Objectives:The prevalence of idiopathic normal pressure hydrocephalus (iNPH) and vascular comorbidity increases with age. It has not been clarified if high age and vascular disease are negative predictors of shunt surgery outcome in patients with iNPH.The aim of this study was to investigate the impact of high age and vascular comorbidity on outcome after shunt surgery in patients with iNPH.Methods: All 332 patients with iNPH who were treated with shunts between 2011 and 2015 at a single centre were consecutively included. Hellström iNPH scale, without the neuropsychological tests, was calculated preoperatively and at follow-up 12 months after shunt surgery. Outcome was defined as the difference between the post-operative and preoperative iNPH scale scores. A multivariable model was used to investigate the predictive effects of age and vascular comorbidity on shunt surgery outcome. Results:In a multivariable analysis of covariance (ANCOVA) with post-operative outcome as the dependent variable, increasing age (years, B = −0.63, P < .001) and history of ischaemic stroke (B = −10.06, P = .0038) were negative predictors of shunt surgery outcome after controlling for waiting time for surgery, symptom severity at preoperative control, presence of diabetes mellitus, hypertension, hyperlipidaemia, history of myocardial infarction, duration of symptoms and shunt complications. Conclusions:High age and established cerebrovascular disease are associated with less favourable outcome after shunt surgery in patients with iNPH.
Background Lumbar punctures are a common examination in the work-up of patients with idiopathic normal pressure hydrocephalus (iNPH) and cerebrospinal fluid (CSF) biomarkers should therefore be available for use in selection of shunt candidates. The aim of this study was to investigate if CSF biomarkers are associated with outcome after shunt surgery alone or in combination with comorbidity and imaging markers, and investigate associations between CSF biomarkers and symptoms. Methods Preoperative CSF biomarkers were analyzed in 455 patients operated with shunt surgery for iNPH at a single center during 2011–2018. Symptoms before and 12 months after shunt surgery were graded with the Swedish iNPH scale. Neurofilament light chain protein (NfL), total tau (T-tau), phosphorylated tau (P-tau) and amyloid beta1-42 (Aβ1-42) CSF levels were measured. Evans’ index and disproportionately enlarged subarachnoid space hydrocephalus were measured on preoperative CT-scans. Preoperative evaluation and follow-up 12 months after shunt surgery were available in 376 patients. Results Higher levels of NfL and T-tau were associated with less improvement after shunt surgery (β = − 3.10, p = 0.016 and β = − 2.45, p = 0.012, respectively). Patients whose symptoms deteriorated after shunt surgery had higher preoperative levels of NfL (1250 ng/L [IQR:1020–2220] vs. 1020 [770–1649], p < 0.001) and T-tau (221 ng/L [IQR: 159–346] vs. 190 [135–261], p = 0.0039) than patients with postoperative improvement on the iNPH scale. Among the patients who improved ≥ 5 levels on the iNPH scale (55%), NfL was abnormal in 22%, T-tau in 14%, P-tau in 6% and Aβ1-42 in 45%, compared with normal reference limits. The inclusion of CSF biomarkers, imaging markers and comorbidity in multivariate predictive Orthogonal Projections to Latent Structures (OPLS) models to did not improve predictability in outcome after shunt surgery. Conclusions Higher levels of T-tau and NfL were associated with a less favorable response to shunt surgery, suggesting a more active neurodegeneration in this group of patients. However, CSF levels of these biomarkers can be elevated also in patients who respond to shunt surgery. Thus, none of these CSF biomarkers, alone or used in combination, are suitable for excluding patients from surgery.
Background Hemangioblastomas of the central nervous system are a prominent feature of von Hippel-Lindau-disease (vHL). Hemangioblastomas are known to secrete vascular endothelial growth factor (VEGF), suggesting a potential role of VEGF as a biomarker for tumor growth. Methods Plasma VEGF samples from 24 patients with von Hippel-Lindau disease were analyzed by solid-phase proximity ligation assay (PLA). Levels were monitored over time together with numeric and volumetric CNS tumor burden, and compared to plasma VEGF levels in healthy controls. Results The mean yearly progression in tumor volume was 65.5%. Yearly risk of developing one or several new CNS tumor(s) was 50%. No significant correlation between tumor burden and levels of VEGF was seen. VEGF levels in patients (31.55–92.04; mean 55.83, median 56.41) as measured by immunodetection in a solid-phase PLA did not differ significantly from controls (37.38–104.56; mean 58.89, median 54.12) (p = 0,266). Conclusion The increase in total CNS tumor volume in vHL occurred in a saltatory manner. The risk of developing a new lesion was 50% per year. We found no evidence for VEGF secretion from CNS hemangioblastomas in vHL in circulating blood. Other potential biomarkers should be explored to assess progression of tumor burden in vHL.
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