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BACKGROUND AND PURPOSE: Nuclear factor erythroid 2-related factor 2 (NRF2; encoded by the NFE2L2 gene) has been implicated in outcome following aneurysmal subarachnoid haemorrhage (aSAH) through its activity as a regulator of inflammation, oxidative injury and blood breakdown product clearance. The aim of this study was to identify whether genetic variation in NFE2L2 is associated with clinical outcome following aSAH. METHODS: Ten tagging single nucleotide polymorphisms (SNPs) in NFE2L2 were genotyped and tested for association with dichotomized clinical outcome, assessed by the modified Rankin scale, in both a discovery and a validation cohort. In silico functional analysis was performed using a range of bioinformatic tools. RESULTS: One SNP, rs10183914, was significantly associated with outcome following aSAH in both the discovery (n = 1007) and validation cohorts (n = 466). The risk of poor outcome was estimated to be 1.33-fold (95% confidence interval 1.12-1.58) higher in individuals with the T allele of rs10183914 (pmeta-analysis = 0.001). In silico functional analysis identified rs10183914 as a potentially regulatory variant with effects on transcription factor binding in addition to alternative splicing with the T allele, associated with a significant reduction in the NFE2L2 intron excision ratio (psQTL = 1.3 × 10-7 ). CONCLUSIONS: The NFE2L2 SNP, rs10183914, is significantly associated with outcome following aSAH. This is consistent with a clinically relevant pathophysiological role for oxidative and inflammatory brain injury due to blood and its breakdown products in aSAH. Furthermore, our findings support NRF2 as a potential therapeutic target following aSAH and other forms of intracranial haemorrhage.
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Hemorragia Subaracnóidea , Humanos , Hemorragia Subaracnóidea/genética , Fator 2 Relacionado a NF-E2/genética , Polimorfismo de Nucleotídeo Único/genética , Genótipo , AlelosRESUMO
OBJECTIVE: Acute hydrocephalus is a frequent complication after aneurysmal subarachnoid hemorrhage (aSAH). Among patients needing CSF diversion, some cannot be weaned. Little is known about the comparative neurological, neuropsychological, and health-related quality-of-life (HRQOL) outcomes in patients with successful and unsuccessful CSF weaning. The authors aimed to assess outcomes of patients by comparing those with successful and unsuccessful CSF weaning; the latter was defined as occurring in patients with permanent CSF diversion at 3 months post-aSAH. METHODS: The authors included prospectively recruited alert (i.e., Glasgow Coma Scale score 13-15) patients with aSAH in this retrospective study from six Swiss neurovascular centers. Patients underwent serial neurological (National Institutes of Health Stroke Scale), neuropsychological (Montreal Cognitive Assessment), disability (modified Rankin Scale), and HRQOL (EuroQol-5D) examinations at < 72 hours, 14-28 days, and 3 months post-aSAH. RESULTS: Of 126 included patients, 54 (42.9%) developed acute hydrocephalus needing CSF diversion, of whom 37 (68.5%) could be successfully weaned and 17 (31.5%) required permanent CSF diversion. Patients with unsuccessful weaning were older (64.5 vs 50.8 years, p = 0.003) and had a higher rate of intraventricular hemorrhage (52.9% vs 24.3%, p = 0.04). Patients who succeed in restoration of physiological CSF dynamics improve on average by 2 points on the Montreal Cognitive Assessment between 48-72 hours and 14-28 days, whereas those in whom weaning fails worsen by 4 points (adjusted coefficient 6.80, 95% CI 1.57-12.04, p = 0.01). They show better neuropsychological recovery between 48-72 hours and 3 months, compared to patients in whom weaning fails (adjusted coefficient 7.60, 95% CI 3.09-12.11, p = 0.02). Patients who receive permanent CSF diversion (ventriculoperitoneal shunt) show significant neuropsychological improvement thereafter, catching up the delay in neuropsychological improvement between 14-28 days and 3 months post-aSAH. Neurological, disability, and HRQOL outcomes at 3 months were similar. CONCLUSIONS: These results show a temporary but clinically meaningful cognitive benefit in the first weeks after aSAH in successfully weaned patients. The resolution of this difference over time may be due to the positive effects of permanent CSF diversion and underlines its importance. Patients who do not show progressive neuropsychological improvement after weaning should be considered for repeat CT imaging to rule out chronic (untreated) hydrocephalus.
