Impact of anti-CGRP monoclonal antibodies on migraine attack accompanying symptoms: A real-world evidence study.

BACKGROUND: Clinical trials on anti-calcitonin gene-related peptide monoclonal antibodies poorly investigated their impact on migraine accompanying symptoms. OBJECTIVE: To evaluate the impact of basal accompanying symptoms on anti-CGRP monoclonal antibodies treatment response and their evolution after six months of treatment in migraine patients. METHODS: Patients with migraine diagnosis seen in the Headache Clinic and treated with erenumab, galcanezumab or fremanezumab were prospectively recruited. They completed a daily eDiary which provided data on headache frequency and the following accompanying symptoms of each day: photophobia, phonophobia, nausea, dizziness, and aura. Patients were classified as responders or non-responders based on 50% or greater reduction in headache days per month at month 6 (≥50% response rate). Accompanying symptoms ratios based on headache days per month were assessed per patient at baseline and after three and six months. Comparisons for basal characteristics, basal accompanying symptoms ratios and their evolution after six months between responders and non-responders were performed. RESULTS: One hundred and fifty-eight patients were included, 44% (69/158) showed ≥50% response rate after six months. A significant reduction in headache days per month in both groups was found at month 6 (-9.4 days/month in ≥50% response rate group; p < 0.001, -2.2 days/month in <50% response rate group; p = 0.004). Additionally, significant decreases in photophobia (-19.5%, p < 0.001), phonophobia (-12.1%, p = 0.010) and aura ratios (-25.1%, p = 0.008) were found in ≥50% response rate group. No statistically significant reductions were found in nausea and dizziness in any group since their reduction was correlated with the decrease in headache days per month. Higher photophobia ratios at baseline were predictive of an increased response between months 3 and 6 (Incidence Risk Ratio = 0.928, p = 0.040). CONCLUSIONS: The days per month with photophobia, phonophobia and aura decreased at a higher rate than headache days per month after six months in the ≥50% response group. Higher photophobia ratios were associated with higher response rates between three and six months. It could indicate an involvement of peripheral CGRP in photophobia as well as a central modulation of migraine through these treatments which mainly act on the periphery.

Rapid resolution of migraine symptoms after initiating the preventive treatment eptinezumab during a migraine attack: results from the randomized RELIEF trial.

BACKGROUND: Eptinezumab is an anti-calcitonin gene-related peptide (CGRP) monoclonal antibody approved for the preventive treatment of migraine. In the phase 3 RELIEF study, eptinezumab resulted in shorter time to headache pain freedom and time to absence of most bothersome symptom (MBS; including nausea, photophobia, or phonophobia) compared with placebo when administered during a migraine attack. The objective of this exploratory analysis was to examine the earliest time points that eptinezumab separated from placebo (P < .05) on headache- and migraine-associated symptoms when administered during a migraine attack. METHODS: RELIEF, a multicenter, parallel-group, double-blind trial, occurred from November 7, 2019, through July 8, 2020. Adults considered candidates for preventive treatment were randomized to eptinezumab 100 mg (N = 238) or placebo (N = 242) administered intravenously over 30 min within 1-6 h of migraine onset. Outcome measures included headache pain freedom/relief and absence of MBS, patient's choice of photophobia, phonophobia, or nausea, at regular intervals from 0.5 to 48 h after infusion start. Censoring was applied at time of acute rescue medication use. RESULTS: At hour 1, more eptinezumab-treated patients achieved headache pain freedom (9.7%), headache pain relief (38.7%), and absence of MBS (33.2%) versus placebo (4.1%, 26.9%, and 22.1%, respectively; P < .05 all), with separation from placebo (P < .05) through hour 48. Eptinezumab separated from placebo (P < .05) at hour 1 in absence-of-photophobia (29.4% vs 17.0%) and absence-of-phonophobia (41.2% vs 27.2%) and through hour 48. Initial separation from placebo (P < .05) in absence-of-nausea occurred at end-of-infusion (0.5 h; 36.7% vs 25.4%, respectively). CONCLUSION: Preventive treatment with eptinezumab initiated during a migraine attack resulted in more patients achieving headache pain freedom/relief and absence of MBS, with separation from placebo (P < .05) as early as 0.5-1 h following the start of infusion. Rapid resolution of headache- and migraine-associated symptoms by a peripherally acting, intravenously administered antibody suggest a peripheral site of pharmacological action for CGRP blockade. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT04152083 .

