Prevalence and impact of visual aura in migraine and probable migraine: a population study

Visual aura (VA) presents in 98% of cases of migraine with aura. However, data on its prevalence and impact in individuals with migraine and probable migraine (PM) are limited. Data from the nation-wide, population-based Circannual Change in Headache and Sleep Study were collected. Participants with VA rating scale scores ≥ 3 were classified as having VA. Of 3,030 participants, 170 (5.6%) and 337 (11.1%) had migraine and PM, respectively; VA prevalence did not differ between these cohorts (29.4% [50/170] vs. 24.3% [82/337], p = 0.219). Participants with migraine with VA had a higher headache frequency per month (4.0 [2.0–10.0] vs. 2.0 [1.0–4.8], p = 0.014) and more severe cutaneous allodynia (12-item Allodynia Symptom Checklist score; 3.0 [1.0–8.0] vs. 2.0 [0.0–4.8], p = 0.046) than those without VA. Participants with PM with VA had a higher headache frequency per month (2.0 [2.0–8.0] vs. 2.0 [0.6–4.0], p = 0.001), greater disability (Migraine Disability Assessment score; 10.0 [5.0–26.3] vs. 5.0 [2.0–12.0], p < 0.001), and more severe cutaneous allodynia (12-item Allodynia Symptom Checklist score, 2.5 [0.0–6.0] vs. 0.0 [0.0–3.0], p < 0.001) than those without VA. VA prevalence was similar between migraine and PM. Some symptoms were more severe in the presence of VA.

Efficacy and safety of anti-CGRP(r) monoclonal antibodies in real clinical practice: preliminary analysis after three months of therapy

Monoclonal antibodies inhibiting calcitonin gene related peptide (CGRP) or its receptor have been widely used for migraine prophylactic therapy for the past three years. Evaluation of their efficacy and safety of therapy in real clinical practice is needed.Objective: to evaluate the efficacy and safety of Erenumab, a monoclonal antibody inhibiting the CGRP receptor during three months of therapy.Patients and methods. Sixty-eight patients (58 women and 10 men, mean age 37±10.4 years) with episodic or chronic migraine who were treated with Erenumab were observed. Patients were assessed with MIDAS, WPAI, and HADS scales; the presence of cutaneous allodynia was evaluated with ASC-12 questionnaire. Patients kept a headache diary and marked adverse events during the whole treatment period.Results and discussion. 47 patients (69%) had chronic migraine and 32 (71.9%) had medication overuse headache. In 48 patients (70%) after 3 injections of Erenumab the number of days with migraine decreased by 50% or more. In 7 patients (10%), the reduction in headache days was more than 75%; 20 (29%) did not experience sufficient effect after three months of therapy. Nineteen adverse events were noted in 15 (22%) patients. Severe constipation led to discontinuation of treatment in two patients (3%).Conclusion. The study showed the efficacy and safety of Erenumab for migraine prophylaxis in both patients with episodic and chronic migraine.

Cutaneous allodynia in pediatric and adolescent patients and their mothers: A comparative study

Background Allodynia in adults with migraine is related to disease duration. In pediatric patients with migraine, the same proportion reported allodynia in the first six months of migraine presentation as in prolonged disease. This study examined a possible association between migraine pediatric allodynia and maternal allodynia. Methods We interviewed children with migraine first, and then their mothers, regarding allodynia and headache symptoms. We reviewed hospital charts on pediatric medical background and headache symptoms. Mothers and children older than 11 years filled the Strengths and Difficulties Questionnaire. Results Ninety-eight children with migraine, mean age 13.49 ± 3.1 years, and their mothers, mean age 43.5 ± 6.2 years were recruited to the study. Pediatric allodynia was associated with maternal allodynia; the latter was reported in 82.8% of children with allodynia versus 35.3% of children without allodynia (p < 0.001). Maternal migraine was reported in 44 (68.7%) of children with allodynia versus 16.3% without allodynia, p < 0.001. No difference was found in Strengths and Difficulties Questionnaire scores, between children with and without allodynia. Conclusions Pediatric allodynia is associated with maternal migraine. Genetic and environmental factors such as maternal behavior may contribute to reduced pain threshold.

Relationship between the Somatosensory Cortex Morphology, Cutaneous Allodynia, and Clinical Features of Patients with Migraine

Recent studies have demonstrated the presence of brain alterations in patients with migraine. Functional and vascular changes in the brain are related to the presence and severity of cutaneous allodynia. However, the association between brain structural changes and cutaneous allodynia has not been yet investigated in patients with migraine. Thus, the purpose of this study was to evaluate the correlation between the severity of cutaneous allodynia, migraine features, and the thickness and volume of the somatosensory cortex. Forty-five patients with migraine, with and without aura and chronic migraine, were included. Volunteers filled out the Allodynia Symptom Questionnaire (ASC-12/Brazil) and were evaluated via magnetic resonance imaging (MRI). The images were inspected by a blinded neuroradiologist and analyzed with Freesurfer software. Correlation tests and a linear regression model were used to evaluate the relationship among the outcomes. The somatosensory cortex thickness and volume were not different among migraine subgroups (p > 0.05). There was no significant correlation between the somatosensory thickness and volume with the ASC-12/Brazil, migraine frequency, intensity, migraine onset or aura frequency. The ASC-12/Brazil score variability cannot be predicted by the somatosensory cortex thickness or volume. The results show that the somatosensory cortex morphology is neither associated with cutaneous allodynia nor with migraine features among migraineurs.

