statistical significance. DISCUSSION: Our pilot observational study of unselected AIS patients with LVO treated with reperfusion therapies demonstrated that pre-treatment low HIR in perfusion imaging and IVT were associated with better functional outcomes.
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AVC Isquêmico , Terapia Trombolítica , Humanos , Masculino , Feminino , AVC Isquêmico/terapia , AVC Isquêmico/diagnóstico por imagem , Idoso , Terapia Trombolítica/métodos , Pessoa de Meia-Idade , Resultado do Tratamento , Fibrinolíticos/administração & dosagem , Fibrinolíticos/uso terapêutico , Estudos Prospectivos , Idoso de 80 Anos ou mais , Reperfusão/métodos , Imagem de Perfusão/métodos , Ativador de Plasminogênio Tecidual/administração & dosagem , Ativador de Plasminogênio Tecidual/uso terapêutico , Circulação Cerebrovascular/fisiologia , Angiografia por Tomografia ComputadorizadaRESUMO
BACKGROUND: Epidemiological data are sparse regarding the risk of stroke in patients with multiple sclerosis (MS). OBJECTIVE: To estimate the following: (1) the pooled prevalence of all-cause stroke, acute ischaemic stroke (AIS) and intracerebral haemorrhage (ICH) in MS patients; (2) the relative risk for all-cause stroke, AIS and ICH in MS patients compared to the general population; (3) associations between patient characteristics and the risk for AIS and ICH in MS patients. METHODS: Systematic review and meta-analysis of registry-based and cohort studies. RESULTS: Thirteen observational studies comprising 146,381 MS patients were included. The pooled prevalence of all-cause stroke was 2.7% (95% confidence interval [CI] 1.3-4.6%), with the relative risk of all-cause stroke being higher in MS patients compared to the general population (RR: 2.55; 95% CI 1.97-3.29). Subgroup analyses per stroke subtype revealed a pooled AIS prevalence of 2.1% (95% CI 0.8-4.1%) and a pooled ICH prevalence of 0.6% (95% CI 0.2-1.2%). Compared to the general population, patients with MS were found to harbour an increased risk for AIS (RR: 2.79; 95% CI 2.27-3.41) and ICH (RR: 2.31; 95% CI 1.04-5.11), respectively. The pooled prevalence of cardiovascular risk factors in MS patients was 11.5% (95% CI 2.9-24.7%) for dyslipidaemia, 18.2% (95% CI 5.9-35.3%) for hypertension and 5.4% (95% CI 2.1-10.2%) for diabetes. In meta-regression, age was negatively associated with AIS risk (ß = - .03, p = 0.04), with a 1-year increase in age resulting in a significant 3% (95%CI 0-5) attenuation of the risk of AIS. CONCLUSION: The findings of the present meta-analysis indicate that MS is associated with an increased risk for ischaemic and haemorrhagic stroke. Future well-designed epidemiological studies are warranted to corroborate the robustness of the present findings in the MS population.
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Esclerose Múltipla , Acidente Vascular Cerebral , Humanos , Esclerose Múltipla/epidemiologia , Prevalência , Acidente Vascular Cerebral/epidemiologia , Estudos Observacionais como Assunto , Fatores de RiscoRESUMO
Background: While obesity has been shown to elevate the risk of developing multiple sclerosis (MS), there is a lack of strong evidence regarding its role in the disability progression and status of MS patients. Methods: This systematic review and meta-analysis aimed to provide comparative estimates of WC and BMI in patients with MS (PwMS) and to investigate potential associations between the waist circumference (WC) and body mass index (BMI) and demographic and specific MS characteristics. Adhering to PRISMA guidelines, a detailed search of the MEDLINE PubMed, Cochrane Library, and Scopus databases was conducted. Results: A total of 16 studies were included. The pooled mean WC and BMI among PwMS was estimated to be 87.27 cm (95%CI [84.07; 90.47]) and 25.73 (95%CI [25.15; 26.31]), respectively. Meta-regression models established a significant bidirectional relationship between WC and the Expanded Disability Scale (EDSS) (p < 0.001) but not between BMI and EDSS (p = 0.45). Sensitivity analyses showed no association between WC and age (p = 0.48) and a tendency between WC and disease duration (p = 0.08). Conclusions: Although WC measurements classify PwMS as normal weight, BMI measurements classify them as overweight. Therefore, WC should complement BMI evaluations in clinical practice. Additionally, our findings highlight the significant association between abdominal fat, as indicated by WC, and disease progression. Considering the heightened risk of cardiovascular comorbidity and mortality among PwMS, we recommend integrating both WC and BMI as standard anthropometric measurements in routine clinical examinations and targeted prevention strategies for PwMS.