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Hidrocefalia , Hemorragia Subaracnóidea , Humanos , Hemorragia Subaracnóidea/complicações , Hemorragia Subaracnóidea/cirurgia , Estudos Retrospectivos , Suíça , Desmame , Hidrocefalia/cirurgia , Hidrocefalia/complicaçõesRESUMO
OBJECTIVE: This study was undertaken to identify susceptibility loci for cluster headache and obtain insights into relevant disease pathways. METHODS: We carried out a genome-wide association study, where 852 UK and 591 Swedish cluster headache cases were compared with 5,614 and 1,134 controls, respectively. Following quality control and imputation, single variant association testing was conducted using a logistic mixed model for each cohort. The 2 cohorts were subsequently combined in a merged analysis. Downstream analyses, such as gene-set enrichment, functional variant annotation, prediction and pathway analyses, were performed. RESULTS: Initial independent analysis identified 2 replicable cluster headache susceptibility loci on chromosome 2. A merged analysis identified an additional locus on chromosome 1 and confirmed a locus significant in the UK analysis on chromosome 6, which overlaps with a previously known migraine locus. The lead single nucleotide polymorphisms were rs113658130 (p = 1.92 × 10-17 , odds ratio [OR] = 1.51, 95% confidence interval [CI] = 1.37-1.66) and rs4519530 (p = 6.98 × 10-17 , OR = 1.47, 95% CI = 1.34-1.61) on chromosome 2, rs12121134 on chromosome 1 (p = 1.66 × 10-8 , OR = 1.36, 95% CI = 1.22-1.52), and rs11153082 (p = 1.85 × 10-8 , OR = 1.30, 95% CI = 1.19-1.42) on chromosome 6. Downstream analyses implicated immunological processes in the pathogenesis of cluster headache. INTERPRETATION: We identified and replicated several genome-wide significant associations supporting a genetic predisposition in cluster headache in a genome-wide association study involving 1,443 cases. Replication in larger independent cohorts combined with comprehensive phenotyping, in relation to, for example, treatment response and cluster headache subtypes, could provide unprecedented insights into genotype-phenotype correlations and the pathophysiological pathways underlying cluster headache. ANN NEUROL 2021;90:193-202.
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Cefaleia Histamínica/epidemiologia , Cefaleia Histamínica/genética , Loci Gênicos/genética , Predisposição Genética para Doença/epidemiologia , Predisposição Genética para Doença/genética , Estudo de Associação Genômica Ampla/métodos , Estudos de Casos e Controles , Cefaleia Histamínica/diagnóstico , Estudos de Coortes , Feminino , Humanos , Masculino , Suécia/epidemiologia , Reino Unido/epidemiologiaRESUMO
OBJECTIVE: After aneurysmal subarachnoid haemorrhage (aSAH), extracellular haemoglobin (Hb) in the subarachnoid space is bound by haptoglobin, neutralising Hb toxicity and helping its clearance. Two exons in the HP gene (encoding haptoglobin) exhibit copy number variation (CNV), giving rise to HP1 and HP2 alleles, which influence haptoglobin expression level and possibly haptoglobin function. We hypothesised that the HP CNV associates with long-term outcome beyond the first year after aSAH. METHODS: The HP CNV was typed using quantitative PCR in 1299 aSAH survivors in the Genetics and Observational Subarachnoid Haemorrhage (GOSH) Study, a retrospective multicentre cohort study with a median follow-up of 18 months. To investigate mediation of the HP CNV effect by haptoglobin expression level, as opposed to functional differences, we used rs2000999, a single nucleotide polymorphism associated with haptoglobin expression independent of the HP CNV. Outcome was assessed using modified Rankin and Glasgow Outcome Scores. SAH volume was dichotomised on the Fisher grade. Haemoglobin-haptoglobin complexes were measured in cerebrospinal fluid (CSF) of 44 patients with aSAH and related to the HP CNV. RESULTS: The HP2 allele associated with a favourable long-term outcome after high-volume but not low-volume aSAH (multivariable logistic regression). However rs2000999 did not predict outcome. The HP2 allele associated with lower CSF haemoglobin-haptoglobin complex levels. The CSF Hb concentration after high-volume and low-volume aSAH was, respectively, higher and lower than the Hb-binding capacity of CSF haptoglobin. CONCLUSION: The HP2 allele carries a favourable long-term prognosis after high-volume aSAH. Haptoglobin and the Hb clearance pathway are therapeutic targets after aSAH.
