César Ramón

Interictal increase of CGRP levels in peripheral blood as a biomarker for chronic migraine

Objective: To determine calcitonin gene-related peptide (CGRP) levels outside migraine attacks in peripheral blood as a potential biomarker for chronic migraine (CM). Methods: Women older than 17 years and diagnosed with CM were recruited. Matched healthy women with no headache history and women with episodic migraine (EM) served as control groups, together with a series of patients with episodic cluster headache in a pain-free period. CGRP 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. For ethical reasons, preventatives were not stopped. Results: We assessed plasma samples from 103 women with CM, 31 matched healthy women, 43 matched women with EM, and 14 patients with episodic cluster headache matched for age. CGRP levels were significantly increased in CM (74.90 pg/mL) as compared with control healthy women (33.74 pg/mL), women with EM (46.37 pg/mL), and patients with episodic cluster headache (45.87 pg/mL). Thresholds of 43.45 and 58.22 pg/mL optimize the sensitivity and specificity to differentiate CM from healthy controls and EM, respectively. In the CM group, CGRP levels were significantly increased in women with a history of migraine with aura vs those only experiencing migraine without aura. Variables such as age, analgesic overuse, depression, fibromyalgia, vascular risk factors, history of triptan consumption, or kind of preventative treatment did not significantly influence CGRP levels. Conclusion: Increased CGRP level measured in peripheral blood outside migraine attacks and in the absence of symptomatic medication could be a biomarker helping in the diagnosis of CM.

CGRP and VIP Levels as Predictors of Efficacy of Onabotulinumtoxin Type A in Chronic Migraine

Onabotulinumtoxin type A (onabotA) has shown efficacy in chronic migraine (CM). Its precise mechanism of action, however, is unknown.

OnabotulinumtoxinA decreases interictal CGRP plasma levels in patients with chronic migraine.

Abstract OnabotulinumtoxinA (onabotA) has shown efficacy in chronic migraine (CM). Its mechanism of action, however, remains obscure. We have analysed whether treatment with onabotA is able to induce changes in interictal plasma calcitonin gene-related peptide (CGRP) concentrations, which have been shown to be increased in patients with CM. Calcitonin gene-related peptide levels were determined in samples obtained from the right antecubital vein using ELISA, outside a migraine attack and having taken no symptomatic medication in the previous 24 hours, in 83 patients with CM (average age 44 years; 94% females) before and 1 month after treatment with 155 to 195 U of onabotA. CGRP levels after onabotA treatment (median, 51.89 pg/mL; range, 199.4-10.2) were significantly lower as compared with CGRP levels obtained before onabotA treatment (median, 74.09 pg/mL; range, 241.0-11.4; P = 0.001). Pretreatment CGRP levels in responders (76.85 pg/mL) were significantly higher than those seen in nonresponders (50.45 pg/mL; P = 0.001). One month after treatment, the CGRP levels did not change in nonresponders (51.89 pg/mL; P not significant), but significantly decreased in responders (52.48 pg/mL; P = 0.003). A number of demographic factors, clinical features, and comorbidities were not different in responders as compared with those of nonresponders. These results confirm that interictal CGRP levels can be of help in predicting the response to onabotA and suggest that the mechanism of action of onabotA in CM is the reversal of sensitization as a result of the inhibition of CGRP release.

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.

Increased VIP levels in peripheral blood outside migraine attacks as a potential biomarker of cranial parasympathetic activation in chronic migraine.

Aim The aim of this article is to determine vasoactive intestinal peptide (VIP) levels outside migraine attacks in peripheral blood as a potential biomarker for chronic migraine (CM). Methods Women older than 17 and diagnosed as CM were recruited. Matched healthy women with no headache history and women with episodic migraine (EM) served as control groups, together with a series of patients with episodic cluster headache in a pain-free period. VIP levels were determined in blood samples obtained from the right antecubital vein by ELISA outside a migraine attack, the patients having taken no symptomatic medication the day before. For ethical reasons, preventives were not stopped. Results We assessed plasma samples from 119 women with CM, 33 healthy women, 51 matched women with EM and 18 patients (16 males) with cluster headache matched for age. VIP levels were significantly increased in CM (165.1 pg/ml) as compared to control healthy women (88.5 pg/ml) and episodic cluster headache patients (101.1 pg/ml). VIP levels in EM (134.9 pg/ml) were significantly higher compared to controls and numerically lower than those of CM. Thresholds of 71.8 and 164.5 pg/ml optimized the sensitivity and specificity to differentiate CM from healthy controls and EM, respectively. Variables such as age, CM duration, the presence of aura, analgesic overuse, depression, fibromyalgia, vascular risk factors, history of triptan consumption or kind of preventive treatment did not significantly influence VIP levels. Conclusion Increased interictal VIP level measured in peripheral blood could be a biomarker helping in CM diagnosis, though it does not clearly differentiate between EM and CM.

