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.

Are there differences between patients with unifocal nummular headache and those who progress to bifocal nummular headache? A retrospective observational study.

OBJECTIVES: This retrospective observational cohort study aimed to compare clinical characteristics and treatment responses in patients exclusively experiencing unifocal nummular headache (NH) with those who develop the bifocal variant. METHODS: A retrospective study was conducted on patients diagnosed with NH who attended a neurology (headache) outpatient clinic between January 2018 and December 2022. The cohort was divided into two groups: Group 1, exclusive unifocal NH; and Group 2, those developing a secondary focal area of pain, i.e., bifocal NH. Data were collected on demographic characteristics, clinical features, other headache comorbidities, and treatment-related information. RESULTS: A total of 23 patients were included in this study: 12 were categorized as unifocal NH (Group 1) and 11 as bifocal NH (Group 2). There were no differences between the two groups in terms of demographic characteristics, clinical features, or treatment response. Nonetheless, patients with bifocal NH exhibited spontaneous remission rates in the first pain area when compared to the unifocal NH group, with statistically significant differences (36% vs. 0%, p = 0.020). CONCLUSION: In our sample, patients with bifocal NH demonstrated spontaneous remission rates in the initial pain area, a phenomenon not observed in patients with unifocal NH. It is worth noting the limited sample size in the present study, highlighting the need for larger cohorts to validate and further explore our findings.

Heparin-Bonded Expanded Polytetrafluoroethylene Is a Solution for Infrapopliteal Revascularization in the Absence of an Adequate Autologous Vein Graft.

BACKGROUND: To analyze the outcomes of heparin-bonded expanded polytetrafluoroethylene (HePTFE) graft as an alternative conduit in infrapopliteal revascularization of chronic limb-threatening ischemia (CLTI) in the absence of an autologous vein conduit. METHODS: A single-center retrospective analysis of patients with CLTI submitted to infrapopliteal bypasses with autologous vein graft (VEIN group) or HePTFE graft (HePTFE group) was implemented. Primary end points were freedom from CLTI at 12 months and recurrence of CLTI at 3 years. Secondary end points included freedom from major amputation, amputation-free survival (AFS), survival, and primary (PP) and secondary patency (SP) rates at 3 years of follow-up. RESULTS: A total of 348 limbs submitted to infrapopliteal bypasses, 214 with venous graft and 134 with HePTFE graft, were followed-up for a median of 25 months. Most patients of the HePTFE group were male (69%), with a median age of 76 years (interquartile range [IQR] 15). Fifty-nine percent of the limbs of the HePTFE group had Wound grade ≥2, being 46% of them infected. Eighty-eight percent were GLASS stage III. Freedom from CLTI was not significantly different between HePTFE and VEIN groups (75% vs. 84%, adjusted hazard ratio [aHR] 0.88, confidence interval [CI] 0.66-1.18, P = 0.401). Recurrence of CLTI was higher in the HePTFE group (42% vs.18% at 3 years; aHR 2.82, CI 1.59-5.00, P < 0.001). The VEIN group achieved higher rates of freedom from major amputation (87% vs.69% at 3 years; aHR 2.21, CI 1.31-3.75, P = 0.003) and AFS (59% vs. 37% at 3 years; aHR 1.39, CI 1.02-1.88, P = 0.036), but no significance in survival (aHR 1.10, CI 0.72-1.66, P = 0.667). Patency rates were inferior in the HePTFE group, with 2-year PP and SP rates of 52% vs. 74%, and 76% vs. 90%, respectively (PP: aHR 1.70, CI 1.11-2.59, P = 0.014; SP: aHR 2.51, CI 1.42-4.42, P = 0.001). CONCLUSIONS: Infrapopliteal bypass with autologous vein graft is the gold standard to treat CLTI limbs. HePTFE graft should be regarded as an alternative for complex infrapopliteal revascularization when lacking an autologous vein conduct.