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Haptoglobinas/genética , Aneurisma Intracraniano/genética , Hemorragia Subaracnóidea/genética , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Criança , Estudos de Coortes , Variações do Número de Cópias de DNA/genética , Feminino , Genótipo , Humanos , Aneurisma Intracraniano/complicações , Aneurisma Intracraniano/mortalidade , Masculino , Pessoa de Meia-Idade , Polimorfismo de Nucleotídeo Único/genética , Recuperação de Função Fisiológica , Hemorragia Subaracnóidea/mortalidade , Taxa de Sobrevida , Adulto JovemRESUMO
The purpose of the present study is to analyze the impact of intraoperative resection control modalities on overall survival (OS) and progression-free survival (PFS) following gross total resection (GTR) of glioblastoma. We analyzed data of 76 glioblastoma patients (30f, mean age 57.4 ± 11.6 years) operated at our institution between 2009 and 2012. Patients were only included if GTR was achieved as judged by early postoperative high-field MRI. Intraoperative technical resection control modalities comprised intraoperative ultrasound (ioUS, n = 48), intraoperative low-field MRI (ioMRI, n = 22), and a control group without either modality (n = 11). The primary endpoint of our study was OS, and the secondary endpoint was PFS-both analyzed in Kaplan-Meier plots and Cox proportional hazards models. Median OS in all 76 glioblastoma patients after GTR was 20.4 months (95 % confidence interval (CI) 18.5-29.0)-median OS in patients where GTR was achieved using ioUS was prolonged (21.9 months) compared to those without ioUS usage (18.8 months). A multiple Cox model adjusting for age, preop Karnofsky performance status, tumor volume, and the use of 5-aminolevulinic acid showed a beneficial effect of ioUS use, and the estimated hazard ratio was 0.63 (95 % CI 0.31-1.2, p = 0.18) in favor of ioUS, however not reaching statistical significance. A similar effect was found for PFS (hazard ratio 0.59, p = 0.072). GTR of glioblastoma performed with ioUS guidance was associated with prolonged OS and PFS. IoUS should be compared to other resection control devices in larger patient cohorts.
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Neoplasias Encefálicas/mortalidade , Neoplasias Encefálicas/cirurgia , Glioblastoma/mortalidade , Glioblastoma/cirurgia , Procedimentos Neurocirúrgicos , Intervalo Livre de Doença , Feminino , Glioblastoma/diagnóstico , Humanos , Avaliação de Estado de Karnofsky/estatística & dados numéricos , Masculino , Neoplasia Residual/mortalidade , Neoplasia Residual/patologia , Modelos de Riscos Proporcionais , Resultado do TratamentoRESUMO
Background: The relationship between baseline perihematomal edema (PHE) and inflammation, and their impact on survival after intracerebral hemorrhage (ICH) are not well understood. Objective: Assess the association between baseline PHE, baseline C-reactive protein (CRP), and early death after ICH. Methods: Analysis of pooled data from multicenter ICH registries. We included patients presenting within 24 h of symptom onset, using multifactorial linear regression model to assess the association between CRP and edema extension distance (EED), and a multifactorial Cox regression model to assess the association between CRP, PHE volume and 30-day mortality. Results: We included 1,034 patients. Median age was 69 (interquartile range [IQR] 59-79), median baseline ICH volume 11.5 (IQR 4.3-28.9) mL, and median baseline CRP 2.5 (IQR 1.5-7.0) mg/L. In the multifactorial analysis [adjusting for cohort, age, sex, log-ICH volume, ICH location, intraventricular hemorrhage (IVH), statin use, glucose, and systolic blood pressure], baseline log-CRP was not associated with baseline EED: for a 50% increase in CRP the difference in expected mean EED was 0.004 cm (95%CI 0.000-0.008, p = 0.055). In a further multifactorial analysis, after adjusting for key predictors of mortality, neither a 50% increase in PHE volume nor CRP were associated with higher 30-day mortality (HR 0.97; 95%CI 0.90-1.05, p = 0.51 and HR 0.98; 95%CI 0.93-1.03, p = 0.41, respectively). Conclusion: Higher baseline CRP is not associated with higher baseline edema, which is also not associated with mortality. Edema at baseline might be driven by different pathophysiological processes with different effects on outcome.
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The size of the human head is highly heritable, but genetic drivers of its variation within the general population remain unmapped. We perform a genome-wide association study on head size (N = 80,890) and identify 67 genetic loci, of which 50 are novel. Neuroimaging studies show that 17 variants affect specific brain areas, but most have widespread effects. Gene set enrichment is observed for various cancers and the p53, Wnt, and ErbB signaling pathways. Genes harboring lead variants are enriched for macrocephaly syndrome genes (37-fold) and high-fidelity cancer genes (9-fold), which is not seen for human height variants. Head size variants are also near genes preferentially expressed in intermediate progenitor cells, neural cells linked to evolutionary brain expansion. Our results indicate that genes regulating early brain and cranial growth incline to neoplasia later in life, irrespective of height. This warrants investigation of clinical implications of the link between head size and cancer.
