Brian M. Grosberg

Effect of noninvasive vagus nerve stimulation on acute migraine: an open-label pilot study.

Background We sought to assess a novel, noninvasive, portable vagal nerve stimulator (nVNS) for acute treatment of migraine. Methods Participants with migraine with or without aura were eligible for an open-label, single-arm, multiple-attack study. Up to four migraine attacks were treated with two 90-second doses, at 15-minute intervals delivered to the right cervical branch of the vagus nerve within a six-week time period. Subjects were asked to self-treat at moderate or severe pain, or after 20 minutes of mild pain. Results Of 30 enrolled patients (25 females, five males, median age 39), two treated no attacks, and one treated aura only, leaving a Full Analysis Set of 27 treating 80 attacks with pain. An adverse event was reported in 13 patients, notably: neck twitching (n = 1), raspy voice (n = 1) and redness at the device site (n = 1). No unanticipated, serious or severe adverse events were reported. The pain-free rate at two hours was four of 19 (21%) for the first treated attack with a moderate or severe headache at baseline. For all moderate or severe attacks at baseline, the pain-free rate was 12/54 (22%). Conclusions nVNS may be an effective and well-tolerated acute treatment for migraine in certain patients.

OnabotulinumtoxinA improves quality of life and reduces impact of chronic migraine

Objective: To assess the effects of treatment with onabotulinumtoxinA (Botox, Allergan, Inc., Irvine, CA) on health-related quality of life (HRQoL) and headache impact in adults with chronic migraine (CM). Methods: The Phase III Research Evaluating Migraine Prophylaxis Therapy (PREEMPT) clinical program (PREEMPT 1 and 2) included a 24-week, double-blind phase (2 12-week cycles) followed by a 32-week, open-label phase (3 cycles). Thirty-one injections of 5U each (155 U of onabotulinumtoxinA or placebo) were administered to fixed sites. An additional 40 U could be administered “following the pain.” Prespecified analysis of headache impact (Headache Impact Test [HIT]–6) and HRQoL (Migraine-Specific Quality of Life Questionnaire v2.1 [MSQ]) assessments were performed. Because the studies were similar in design and did not notably differ in outcome, pooled results are presented here. Results: A total of 1,384 subjects were included in the pooled analyses (onabotulinumtoxinA, n = 688; placebo, n = 696). Baseline mean total HIT-6 and MSQ v2.1 scores were comparable between groups; 93.1% were severely impacted based on HIT-6 scores ≥60. At 24 weeks, in comparison with placebo, onabotulinumtoxinA treatment significantly reduced HIT-6 scores and the proportion of patients with HIT-6 scores in the severe range at all timepoints including week 24 (p < 0.001). OnabotulinumtoxinA treatment significantly improved all domains of the MSQ v2.1 at 24 weeks (p < 0.001). Conclusions: Treatment of CM with onabotulinumtoxinA is associated with significant and clinically meaningful reductions in headache impact and improvements in HRQoL. Classification of evidence: This study provides Class 1A evidence that onabotulinumtoxinA treatment reduces headache impact and improves HRQoL.

Peripheral Nerve Blocks and Trigger Point Injections in Headache Management – A Systematic Review and Suggestions for Future Research

(Headache 2010;50:943‐952)