Evaluating the clinical utility of the patient-identified most bothersome symptom measure from PROMISE-2 for research in migraine prevention.

OBJECTIVE: To assess the utility of the novel patient-identified (PI) most bothersome symptom (MBS) measure from PROMISE-2, a phase 3 trial of eptinezumab for the preventive treatment of chronic migraine. BACKGROUND: Relief of bothersome migraine symptoms can influence satisfaction with treatment and therapeutic persistence. Understanding the impact of preventive treatment on a PI-MBS could improve clinical decision-making. METHODS: In PROMISE-2, patients with chronic migraine received eptinezumab 100, 300 mg, or placebo administered intravenously every 12 weeks for up to 2 doses (n = 1072). PI-MBS was an exploratory outcome requiring each patient to self-report their MBS in response to an open-ended question. At baseline and week 12, patients rated overall improvement in PI-MBS. The relationships among PI-MBS at week 12 and change in monthly migraine days (MMDs) from baseline to month 3 (weeks 9-12), Patient Global Impression of Change at week 12, and changes from baseline to week 12 in the 6-item Headache Impact Test total, EuroQol 5-dimensions 5-levels visual analog scale, and 36-item Short-Form Health Survey component scores were assessed. RESULTS: Treatment groups had similar baseline characteristics and reported a total of 23 unique PI-MBS, most commonly light sensitivity (200/1072, 18.7%), nausea/vomiting (162/1072, 15.1%), and pain with activity (147/1072, 13.7%). Improvements in PI-MBS at week 12 correlated with changes in MMDs (ρ = -0.49; p < 0.0001) and other patient-reported outcomes. Controlling for changes in MMDs, PI-MBS improvement predicted other patient-reported outcomes in expected directions. The magnitude of the standardized mean differences between placebo and active treatment for PI-MBS were 0.31 (p < 0.0001 vs. placebo) and 0.54 (p < 0.0001 vs. placebo) for eptinezumab 100 and 300 mg, respectively. CONCLUSIONS: Improvement in PI-MBS at week 12 was associated with improvement in other patient-reported outcome measures, and PI-MBS may be an important patient-centered measure of treatment benefits in patients with chronic migraine.

A randomized study of IV prochlorperazine plus diphenhydramine versus IV hydromorphone for migraine-associated symptoms: A post hoc analysis.

OBJECTIVE: We conducted a randomized trial among emergency department patients with migraine to determine the relative impact on migraine-associated symptoms of hydromorphone, an opioid, versus prochlorperazine, an antidopaminergic antiemetic. METHODS: This was a post hoc analysis of data from a double-blind study registered at http://clinicaltrials.gov (NCT02389829). Patients who met International Classification of Headache Disorders, 3rd edition criteria for migraine without aura or for probable migraine without aura were eligible for participation. Participants received either hydromorphone 1 mg IV or prochlorperazine 10 mg IV plus diphenhydramine 25 mg IV and could receive a second dose of the same medication 1 h later if needed. The outcomes were sustained relief of nausea, photophobia, and phonophobia. RESULTS: A total of 127 patients were enrolled, of whom 63 received prochlorperazine and 64 received hydromorphone. Of 49 patients in the prochlorperazine arm who reported nausea at baseline, 34 (69.4%) reported complete resolution without relapse versus 15/49 (30.6%) in the hydromorphone arm (absolute risk reduction [ARR] = 38.8%, 95% CI: 20.5%-57.0%, p < 0.001). Of 55 patients in the prochlorperazine arm who reported photophobia at baseline, 23 (41.8%) reported complete resolution without relapse versus 13/62 (20.9%) patients treated with hydromorphone (ARR = 20.8%, 95% CI: 4.3%-37.3%, p = 0.014). Of 56 patients in the prochlorperazine arm who reported phonophobia at baseline, 25 (44.6%) reported complete resolution without relapse versus 16/59 (27.1%) in the hydromorphone arm (ARR = 17.5%, 95% CI: 0.3%-34.8%, p = 0.049). For adverse events, three patients in the prochlorperazine arm reported anxiety or restlessness, and nine patients in the hydromorphone arm reported dizziness or weakness. CONCLUSIONS: Prochlorperazine plus diphenhydramine is more efficacious than hydromorphone for the treatment of migraine-associated symptoms.