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Estudo de Associação Genômica Ampla , Cabeça , Neoplasias , Humanos , Cabeça/anatomia & histologia , Neoplasias/genética , Neoplasias/patologia , Feminino , Masculino , Polimorfismo de Nucleotídeo Único/genética , Variação Genética , Tamanho do Órgão/genética , Transdução de Sinais/genética , Adulto , Predisposição Genética para DoençaRESUMO
Introduction: Anterior-only multilevel cervical decompression and fusion surgery (AMCS) on 3-5-levels is challenging due to potential complications. Also, outcome predictors after AMCS are poorly understood. Research Question: We hypothesize that in patients with at most mild/moderate cervical kyphosis (CK) of the cervical spine, restoration of cervical lordosis (CL) positively influences clinical outcomes. Methods: Analysis of consecutive patients presenting with symptomatic degenerative cervical disease or non-union undergoing AMCS. We measured CL from C2 to C7, Cobb angle of fused levels (fusion angle, FA), C7-Slope, and sagittal vertical axis C2-7 (cSVA, stratified into ≤4cm∖>4cm). Patients with excellent outcome were grouped in BEST-outcomes and with moderate/poor outcomes in WORST-outcomes. Results: We included 244 patients. Fifty-four percent had 3-, 39% 4-level and 7% had 5-level fusion. At mean follow-up of 26 months, 41% of patients achieved BEST-outcome and 23% WORST-outcome. Complications and reoperation rates did not significantly differ. Non-union significantly influenced outcomes. The number of patients with non-union was significantly higher in patients with a preoperative cSVA>4cm (OR 13.1 (95%CI:1.8-96.8). Our model, based on the multivariable analysis with WORST-outcome as outcome variable showed a high accuracy (NPV=73%, PPV=77%, specificity=79%, sensitivity=71%). Discussion and Conclusion: In 3-5-level AMCS, improvement of FA and cSVA were independent predictors of clinical outcome. Improvement of CL positively influenced clinical outcomes and rates of non-union.
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Timely treatment of aneurysmal subarachnoid haemorrhage (aSAH) is key to prevent further rupture and poor outcome. We evaluated complications and outcome adjusting for time from haemorrhage to treatment. Retrospective analysis of aSAH patients admitted between 2006 and 2020. Data was collected using standardized case report forms. We compared risk factors using multivariable logistic regression. We included 853 patients, 698 (81.8%) were treated within 24 h. Patients with higher Hunt and Hess grades were admitted and treated significantly faster than those with lower grades (overall p-value < 0.001). Fifteen patients (1.8%) rebled before intervention. In the multivariable logistic analysis adjusting for timing, Barrow Neurological Institute score and intracerebral haemorrhage were significantly associated with rebleeding (overall p-value 0.006; OR 3.12, 95%CI 1.09-8.92, p = 0.03, respectively) but timing was not. Treatment > 24 h was associated with higher mortality and cerebral infarction in only the subgroup of lower grades aSAH (OR 3.13, 1.02-9.58 95%CI, p-value = 0.05; OR 7.69, 2.44-25.00, p-value < 0.001, respectively). Therefore treatment > 24 h after rupture is associated with higher mortality and cerebral infarction rates in lower grades aSAH. Delay in treatment primarily affects lower grade aSAH patients. Patients with lower grade aSAH ought to be treated with the same urgency as higher-grade aSAH.
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Aneurisma Roto , Aneurisma Intracraniano , Hemorragia Subaracnóidea , Humanos , Hemorragia Subaracnóidea/terapia , Hemorragia Subaracnóidea/complicações , Estudos Retrospectivos , Fatores de Risco , Infarto Cerebral/complicações , Aneurisma Roto/terapia , Aneurisma Roto/complicações , Resultado do Tratamento , Aneurisma Intracraniano/complicações , Aneurisma Intracraniano/terapiaRESUMO
BACKGROUND: Cerebral amyloid angiopathy (CAA), a common cause of intracerebral hemorrhage (ICH), is diagnosed using the Boston criteria including magnetic resonance imaging (MRI) biomarkers (cerebral microbleeds (CMBs) and cortical superficial siderosis (cSS). The simplified Edinburgh criteria include computed tomography (CT) biomarkers (subarachnoid extension (SAE) and finger-like projections (FLPs)). The underlying mechanisms and diagnostic accuracy of CT compared to MRI biomarkers of CAA are unknown. METHODS: We included 140 survivors of spontaneous lobar supratentorial ICH with both acute CT and MRI. We assessed associations between MRI and CT biomarkers and the diagnostic accuracy of CT- compared to MRI-based criteria. RESULTS: FLPs were more common in patients with strictly lobar CMB (44.7% vs 23.5%; p = 0.014) and SAE was more common in patients with cSS (61.3% vs 31.2%; p = 0.002). The high probability of the CAA category of the simplified Edinburgh criteria showed 87.2% (95% confidence interval (CI): 78.3-93.4) specificity, 29.6% (95% CI: 18.0-43.6) sensitivity, 59.3% (95% CI: 38.8-77.6) positive predictive value, and 66.4% (95%: CI 56.9-75.0) negative predictive value, 2.3 (95% CI: 1.2-4.6) positive likelihood ratio and 0.8 (95% CI 0.7-1.0) negative likelihood ratio for probable CAA (vs non-probable CAA), defined by the modified Boston criteria; the area under the receiver operating characteristic curve (AUROC) was 0.62 (95% CI: 0.54-0.71). CONCLUSION: In lobar ICH survivors, we found associations between putative biomarkers of parenchymal CAA (FLP and strictly lobar CMBs) and putative biomarkers of leptomeningeal CAA (SAE and cSS). In a hospital population, CT biomarkers might help rule-in probable CAA (diagnosed using the Boston criteria), but their absence is probably not as useful to rule it out, suggesting an important continued role for MRI in ICH survivors with suspected CAA.
