Long-term effectiveness and tolerability of galcanezumab in patients with migraine excluded from clinical trials: real world evidence of 1055 patients with 1 year follow-up from the Galca-Only registry.

BACKGROUND: Galcanezumab has shown efficacy and effectiveness in the treatment of episodic and chronic migraine (CM), however, the population represented in randomized clinical trials (RCTs) differs from the population observed in real-world setting. To describe the long-term effectiveness and tolerability of galcanezumab in clinical practice in patients excluded from RCTs. METHODS: Multicenter prospective cohort study of consecutive patients with chronic and high-frequency episodic migraine (HFEM) with prior failure to three or more migraine preventive drugs, treated with galcanezumab and followed up for 12 months. RESULTS: We enrolled 1055 patients, aged 50 (IQR: 42-58), 82.9% female, 76.4% chronic migraine, 69% with at least one exclusion criteria for RCTs, including age > 65 (n = 121), concomitant use of onabotulinumtoxinA (n = 185), daily headache at baseline (n = 347), chronic painful syndromes (n = 206), fibromyalgia (n = 101) or treatment resistance (n = 957). The median number of prior preventive treatments was 4 (IQR: 3-5). The retention rate was 90.8%, 76.8% and 71.4% at 3, 6 and 12 months. The main reasons for treatment discontinuation were lack of effectiveness (21.1%) and inadequate tolerability (6.6%). The 30%, 50% and 75% responder rates were 62.6%, 49.8% and 24.2% between weeks 8-12; 60.9%, 48.8% and 24.6% between weeks 20-24; and 59.7%, 48.3% and 24.6% between weeks 44-48. Daily headache at baseline (OR: 0.619; 95%CI: 0.469-0.817) and patient's age (OR: 1.016; 95%CI: 1.005-1.026) were associated with 50% response at weeks 20-24. The variables that were associated with a higher reduction of headache days between weeks 20-24 were patient's age (0.068; 95% CI: 0.018-0.119) and headache days per month at baseline (0.451; 95% CI: 0.319-0.583), while psychiatric comorbidity (-1.587; 95% CI: -2.626-0.538) and daily headache at baseline (-2.718; 95% CI: -4.58-0.869) were associated with fewer reduction in the number of headache days between weeks 20-24. CONCLUSION: This study provides class III evidence of effectiveness and tolerability of galcanezumab in patients with HFEM and CM with comorbidities that would result in exclusion of the pivotal RCTs. Nonetheless, the clinical results over a 12-month period were similar to the efficacy observed in randomized controlled trials. Few patients discontinued the drug due to inadequate tolerability.

Peripheral, Interictal Serum S100B Levels are Not Increased in Chronic Migraine Patients.

BACKGROUND: The trigemino-vascular system (TVS) plays a key role in migraine pathophysiology. Glial cells are abundant in the TVS system and mainly in the trigeminal ganglion. S100B protein is a calcium-binding protein, found in the cytoplasm of glial cells in the central nervous system, which is released in response to inflammatory stimuli. Previous works analyzing S100B in migraineurs have offered contradictory results. OBJECTIVE: In this case-control study, we analyzed serum levels of S100B as a possible biomarker of the glial TVS activation in chronic migraine (CM). PATIENTS AND METHODS: The study group consisted of patients attending our clinic with CM and, as control groups, patients with episodic migraine (EM), cluster headache (CH) outside of a bout and healthy volunteers (HV) with no headache history. S100B levels were determined interictally in peripheral blood samples by ELISA. RESULTS: We assessed serum samples from 43 patients with CM, 19 with EM, 29 HV (mostly women), and 22 with (CH). S100B levels in CM (mean 22.9 ± 9.8 pg/mL) were not different (P = .727) when compared to EM patients (21.2 ± 9.3 pg/mL), difference of 1.7 (95% CI -5.7 to 8.9), CH patients (22.4 ± 7.8 pg/mL), difference of 0.5 (-5.7 to 6.7), and HV (20.6 ± 8.3 pg/mL), difference of 2.3 (-3.7 to 8.3). CONCLUSION: In contrast to other neuropeptides such as calcitonin gene-related-peptide and vasoactive intestinal peptide, which are increased in CM, interictal serum S100B levels are not elevated in these patients. According to our results, S100B levels do not seem to be a useful peripheral biomarker of the glial TVS activation in CM.

Dual energy CT in the management of antiplatelet therapy in patients with acute ischemic stroke for carotid obstruction.