The Role of Neurohospitalism in a Specialized Cardiovascular Hospital.

INTRODUCTION: Cardiology and cardiothoracic surgery are among the specialties that most commonly require neurology inpatient consultations. We aimed to study the neurology referrals by the cardiovascular-specialized hospital included in our tertiary hospital center. METHODS: Retrospective study of consecutive patients referred for neurology inpatient consultation between January 1, 2020, and December 31, 2022. We analyzed referrals, patients' characteristics, and the approach taken. A detailed subanalysis was performed for patients diagnosed with acute ischemic stroke (AIS). RESULTS: 143 patients were observed (mean age 67.3 years, 46 [32.2%] females). Most frequent referral reasons were suspected AIS deficits (39.2%), altered mental status (19.6%), suspected seizures (13.3%), and neuroprognostication (11.9%). Mean referral-to-consult time was 2.7 days, and 117 (81.8%) consults were in-person. Additional investigation, treatment changes, and outpatient clinic referral were proposed, respectively, in 79.7%, 60.1%, and 19.6% of patients. Most common diagnoses were AIS (45.5%), hypoxic-ischemic encephalopathy (18.9%), and delirium (7.0%). Regarding patients with AIS (n = 62), most common stroke causes were post-cardiac procedure (44.6%), infective endocarditis (18.5%), aortic dissection (10.8%), acute myocardial infarction (10.8%), and anticoagulant withdrawal in patients with atrial fibrillation (6.2%). Thirty-four AIS patients were diagnosed less than 24 h since last seen well, of which four (6.2%) were treated (three with thrombolysis and one with mechanical thrombectomy). CONCLUSION: AIS is the most common reason for referral in our cardiovascular hospital. Our results highlight the importance of the availability of a neurologist/neurohospitalist with stroke expertise for consultation of inpatients admitted in a specialized cardiovascular hospital.

Evaluation of global limb anatomic staging system for patients with chronic limb-threatening ischemia treated with autogenous bypass grafts.

OBJECTIVE: We evaluated the relationship of the global limb anatomic staging system (GLASS) stage with the clinical outcomes for patients with chronic limb-threatening ischemia (CLTI) who had undergone distal bypass with vein grafting. METHODS: We performed a single-center, retrospective analysis of patients with CLTI who had undergone distal bypass with vein grafting from January 2012 to December 2019. The primary end point was freedom from CLTI, including amputation-free survival, complete wound healing, and no ischemic rest pain. The secondary end points included a composite outcome of recurrence (patients who had achieved freedom from CLTI but had developed a new wound or ischemic rest pain), major limb amputation, amputation free-survival, overall survival, major adverse limb events, limb-based patency, and primary and secondary patency rates. RESULTS: A total of 190 patients had undergone 211 distal bypasses with a median follow-up of 30 months. Of these patients, 80% had had diabetes or end-stage renal disease requiring dialysis. Most patients (63%) had experienced major or extensive tissue loss (WIfI [wound, ischemia, foot infection] wound class ≥2), and more than one half of these had had some degree of infection of the foot. A severe anatomic pattern (GLASS stage III) was predominant, with a prevalence of 78%. No significant differences were found between GLASS stage I and II and GLASS stage III groups for all the outcomes analyzed. Approximately 80% of the 211 revascularized limbs were free of CLTI at 12 months after treatment. At 4 years of follow-up, we observed that 25% of the patients had had CLTI recurrence, 83% were free from major amputation, and 61% were free from major adverse limb events. Limb-based patency, primary patency, and secondary patency were 79%, 80%, and 93% at 1 year and 64%, 65%, and 81% at 4 years, respectively. CONCLUSIONS: The GLASS stage was not related to patency or the clinical outcomes after distal bypass with vein grafting. Distal open revascularization resulted in excellent rates of freedom from CLTI with low rates of CLTI recurrence, two key time-integrated outcomes of clinical disease severity for patients with CLTI.