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Angiopatia Amiloide Cerebral , Acidente Vascular Cerebral , Humanos , Hemorragia Cerebral/epidemiologia , Angiopatia Amiloide Cerebral/complicações , Angiopatia Amiloide Cerebral/diagnóstico por imagem , Imageamento por Ressonância Magnética , Tomografia Computadorizada por Raios X , BiomarcadoresRESUMO
BACKGROUND: Intracerebral haemorrhage (ICH) is a severe clinical consequence of cerebral small vessel disease (SVD), but associations between renal impairment and SVD in patients with ICH have not been fully characterised. METHODS: Using data from the CROMIS-2 ICH observational study, we compared SVD neuroimaging markers and total burden (score 0-3) identified using CT brain imaging in patients with and without renal impairment (estimated glomerular filtration rate, eGFR<60). We assessed functional outcome at 6-month follow-up using the modified Rankin scale. RESULTS: 1027 participants were included (mean age 72.8, 57.1% male); 274 with and 753 without renal impairment. 18.7% of the eGFR<60 group had moderate-to-severe SVD burden (score 2-3), compared with 14.0% of those with eGFR>60 (p = 0.039). SVD burden was associated with renal impairment after adjusting for hypertension (OR 1.36, 95% CI 1.04-1.77, p = 0.023), but not after adjusting for age. Cerebral atrophy was more prevalent in patients with eGFR<60 (81.2% vs. 72.0%, p = 0.002), as were WMH (45.6% vs. 36.6%, p = 0.026). Neither was associated with renal function after adjusting for age and vascular risk factors. Renal impairment was associated with functional outcome (OR 0.65, 95% CI 0.47-0.89, p = 0.007), but not after adjusting for age, pre-morbid function and comorbidities (OR 0.95, 95% CI 0.65-1.38, p = 0.774). CONCLUSION: In acute ICH, renal impairment is associated with a higher cerebral SVD burden independent of hypertension, but not age. Reduced eGFR is associated with worse functional outcome, but not independent of age and comorbidities. Since CT has limited sensitivity to detect SVD severity and distribution, further studies including MRI are needed.
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Doenças de Pequenos Vasos Cerebrais , Hipertensão , Humanos , Masculino , Feminino , Estudos Prospectivos , Hemorragia Cerebral/complicações , Hemorragia Cerebral/diagnóstico por imagem , Hemorragia Cerebral/epidemiologia , Doenças de Pequenos Vasos Cerebrais/complicações , Doenças de Pequenos Vasos Cerebrais/diagnóstico por imagem , Imageamento por Ressonância Magnética , Hipertensão/complicações , Rim/diagnóstico por imagem , Rim/fisiologiaRESUMO
Candidate gene studies have identified genetic variants associated with clinical outcomes following aneurysmal subarachnoid haemorrhage (aSAH), but no genome-wide association studies have been performed to date. Here we report the results of the discovery phase of a two-stage genome-wide meta-analysis of outcome after aSAH. We identified 157 independent loci harbouring 756 genetic variants associated with outcome after aSAH (p < 1 × 10-4), which require validation. A single variant (rs12949158), in SPNS2, achieved genome-wide significance (p = 4.29 × 10-8) implicating sphingosine-1-phosphate signalling in outcome after aSAH. A large multicentre international effort to recruit samples for validation is required and ongoing. Validation of these findings will provide significant insight into the pathophysiology of outcomes after aSAH with potential implications for treatment.