BACKGROUND AND PURPOSE: Acute tandem occlusions often require carotid stenting. Combination of mechanical and pharmacologic therapies in addition to antiplatelet drugs administered to prevent acute stent thrombosis might increase the risk of intracerebral hemorrhage. We present a protocol of antiplatelet regimen based on early post-procedural dual-energy CT (DE-CT). MATERIAL AND METHODS: Fifty consecutive stroke patients with tandem occlusions treated with acute carotid stenting after intracranial thrombectomy and TICI 2b/3 were reviewed. All patients received intravenous lysine acetylsalicylate during the procedure. Dual (aspirin+clopidogrel with or without clopidogrel load, groups A and B, respectively) or mono (aspirin) antiplatelet regimen (group C) was administered 12-24 h later according to brain DE-CT findings. Carotid ultrasonography was performed at 24 h and before discharge. We evaluated the rate of subsequent symptomatic intracranial hemorrhage (SICH) and acute stent thrombosis in each group. RESULTS: Between June 2014 and December 2016, 50 patients were included (mean age 66 years, 76% men, baseline NIHSS 16, median time from symptom onset to recanalization 266 min). According to DE-CT, 24 patients were assigned to group A, 19 to group B and 7 to group C (4 of them had SICH at that time). One patient suffered a subsequent SICH (belonging to group B). There was only one stent thrombosis without clinical repercussions in group B. CONCLUSIONS: DE-CT may contribute to select antiplatelet regimen after acute carotid stenting in tandem occlusions.

Neuropeptides as a Marker for Chronic Headache.

PURPOSE OF REVIEW: The purpose of this review is to revise current evidence on trigemino-vascular system (TVS) neuropeptides as potential biomarkers for chronic primary headaches, mainly for chronic migraine (CM). RECENT FINDINGS: Within sensory neuropeptides, released by an activated trigeminal nerve, calcitonin gene-related peptide (CGRP) levels seem to be a good biomarker of acute migraine and somewhat sensitive and specific for CM. CGRP, however, is not increased in 20-30% of CM patients, which suggests that CGRP is not the only neuropeptide involved in migraine pain generation and maintenance. Data for other sensory neuropeptides are inconsistent (neurokinin, substance P) or absent (amylin and cholecystokinin-8). Among parasympathetic neuropeptides, vasoactive intestinal polypeptide (VIP) is increased interictally in CM, and in at least some migraine cases ictally, pituitary adenylate cyclase-activating peptide (PACAP) has been shown to be increased ictally in jugular blood, but interictal, peripheral data do not indicate such an increase, and there are no data for other parasympathetic peptides. Finally, S100B, as a potential marker of glial TVS activation, has been studied with inconsistent results in migraine patients. Current data on TVS neuropeptides as potential migraine biomarkers must be taken with caution, even for the promising case of CGRP. We do not know with certainty whether increased levels are the reflection of TVS activation, the reliability and homogeneity of the different laboratory tests, or what is the influence on these measurements of the short half-life of many of these peptides or of preventive treatments. One further limitation would be whether the described increases in levels of some neuropeptides such as CGRP are specific for migraine versus other headaches.

No Change in Interictal PACAP Levels in Peripheral Blood in Women With Chronic Migraine.

OBJECTIVE: To determine total pituitary adenylate cyclase activating polypeptide (PACAP) in peripheral blood as a potential marker of the activation of the parasympathetic arm of the trigemino-vascular system in chronic migraine (CM) in a case-control study. METHODS: Women older than 17 and diagnosed as CM were recruited. Healthy women with no headache history and women with episodic migraine (EM) served as control groups. Total PACAP and vasoactive intestinal peptide (VIP) levels were determined in blood samples obtained from the right antecubital vein by ELISA outside a migraine attack and having taken no symptomatic medication the day before. RESULTS: We assessed serum samples from 86 women with CM, 32 healthy women, and 35 women with EM. There were no differences in PACAP levels in CM patients (109.8 ± 43.8, 97.4 [32.5-253.1] pg/mL), controls (108.7 ± 43.0, 98.7 [50.7-197.3] pg/mL), or EM patients (98.8 ± 34.3, 94.2 [52.0-190.7] pg/mL). VIP levels were significantly increased (P = .027) in CM as compared to control healthy women (136.0 ± 111.5 pg/mL; 103.1 [20.5-534.0] pg/mL vs 88.6 ± 61.0 pg/mL; 66.0 [21.1-256.1]) and EM patients (103.0 ± 56.7 pg/mL; 103.5 [15.2-263.0] pg/mL). In the range of this study variables such as age, CM duration, the presence of aura, analgesic overuse, depression, fibromyalgia, vascular risk factors, history of triptan consumption or kind of preventative treatment did not significantly influence PACAP or VIP levels. CONCLUSION: In contrast to VIP, interictal PACAP level measured in peripheral blood does not seem to be a biomarker reflecting parasympathetic activation in CM.

