Migraines represent one of the most prevalent and debilitating neurological disorders. In terms of quality-of-life impairment and the degree of disability incurred, severe migraine attacks align with the World Health Organization (WHO) level 7 disability, comparable to conditions such as tetraparesis, psychosis, and dementia. The severity of migraine attacks is influenced not only by the intensity of the headache but also by the severity of accompanying non-pain symptoms, which include nausea, vomiting, photophobia, phonophobia, dizziness, and cognitive impairment, as well as the frequency of recurrence. The presence of nausea or vomiting during a migraine attack is indicative of migraine-associated gastroparesis, which adversely affects the bioavailability and efficacy of oral medications. Consequently, these factors contribute to the limited effectiveness of standard tablet formulations in aborting migraine attacks. This article explores contemporary approaches to treating migraine attacks and new criteria for assessing therapeutic efficacy. Particular emphasis is placed on the effectiveness of orally disintegrating tablets (ODT) of rizatriptan compared with sumatriptan and zolmitriptan. Optimal management of a migraine attack necessitates an individualized approach that considers the severity of the condition, the spectrum of clinical manifestations, and the selection of an appropriate pharmaceutical formulation. Strong evidence supports the assertion that rizatriptan 10 mg ODT (Kaporiza) is one of the most rapid, effective, and convenient options for the abortive treatment of migraine attacks in the majority of patients.

Post-dural puncture headache (PDPH) is a common complication of neuraxial anesthesia, particularly in the obstetric population, where its incidence is higher due to the frequent use of epidural techniques and the occurrence of accidental dural puncture. The condition arises from cerebrospinal fluid leakage following disruption of the dura mater, leading to intracranial hypotension, compensatory cerebral vasodilation, and traction of pain-sensitive structures, which collectively explain its characteristic orthostatic presentation. Pregnancy-related physiological changes, including increased intra-abdominal pressure and epidural venous engorgement, further contribute to its development and severity. Clinically, PDPH presents as a positional headache that worsens in the upright position and improves with recumbency, often accompanied by nausea, photophobia, diplopia, and auditory symptoms. Diagnosis is primarily clinical and relies on a history of recent neuraxial procedures and the absence of red flag neurological signs. However, careful evaluation is necessary to exclude other serious postpartum conditions such as preeclampsia, cerebral venous sinus thrombosis, and intracranial hemorrhage. Prevention focuses on optimizing procedural techniques, including the use of small-gauge atraumatic needles, minimizing puncture attempts, and ensuring proper training. Management strategies depend on symptom severity and range from conservative measures, such as hydration, analgesics, and caffeine, to pharmacological interventions. In moderate-to-severe cases, the epidural blood patch remains the gold standard treatment, offering high success rates. Given its potential impact on maternal function, breastfeeding, and mental health, a multidisciplinary and patient-centered approach is essential to improve outcomes and reduce long-term complications.

A population pharmacokinetic (popPK) model was developed for ubrogepant using data from 10 Phase 1, 1 Phase 2, and 2 Phase 3 studies. The data were described by a 2-compartment model with linear elimination and transit compartment absorption. Formulation, food intake, race, gender, and hepatic impairment had a statistically significant impact on ubrogepant PK. Significant exposure-response relationships were found for 2 h pain relief and pain freedom, and 24 h sustained pain relief and sustained pain freedom. Ubrogepant significantly improved the symptoms of phonophobia and photophobia, and the most bothersome migraine symptom, with a modest trend with ubrogepant dose. A Phase 3 study evaluating ubrogepant use during the prodrome was incorporated into the popPK model, and the mean transit time and inter-individual variability were re-estimated. Exposure-response analysis across multiple endpoints in the prodrome study (including absence of moderate/severe headache within 24 or 48 h, absence of headache of any intensity within 24 h, and ability to function normally within 24 h) showed a treatment effect with improved outcomes after receiving ubrogepant.