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Hemorragia Subaracnóidea , Humanos , Hemorragia Subaracnóidea/complicações , Estudo de Associação Genômica Ampla , Estudos Longitudinais , Resultado do TratamentoRESUMO
Endometriosis is a common condition associated with debilitating pelvic pain and infertility. A genome-wide association study meta-analysis, including 60,674 cases and 701,926 controls of European and East Asian descent, identified 42 genome-wide significant loci comprising 49 distinct association signals. Effect sizes were largest for stage 3/4 disease, driven by ovarian endometriosis. Identified signals explained up to 5.01% of disease variance and regulated expression or methylation of genes in endometrium and blood, many of which were associated with pain perception/maintenance (SRP14/BMF, GDAP1, MLLT10, BSN and NGF). We observed significant genetic correlations between endometriosis and 11 pain conditions, including migraine, back and multisite chronic pain (MCP), as well as inflammatory conditions, including asthma and osteoarthritis. Multitrait genetic analyses identified substantial sharing of variants associated with endometriosis and MCP/migraine. Targeted investigations of genetically regulated mechanisms shared between endometriosis and other pain conditions are needed to aid the development of new treatments and facilitate early symptomatic intervention.
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Endometriose , Feminino , Humanos , Endometriose/genética , Endometriose/metabolismo , Predisposição Genética para Doença , Estudo de Associação Genômica Ampla , Dor , ComorbidadeRESUMO
OBJECTIVE: Three-column osteotomy (3CO) is used for severe spinal deformities. Associated complications include sagittal translation (ST), which can lead to neurological symptoms. Mismatch between the surgical center of rotation (COR) and the concept of the ideal COR is a potential cause of ST. Matching surgical with conceptual COR is difficult with pedicle subtraction osteotomy (PSO) and vertebral column resection (VCR). This mismatch influences correction geometry, which can prevent maximum possible correction. The authors' objective was to examine the sagittal correction geometry and surgical COR of thoracic and lumbar 3CO. METHODS: In a retrospective study of patients with PSO or VCR for severe sagittal plane deformity, analysis of surgical COR was performed using pre- and postoperative CT scans in the PSO group and digital radiographs in the VCR group. Radiographic analysis included standard deformity measurements and regional kyphosis angle (RKA). All patients had 2-year follow-up, including neurological outcome. Preoperative CT scans were studied for rigid osteotomy sites versus mobile osteotomy sites. Additional radiographic analysis of surgical COR was based on established techniques superimposing pre- and postoperative images. Position of the COR was defined in a rectangular net layered onto the osteotomy vertebrae (OVs). RESULTS: The study included 34 patients undergoing PSO and 35 undergoing VCR, with mean ages of 57 and 29 years and mean RKA corrections of 31° and 49°, respectively. In the PSO group, COR was mainly in the anterior column, and surgical and conceptual COR matched in 22 patients (65%). Smaller RKA correction (27° vs 32°, p = 0.09) was seen in patients with anterior eccentric COR. Patients with rigid osteotomy sites were more likely to have an anterior eccentric COR (41% vs 11%, p = 0.05). In the VCR group, 20 patients (57%) had single-level VCR and 15 (43%) had multilevel VCR. COR was mainly located in the anterior or middle column. Mismatch between surgical and conceptual COR occurred in 24 (69%) patients. Larger RKA correction (63° vs 45°, p = 0.03) was seen in patients with anterior column COR. Patients with any posterior COR had a smaller RKA correction compared to the rest of the patients (42° vs 61°, p = 0.007). CONCLUSIONS: Matching the surgical with the conceptual COR is difficult and in this study failed in one- to two-thirds of all patients. In order to avoid ST during correction of severe deformities, temporary rods, tracking rods, or special instruments should be used for correction maneuvers.
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Adult spinal ependymoma presents a rare low-grade tumor entity. Due to its incidence peak in the fourth decade of life, it mostly affects patients during a professionally and physically active time of life. We performed a retrospective monocentric study, including all patients operated upon for spinal ependymoma between 2009 and 2020. We prospectively collected data on professional reintegration, physical activities and quality-of-life parameters using EQ-5D and SF-36. Issues encountered were assessed using existing spinal-cord-specific questionnaires and free-text questions. In total, 65 of 114 patients agreed to participate. Most patients suffered from only mild pre- and postoperative impairment on the modified McCormick scale, but 67% confirmed difficulties performing physical activities in which they previously engaged due to pain, coordination problems and fear of injuries after a median follow-up of 5.4 years. We observed a shift from full- to part-time employment and patients unable to work, independently from tumor dignity, age and neurological function. Despite its benign nature and occurrence of formal only mild neurological deficits, patients described severe difficulties returning to their preoperative physical activity and profession. Clinical scores such as the McCormick grade and muscle strength may not reflect the entire self-perceived impairment appropriately.