Cortical spreading depolarisation-induced facial hyperalgesia, photophobia and hypomotility are ameliorated by sumatriptan and olcegepant.

Cortical spreading depolarisation (CSD), the neural mechanism underlying migraine aura, may cause headache by sensitising the trigeminal system. Photophobia, the most bothersome accompanying symptom during migraine attacks, is more prevalent in migraine with aura than in migraine without aura. Whether CSD plays a role in developing photophobia remains unknown. Moreover, migraine-induced physical hypoactivity contributes to loss of productivity. We aimed to investigate the development of trigeminal sensitisation, photophobia and locomotive abnormality after KCl-induced CSD using 86 male C57BL/6 mice. Sham-operated mice were used as controls. We confirmed the presence of trigeminal sensitisation and photophobia at 24 h after CSD. CSD-subjected mice also exhibited significantly reduced locomotive activity in both light and dark zones. Hence, the CSD-induced hypomobility was likely to be independent of photophobia. The 5-HT1B/1D agonist, sumatriptan, corrected all these CSD-induced abnormalities. Moreover, dose dependency was demonstrated in the ameliorating effect of the calcitonin gene-related peptide (CGRP) receptor antagonist, olcegepant, on these abnormalities. Sumatriptan and olcegepant improved mouse locomotion with therapeutic lags ranging from 20 to 30 min. Collectively, CSD caused trigeminal sensitisation, photophobia and hypomobility that persisted for at least 24 h by a mechanism involving the 5-HT1B/1D and CGRP activity.

Adie's tonic pupil presenting with unilateral photophobia successfully treated with dilute pilocarpine.

A 40-year-old healthy man presented with a 4-month history of photophobia, blurred vision and a right dilated pupil. Examination revealed a right pupil that was not reactive to light but constricted strongly to a near target and slowly redilated when he looked back in the distance. Pharmacological testing with dilute pilocarpine 0.1% resulted in constriction of the right pupil but no change in the left pupil. This also resulted in resolution of his photophobia and blurry vision. Neurological examination was otherwise normal, and a diagnosis of Adie's tonic pupil was made. The main differential diagnosis to consider for a large pupil is a third nerve palsy, pharmacological mydriasis, tonic pupil and local iris processes, such as iris sphincter tears from trauma. Knowledge of the key features of these conditions can avoid wasted resources from unnecessary testing. Dilute pilocarpine 0.1% three times a day can be considered as a pharmacological therapy for symptomatic relief.

IM ketorolac vs diclofenac potassium powder for oral solution for the acute treatment of severe migraine: a randomized controlled trial.

BACKGROUND: Diclofenac potassium for oral solution (CAMBIA®) may be an alternative for patients who would otherwise need to be seen in a healthcare setting for parenteral ketorolac. CAMBIA® is FDA-approved for the abortive treatment of migraine and has demonstrated superiority over generic diclofenac tablets with rapid migraine reduction. This study assessed for efficacy of CAMBIA® as an alternative outpatient treatment for refractory migraine to parenteral ketorolac. METHODS: We performed an exploratory, single-center, double-blind, double-dummy randomized controlled trial comparing CAMBIA® with IM ketorolac. Participants were randomized to receive either ketorolac 60 mg IM with dummy oral solution or CAMBIA® 50 mg, together with IM injection of normal saline. The primary endpoint was headache severity, self-rated on a scale 0-3. Secondary endpoints included self-rated nausea, disability, and photo- or phonophobia, as well as presence of side effects and need for additional rescue therapy. RESULTS: A total of 23 patients were enrolled. Ten patients received the study drug and 13 patients received IM ketorolac as the control. There were no major differences observed with respect to the primary outcome of mean headache severity at successive time points over a 24-h follow-up period. No major differences were found with respect to average disability, nausea, and photo- or phonophobia ratings. No major adverse events were reported. CONCLUSION: In treatment of refractory migraine headache, CAMBIA® may provide similar benefits as IM ketorolac without increasing the risk of treatment failure, major bleeding, or cardiovascular events. However, larger studies are needed to confirm this finding. TRIAL REGISTRATION: Clinicaltrials.gov: NCT # 02664116, Titled "IM Ketorolac vs Diclofenac Potassium Powder for Oral Solution (CAMBIA®) for the Acute Treatment of Severe Migraine". Registered 26 January 2016, https://clinicaltrials.gov/ct2/show/NCT02664116?term=02664116&rank=1.