Migraines are a common neurological disorder that significantly reduces quality of life. The sensitization of trigeminal afferents is a key factor in the development of the pain syndrome associated with migraine. Carbon monoxide (CO) is produced endogenously by heme oxygenase (HO), widely expressed in structures involved in pain processing. In our study, the role of CO in an acute and chronic nitroglycerin (NTG)-induced rat migraine model was investigated using behavioral, electrophysiological, biochemical and histological methods. The repeated administration of a CO donor (CORM-2) or an HO-1 inducer (CoPP) decreased mechanical hypersensitivity and photophobia of rats in the NTG-induced migraine model. Additionally, CORM-2 and CoPP prevented an increase in trigeminal afferent excitability, which was evaluated by the frequency of action potentials in response to KCl application. Preliminary CORM-2 or CoPP injections promoted mast cell stability in the meninges and prevented NTG-induced CGRP elevation in blood plasma. Our results suggest that exogenously or endogenously produced CO has a protective potential in preventing inflammation and the sensitization of peripheral trigeminal afferents, the activity of which underlies the occurrence of pain in migraine. This could contribute to the development of new approaches for migraine prevention.

Objectives: Oculocutaneous albinism (OCA), a group of inherited disorders characterized by deficient melanin synthesis, leads to hypopigmentation of the skin, hair, and eyes. OCA type 2 (OCA2) is caused by mutations in OCA2. This study aimed to characterize the comprehensive clinical and genetic spectrum of OCA2, and to identify the key ocular determinants of visual acuity. Methods: We enrolled 90 probands clinically diagnosed with albinism. Whole-exome sequencing and comprehensive ophthalmic examinations were performed. Results: OCA2 was confirmed in 29 probands (32.2%). Visual impairment was distributed as mild/no impairment (30.8%), moderate (53.8%), and severe/blindness (15.4%). All patients exhibited nystagmus and photophobia. Ocular phenotype grading showed distinct distributions: iris translucency (n = 25) was 68% grade 3, 20% grade 2, 8% grade 1, and 4% grade 4; fundus hypopigmentation (n = 26) was 42.3% grade 1, 30.8% grade 2, and 26.9% grade 3; and foveal hypoplasia (n = 20) was 70% grade 4, 25% grade 3, and 5% grade 1. We identified 33 OCA2 variants (26 compound heterozygous and 3 homozygous), with missense variants accounting for 62.1% of alleles. Five variants were identified to be novel. The severity of foveal hypoplasia demonstrated a strong, statistically significant negative correlation with visual acuity (r = -0.71, p < 0.001). Conclusions: OCA2 accounts for 32.2% of albinism cases, with moderate visual impairment being the most common (53.8%). Graded phenotyping demonstrated moderate-to-severe iris translucency (88%), mild fundus hypopigmentation (42.3%), and severe (grade 4) foveal hypoplasia (70%). The severity of foveal hypoplasia emerged as an important determinant of visual acuity.

This study aims to develop and optimize a thermoreversible in-situ nasal gel of Zavegepant for effective and rapid treatment of acute migraine, enhancing brain targeting and bioavailability while overcoming limitations of oral formulations. A 3[2] full factorial design was employed to evaluate the effects of Pluronic F-127 (X1) and xanthan gum (X2) on gelation temperature (Y1) and mucoadhesive strength (Y2). Nine formulations (VF1-VF9) were developed and evaluated for physicochemical properties, gelation behavior, mucoadhesion, in-vitro drug release, ex vivo permeation, and in vivo anti-migraine efficacy using a nitroglycerin-induced migraine model in rats. Optimized batch VF2 containing 20% Pluronic F-127 and 0.2% xanthan gum showed a gelation temperature of 34.94 °C and mucoadhesive strength of 5812.2 dyne/cm[2] with minimal prediction error (< 5%). VF2 exhibited sustained ex vivo drug release (83.67% at 8 h) and steady-state flux of 522.94 μg/cm[2]/h. In vivo studies demonstrated significant improvement in locomotor activity, photophobia, and mechanical allodynia, with biochemical normalization of CGRP (41.16 pg/mg), MDA, NO, GSH, and SOD levels, comparable to sumatriptan. Stability over 3 months confirmed formulation robustness. The optimized thermosensitive nasal gel (VF2) of Zavegepant presents a promising, non-invasive strategy for acute migraine therapy with sustained drug release, enhanced mucosal retention, and putative CNS delivery via olfactory and trigeminal pathway. Its clinical potential lies in offering fast, localized treatment with fewer systemic side effects and improved patient compliance.