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Ependimoma , Neoplasias da Medula Espinal , Adulto , Ependimoma/patologia , Ependimoma/cirurgia , Humanos , Procedimentos Neurocirúrgicos , Qualidade de Vida , Estudos Retrospectivos , Retorno ao Trabalho , Neoplasias da Medula Espinal/patologia , Neoplasias da Medula Espinal/cirurgia , Resultado do TratamentoRESUMO
STUDY DESIGN: Retrospective, single-center case study. OBJECTIVE: Postoperative cervical imbalance with cervical sagittal vertical axis (cSVA) >4 cm can be predicted in 3-level to 5-level anterior-only cervical multilevel fusion surgery (ACMS). SUMMARY OF BACKGROUND DATA: Previous studies established correlations between cervical kyphosis (CK) correction and postoperative balance (cSVA ≤4 cm) with improved clinical outcomes. Understanding of what influences restoration of cervical lordosis (CL) in patients with degenerative disease with mild to moderate CK subjected to ACMS is important. To achieve a better understanding of geometric changes after ACMS, this study examines factors predicting perioperative alignment changes and regional interdependencies. MATERIALS AND METHODS: Analysis of patients with ACMS. Analysis included patient baseline characteristics, demographics and complications, and focused on radiographic measures including CL C2-7, fusion angle (FA), C7-Slope (C7S), T1-slope (T1S), T1-CL mismatch, and cSVA (cSVA ≤4 cm/>4 cm). We aimed to predict postoperative imbalance (cSVA >4 cm) and conducted a multivariable logistic regression analysis. RESULTS: Inclusion of 126 patients with 3-level to 5-level ACMS, mean age was 56 years and 4 fusion levels on average. Preoperative CK was present in 9%, mean FA-correction was 8 degrees, maximum 46 degrees. Postoperatively, 14 patients had cSVA >4 cm. A neural network model for prediction of cSVA >4 cm was established including preoperative cSVA, preoperative CL and correction of FA. The model achieved high performance (positive predictive value=100%, negative predictive value=94%, specificity=100%, sensitivity=20%). Also, variables such as nonunion, chronic lumbar pain or thoracolumbar multilevel fusion influenced the postoperative cSVA >4 cm rate. Alignment analysis highlighted strong correlations between C7S/T1S and cSVA/C2-tilt ( r =0.06/ r =0.7, P <0.0001). A formula was established to transfer cSVA data into C2-tilt data. CONCLUSION: This study identified independent variables predicting postoperative cSVA >4 cm including FA, which can be influenced by the surgeon. Our model supports the decision-making process targeting a postoperative cSVA ≤4 cm.
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Cifose , Lordose , Vértebras Cervicais/diagnóstico por imagem , Vértebras Cervicais/cirurgia , Descompressão , Humanos , Cifose/diagnóstico por imagem , Cifose/cirurgia , Lordose/diagnóstico por imagem , Lordose/cirurgia , Pessoa de Meia-Idade , Estudos Retrospectivos , Vértebras Torácicas/cirurgiaRESUMO
BACKGROUND: Aneurysm treatment during cerebral vasospasm (CVS) phase is frequently considered as particularly dangerous, mainly because of the risk of cerebral infarct. OBJECTIVE: We aimed to evaluate the risk of aneurysmal subarachnoid haemorrhage (aSAH)-specific complications and functional outcome in patients treated during CVS phase. METHODS: We retrospectively analysed a large, retro- and prospectively collected database of aSAH patients admitted to our department between March 2006 and March 2020. We conducted a uni- and multivariable logistic regression analysis to evaluate influencing factors on rebleeding, cerebral infarct, Glasgow Outcome Score (GOS) at discharge and mortality and assessed the rate of angiographic vasospasm on admission. RESULTS: We included 853 patients. The majority of patients were female (66.6%), mean age was 57.3 years. Out of 853 included patients, 92 (10.8%) were treated during CVS phase, 312 (36.6%) underwent clipping and 541 (63.4%) endovascular treatment. Treatment during CVS phase was significantly associated with cerebral infarct in the multivariable logistic regression analysis, unrelated to the nature of intervention (OR 2.42, 1.29-4.54 95% CI p-value = 0.006). However, patients treated during CVS phase did not have increased risk of unfavourable outcome by GOS on discharge. In addition, they did not have a higher rate of rebleeding or mortality. CONCLUSIONS: Treatment during CVS phase was significantly associated with a higher rate of cerebral infarct as confirmed by imaging. This did not reflect on GOS on discharge, rebleeding, or mortality. Aneurysm treatment during CVS phase is relatively safe and should not be postponed due to the risk of rebleeding and subsequent devastating deterioration.