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BACKGROUND: Paraneoplastic Neurological Syndromes (PNS) comprise a diverse group of disorders propagated by immune-mediated effects of malignant tumors on neural tissue. METHODS: A single-center longitudinal study was performed including consecutive adult patients treated at a tertiary academic hospital between 2015 and 2023 and diagnosed with PNS. PNS were ascertained using the 2004 and the revised 2021 PNS-Care diagnostic criteria. RESULTS: Thirteen patients who fulfilled the 2004 definite PNS criteria were included. PNS comprise diverse neurological syndromes, with neuromuscular junction disorders (54%) and limbic encephalitis (31%) being predominant. PNS-related antibodies were detected in 85% of cases, including anti-AChR (n = 4), anti-P/Q-VGCC (n = 3), anti-Hu (n = 3), anti-Yo (n = 1), anti-Ma (n = 1), anti-titin (n = 1), anti-IgLON5 (n = 1), and anti-GAD65 (n = 1). Thymoma (31%), small-cell lung cancer (23%), and papillary thyroid carcinoma (18%) were the most frequent tumors. Imaging abnormalities were evident in 33% of cases. Early immunotherapy within 4-weeks from symptom onset was associated with favorable outcomes. At a mean follow-up of 2 ± 1 years, two patients with anti-Hu and anti-Yo antibodies died (18%). Four and three patients fulfilled the 2021 PNS-Care diagnostic criteria for definite and probable PNS, respectively. CONCLUSIONS: This study highlights the clinical heterogeneity of PNS, emphasizing the need for early suspicion and prompt treatment initiation for optimal outcomes.
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INTRODUCTION: Mounting evidence suggests that glucagon-like-peptide-1 receptor-agonists (GLP-1 RAs) attenuate cardiovascular-risk in type-2 diabetes (T2DM). Tirzepatide is the first-in-class, dual glucose-dependent-insulinotropic-polypeptide GIP/GLP-1 RA approved for T2DM. PATIENTS AND METHODS: A systematic review and meta-analysis of randomized-controlled clinical trials (RCTs) was performed to estimate: (i) the incidence of major adverse cardiovascular events (MACE); and (ii) incidence of stroke, fatal, and nonfatal stroke in T2DM-patients treated with GLP-1 or GIP/GLP-1 RAs (vs placebo). RESULTS: Thirteen RCTs (9 and 4 on GLP-1 RAs and tirzepatide, respectively) comprising 65,878 T2DM patients were included. Compared to placebo, GLP-1RAs or GIP/GLP-1 RAs reduced MACE (OR: 0.87; 95% CI: 0.81-0.94; p < 0.01; I2 = 37%), all-cause mortality (OR: 0.88; 95% CI: 0.82-0.96; p < 0.01; I2 = 21%) and cardiovascular-mortality (OR: 0.88; 95% CI: 0.80-0.96; p < 0.01; I2 = 14%), without differences between GLP-1 versus GIP/GLP-1 RAs. Additionally, GLP-1 RAs reduced the odds of stroke (OR: 0.84; 95% CI: 0.76-0.93; p < 0.01; I2 = 0%) and nonfatal stroke (OR: 0.85; 95% CI: 0.76-0.94; p < 0.01; I2 = 0%), whereas no association between fatal stroke and GLP-1RAs was uncovered (OR: 0.80; 95% CI: 0.61-1.05; p = 0.105; I2 = 0%). In secondary analyses, GLP-1 RAs prevented ischemic stroke (OR: 0.74; 95% CI: 0.61-0.91; p < 0.01; I2 = 0%) and MACE-recurrence, but not hemorrhagic stroke (OR: 0.92; 95% CI: 0.51-1.66; p = 0.792; I2 = 0%). There was no association between GLP-1RAs or GIP/GLP-1 RAs and fatal or nonfatal myocardial infarction. DISCUSSION AND CONCLUSION: GLP-1 and GIP/GLP-1 RAs reduce cardiovascular-risk and mortality in T2DM. While there is solid evidence that GLP-1 RAs significantly attenuate the risk of ischemic stroke in T2DM, dedicated RCTs are needed to evaluate the efficacy of novel GIP/GLP-1 RAs for primary and secondary stroke prevention.