Clinical pattern and response to treatment of primary stabbing headache: Retrospective case series study from a Portuguese tertiary hospital.

OBJECTIVES: This retrospective case series study aimed to investigate the demographic and clinical patterns of primary stabbing headache (PSH). In addition, we tried to identify subgroups of treatment responses in a neurology outpatient consultation at a Portuguese tertiary hospital. METHODS: Clinical records were retrospectively reviewed and patients meeting the International Classification of Headache Disorders, 3rd edition, criteria for PSH were identified from January 2014 to December 2020. We collected data regarding demographic characteristics, clinical features of the headache, primary headache comorbidities, and information about treatment-related do PSH. RESULTS: Of 1857 patients, 32 (1.7%; mean [SD] age of onset 56 [3.5] years) had the final diagnosis of PSH. Regarding headache characteristics, 20 patients (62.5%) reported episodes of stabbing in fixed locations and 12 (37.5%) in multiple areas; the duration of each attack was between ≤5 s (seven [21.9%]), 5-60 s (20 [62.5%]), and ≥60 s (five [15.6%]). In all, 18 patients (56.3%) had an episodic course (vs. six of 32 [18.8%] an acute course and eight of 32 [25%] a chronic course). In all, 17 patients started medical treatment (53.1%), with total or partial improvement in 10 (58.8%) of them. It was found that patients with pain in fixed locations had a better response to treatment when compared to patients with multiple locations, in a statistically significant way (eight of 11 vs. two of six, p = 0.023). CONCLUSION: In our sample, the mean age of onset of PSH was >50 years and there was a wide range of PSH duration. The duration of each attack (>5 s), the pain in fixed locations, non-daily episodes of the pain in each attack, and the intermittent course of headache were the most prevalent clinical features. Finally, patients with stabbing in localized areas had a better response to treatment.

REM sleep absence in patients referred to polysomnography for REM sleep behavior disorder.

Detection of REM sleep behavior disorder (RBD) with polysomnography (PSG) is relevant for the diagnosis of α-synucleinopathies. However, some patients referred for suspicion of RBD do not present REM sleep at PSG (NoREMSusRBD), rendering the study inconclusive. Our objective was to investigate disorders possibility associated with REM sleep absence in patients referred to PSG for investigation of RBD, in particular α-synucleinopathies. A sleep-lab database was revised to select NoREMSusRBD (n = 15) and patients: with no REM sleep referred for suspicion of other sleep disorder (NoREMSusOther, n = 28); referred for RBD suspicion with negative PSG (NegativeRBD, n = 24); α-synucleinopathies with no REM sleep (NoREMα, n = 23) and idiopathic RBD (iRBD, n = 26). NoREMSusRBD patients were compared with the other groups regarding PSG data and the emergence of prodromal features or established criteria for α-synucleinopathy. Severe Obstructive Sleep Apnea (OSA) was significantly more frequent in the NoREMsusRBD compared to the NoREMα and iRBD groups. No patient in the NoREMSusRBD developed a α-synucleinopathy (2 cases on the iRBD group). The prevalence of prodromal features in NoREMSusRBD (n = 7, 46.7%) was similar to that of iRBD (n = 18, 69.2%) and significantly higher than in the other groups. Apnea-Hypopnea Indices (AHI) were significantly higher in the NoREMSusRBD compared with iRBD and NoREMα. Our study suggests that the absence of REM sleep in NoREMSusRBD could be caused by OSA but does not exclude the possibility of underlying α- synucleinopathy, suggested by an increased prevalence of prodromal features. These data support the need for excluding OSA in patients suspected for RBD and recommends follow-up of NoREMSusRBD patients to uncover a possible α- synucleinopathy.

Headache Phenotypes in Idiopathic Intracranial Hypertension and Its Short-Term Outcomes: A Retrospective Case Series Study.