Assuntos
Aneurisma Intracraniano , Hemorragia Subaracnóidea , Vasoespasmo Intracraniano , Angiografia/efeitos adversos , Infarto Cerebral/complicações , Feminino , Humanos , Aneurisma Intracraniano/complicações , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Hemorragia Subaracnóidea/complicações , Hemorragia Subaracnóidea/diagnóstico por imagem , Hemorragia Subaracnóidea/terapia , Resultado do Tratamento , Vasoespasmo Intracraniano/diagnóstico por imagem , Vasoespasmo Intracraniano/epidemiologia , Vasoespasmo Intracraniano/etiologiaRESUMO
BACKGROUND: Literature is inconclusive regarding the association between antiplatelet agents use and outcome after aneurysmal subarachnoid hemorrhage. AIMS: To investigate the association between clinical outcome and prehemorrhage use in aneurysmal subarachnoid hemorrhage patients as well as the impact of thrombocyte transfusion on rebleed and clinical outcome. METHODS: Data were collected from prospective databases of two European tertiary reference centers for aneurysmal subarachnoid hemorrhage patients. Patients were divided into "antiplatelet-user" and "non-user" according to the use of acetylsalicylic acid prior to the hemorrhage. Primary outcome was poor clinical outcome at six months (Glasgow Outcome Scale score 1-3). Secondary outcomes were in-hospital mortality and impact of thrombocyte transfusion. RESULTS: Of the 1033 patients, 161 (15.6%) were antiplatelet users. The antiplatelet users were older with higher incidence of cardiovascular risk factors. Antiplatelet use was associated with poor outcome and in-hospital mortality. After correction for age, sex, World Federation of Neurosurgical Societies score, infarction and heart disorder, pre-hemorrhage acetylsalicylic acid use was only associated with poor clinical outcome at six months (adjusted OR 1.80, 95% CI 1.08-3.02). Thrombocyte transfusion was not associated with a reduction in rebleed or poor clinical outcome. CONCLUSION: In this multicenter study, the prehemorrhage acetylsalicylic acid use in aneurysmal subarachnoid hemorrhage patients was independently associated with poor clinical outcome at six months. Thrombocyte transfusion was not associated with the rebleed rate or poor clinical outcome at six months.
Assuntos
Acidente Vascular Cerebral , Hemorragia Subaracnóidea , Aspirina/uso terapêutico , Escala de Resultado de Glasgow , Humanos , Acidente Vascular Cerebral/complicações , Hemorragia Subaracnóidea/complicações , Hemorragia Subaracnóidea/tratamento farmacológico , Resultado do TratamentoRESUMO
Aneurysmal subarachnoid haemorrhage (aSAH) results in persistent clinical deficits which prevent survivors from returning to normal daily functioning. Only a small fraction of the variation in clinical outcome following aSAH is explained by known clinical, demographic and imaging variables; meaning additional unknown factors must play a key role in clinical outcome. There is a growing body of evidence that genetic variation is important in determining outcome following aSAH. Understanding genetic determinants of outcome will help to improve prognostic modelling, stratify patients in clinical trials and target novel strategies to treat this devastating disease. This protocol details a two-stage genome-wide association study to identify susceptibility loci for clinical outcome after aSAH using individual patient-level data from multiple international cohorts. Clinical outcome will be assessed using the modified Rankin Scale or Glasgow Outcome Scale at 1-24 months. The stage 1 discovery will involve meta-analysis of individual-level genotypes from different cohorts, controlling for key covariates. Based on statistical significance, supplemented by biological relevance, top single nucleotide polymorphisms will be selected for replication at stage 2. The study has national and local ethical approval. The results of this study will be rapidly communicated to clinicians, researchers and patients through open-access publication(s), presentation(s) at international conferences and via our patient and public network.
Assuntos
Hemorragia Subaracnóidea , Estudo de Associação Genômica Ampla , Genótipo , Humanos , Metanálise como Assunto , Polimorfismo de Nucleotídeo Único/genética , Prognóstico , Hemorragia Subaracnóidea/genéticaRESUMO
Classic bladder exstrophy represents the most severe end of all human congenital anomalies of the kidney and urinary tract and is associated with bladder cancer susceptibility. Previous genetic studies identified one locus to be involved in classic bladder exstrophy, but were limited to a restrict number of cohort. Here we show the largest classic bladder exstrophy genome-wide association analysis to date where we identify eight genome-wide significant loci, seven of which are novel. In these regions reside ten coding and four non-coding genes. Among the coding genes is EFNA1, strongly expressed in mouse embryonic genital tubercle, urethra, and primitive bladder. Re-sequence of EFNA1 in the investigated classic bladder exstrophy cohort of our study displays an enrichment of rare protein altering variants. We show that all coding genes are expressed and/or significantly regulated in both mouse and human embryonic developmental bladder stages. Furthermore, nine of the coding genes residing in the regions of genome-wide significance are differentially expressed in bladder cancers. Our data suggest genetic drivers for classic bladder exstrophy, as well as a possible role for these drivers to relevant bladder cancer susceptibility.