Ubrogepant for the Treatment of Migraine.

BACKGROUND: Ubrogepant is an oral, small-molecule calcitonin gene-related peptide receptor antagonist for acute migraine treatment. METHODS: We conducted a randomized trial to evaluate the efficacy, safety, and side-effect profile of ubrogepant. We assigned adults with migraine, with or without aura, in a 1:1:1 ratio to receive an initial dose of placebo, ubrogepant at a dose of 50 mg, or ubrogepant at a dose of 100 mg for treatment of a single migraine attack, with the option to take a second dose. The coprimary efficacy end points were freedom from pain at 2 hours after the initial dose and absence of the most bothersome migraine-associated symptom at 2 hours. Secondary end points included pain relief (at 2 hours), sustained pain relief (from 2 to 24 hours), sustained freedom from pain (from 2 to 24 hours), and absence of symptoms associated with migraine (photophobia, phonophobia, and nausea) at 2 hours. RESULTS: A total of 1672 participants were enrolled; 559 were assigned to receive placebo, 556 to receive 50 mg of ubrogepant, and 557 to receive 100 mg of ubrogepant. The percentage of participants who had freedom from pain at 2 hours was 11.8% in the placebo group, 19.2% in the 50-mg ubrogepant group (P = 0.002, adjusted for multiplicity, for the comparison with placebo), and 21.2% in the 100-mg ubrogepant group (P<0.001). The percentage of participants who had freedom from the most bothersome symptom at 2 hours was 27.8% in the placebo group, 38.6% in the 50-mg ubrogepant group (P = 0.002), and 37.7% in the 100-mg ubrogepant group (P = 0.002). Adverse events within 48 hours after the initial or optional second dose were reported in 12.8% of participants in the placebo group, in 9.4% in the 50-mg ubrogepant group, and in 16.3% in the 100-mg ubrogepant group. The most common adverse events were nausea, somnolence, and dry mouth (reported in 0.4 to 4.1%); these events were more frequent in the 100-mg ubrogepant group (reported in 2.1 to 4.1%). Serious adverse events reported within 30 days in the ubrogepant groups included appendicitis, spontaneous abortion, pericardial effusion, and seizure; none of the events occurred within 48 hours after the dose. CONCLUSIONS: A higher percentage of participants who received ubrogepant than of those who received placebo had freedom from pain and absence of the most bothersome symptom at 2 hours after the dose. The most commonly reported adverse events were nausea, somnolence, and dry mouth. Further trials are needed to determine the durability and safety of ubrogepant for acute migraine treatment and to compare it with other drugs for migraine. (Funded by Allergan; ClinicalTrials.gov number, NCT02828020.).

Toxic Keratitis After Application of Custard Apple Seed for Head Lice Infestation.

PURPOSE: To report the clinical features and outcomes of toxic keratitis after application of powdered custard apple seeds for hair washing for head lice infestation. METHODS: Retrospective review of all patients with toxic keratitis after application of powdered custard apple seed for head lice infestation during the time period from January 2015 to December 2017. Demographic details, clinical features, and visual outcomes were documented. RESULTS: Thirty-one eyes of 19 patients with toxic keratitis after application of crushed custard apple seeds for head lice infestation were included in the study. Eighteen females and 1 male with a median age of 14 years [interquartile range (IQR) 12-34 years] presented with severe epiphora, congestion, photophobia, and defective vision (median logMar visual acuity 0.4, IQR 0.2-0.8) after application of custard apple seed powder for hair washing. Ten eyes (32.2%) had an epithelial defect (median size 9 mm, IQR 5-12 mm), and 21 (67.7%) eyes had punctate epithelial erosions. All the patients were treated with topical antibiotics, and at 3 days follow-up, all of them had resolution of symptoms and signs with a median logarithm of the minimum angle of resolution (logMAR) visual acuity of 0 (IQR 0-0.2). CONCLUSIONS: Health education about the harmful effect of this traditional practice for head lice infestation will prevent further similar events.

Photophobia and sensations of dryness in patients with migraine occur independent of baseline tear volume and improve following botulinum toxin A injections.

