Redefining migraine prevention: early treatment with anti-CGRP monoclonal antibodies enhances response in the real world.

BACKGROUND: Anti-CGRP monoclonal antibodies (anti-CGRP MAbs) are approved and available treatments for migraine prevention. Patients do not respond alike and many countries have reimbursement policies, which hinder treatments to those who might respond. This study aimed to investigate clinical factors associated with good and excellent response to anti-CGRP MAbs at 6 months. METHODS: European multicentre, prospective, real-world study, including high-frequency episodic or chronic migraine (CM) patients treated since March 2018 with anti-CGRP MAbs. We defined good and excellent responses as ≥50% and ≥75% reduction in monthly headache days (MHD) at 6 months, respectively. Generalised mixed-effect regression models (GLMMs) were used to identify variables independently associated with treatment response. RESULTS: Of the 5818 included patients, 82.3% were females and the median age was 48.0 (40.0-55.0) years. At baseline, the median of MHD was 20.0 (14.0-28.0) days/months and 72.2% had a diagnosis of CM. At 6 months (n=4963), 56.5% (2804/4963) were good responders and 26.7% (1324/4963) were excellent responders. In the GLMM model, older age (1.08 (95% CI 1.02 to 1.15), p=0.016), the presence of unilateral pain (1.39 (95% CI 1.21 to 1.60), p<0.001), the absence of depression (0.840 (95% CI 0.731 to 0.966), p=0.014), less monthly migraine days (0.923 (95% CI 0.862 to 0.989), p=0.023) and lower Migraine Disability Assessment at baseline (0.874 (95% CI 0.819 to 0.932), p<0.001) were predictors of good response (AUC of 0.648 (95% CI 0.616 to 0.680)). These variables were also significant predictors of excellent response (AUC of 0.691 (95% CI 0.651 to 0.731)). Sex was not significant in the GLMM models. CONCLUSIONS: This is the largest real-world study of migraine patients treated with anti-CGRP MAbs. It provides evidence that higher migraine frequency and greater disability at baseline reduce the likelihood of responding to anti-CGRP MAbs, informing physicians and policy-makers on the need for an earlier treatment in order to offer the best chance of treatment success.

Therapeutic Cerebral Fluid Puncture in Patients with Idiopathic Intracranial Hypertension: No Short-Term Effect on Neurocognitive Function.

BACKGROUND: Idiopathic intracranial hypertension (IIH) is typically characterized by headaches and vision loss. However, neurocognitive deficits are also described. Our study aimed to test the influence of therapeutic lumbar puncture on the latter. METHODS: A total of 15 patients with IIH were tested with a battery of neurocognitive tests at baseline and after therapeutic lumbar drainage. Hereby, Logical Memory of the Wechsler Memory Scale-Revised Edition (WMS-R), the California Verbal Learning Test Short Version (CVLT), alertness, selective attention, and word fluency were used. Changes in cognitive functioning in the course of CSF pressure lowering were analysed and compared with age, sex, and education-matched healthy controls. RESULTS: Before intervention, scores of Logical Memory, the RWT, and the HADS-D were significantly lower in IIH patients compared to matched controls. After short-term normalization of CSF pressure, the RWT improved significantly. Additionally, significant positive correlations were found between headache intensity and subjective impairment, as well as between BMI and CSF opening pressure. CONCLUSIONS: Our findings confirm lower performance in terms of long-term verbal memory and word fluency compared to controls, as well as depressive symptoms in IIH patients. Significant improvement after short-term normalization of intracranial pressure by means of CSF drainage was seen only for word fluency. This indicates that short-term normalization of CSF pressure is not sufficient to normalize observed neurocognitive deficits.

The Impact of Postoperative Tumor Burden on Patients With Brain Metastases.

Background: Brain metastases were considered to be well-defined lesions, but recent research points to infiltrating behavior. Impact of postoperative residual tumor burden (RTB) and extent of resection are still not defined enough. Patients and Methods: Adult patients with surgery of brain metastases between April 2007 and January 2020 were analyzed. Early postoperative MRI (<72 h) was used to segment RTB. Survival analysis was performed and cutoff values for RTB were revealed. Separate (subgroup) analyses regarding postoperative radiotherapy, age, and histopathological entities were performed. Results: A total of 704 patients were included. Complete cytoreduction was achieved in 487/704 (69.2%) patients, median preoperative tumor burden was 12.4 cm3 (IQR 5.2-25.8 cm3), median RTB was 0.14 cm3 (IQR 0.0-2.05 cm3), and median postoperative tumor volume of the targeted BM was 0.0 cm3 (IQR 0.0-0.1 cm3). Median overall survival was 6 months (IQR 2-18). In multivariate analysis, preoperative KPSS (HR 0.981982, 95% CI, 0.9761-0.9873, p < 0.001), age (HR 1.012363; 95% CI, 1.0043-1.0205, p = 0.0026), and preoperative (HR 1.004906; 95% CI, 1.0003-1.0095, p = 0.00362) and postoperative tumor burden (HR 1.017983; 95% CI; 1.0058-1.0303, p = 0.0036) were significant. Maximally selected log rank statistics showed a significant cutoff for RTB of 1.78 cm3 (p = 0.0022) for all and 0.28 cm3 (p = 0.0047) for targeted metastasis and cutoff for the age of 67 years (p < 0.001). (Stereotactic) Radiotherapy had a significant impact on survival (p < 0.001). Conclusions: RTB is a strong predictor for survival. Maximal cytoreduction, as confirmed by postoperative MRI, should be achieved whenever possible, regardless of type of postoperative radiotherapy.