CLINICAL AND PROGNOSTIC SUBFORMS OF NEW DAILY-PERSISTENT HEADACHE

Background: According to the International Classification of Headache Disorders (ICHD)–2, primary daily headaches unremitting from onset are classified as new daily-persistent headache (NDPH) only if migraine features are absent. When migraine features are present, classification is problematic. Methods: We developed a revised NDPH definition not excluding migraine features (NDPH-R), and applied it to consecutive patients seen at the Montefiore Headache Center. We divided this group into patients meeting ICHD-2 criteria (NDPH-ICHD) and those with too many migraine features for ICHD-2 (NDPH-mf). We compared clinical and demographic features in these groups, identifying 3 prognostic subgroups: persisting, remitting, and relapsing-remitting. Remitting and relapsing-remitting patients were combined into a nonpersisting group. Results: Of 71 NDPH-R patients, 31 (43.7%) also met NDPH-ICHD-2 criteria. The NDPH-mf and the NDPH-ICHD-2 groups were similar in most clinical features though the NDPH-mf group was younger, included more women, and had a higher frequency of depression. The groups were similar in the prevalence of allodynia, triptan responsiveness, and prognosis. NDPH-R prognostic subforms were also very similar, although the persisting subform was more likely to be of white race, to have anxiety or depression, and to have a younger onset age. Conclusions: Current International Classification of Headache Disorders (ICHD)–2 criteria exclude the majority of patients with primary headache unremitting from onset. The proposed criteria for revised new daily-persistent headache definition not excluding migraine features (NDPH-R) classify these patients into a relatively homogeneous group based on demographics, clinical features, and prognosis. Both new daily-persistent headache with too many migraine features for ICHD-2 and new daily-persistent headache meeting ICHD-2 criteria include patients in equal proportions that fall into the persisting, remitting, and relapsing-remitting subgroups. Our criteria for NDPH-R should be considered for inclusion in ICHD-3.

Reduction in perceived stress as a migraine trigger Testing the “let-down headache” hypothesis

Objective: To test whether level of perceived stress and reductions in levels of perceived stress (i.e., “let-down”) are associated with the onset of migraine attacks in persons with migraine. Methods: Patients with migraine from a tertiary headache center were invited to participate in a 3-month electronic diary study. Participants entered data daily regarding migraine attack experience, subjective stress ratings, and other data. Stress was assessed using 2 measures: the Perceived Stress Scale and the Self-Reported Stress Scale. Logit-normal, random-effects models were used to estimate the odds ratio for migraine occurrence as a function of level of stress over several time frames. Results: Of 22 enrolled participants, 17 (median age 43.8 years) completed >30 days of diaries, yielding 2,011 diary entries including 110 eligible migraine attacks (median 5 attacks per person). Level of stress was not generally associated with migraine occurrence. However, decline in stress from one evening diary to the next was associated with increased migraine onset over the subsequent 6, 12, and 18 hours, with odds ratios ranging from 1.5 to 1.9 (all p values < 0.05) for the Perceived Stress Scale. Decline in stress was associated with migraine onset after controlling for level of stress for all time points. Findings were similar using the Self-Reported Stress Scale. Conclusions: Reduction in stress from one day to the next is associated with migraine onset the next day. Decline in stress may be a marker for an impending migraine attack and may create opportunities for preemptive pharmacologic or behavioral interventions.

Retinal migraine reappraised

Retinal migraine is usually characterized by attacks of fully reversible monocular visual loss associated with migraine headache. Herein we summarize the clinical features and prognosis of 46 patients (six new cases and 40 from the literature) with retinal migraine based upon the International Classification of Headache Disorders-2 (ICHD-2) criteria. In our review, retinal migraine is most common in women in the second to third decade of life. Contrary to ICHD-2 criteria, most have a history of migraine with aura. In the typical attack monocular visual features consist of partial or complete visual loss lasting <1 h, ipsilateral to the headache. Nearly half of reported cases with recurrent transient monocular visual loss subsequently experienced permanent monocular visual loss. Although the ICHD-2 diagnostic criteria for retinal migraine require reversible visual loss, our findings suggest that irreversible visual loss is part of the retinal migraine spectrum, perhaps representing an ocular form of migrainous infarction. Based on this observation, the authors recommend migraine prophylactic treatment in an attempt to prevent permanent visual loss, even if attacks are infrequent. We also propose a revision to the ICHD-2 diagnostic criteria for retinal migraine.