BACKGROUND: To evaluate the efficacy of botulinum toxin A (BoNT-A) in reducing photophobia and dry eye symptoms in individuals with chronic migraine. Additionally, we aimed to evaluate tear film volume as a potential contributor to symptoms in these patients. METHODS: Retrospective review of 76 patients who received BoNT-A for chronic migraine between 23 August 2017 and 13 December 2017 at the Miami Veterans Affairs Medical Center Neurotoxin Clinic. Demographic data and all comorbidities were queried via chart review. Standardised validated surveys were administered to assess symptoms prior to and after BoNT-A injection. Preinjection tear volumes were obtained using the phenol red thread (PRT) test. RESULTS: Preinjection migraine, photophobia and dry eye symptom scores were all significantly correlated, p<0.05, and none were associated with preinjection PRT results. After BoNT-A, improvements in migraine, photophobia and dry eye symptoms were also significantly correlated, p<0.05 and similarly did not associate with preinjection PRT results. Photophobia scores significantly improved following BoNT-A, while dry eye symptoms significantly improved in those with severe symptoms at baseline (DEQ-5 score ≥12), p=0.027. In logistic regression analysis of all individuals with dry eye symptoms (DEQ-5 ≥6), individuals with more severe dry eye symptoms were more likely improve, OR 1.27, 95% CI 1.06 to 1.51, p<0.01. CONCLUSIONS: BoNT-A significantly improved photophobia in patients being treated for migraine and also improved dry eye symptoms in patients with severe symptoms at baseline, independent of baseline tear film volume. These improvements may be due to modulation of shared trigeminal neural pathways.

Efficacy and safety of DFN-11 (sumatriptan injection, 3 mg) in adults with episodic migraine: an 8-week open-label extension study.

BACKGROUND: DFN-11, a 3 mg sumatriptan subcutaneous (SC) autoinjector for acute treatment of migraine, has not been assessed previously in multiple attacks. The objective of this study was to evaluate the efficacy, tolerability, and safety of DFN-11 in the acute treatment of multiple migraine attacks. METHODS: This was an 8-week open-label extension of multicenter, randomized, double-blind, placebo-controlled US study. Subjects averaging 2 to 6 episodic migraine attacks per month were randomized to DFN-11 or placebo to treat a single attack of moderate-to-severe intensity and then entered the extension study to assess the efficacy, tolerability, and safety of DFN-11 in multiple attacks of any pain intensity. RESULTS: Overall, 234 subjects enrolled in the open-label period, and 29 (12.4%) discontinued early. A total of 848 migraine episodes were treated with 1042 doses of open-label DFN-11 and subjects treated a mean (SD) of 3.9 (2.3) attacks. At 2 h postdose in attacks 1 (N = 216), 2 (N = 186), 3 (N = 142) and 4 (N = 110), respectively, pain freedom rates were 57.6%, 64.6%, 61.6%, and 66.3%; pain relief rates were 83.4%, 88.4%, 84.1%, and 81.7%; most bothersome symptom (MBS)-free rates were 69.0%, 76.5%, 77.7%, and 74.7%; nausea-free rates were 78.1%, 84.6%, 86.5%, and 85.7%; photophobia-free rates were 75.3%, 76.4%, 72.3%, and 77.5%; and phonophobia-free rates were 75.2%, 77.5%, 73.6%, and 76.0%. Overall, 40.6% (89/219) of subjects reported treatment-emergent adverse events (TEAE), the most common of which were associated with the injection site: swelling (12.8%), pain (11.4%), irritation (6.4%), and bruising (6.4%). Most subjects (65.2%, 58/89) had mild TEAEs; severe TEAEs were reported by 1 subject (treatment-related jaw tightness). Five subjects (2.1%) discontinued due to adverse events, which included mild throat tightness (n = 2), moderate hernia pain (n = 1), moderate hypersensitivity (n = 1), and 1 subject with mild nausea and moderate injection site swelling. There were no serious TEAEs and no new or unexpected safety findings. CONCLUSION: DFN-11 was effective, tolerable, and safe in the acute treatment of 4 migraine attacks over 8 weeks, with consistent responses on pain and associated symptoms. Most TEAEs were mild, with a very low incidence of triptan-related TEAEs. DFN-11 is potentially an effective and safe alternative for the acute treatment of migraine. TRIAL REGISTRATION: ClinicalTrials.gov, NCT02569853 . Registered 07 October 2015.

An item response theory based integrated model of headache, nausea, photophobia, and phonophobia in migraine patients.