Prevalence of cranial autonomic parasympathetic symptoms in chronic migraine: Usefulness of a new scale.

BACKGROUND: Cranial autonomic symptoms (CAS) seem to appear in around half of migraine patients. OBJECTIVE: Our aim was to analyse the prevalence and profile of CAS, mainly of cranial autonomic parasympathetic symptoms (CAPS), in a series of patients with chronic migraine (CM) according the new criteria for autonomic symptoms in the current IHS classification. PATIENTS AND METHODS: We recruited consecutive CM patients attending our headache clinic. Five CPAS were surveyed: lacrimation, conjunctival injection, eyelid oedema, ear fullness and nasal congestion. They were graded as 0 (absent), 1 (present and mild) and 2 (present and conspicuous); therefore the score in this CAPS scale ranges from 0 to 10 points. As a cranial autonomic sympathetic symptom (CSAS), we also asked about the presence of ptosis. RESULTS: We interviewed 100 CM patients. Their mean age was 45 years (18-63 years); 93 were females. Eighteen had no CAPS, while 82 reported at least one CAPS. There were only six patients with scores higher than 5, the mean and median CAPS being 2.1 and 2, respectively. Prevalence of CAPS was lacrimation (49%), conjunctival injection (44%), eyelid oedema (39%), ear fullness (30%) and nasal congestion (20%). Ptosis was reported by 42. CONCLUSION: These results, by using for the first time an easy quantitative scale, confirm that (mild) CAPS are not the exception but the rule in CM patients. The score in this CAPS scale could be of help as a further endpoint in clinical trials or to be correlated with potential biomarkers of parasympathetic activation in primary headaches.

Acute cervical artery dissection after a dental procedure due to a second inferior molar infection.

Periodontal infections might represent one of the causative factors for cervical artery dissection. We present a case of a 49-year-old woman admitted due to headache. The patient had been suffering from a right second inferior molar infection with a cervical phlegmon for 1 week prior to admission. On 2 October 2014, the patient went to the dentist and a molar extraction was performed in the morning. In the afternoon, the patient began to experience right hemifacial pain that progressed towards an intense and bilateral headache. Neurological status at the time of admission revealed right miosis, ptosis and conjuntival hyperaemia. A CT angiography showed a right internal carotid artery dissection provoking a high-degree stenosis. The relationship between periodontal infection and vascular disease has been previously presented. Microbial agents may directly, and inflammatory and immunological host response indirectly, influence inflammatory changes in cervical arteries favouring dissections with minor traumas.

Long-term experience with onabotulinumtoxinA in the treatment of chronic migraine: What happens after one year?

BACKGROUND: OnabotulinumtoxinA (onabotA) has shown its efficacy over placebo in chronic migraine (CM), but clinical trials lasted only up to one year. OBJECTIVE: The objective of this article is to analyse our experience with onabotA treatment of CM, paying special attention to what happens after one year. PATIENTS AND METHODS: We reviewed the charts of patients with CM on onabotA. Patients were injected quarterly during the first year but the fifth appointment was delayed to the fourth month to explore the need for further injections. RESULTS: We treated 132 CM patients (mean age 47 years; 119 women). A total of 108 (81.8%) showed response during the first year. Adverse events, always transient and mild-moderate, were seen in 19 (14.4%) patients during the first year; two showed frontotemporal muscle atrophy after being treated for more than five years. The mean number of treatments was 7.7 (limits 2-29). Among those 108 patients with treatment longer than one year, 49 (45.4%) worsened prior to the next treatment, which obliged us to return to quarterly injections and injections were stopped in 14: in 10 (9.3%) due to a lack of response and in four due to the disappearance of attacks. In responders, after an average of two years of treatment, consumption of any acute medication was reduced by 53% (62.5% in triptan overusers) and emergency visits decreased 61%. CONCLUSIONS: Our results confirm the long-term response to onabotA in three-quarters of CM patients. After one year, lack of response occurs in about one out of 10 patients and injections can be delayed, but not stopped, to four months in around 40% of patients. Except for local muscle atrophy in two cases treated more than five years, adverse events are comparable to those already described in short-term clinical trials.