Role of acetazolamide in treatment of patients with menstrual migraine

Objective: According to the ICHD-3 criteria, menstrual migraine (MM) is divided into two groups: pure menstrual migraine (PMM) and menstrually-related migraine (MRM). The present study aimed to evaluate and compare the severity of headache using a visual analog scale (VAS) and the effect on quality of life using the Headache Impact Test (HIT) and Migraine Disability Assessment (MIDAS) tests before and after 3 months of treatment in using short-term prophylaxis with acetazolamide. Methods: Patients who presented to the headache outpatient clinic of the neurology department with a diagnosis of MM were retrospectively reviewed. Acetazolamide was given at a dosage of 500 mg daily for 5 days starting two days before the predicted onset of the menstrual cycle as a short-term prophylactic treatment. VAS, MIDAS, and HIT assessments were performed before and after treatment. Results: A total of 26 patients with PMM and 26 patients with MRM were identified. After acetazolamide treatment, statistically significant improvement was found in MIDAS, VAS and HIT scores in both groups of patients. The post-treatment MIDAS score was significantly lower in the MRM group, but there was no significant difference in post-treatment VAS and HIT scores between the groups. Conclusion: Using acetazolamide for short-term prophylaxis in patients with MM leads to decreased severity and frequency of headache and improvement in quality of life. The study is the first in the literature to use acetazolamide for short-term prophylaxis in patients diagnosed with MM.

Acute and Preventive Management of Migraine during Menstruation and Menopause

Migraine course is influenced by female reproductive milestones, including menstruation and perimenopause; menstrual migraine (MM) represents a distinct clinical entity. Increased susceptibility to migraine during menstruation and in perimenopause is probably due to fluctuations in estrogen levels. The present review provides suggestions for the treatment of MM and perimenopausal migraine. MM is characterized by long, severe, and poorly treatable headaches, for which the use of long-acting triptans and/or combined treatment with triptans and common analgesics is advisable. Short-term prophylaxis with triptans and/or estrogen treatment is another viable option in women with regular menstrual cycles or treated with combined hormonal contraceptives; conventional prevention may also be considered depending on the attack-related disability and the presence of attacks unrelated to menstruation. In women with perimenopausal migraine, hormonal treatments should aim at avoiding estrogen fluctuations. Future research on migraine treatments will benefit from the ascertainment of the interplay between female sex hormones and the mechanisms of migraine pathogenesis, including the calcitonin gene-related peptide pathway.

Short-term prophylaxis for children and adolescents with hereditary angioedema

Background: Hereditary Angioedema (HAE) is a rare, autosomal dominant, life threatening disease, secondary to the deficiency of C1-inhibitor, dysfunction of C1-inhibitor or inadequate control of the contact pathway. Presentation includes recurrent swelling of the skin, upper airway and the abdomen. Trauma can precipitate attacks, which in the airway can lead to asphyxia. For this reason, short term prophylaxis (STP) may be indicated before medical, surgical and dental procedures. The goal of the manuscript is to review short term prophylaxis for children of all ages. Methods: We searched the following search words: children, pediatric, adolescent, plasma derived C1-inhibitor, recombinant C1-inhibitor, surgery, medical procedures, prophylaxis, dental, Hereditary Angioedema, tranexamic acid, androgens, fresh frozen plasma, short term prophylaxis, lanadelumab, subcutaneous C1-inhibitor in Google Scholar and in PubMed to develop our results. Results: STP should be discussed at every visit. Plans should be individualized based upon the procedure, therapies available and shared decision making with patient/parent. For high risk procedures plasma derived C1-inhibitor should be used at 20 units/kg just prior to the procedure. Alternative agents for STP include recombinant C1-inhibitor, fresh frozen plasma, androgens, or tranexamic acid. In all cases, with or without the use of STP, 2 doses of on-demand therapy should be available in case of an attack. Conclusion: Herein, we review the published data on STP for pediatric patients with HAE and discuss first-line options, and off label use of medications, as well as review the guidelines pertaining to short term prophylaxis.

Prophylactic management of patients with von Willebrand disease

Von Willebrand disease, the most common inherited bleeding disorder that affects both males and females, is due to quantitative or qualitative defects of the multimeric glycoprotein von Willebrand factor, which cause mucous membrane bleeding but also soft tissue bleeding owing to the secondary deficiency of factor VIII. The aim of treatment is to correct this dual defect of hemostasis. In addition to the episodic management of bleeding episodes, therapy includes their short- or long-term prevention. Short-term prophylaxis is mainly warranted in order to provide effective hemostatic coverage to patients undergoing surgery or invasive procedures and to affected women at the time of delivery or during menstruations associated with excessive bleeding. The aim of long-term prophylaxis is to prevent bleeding in particular categories of patients at increased risk of frequent and spontaneous bleeding in the joints, nose, and gastrointestinal tract.

Short-term Prophylaxis for Delivery in Pregnant Women with Hereditary Angioedema with Normal C1-Inhibitor

Objective To verify the efficacy of short-term prophylaxis for vaginal or cesarean section childbirth with plasma-derived C1-inhibitor concentrate in pregnant women. They should have hereditary angioedema (HAE) and normal plasma C1-inhibitor. Methods Case report of pregnant women diagnosed with HAE with normal C1-inhibitor who had been treated with intravenous C1-inhibitor concentrate for prophylaxis of angioedema attacks when hospitalized for delivery. The exon 9 of the Factor 12 (F12) genotyping gene was performed by automatic sequencing in all patients. Results Three cases of pregnant women with HAE with normal serum level of C1-inhibitor are reported. The genetic test detected the presence of a pathogenic mutation in the F12 gene. Deliveries occurred uneventfully and patients had no HAE symptoms in the following 72 hours. Conclusion C1-inhibitor concentrate could be useful to prevent angioedema attacks during and after delivery.