Intracranial pressure directly predicts headache morbidity in idiopathic intracranial hypertension

Objective Headache is the predominant disabler in idiopathic intracranial hypertension (IIH). The aim was to characterise headache and investigate the association with intracranial pressure. Methods IIH:WT was a randomised controlled parallel group multicentre trial in the United Kingdom investigating weight management methods in IIH. Participants with active IIH (evidenced by papilloedema) and a body mass index (BMI) ≥35 kg/m2 were recruited. At baseline, 12 months and 24 months headache characteristics and quality of life outcome measures were collected and lumbar puncture measurements were performed. Results Sixty-six women with active IIH were included with a mean age of 32.0 years (SD ± 7.8), and mean body mass index of 43.9 ± 7.0 kg/m2. The headache phenotype was migraine-like in 90%. Headache severity correlated with ICP at baseline (r = 0.285; p = 0.024); change in headache severity and monthly headache days correlated with change in ICP at 12 months (r = 0.454, p = 0.001 and r = 0.419, p = 0.002 respectively). Cutaneous allodynia was significantly correlated with ICP at 12 months. (r = 0.479, p < 0.001). Boot strap analysis noted a positive association between ICP at 12 and 24 months and enabled prediction of both change in headache severity and monthly headache days. ICP was associated with significant improvements in quality of life (SF-36). Conclusions We demonstrate a positive relationship between ICP and headache and cutaneous allodynia, which has not been previously reported in IIH. Those with the greatest reduction in ICP over 12 months had the greatest reduction in headache frequency and severity; this was associated with improvement of quality of life measures. Trial registration This work provides Class IIa evidence of the association of raised intracranial pressure and headache. ClinicalTrials.gov number, NCT02124486.

A prolactin-dependent sexually dimorphic mechanism of migraine chronification

Objective Determination of possible sex differences in mechanisms promoting migraine progression and the contribution of prolactin and the prolactin long (PRLR-L) and short (PRLR-S) receptor isoforms. Background The majority of patients with chronic migraine and medication overuse headache are female. Prolactin is present at higher levels in women and increases migraine. Prolactin signaling at the PRLR-S selectively sensitizes nociceptors in female rodents, while expression of the PRLR-L is protective. Methods Medication overuse headache was modeled by repeated sumatriptan administration in male and female mice. Periorbital and hindpaw cutaneous allodynia served as a surrogate of migraine-like pain. PRLR-L and PRLR-S isoforms were measured in the trigeminal ganglion with western blotting. Possible co-localization of PRLR with serotonin 5HT1B and 5HT1D receptors was determined with RNAscope. Cabergoline, a dopamine receptor agonist that inhibits circulating prolactin, was co-administered with sumatriptan. Nasal administration of CRISPR/Cas9 plasmid was used to edit expression of both PRLR isoforms. Results PRLR was co-localized with 5HT1B or 5HT1D receptors in the ophthalmic region of female trigeminal ganglion. A single injection of sumatriptan increased serum PRL levels in female mice. Repeated sumatriptan promoted cutaneous allodynia in both sexes but down-regulated trigeminal ganglion PRLR-L, without altering PRLR-S, only in females. Co-administration of sumatriptan with cabergoline prevented allodynia and down-regulation of PRLR-L only in females. CRISPR/Cas9 editing of both PRLR isoforms in the trigeminal ganglion prevented sumatriptan-induced periorbital allodynia in females. Interpretation We identified a sexually dimorphic mechanism of migraine chronification that involves down-regulation of PRLR-L and increased signaling of circulating prolactin at PRLR-S. These studies reveal a previously unrecognized neuroendocrine mechanism linking the hypothalamus to nociceptor sensitization that increases the risk of migraine pain in females and suggest opportunities for novel sex-specific therapies including gene editing through nasal delivery of CRISPR/Cas9 constructs.

Laparoscopic surgical approach for the treatment of piriformis syndrome: Intrapelvic decompression technique

Introduction: Piriformis syndrome is an uncommon disease resulting from the piriformis muscle’s compression of the sciatic nerve. Pain and numbness in the buttocks and down the leg are the most common symptoms. This study analyzes the laparoscopic surgical treatment of piriformis syndrome. Methods: We report three cases of piriformis syndrome diagnosed in our hospital. The first case was a 40 years old woman with a 7-year history of intermittent low back pain and sciatica on her right side. Hyperesthesia and cutaneous allodynia were observed in the right sciatic nerve dermatome. The second case was a 30 years old woman with a 2-year history of sciatica on her left side. The third case was a 30 years old woman with a 2-year history of sciatica on her right side. All the patients underwent laparoscopic decompression surgery, which was performed to release the sciatic nerve or sacral nerve roots. Results: The patients were reexamined at the postoperative 3rd and 6th months. Their visual analog scale (VAS) scores were found to be decreased from 10/10, 9/10, and 7/10 to 0/10, 1/10, and 0/10, respectively. Conclusion: Due to the very few cases in the literature, pelvic piriformis syndrome is an exclusively clinical diagnosis. If the sciatica is refractory to conservative treatments, laparoscopic exploration and decompression surgery of the pelvic nerves and piriformis muscle could be an option.