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Doenças Cardiovasculares , Diabetes Mellitus Tipo 2 , Receptor do Peptídeo Semelhante ao Glucagon 1 , Hipoglicemiantes , Acidente Vascular Cerebral , Humanos , Diabetes Mellitus Tipo 2/tratamento farmacológico , Diabetes Mellitus Tipo 2/complicações , Receptor do Peptídeo Semelhante ao Glucagon 1/agonistas , Acidente Vascular Cerebral/mortalidade , Doenças Cardiovasculares/mortalidade , Doenças Cardiovasculares/tratamento farmacológico , Doenças Cardiovasculares/prevenção & controle , Hipoglicemiantes/uso terapêutico , Hipoglicemiantes/farmacologia , Hipoglicemiantes/efeitos adversos , Ensaios Clínicos Controlados Aleatórios como Assunto , Receptores dos Hormônios Gastrointestinais/agonistas , Peptídeo 1 Semelhante ao Glucagon/agonistas , Peptídeo 1 Semelhante ao Glucagon/uso terapêutico , Polipeptídeo Inibidor Gástrico/uso terapêutico , Polipeptídeo Inibidor Gástrico/farmacologia , Receptor do Peptídeo Semelhante ao Glucagon 2RESUMO
INTRODUCTION: Neurogenic bladder as well as fatigue related symptoms are common in patients with Multiple Sclerosis (MS) and have a significant impact on the patients' Quality of Life (QoL). The aim of this study is to investigate the relationship between fatigue related symptomatology (FRS) and Urinary Quality of Life (UQoL). METHODS: A total of 120 consecutive MS patients were recruited from the Outpatient Clinic of Demyelinating Diseases (Second Dept. of Neurology, Attikon University Hospital Greece). Participants were then asked to complete the Modified Fatigue Impact Scale (MFIS) and the Short Form Qualiveen questionnaire. Demographic and bladder function related characteristics (incontinence, urinary frequency, use of intermittent catheterization) were collected. RESULTS: The physical and cognitive dimensions of MFIS had a moderate to high correlation with SF Qualiveen (r = 0.403, p <.000), (r = 0.329, p <.000).Multiple linear regression produced a fitted model (R2 = 0.150, F(3,111) = 5.554, p =.001) in IC use (ß = 1.086, p =.036) and the physical dimension of MFIS (ß = 0.66, p =.046) significantly predicted the SF Qualiveen score. CONCLUSION: UQoL had a moderate correlation with both physical and cognitive dimensions of fatigue. Patients with MS who experience lower levels of physical fatigue and/or manage their neurogenic bladder symptomatology (mainly with the use of intermittent catheterization) appear to have higher levels of UQoL. Due to the versatile and subjective nature of both fatigue related and neurogenic bladder symptoms, more focused studies utilizing objective evaluation tools (e.g urodynamic urine bladder study) are necessary.