This study developed an integrated model of severity scores of migraine headache and the incidence of nausea, photophobia, and phonophobia to predict the natural time course of migraine symptoms, which are likely to occur by a common disease progression mechanism. Data were acquired from two phase 3 clinical trials conducted during the development of eletriptan. Only the placebo arm was used for analysis. A conventional proportional odds model was compared with an item response theory (IRT) based approach. Results suggested that the IRT based approach led to a better model fit, successfully revealing the difference in relief rates among different symptoms, which was the fastest in phonophobia and the slowest in headache. Simulation with the developed model suggested that using headache scores at 4 h post-dose attained greatest statistical power, yielding sample size of 100 per arm given drug effect of 40%, as compared to that of 200 per arm when 2 h post-dose scores were used as in the original eletriptan protocol. This work demonstrated the usefulness of an IRT based model as applied to analyzing multidimensional migraine symptoms and designing clinical trials. Our model can be similarly applied to analyzing other multiple endpoints sharing a common underlying mechanism.

Cerebrolysin attenuates hyperalgesia, photophobia, and neuroinflammation in a nitroglycerin-induced migraine model in rats.

Chronic migraine dramatically affects the quality of life in the migraineurs. This study examined the effect of chronic cerebrolysin (CBL) treatment on the migraine-associated symptoms in a rat model of migraine. Experiments were carried out on 8 weeks, male Wistar rats. Chronic migraine was modeled by injection (10 mg/kg, i.p) of nitroglycerin (NTG) on days 3, 5, 7, and 9. CBL (2.5 and 5 ml/kg, i.p.) was injected every day for 10 days. Mechanical and thermal withdrawal thresholds of the hind paw were examined by von Frey hairs and hot plate, respectively. Head grooming behavior was evaluated one hour following injection of NTG. Light-aversive behaviors were determined in the modified elevated plus-maze (EPM) on even days and in the light/dark box on odd days. After behavioral experiments, blood concentrations of calcitonin gene-related peptide (CGRP), pituitary adenylate cyclase-activating polypeptide (PACAP), tumor necrosis factor-a (TNF-α), and interleukin-1ß (IL-1ß) were assessed by rat specific enzyme-linked immunosorbent assay (ELISA) kits. Our results indicated that NTG significantly increased migraine-related behavioral and molecular symptoms in the animals, whereas CBL treatment markedly reduced mechanical and thermal hyperalgesia, head grooming, and light-aversive behaviors induced by NTG. Also, blood levels of CGRP, PACAP, and pro-inflammatory cytokines (TNF-α and IL-1ß) significantly decreased by CBL administration. Chronic CBL treatment showed antinociceptive and light-aversive reducing effects in the NTG-induced animal model of chronic migraine and may represent a valuable therapy for those suffering from migraine.

Use of Most Bothersome Symptom as a Coprimary Endpoint in Migraine Clinical Trials: A Post-Hoc Analysis of the Pivotal ZOTRIP Randomized, Controlled Trial.

OBJECTIVE: To better understand the utility of using pain freedom and most bothersome headache-associated symptom (MBS) freedom as co-primary endpoints in clinical trials of acute migraine interventions. BACKGROUND: Adhesive dermally applied microarray (ADAM) is an investigational system for intracutaneous drug administration. The recently completed pivotal Phase 2b/3 study (ZOTRIP), evaluating ADAM zolmitriptan for the treatment of acute moderate to severe migraine, was one of the first large studies to incorporate MBS freedom and pain freedom as co-primary endpoints per recently issued guidance by the US Food and Drug Administration. In this trial, the proportion of patients treated with ADAM zolmitriptan 3.8 mg, who were pain-free and MBS-free at 2 hours post-dose, was significantly higher than for placebo. METHODS: We undertook a post-hoc analysis of data from the ZOTRIP trial to examine how the outcomes from this trial compare to what might have been achieved using the conventional co-primary endpoints of pain relief, nausea, photophobia, and phonophobia. RESULTS: Of the 159 patients treated with ADAM zolmitriptan 3.8 mg or placebo, prospectively designated MBS were photophobia (n = 79), phonophobia (n = 43), and nausea (n = 37). Two-hour pain free rates in those with photophobia as the MBS were 36% for ADAM zolmitriptan 3.8 mg and 14% for placebo (P = .02). Corresponding rates for those with phonophobia as the MBS were 14% and 41% (P = .05). For those whose MBS was nausea, corresponding values were 56% and 16%, respectively (P = .01). Two-hour freedom from the MBS for active drug vs placebo were 67% vs 35% (P < .01) for photophobia, 55% vs 43% (P = .45) for phonophobia, and 89% vs 58% for nausea (P = .04). MBS freedom but not pain freedom was achieved in 28%. Only 1 patient (1%) achieved pain freedom, but not MBS freedom. The proportion with both pain and MBS freedom was highest (56%) among those whose MBS was nausea. CONCLUSION: In this study, the use of MBS was feasible and seemed to compare favorably to the previously required 4 co-primary endpoints.