Comparison of cervical muscle isometric force between migraine subgroups or migraine-associated neck pain: a controlled study

This study aimed to verify if migraine frequency or migraine-associated neck pain were associated with a reduction of normalized force and altered electromyographic activity during maximal cervical muscle isometric contractions. Additionally, it aimed to assess the correlation of normalized isometric force with years with migraine, headache frequency, headache intensity, migraine-related disability, and severity of cutaneous allodynia. The sample comprises 71 women with migraine (40/31 episodic/chronic, 42/18 with/without neck pain) and 32 women without headache. Cervical muscle isometric force in flexion, extension, and lateral flexion was assessed synchronized with the acquisition of superficial electromyography from the cervical muscles. Women with episodic migraine presented lower normalized isometric force in extension, flexion, and right and left lateral flexions than controls (P < 0.05). Women with migraine and neck pain exhibited lower cervical extension and right/left lateral-flexions normalized isometric force than controls (P < 0.05). No significant differences were observed in antagonist activity. Normalized isometric force in all directions showed weak to moderate correlations with the severity of self-reported symptoms of cutaneous allodynia (− 0.25 ≥ r ≥ − 0.39). No additional linear correlation with clinical migraine features was observed. In conclusion, cervical muscle weakness may be associated with episodic migraine and neck pain concurrent with migraine attacks without altered antagonist activity. Additionally, it may also be related to the severity of cutaneous allodynia.

Efficacy of erenumab in chronic migraine patients with and without ictal allodynia

Background Ictal cutaneous allodynia, common in chronic migraine, is associated with reduced responses to acute treatment with triptans. Allodynia’s impact on the efficacy of newer preventive treatments such as erenumab is unknown. Methods Post-hoc subgroup analysis of a double-blind, randomized, placebo-controlled 12-week study of erenumab in chronic migraine, contrasting those with no allodynia with those with moderate-severe allodynia assessed with the Allodynia Symptom Checklist-12, was undertaken. Results Of 648 randomized individuals with baseline Allodynia Symptom Checklist-12 scores, 386 (59.6%) had no allodynia and 153 (23.6%) had moderate-to-severe allodynia. Mean (standard deviation) baseline monthly migraine days were 17.6 (4.8) and 18.9 (4.3), respectively. Compared to placebo, the erenumab group had greater reductions in monthly migraine days and monthly acute migraine-specific medication days in both no allodynia and allodynia subgroups. Mean (95% confidence interval) treatment differences in change from baseline for monthly migraine days at week 12 were −2.5 (−3.7, −1.4) in the no allodynia subgroup and −3.3 (−5.3, −1.3) in the moderate-severe allodynia subgroup. Change in acute migraine-specific medication days were −3.3 (−4.3, −2.3) and −2.5 (−4.3, −0.8), respectively. Conclusions Erenumab’s efficacy in reducing monthly migraine days and acute migraine-specific medication days in chronic migraine was not impacted by the presence of moderate-severe ictal allodynia. Trial registration: ClinicalTrials.gov NCT02066415

Intracranial Pressure Directly Predicts Headache Morbidity in Idiopathic Intracranial Hypertension

Objective: Headache is the predominant disabler in idiopathic intracranial hypertension (IIH). The aim was to characterise headache and investigate the association with intracranial pressure.Methods: IIH:WT was a randomised controlled parallel group multicentre trial in the United Kingdom investigating weight management methods in IIH. Participants with active IIH (evidenced by papilloedema) and a body mass index (BMI) ≥35kg/m2 were recruited. At baseline, 12 months and 24 months headache characteristics and quality of life outcome measures were collected and lumbar puncture measurements were performed.Results: Sixty-six women with active IIH were included with a mean age of 32.0 years (SD ± 7.8), and mean body mass index of 43.9 ± 7.0 kg/m2. The headache phenotype was migraine-like in 86%. Headache severity correlated with ICP at baseline (r=0.285; p=0.024); change in headache severity and monthly headache days correlated with change in ICP at 12 months (r=0.454, p=0.001 and r=0.419, p=0.002 respectively). Cutaneous allodynia was significantly correlated with ICP at 12 months. (r=0.479, p<0.001). Boot strap analysis noted a positive association between ICP at 12 and 24 months and enabled prediction of both change in headache severity and monthly headache days. ICP was associated with significant improvements in quality of life (SF-36).Conclusions: We demonstrate a positive relationship between ICP and headache and cutaneous allodynia, which has not been previously reported in IIH. Those with the greatest reduction in ICP over 12 months had the greatest reduction in headache frequency and severity; this was associated with improvement of quality of life measures.Classification of evidence: This work provides Class IIa evidence of the association of raised intracranial pressure and headache. ClinicalTrials.gov number, NCT02124486.