What Differences Exist in the Appropriate Treatment of Congenital Versus Acquired Adult Chiari Type I Malformation

Chiari type I malformation is found in 1 out of 20 magnetic resonance imaging (MRI) studies. Isolated tonsillar herniation is of limited utility and should be considered within the clinical context because these patients can be asymptomatic. Cine MRI showing compression of the cerebrospinal fluid (CSF) spaces in the foramen magnum area is a crucial technique for making treatment decisions. Congenital malformation is thought to be due to a volumetric small posterior fossa. The most common symptom in these patients is cough headache. Posterior fossa reconstruction is mandatory in patients with progressive symptoms/signs, hydrocephalus, or syringomyelia, but not in patients who are asymptomatic or those with stable and tolerable symptoms. Acquired tonsillar descent can be secondary to a variety of disorders conditioning disproportion between the volume of the cranial cavity and that of the intracranial contents, or to CSF hypovolemia, which is the most common cause for acquired herniation. CSF hypovolemia can be spontaneous or secondary to CSF removal. Treatment of acquired tonsillar herniation depends on the responsible etiology.

Clues in the Differential Diagnosis of Primary vs Secondary Cough, Exercise, and Sexual Headaches

Activity‐related headaches can be provoked by Valsalva maneuvers (“cough headache”), prolonged exercise (“exertional headache”) and sexual excitation (“sexual headache”). These entities are a challenging diagnostic problem as can be primary or secondary and the etiologies for secondary cases differ depending on the headache type. In this paper we review the clinical clues which help us in the differential diagnosis of patients consulting due to activity‐related headaches. Cough headache is the most common in terms of consultation. Primary cough headache should be suspected in patients older than 50 years, if pain does not predominate in the occipital area, if pain lasts seconds, when there are no other symptoms/signs and if indomethacin relieves the headache attacks. Almost half of cough headaches are secondary, usually to a Chiari type I malformation. Secondary cough headache should be suspected in young people, when pain is occipital and lasts longer than one minute, and especially if there are other symptoms/signs and if there is no response to indomethacin. Every patient with cough headache needs cranio‐cervical MRI. Primary exercise/sexual headaches are more common than secondary, which should be suspected in women especially with one episode, when there are other symptoms/signs, in people older than 40 and if the headache lasts longer than 24 hours. These patients must have quickly a CT and then brain MRI with MRA or an angioCT to exclude space‐occupying lesions or subarachnoid hemorrhage.

No Relationship Between Patent Foramen Ovale and Migraine Frequency.

Pathophysiology of migraine is not fully known. A link has been proposed between migraine and patent foramen ovale (PFO). However, there are conflicting data regarding the causal relationship between PFO and migraine.

Calcitonin gene-related peptide in peripheral blood as a biomarker for migraine

Purpose of review There is no available biomarker for any of the primary headaches, including migraine. As demonstrated in jugular blood, during a migraine attack, trigeminal activation releases several neuropeptides, very especially calcitonin gene-related peptide (CGRP), which gives rise to the typical throbbing migraine pain. Here, we review the current evidence for measurement of peripheral CGRP levels as a potential biomarker for trigemino-vascular activation in migraine. Recent findings Several studies, including a limited number of migraine patients, have shown increased peripheral CGRP levels during migraine attacks. The maximum increase in plasma CGRP levels was reached within 2 h of the onset of the attacks and can be reverted by triptans. In addition, CGRP levels measured in peripheral blood outside migraine attacks and in the absence of symptomatic medication have been shown to be increased in chronic migraine patients. Increased CGRP levels were able to predict the response to onabotulinumtoxinA treatment and were reduced 1 month after onabotulinumtypeA therapy. Summary Although CGRP data must be confirmed and expanded in future studies and specificity of CGRP levels should be studied in entities able to resemble migraine, it seems that peripheral CGRP levels are a good biomarker of acute migraine and somewhat specific and sensitive interictally in chronic migraine.

Teaching NeuroImages: Carotid body tumor as a novel cause of cerebral ischemic stroke

An 83-year-old man presented with drowsiness, dysarthria, anosognosia, forced right gaze deviation and left hemianopia, hemiplegia, and hemianesthesia consistent with a right hemispheric stroke. A painless, nonpulsatile, right cervical mass was noted. CT angiography demonstrated a right carotid body