Topical tacrolimus solution in autoimmune polyglandular syndrome-1-associated keratitis.

PURPOSE: To evaluate the efficacy of topical tacrloimus eye drops in the treatment of keratitis associated with autoimmune polyglandular syndrome (APS)-1. METHODS: This is a retrospective review of 10 patients with APS-1. The patients were treated with topical tacrolimus 0.01% solution at The Eye Center, between 1 March 2012 and 30 April 2016. The outcome measures included improvement in visual acuity, photophobia and keratitis following treatment. Clinical assessment was carried out before, during and on the last visit following initiation of therapy. RESULTS: A total of 10 patients were included. There were five male and five female patients. The mean age was 11 years with age range of 3-42 years. The mean duration of treatment with topical tacrolimus was 26 months (range 8-46 months). There was improvement of photophobia in 7 out of 10 patients following therapy with topical tacrolimus. In three patients, the photophobia was persistent. There was no clinically detectable improvement in the severity of keratitis in all patients. The mean best corrected visual acuity was 0.1 before and following therapy. CONCLUSION: Topical tacrolimus is effective in reducing the photophobia in patients with APS-1-associated keratitis, but showed no effects on the severity of keratitis.

Chronic ghrelin treatment reduced photophobia and anxiety-like behaviors in nitroglycerin- induced migraine: role of pituitary adenylate cyclase-activating polypeptide.

Chronic migraine is a debilitating disorder that has a significant impact on patients and society. Nearly all migraineurs frequently reported light sensitivity during a headache attack. Pituitary adenylate cyclase-activating polypeptide (PACAP) plays an important role in the activation of trigeminal system and migraine pain. To identify the effect of chronic ghrelin treatment on endogenous PACAP and associated symptoms of migraine, an experimental chronic migraine model was induced by intermittent intraperitoneal (i.p) injection of nitroglycerin (NTG). Photophobia and anxiety-like behaviors were determined in the modified elevated plus maze on days 2, 4, 6, 8, and 10 and in the light/dark box on days 3, 5, 7, 9, and 11. Blood levels of PACAP and cortisol were assessed by enzyme-linked immunosorbent (ELISA) kits. Chronic injection of NTG evoked photophobia and anxiety-like behaviors and treatment with ghrelin (150 µg/kg) for 11 days effectively attenuated photophobia and anxiety-like behaviors in the both paradigms. We further found that NTG increased the blood levels of PACAP and cortisol, which was significantly reduced by ghrelin treatment. Additionally, staining with Hematoxylin and Eosin (H&E) revealed that ghrelin reduced NTG-induced increase in the number of satellite glial cells in the trigeminal ganglion. Furthermore, for the first time we showed that repeated administrations of NTG increased white blood cell (WBC) counts and mean platelet volume (MPV), and decreased platelet counts. These results indicated that ghrelin decreased migraine associated symptoms possibly through attenuating endogenous PACAP and cortisol levels. Therefore, ghrelin may hold therapeutic potentialities in managing the chronic migraine.

Primary cicatricial alopecia: Other lymphocytic primary cicatricial alopecias and neutrophilic and mixed primary cicatricial alopecias.

Primary cicatricial alopecias can be frustrating for both patients and physicians. Proper diagnosis guides more successful management of these challenging conditions. Part II will cover the remaining lymphocytic primary cicatricial alopecias, which include pseudopelade of Brocq, central centrifugal cicatricial alopecia, alopecia mucinosa, and keratosis follicularis spinulosa decalvans. It will also discuss the neutrophilic and mixed primary cicatricial alopecias, namely folliculitis decalvans, dissecting cellulitis, folliculitis keloidalis, folliculitis (acne) necrotica, and erosive pustular dermatosis.