Background: Idiopathic intracranial hypertension (IIH) presents a complex physiopathology, leading into diverse manifestations, notably variable headache phenotypes. Furthermore, its frequent overlap with migraine complicates the evaluation of treatment benefit for IIH-related headache. Our aim was to investigate if there is any relationship between demographic factors, clinical patterns of headache, treatment response, and headache short-term outcome with the headache phenotype of IIH. Methods: This study was a retrospective analysis of demographic, clinical, and treatment features of patients with idiopathic intracranial hypertension presenting with headache and evaluation of headache outcomes in the first 12 months following treatment. Results: Thirty-two patients were included (median age of onset 29.0 years (interquartile range 25.0 - 38.5), 90% females, median body mass index 32.5 kg/m2; 87.5% (n = 28) with papilledema; median cerebrospinal fluid opening pressure 36.5 cm H2O). Patients presented with migraine (n = 11, 34.4%), tension-type (n = 9, 28.1%), or a not-classifiable headache (n = 12, 37.5%). Regarding treatment and short-term follow-up (12 months), there was a failure of medical treatment in 43.8% (n = 14) and a reduction of headaches (≥ 50%) in 62.5% (n = 20) of the patients. Among headache phenotypes, there were no significant differences regarding demographics, clinical features, clinical patterns, or treatment response at baseline. Also, there were no differences regarding response to treatment or headache outcomes in 1, 3, 6, and 12 months of follow-up. Conclusions: In our study, migraine and unclassifiable types were the most commonly reported headache phenotypes. Headache phenotype does not appear to be an essential factor in allowing clinical distinction, treatment response, or predicting the short-term headache outcome of this intriguing entity.

Infrapopliteal Bypass In Patients On Dialysis: Patency And Survival.

INTRODUCTION: Portugal has one of the highest prevalence of patients on a regular dialysis program. This population has a higher incidence of peripheral arterial disease with higher rates of postoperative morbidity and mortality. Our goal was to compare outcomes between dialysis and non-dialysis patients with chronic limb threatening ischemia (CLTI) submitted to infrapopliteal bypass. MATERIALS AND METHODS: A retrospective single-center study of infrapopliteal bypass for CLTI was performed between 2012 and 2019. Patients were divided in two groups based on dialysis status (group 1 incorporated patients on dialysis). Primary end point was 1-year freedom from CLTI. Secondary end points were limb-salvage, survival and primary (PP) and tertiary patency (TP) rates at 3 years of follow-up. RESULTS: A total of 352 infrapopliteal bypasses were performed in 310 patients with CLTI. Fourteen percent of the revascularizations were performed on dialysis patients (48/352). Median age was 73 years (interquartile range - IQR 15) and 74% (259/352) were male. Median follow-up was 26 months (IQR 42). Overall, 92% (325/352) had tissue loss and 44% (154/352) had some degree of infection. The majority of revascularization procedures were performed with vein grafts (61%, 214/352). The 30-day mortality was 4% (11/310), with no difference between groups (p = 0.627). Kaplan-Meier analysis showed no difference between groups regarding freedom from CLTI (76% vs. 79%; HR 0.96, CI 0.65-1.44, p=0.857), limb-salvage (70% vs. 82%; HR 1.40, CI 0.71-2.78, p=0.327) and survival (62% vs. 64%; HR 1.08, CI 0.60-1.94, p=0.799). PP rates were 39% in group 1 and 64% in group 2 (HR 1.71, CI 1.05-2.79, p=0.030). TP rates were not different between groups (57% and 78%; HR 1.79, CI 0.92-3.47, p=0.082). CONCLUSION: Infrapopliteal bypass for CLTI, on dialysis patients, resulted in lower PP rates. No differences were observed in freedom from CLTI, TP, limb salvage and survival.

[Conventional open surgery of a splenic artery aneurysm following failure of endovascular management]. / Tratamento cirúrgico convencional de um aneurisma da artéria esplénica após fracasso de intervenção endovascular.

