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1.
Brain ; 145(4): 1449-1463, 2022 05 24.
Artigo em Inglês | MEDLINE | ID: mdl-35048960

RESUMO

Increased incidence of stalled capillary blood flow caused by adhesion of leucocytes to the brain microvascular endothelium leads to a 17% reduction of cerebral blood flow and exacerbates short-term memory loss in multiple mouse models of Alzheimer's disease. Here, we report that vascular endothelial growth factor (VEGF) signalling at the luminal side of the brain microvasculature plays an integral role in the capillary stalling phenomenon of the APP/PS1 mouse model. Administration of the anti-mouse VEGF-A164 antibody, an isoform that inhibits blood-brain barrier hyperpermeability, reduced the number of stalled capillaries within an hour of injection, leading to an immediate increase in average capillary blood flow but not capillary diameter. VEGF-A inhibition also reduced the overall endothelial nitric oxide synthase protein concentrations, increased occludin levels and decreased the penetration of circulating Evans Blue dye across the blood-brain barrier into the brain parenchyma, suggesting increased blood-brain barrier integrity. Capillaries prone to neutrophil adhesion after anti-VEGF-A treatment also had lower occludin concentrations than flowing capillaries. Taken together, our findings demonstrate that VEGF-A signalling in APP/PS1 mice contributes to aberrant endothelial nitric oxide synthase /occludin-associated blood-brain barrier permeability, increases the incidence of capillary stalls, and leads to reductions in cerebral blood flow. Reducing leucocyte adhesion by inhibiting luminal VEGF signalling may provide a novel and well-tolerated strategy for improving brain microvascular blood flow in Alzheimer's disease patients.


Assuntos
Doença de Alzheimer , Doença de Alzheimer/metabolismo , Animais , Barreira Hematoencefálica/metabolismo , Encéfalo/metabolismo , Capilares , Permeabilidade Capilar , Circulação Cerebrovascular/fisiologia , Modelos Animais de Doenças , Humanos , Camundongos , Óxido Nítrico Sintase Tipo III/metabolismo , Ocludina/metabolismo , Fator A de Crescimento do Endotélio Vascular , Fatores de Crescimento do Endotélio Vascular/metabolismo
2.
J Headache Pain ; 24(1): 6, 2023 Feb 08.
Artigo em Inglês | MEDLINE | ID: mdl-36755244

RESUMO

OBJECTIVE/ BACKGROUND: Chronic headaches and sports-related concussions are among the most common neurological morbidities in adolescents and young adults. Given that the two can overlap in presentation, studying the effects of one on another has proven difficult. In this longitudinal study, we sought to assess the relationship between chronic headaches and concussions, analyzing the role of historic concussions on chronic headaches, as well as that of premorbid headaches on future concussion incidence, severity, and recovery. METHODS: This multi-center, longitudinal cohort study followed 7,453 youth athletes who were administered demographic and clinical surveys as well as a total of 25,815 Immediate Post-concussion Assessment and Cognitive Testing (ImPACT) assessments between 2009 and 2019. ImPACT was administered at baseline. Throughout the season concussions were examined by physicians and athletic trainers, followed by re-administration of ImPACT post-injury (PI), and at follow-up (FU), a median of 7 days post-concussion. Concussion incidence was calculated as the total number of concussions per patient years. Concussion severity and recovery were calculated as standardized deviations from baseline to PI and then FU in Symptom Score and the four neurocognitive composite ImPACT scores: Verbal Memory, Visual Memory, Processing Speed, and Reaction Time. Data were collected prospectively in a well-organized electronic format supervised by a national research-oriented organization with rigorous quality assurance. Analysis was preformed retrospectively. RESULTS: Of the eligible athletes, 1,147 reported chronic headaches (CH) at the start of the season and 6,306 reported no such history (NH). Median age of the cohort was 15.4 ± 1.6 years, and students were followed for an average of 1.3 ± 0.6 years. A history of concussions (OR 2.31, P < 0.0001) was associated with CH. Specifically, a greater number of past concussions (r2 = 0.95) as well as concussions characterized by a loss of consciousness (P < 0.0001) were associated with more severe headache burden. The CH cohort had a greater future incidence of concussion than the NH cohort (55.6 vs. 43.0 per 100 patient-years, P < 0.0001). However, multivariate analysis controlling for demographic, clinical, academic, and sports-related variables yielded no such effect (OR 0.99, P = 0.85). On multivariable analysis the CH cohort did have greater deviations from baseline to PI and FU in Symptom Score (PI OR per point 1.05, P = 0.01, FU OR per point 1.11, P = 0.04) and Processing Speed (OR per point 1.08, P = 0.04), suggesting greater concussion severity and impaired symptomatic recovery as compared to the NH cohort. CONCLUSION: A history of concussions was a significant contributor to headache burden among American adolescents and young adults. However, those with chronic headaches were not more likely to be diagnosed with a concussion, despite presenting with more severe concussions that had protracted recovery. Our findings not only suggest the need for conservative management among youth athletes with chronic headaches, they also indicate a potential health care gap in this population, in that those with chronic headaches may be referred for concussion diagnosis and management at lower rates than those with no such comorbidity.