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Esclerose Múltipla , Bexiga Urinaria Neurogênica , Humanos , Qualidade de Vida , Bexiga Urinaria Neurogênica/etiologia , Esclerose Múltipla/complicações , Exame Físico , Fadiga/etiologia , Inquéritos e QuestionáriosRESUMO
AIM: Multiple sclerosis (MS) and Systemic Lupus Erythematosus (SLE) are autoimmune disorders that may lead to cognitive impairment. This study aimed to compare the neuropsychological profiles of patients with MS, and MS and coexisting SLE features. METHODS: We included a total of 90 participants, divided into 3 groups: 30 patients with clinically definite relapsing remitting MS, 30 with coexisting MS and incomplete SLE (overlap group) and 30 healthy controls (HC). All participants underwent neuropsychological assessment with the Montreal Cognitive Assessment (MoCA), Symbol Digit Modalities Test (SDMT), Paced Auditory Serial Addition Test (PASAT), and Selective Reminding Test (SRT). RESULTS: Both groups scored lower on the MoCA compared to the HC (p < .001). The overlap group showed the lowest performance on the SDMT and PASAT compared to the other two groups (p < .01), while the MS group scored similarly to the HC in the PASAT (p > .05). Regarding the learning rate and long-term recall, the overlap group had lower scores compared to both the MS and HC (p < .001), but it outperformed both groups in the retention efficacy score (p < .001). The MS group did not differ significantly from the HC in these memory domains (p > .05). CONCLUSION: The overlap group exhibited a broader range of impairments, including slower processing speed, decreased working memory, reduced learning rate, and long-term retrieval deficits. Their retention ability remained intact. The coexistence of MS with SLE pathology had additive impacts on cognitive function.
Assuntos
Transtornos Cognitivos , Disfunção Cognitiva , Lúpus Eritematoso Sistêmico , Esclerose Múltipla Recidivante-Remitente , Esclerose Múltipla , Humanos , Esclerose Múltipla/complicações , Esclerose Múltipla Recidivante-Remitente/patologia , Disfunção Cognitiva/diagnóstico , Disfunção Cognitiva/etiologia , Testes Neuropsicológicos , Lúpus Eritematoso Sistêmico/complicaçõesRESUMO
BACKGROUND: Atrial fibrillation (AF) is a frequent underlying cause of cryptogenic stroke (CS) and its detection can be increased using implantable cardiac monitoring (ICM). We sought to evaluate different risk scores and assess their diagnostic ability in identifying patients with CS with underlying AF on ICM. METHODS: Patients with CS, being admitted to a single tertiary stroke center between 2017 and 2022 and receiving ICM, were prospectively evaluated. The CHA2DS2-VASc, HAVOC, Brown ESUS-AF, and C2HEST scores were calculated at baseline. The primary outcome of interest was the detection of AF, which was defined as at least 1 AF episode on ICM lasting for 2 consecutive minutes or more. The diagnostic accuracy measures and the net reclassification improvement were calculated for the 4 risk scores. Stroke recurrence was evaluated as a secondary outcome. RESULTS: A total of 250 patients with CS were included, and AF was detected by ICM in 20.4% (n=51) during a median monitoring period of 16 months. Patients with CS with AF detection were older compared with the rest (P=0.045). The median HAVOC, Brown ESUS-AF, and C2HEST scores were higher among the patients with AF compared with the patients without AF (all P<0.05), while the median CHA2DS2-VASc score was similar between the 2 groups. The corresponding C statistics for CHA2DS2-VASc, HAVOC, Brown ESUS-AF, and C2HEST for AF prediction were 0.576 (95% CI, 0.482-0.670), 0.612 (95% CI, 0.523-0.700), 0.666 (95% CI, 0.587-0.746), and 0.770 (95% CI, 0.699-0.839). The C2HEST score presented the highest diagnostic performance based on C statistics (P<0.05 after correction for multiple comparisons) and provided significant improvement in net reclassification for AF detection (>70%) compared with the other risk scores. Finally, stroke recurrence was documented in 5.6% of the study population, with no difference regarding the 4 risk scores between patients with and without recurrent stroke. CONCLUSIONS: The C2HEST score was superior to the CHA2DS2-VASc, HAVOC, and Brown ESUS-AF scores for discriminating patients with CS with underlying AF using ICM.