The clinical case of a 73 years old man is reported, complaining for a long time of a persistent abdominal pain in the left upper quadrants, without irradiation and no identified causative factor. These symptoms affected notoriously his quality of life, becoming disabling for his social and professional activities. The investigation by means of CT-scans disclosed a spheric mass, partially calcified, having 44x41mms of maximum size, located between the pancreatic tail and the splenic hilum. A subsequent angio-CT confirmed the diagnosis of a large splenic artery aneurysm and the patient underwent the attempt of an endovascular exclusion by means of an endoprosthesis, which could not be successfully accomplished due to the multiple kinkings and coilings of the splenic artery. Several coils were then used to occlude the aneurismal sac. Contrarily to the expectations, the pain did not disappear after the procedure, becoming even worse, and an open surgical approach was then advised, in another hospital institution, which he promptly accepted. The operation consisted in the resection of the aneurysm and an associated splenectomy, due to multiple infarcts identified in the spleen, consequence of the previous endovascular management. The post operative course was uneventful and he was discharged on day 3. One and four months later he was found in excellent condition and totally pain-free, having resumed his social and professional activities. Based on this clinical case, the authors intend to put an emphasis on this constraint of the endovascular management of peripheral arterial aneurysms, namely on those causing external compression syndromes, painful or others, which can not be relieved by the endovascular exclusion of the aneurysm, as it happened with this patient, thus justifying its presentation and dissemination.

An Epithelioid Hemangioma Camouflaged As Radial Aneurysm.

Epithelioid hemangioma (EH) is an uncommon benign vascular lesion usually present as subcutaneous nodules in the head and neck area. Sometimes, these lesions can occur in the peripheral arteries, and when they do, they can be mistaken for aneurysmal dilatations of that respective vessel. We report a case of a 43-year-old male who underwent surgical recession of a radial aneurysm, which after anatomopathological examination, revealed an EH.

Proteomics to Identify New Blood Biomarkers for Diagnosing Patients With Acute Stroke.

Background Blood biomarkers are a potential tool for early stroke diagnosis. We aimed to perform a pilot and exploratory study on untargeted blood biomarkers in patients with suspected stroke by using mass spectrometry analysis. Methods and Results This was a prospective observational study of consecutive patients with suspected stroke admitted within 6 hours of last being seen well. Blood samples were collected at admission. Patients were divided into 3 groups: ischemic stroke (IS), intracerebral hemorrhage (ICH), and stroke mimics. Quantitative analysis from mass spectrometry data was performed using a supervised approach. Biomarker-based prediction models were developed to differentiate IS from ICH and ICH+stroke mimics. Models were built aiming to minimize misidentification of patients with ICH as having IS. We included 90 patients, one-third within each subgroup. The median age was 71 years (interquartile range, 57-81 years), and 49 participants (54.4%) were women. In quantitative analysis, C3 (complement component 3), ICAM-2 (intercellular adhesion molecule 2), PLGLA (plasminogen like A), STXBP5 (syntaxin-binding protein 5), and IGHV3-64 (immunoglobulin heavy variable 3-64) were the 5 most significantly dysregulated proteins for both comparisons. Biomarker-based models showed 88% sensitivity and 89% negative predictive value for differentiating IS from ICH, and 75% sensitivity and 95% negative predictive value for differentiating IS from ICH+stroke mimics. ICAM-2, STXBP5, PLGLA, C3, and IGHV3-64 displayed the highest importance score in our models, being the most informative for identifying patients with stroke. Conclusions In this proof-of-concept and exploratory study, our biomarker-based prediction models, including ICAM-2, STXBP5, PLGLA, C3, and IGHV3-64, showed 75% to 88% sensitivity for identifying patients with IS, while aiming to minimize misclassification of ICH. Although our methodology provided an internal validation, these results still need validation in other cohorts and with different measurement techniques.