Triggers and short-term prophylaxis in patients with hereditary angioedema

Background: Hereditary angioedema (HAE) is a rare disease that affects 1 in 60,000; however, despite being extremely rare, the severity of the disease can cause significant limitations to quality of life. In addition, attacks can be fatal and require urgent care. Methods: We searched PubMed and Google for Hereditary Angioedema and prophylaxis, short term prophylaxis, surgery, medical procedures, dental work, triggers. Results: The main triggers are estrogens, Angiotensin Converting Enzyme Inhibitors (ACI) inhibitors, trauma, dental work, stress, surgery, manipulation of the upper airway, and medical procedures. Prophylaxis is often used long term to prevent attacks; before known triggers, prophylaxis is referred to as short-term prophylaxis (STP). When to initiate STP, what to use, and what dose to use have not been adequately researched, but there is consensus that, whenever the upper airway is manipulated, STP is essential. In addition, consensus has been reached that an IV C1 inhibitor is the preferred STP agent, and it is my opinion that dosing at 20 units/kg allows dosing for all ages and also allows average-size adults to receive >1000 units because failures at 1000 units have been documented in the literature. Conclusions: This article focused on triggers and preprocedural STP and not on pre-event STP, which is often used before important life events; however, medications and dosing are the same for pre-event prophylaxis.

Isavuconazole Prophylaxis during Early Phases of Allogeneic HSC Transplantation Is Not Associated to an Increase Need of Cyclosporin-a Dose Modification

Background: Isavuconazole is an effective treatment of invasive fungal infections (IFI). Since its broad spectrum of activity and favorable toxicity, it could also be used as a prophylaxis. Experience in use of isavuconazole as prophylaxis of IFI is, however, limited. In allogeneic transplant setting, its feasibility should also be assessed in regard of changes of Cyclosporine (CYA) metabolism. Aim: To evaluate feasibility of the administration of Isavuconazole as short term prophylaxis during early phase of allogeneic transplantation and to study its influence on CYA trough blood levels and CYA dosing. Methods: In a prospective study from July 2017 to April 2019, we treated 34 HSC transplantation using Isavuconazole (ISA) prophylaxis, ISA was administered at dosage of 200 mg /day i.v. (with a loading-dose of 200 mg x 3 /days for the first 48 hours) from day + 2 after HSCT infusion and until day + 30. The patients were selected using the criteria: any underlying diagnosis; age 18-70; any type of allogeneic donor; GVHD prophylaxis including CYA i.v.. Blood trough levels of CYA were measured bi-weekly by ELISA. Blood CYA level was maintained between 100 - 300 mcg/ml by dose adjustment. The need for CYA dose modification, IFI rate and patient outcome (TRM, OS) was studied and compared to an historical control group who received prophylaxis using Fluconazole during day +2 to day +30 (n 29). Results: Groups receiving Isavuconazole or Fluconazole were not significanly different in diagnosis, age, sex, disease status at transplant, donor type, stem cell-source, GVHD-prophylaxis and conditioning regimen. No patients in the Fluco-group had a previous invasive fungal infection (IFI), while 2 patients had a previously IFI in the Isa-group. All patients reached engraftment, neutrophils engraftment was reached in a mean of 19 days and 18 days in the Isa and Fluco-group, respectively. No IFI occurred in the fluco-group, while 1 proven IFI (Blastoschyzomyces Capitatus blood-stream infection) occurred in the Isa-group. Mucositis occurred in 56 patients (88%). Mucositis grade III-IV grade of was registered in 62% and 61%, in the Isa- and Fluco-Group respectively. Isavuconazole was well tolerated, without significant toxicity, no patient needed dose-reduction or suspension. Mean values of trough CyA blood-levels were compared at for 1st, 2nd, 3rd and 4th week and no difference was found between the two groups (Mann Whitney U test p value: 0.2, 0.5, 0.8, 0.9 respectively for 1st, 2nd, 3rd and 4th week), Fig 1. Mean number of CYA-dose adjustments was 1.3 /patient in Isa-group and 1.2/patient in Fluco-group. Difference was not significant (p = 0.6, Mann-Whitney U-test). Overall survival (OS) at 1 year was 64 % in Fluco-group (95% CI: 44-79%) and 66% in Isa-group (95% CI: 44-81%) (log-rank, p value: 0.9). Non-relapse mortality (NRM) at 1 year was 16.3% (95% CI: 5.7-31%) in Isa-group and 14.2% (95% CI:4.3-29%) in Fluco-group (Gray test, p: 0.61). Conclusions: In this prospective study, short term prophylaxis using Isavuconazole, after allogeneic HSC transplant, was found to be feasible. No significant difference with standard fluconazole prophylaxis was found in trough CYA blood levels and in the need of cyclosporin dose modification. Further studies are needed extending the lenght of Isavuconazole prophylaxis. Figure 1 Disclosures No relevant conflicts of interest to declare.