Assuntos
Traumatismos em Atletas , Concussão Encefálica , Transtornos da Cefaleia , Adulto Jovem , Humanos , Adolescente , Estados Unidos/epidemiologia , Concussão Encefálica/complicações , Concussão Encefálica/epidemiologia , Concussão Encefálica/diagnóstico , Estudos Longitudinais , Traumatismos em Atletas/complicações , Traumatismos em Atletas/epidemiologia , Estudos Retrospectivos , Cefaleia/epidemiologia , Cefaleia/complicações , Atletas , Testes Neuropsicológicos , Transtornos da Cefaleia/complicações
3.
J Neurointerv Surg ; 16(1): 15-23, 2023 Dec 19.
Artigo em Inglês | MEDLINE | ID: mdl-36882321

RESUMO

BACKGROUND: Minimally invasive evacuation may help ameliorate outcomes after intracerebral hemorrhage (ICH). However, hospital length of stay (LOS) post-evacuation is often long and costly. OBJECTIVE: To examine factors associated with LOS in a large cohort of patients who underwent minimally invasive endoscopic evacuation. METHODS: Patients presenting to a large health system with spontaneous supratentorial ICH qualified for minimally invasive endoscopic evacuation if they met the following inclusion criteria: age ≥18, premorbid modified Rankin Scale (mRS) score ≤3, hematoma volume ≥15 mL, and presenting National Institutes of Health Stroke Scale (NIHSS) score ≥6. Demographic, clinical, radiographic, and operative characteristics were included in a multivariate logistic regression for hospital and ICU LOS dichotomized into short and prolonged stay at 14 and 7 days, respectively. RESULTS: Among 226 patients who underwent minimally invasive endoscopic evacuation, the median intensive care unit and hospital LOS were 8 (4-15) days and 16 (9-27) days, respectively. A greater extent of functional impairment on presentation (OR per NIHSS point 1.10 (95% CI 1.04 to 1.17), P=0.007), concurrent intraventricular hemorrhage (OR=2.46 (1.25 to 4.86), P=0.02), and deep origin (OR=per point 2.42 (1.21 to 4.83), P=0.01) were associated with prolonged hospital LOS. A longer delay from ictus to evacuation (OR per hour 1.02 (1.01 to 1.04), P=0.007) and longer procedure time (OR per hour 1.91 (1.26 to 2.89), P=0.002) were associated with prolonged ICU LOS. Prolonged hospital and ICU LOS were in turn longitudinally associated with a lower rate of discharge to acute rehabilitation (40% vs 70%, P<0.0001) and worse 6-month mRS outcomes (5 (4-6) vs 3 (2-4), P<0.0001). CONCLUSIONS: We present factors associated with prolonged LOS, which in turn was associated with poor long-term outcomes. Factors associated with LOS may help to inform patient and clinician expectations of recovery, guide protocols for clinical trials, and select suitable populations for minimally invasive endoscopic evacuation.


Assuntos
Hemorragia Cerebral , Acidente Vascular Cerebral , Humanos , Tempo de Internação , Resultado do Tratamento , Hemorragia Cerebral/diagnóstico por imagem , Hemorragia Cerebral/cirurgia , Hematoma/cirurgia , Procedimentos Cirúrgicos Minimamente Invasivos/métodos
4.
J Neurointerv Surg ; 2023 Aug 24.
Artigo em Inglês | MEDLINE | ID: mdl-37620128

RESUMO

BACKGROUND: We explored the clinical significance of the residual hematoma cavity 1 year after minimally invasive intracerebral hemorrhage (ICH) evacuation. METHODS: Patients presenting with spontaneous supratentorial ICH were evaluated for minimally invasive surgical evacuation. Inclusion criteria included age ≥18 years, preoperative hematoma volume (Hv) ≥15 mL, presenting National Institutes of Health Stroke Scale score ≥6, and premorbid modified Rankin Scale (mRS) score ≤3. Patients with longitudinal CT scans at least 3 months after evacuation were included in the study. Remnant cavity volumes (Cv) after evacuation were computed using semi-automatic volumetric segmentation software. Relative cavity volume (rCv) was defined as the ratio of the preoperative Hv to the remnant Cv. RESULTS: 108 patients with a total of 484 head CT scans were included in the study. The median postoperative Cv was 2.4 (IQR 0.0-11) mL, or just 6% (0-33%) of the preoperative Hv. The median residual Cv on the final head CT scan a median of 13 months (range 11-27 months) after surgery had increased to 9.4 (IQR 3.1-18) mL, or 25% (10-60%) of the preoperative Hv. rCv on the final head CT scan was negatively associated with measures of operative success including evacuation percentage, postoperative Hv ≤15 mL, and decreased time from ictus to evacuation. rCv on the final head CT scan was also associated with a worse 6-month functional outcome (ß per mRS point 17.6%, P<0.0001; area under the receiver operating characteristic curve 0.91). CONCLUSION: After minimally invasive ICH evacuation the hematoma lesion decompresses significantly, with a residual Cv just 6% of the original lesion, but then gradually increases in size over time. Early and high percentage ICH evacuation may reduce the remnant Cv over time which, in turn, is associated with improved functional outcomes.

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