Chronic migraine headache prevention with noninvasive vagus nerve stimulation The EVENT study

Objective: To evaluate the feasibility, safety, and tolerability of noninvasive vagus nerve stimulation (nVNS) for the prevention of chronic migraine (CM) attacks. Methods: In this first prospective, multicenter, double-blind, sham-controlled pilot study of nVNS in CM prophylaxis, adults with CM (≥15 headache d/mo) entered the baseline phase (1 month) and were subsequently randomized to nVNS or sham treatment (2 months) before receiving open-label nVNS treatment (6 months). The primary endpoints were safety and tolerability. Efficacy endpoints in the intent-to-treat population included change in the number of headache days per 28 days and acute medication use. Results: Fifty-nine participants (mean age, 39.2 years; mean headache frequency, 21.5 d/mo) were enrolled. During the randomized phase, tolerability was similar for nVNS (n = 30) and sham treatment (n = 29). Most adverse events were mild/moderate and transient. Mean changes in the number of headache days were −1.4 (nVNS) and −0.2 (sham) (Δ = 1.2; p = 0.56). Twenty-seven participants completed the open-label phase. For the 15 completers initially assigned to nVNS, the mean change from baseline in headache days after 8 months of treatment was −7.9 (95% confidence interval −11.9 to −3.8; p < 0.01). Conclusions: Therapy with nVNS was well-tolerated with no safety issues. Persistent prophylactic use may reduce the number of headache days in CM; larger sham-controlled studies are needed. ClinicalTrials.gov identifier: NCT01667250. Classification of evidence: This study provides Class II evidence that for patients with CM, nVNS is safe, is well-tolerated, and did not significantly change the number of headache days. This pilot study lacked the precision to exclude important safety issues or benefits of nVNS.

Diagnosis and management of the primary headache disorders in the emergency department setting

Headache continues to be a frequent cause of emergency department (ED) use, accounting for 2% of all visits. Most of these headaches prove to be benign but painful exacerbations of chronic headache disorders, such as migraine, tension-type, and cluster. The goal of ED management is to provide rapid and quick relief of benign headache, without causing undue side effects, and to recognize headaches with malignant course. Although these headaches have distinct epidemiologies and clinical phenotypes, there is overlapping response to therapy; nonsteroidals, triptans, dihydroergotamine, and the antiemetic dopamine antagonists may play a therapeutic role for each of these acute headaches. This article reviews the diagnostic criteria and management strategies for the primary headache disorders.

Temporomandibular disorders and cutaneous allodynia are associated in individuals with migraine

The objective of this study was to estimate and contrast the occurrence of ictal and interictal cutaneous allodynia (CA) in individuals with migraine with and without temporomandibular disorders (TMD). Both TMD and CA are common in migraine and may be associated with migraine transformation from episodic into a chronic form. Herein we hypothesize that TMD contributes to the development of CA and to more severe headaches. In a clinic-based sample of individuals with episodic migraine, the presence of TMD was assessed using the research diagnostic criteria for myofascial or mixed (myofascial and arthralgic) TMD. Ictal CA was quantified using the validated Allodynia Symptom Checklist (ASC-12). The ASC-12 measures CA over the preceding month by asking 12 questions about the frequency of allodynia symptoms during headaches. Interictal CA was assessed in the domains of heat, cold and mechanical static allodynia using quantitative sensory testing. Our sample consists of 55 individuals; 40 (73%) had TMD (23 with myofascial TMD and 17 with the mixed type). CA of any severity (as assessed by ASC-12) occurred in 40% of those without TMD (reference group), 86.9% of those with myofascial TMD (P = 0.041, RR = 3.2, 95% CI = 1.5–7.0) and in 82.3% of those with mixed TMD (P = 0.02, RR = 2.5, 95% CI = 1.2–5.3). Individuals with TMD were more likely to have moderate or severe CA associated with their headaches. Interictally (quantitative sensory testing), thresholds for heat and mechanical nociception were significantly lower in individuals with TMD. Cold nociceptive thresholds were not significantly different in migraine patients with and without TMD. TMDs were also associated with change in extra-cephalic pain thresholds. In logistical regression, TMD remained associated with CA after adjusting for aura, gender and age. TMD and CA are associated in individuals with migraine.

Patterns of Use of Peripheral Nerve Blocks and Trigger Point Injections Among Headache Practitioners in the USA: Results of the American Headache Society Interventional Procedure Survey (AHS‐IPS)

(Headache 2010;50:937‐942)