Assuntos
Fibrilação Atrial , AVC Isquêmico , Acidente Vascular Cerebral , Humanos , Fibrilação Atrial/complicações , Fibrilação Atrial/diagnóstico , Fibrilação Atrial/epidemiologia , Medição de Risco , Fatores de Risco , Acidente Vascular Cerebral/diagnóstico , Acidente Vascular Cerebral/epidemiologia , Acidente Vascular Cerebral/etiologia , AVC Isquêmico/complicaçõesRESUMO
This review attempted to explore all recent clinical studies that have investigated the clinical and autoimmune impact of gut microbiota interventions in multiple sclerosis (MS), including dietary protocols, probiotics, fecal microbiota transplantation (FMT), and intermittent fasting (IF). Methods: Thirteen studies were held between 2011 and 2023 this demonstrated interventions in gut microbiome among patients with MS and their impact the clinical parameters of the disease. These included specialized dietary interventions, the supply of probiotic mixtures, FMT, and IF. Results: Dietary interventions positively affected various aspects of MS, including relapse rates, EDSS disability scores, MS-related fatigue, and metabolic features. Probiotic mixtures showed promising results on MS-related fatigue, EDSS parameters, inflammation; meanwhile, FMT-though a limited number of studies was included-indicated some clinical improvement in similar variables. IF showed reductions in EDSS scores and significant improvement in patients' emotional statuses. Conclusions: In dietary protocols, clinical MS parameters, including relapse rate, EDSS, MFIS, FSS, and MSQoL54 scales, were significantly improved through the application of a specific diet each time. Probiotic nutritional mixtures promote a shift in inflammation towards an anti-inflammatory cytokine profile in patients with MS. The administration of such mixtures affected disability, mood levels, and quality of life among patients with MS. FMT protocols possibly demonstrate a therapeutic effect in some case reports. IF protocols were found to ameliorate EDSS and FAMS scores. All interventional means of gut microbiome modulation provided significant conclusions on several clinical aspects of MS and highlight the complexity in the relationship between MS and the gut microbiome.
RESUMO
BACKGROUND: Periodic Limb Movements during Sleep (PLMS) have been described to be frequently present in stroke patients. We aimed to evaluate the prevalence and severity of PLMS in acute stroke patients and clarify the association between PLMS and coexisting Sleep Disordered Breathing (SDB). Additionally, we focused on identifying variables that could independently predict the presence of PLMS in patients with acute stroke. The potential impact of PLMS on stroke outcome at three months was investigated as well. METHODS: In this study, we performed overnight polysomnography on consecutive stroke patients within 72 h from symptom onset. Data regarding clinical and imaging characteristics were prospectively collected. National Institute of Health Stroke Scale (NIHSS), modified Rankin Scale (mRS) and Epworth-Sleepiness Scale (ESS) were used to evaluate stroke severity on admission, stroke outcome at three months and history of daytime sleepiness, respectively. We documented PLMS and SDB using standard polysomnography criteria. RESULTS: We prospectively assessed 126 patients with acute stroke [109 with ischemic and 17 with hemorrhagic stroke, mean age 60 ± 11 years, 68% men, median NIHSS score on admission: 3 (IQR: 2-7)]. The overall rate of PLMS in our cohort was 76%, and the rate of SDB among patients with PLMS was 83%. PLMS detection rates differed significantly (p-value: <0.001) according to SDB, with PLMS prevalence increasing with greater SDB severity. SDB could independently (OR:4.869, 95% CI: 1.884-12.784, p-value: 0.001) predict the presence of PLMS in the acute stroke phase in multivariable analyses adjusting for potential confounders. Moreover, baseline stroke severity (NIHSS-score increase in per-1 point: OR: 0.819, 95% CI: 0.737-0.895, p-value < 0.001) and PLMS (OR:0.099, 95% CI: 0.009-0.482, p-value = 0.015) were significantly associated with the likelihood of excellent functional outcome (mRS-scores: 0-1) at 3 months. CONCLUSION: The common presence of mostly severe PLMS in patients with acute stroke and their negative effect on stroke outcomes point out the necessity for early PLMS detection and treatment.