Cristiana Rossi

Proinflammatory cytokines, adhesion molecules, and lymphocyte integrin expression in the internal jugular blood of migraine patients without aura assessed ictally.

Objective.—The aim of the present research was to verify the levels of the soluble adhesion molecules sL‐ and sE‐selectins, intercellular adhesion molecule (sICAM)‐1, and vascular cell adhesion molecule‐1 in serial samples of internal jugular venous blood taken from migraine patients without aura (MWoA) during attacks. The expression of leukocyte function antigen (LFA)‐1 and very late activation antigen (VLA)‐4 was also assessed on lymphocytes obtained from jugular venous blood. Levels of certain proinflammatory cytokines (tumor necrosis factor‐α[TNF‐α], interleukin‐1β[IL‐1β], IL‐4, and IL‐6) were also determined and correlated with those of adhesion molecules.

Endocannabinoids in Chronic Migraine: CSF Findings Suggest a System Failure

Based on experimental evidence of the antinociceptive action of endocannabinoids and their role in the modulation of trigeminovascular system activation, we hypothesized that the endocannabinoid system may be dysfunctional in chronic migraine (CM). We examined whether the concentrations of N-arachidonoylethanolamide (anandamide, AEA), palmitoylethanolamide (PEA), and 2-arachidonoylglycerol (2-AG) in the CSF of patients with CM and with probable CM and probable analgesic-overuse headache (PCM+PAOH) are altered compared with control subjects. The above endocannabinoids were measured by high-performance liquid chromatography (HPLC), and quantified by isotope dilution gas-chromatography/mass-spectrometry. Calcitonin gene-related peptide (CGRP) levels were also determined by RIA method and the end products of nitric oxide (NO), the nitrites, by HPLC. CSF concentrations of AEA were significantly lower and those of PEA slightly but significantly higher both in patients with CM and PCM+PAOH than in nonmigraineur controls (p<0.01 and p<0.02, respectively). A negative correlation was found between AEA and CGRP levels in CM and PCM+PAOH patients (r=0.59, p<0.01 and r=−0.65, p<0.007; respectively). A similar trend was observed between this endocannabinoid and nitrite levels. Reduced levels of AEA in the CSF of CM and PCM+PAOH patients may reflect an impairment of the endocannabinoid system in these patients, which may contribute to chronic head pain and seem to be related to increased CGRP and NO production. These findings support the potential role of the cannabinoid (CB)1 receptor as a possible therapeutic target in CM.

Involvement of corticotrophin-releasing factor and orexin-A in chronic migraine and medication-overuse headache: findings from cerebrospinal fluid.

The study set out to investigate the role of corticotrophin-releasing factor (CRF) and orexin-A in chronic migraine (CM) and medication-overuse headache (MOH). Twenty-seven patients affected by CM and 30 with MOH were enrolled. Control CSF specimens were obtained from 20 age-matched subjects who underwent lumbar puncture for diagnostic purposes, and in all of them CSF and blood tests excluded central nervous system or systemic diseases. Orexin-A and CRF were determined by radioimmunoassay methods. Significantly higher levels of orexin-A and CRF were found in the CSF of MOH and to a lesser extent in patients with CM compared with control subjects (orexin-A: P < 0.001 and P < 0.02; CRF: P < 0.002 and P < 0.0003). A significant positive correlation was also found between CSF orexin-A values and those of CRF (R = 0.71; P < 0.0008), monthly drug intake group (R = 0.39; P < 0.03) and scores of a self-completion 10-item instrument to measure dependence upon a variety of substances, the Leeds Dependence Questionnaire (LDQ) in the MOH group (R = 0.68; P < 0.0003). The significantly higher orexin-A levels found in CM and MOH can be interpreted as a compensatory response to chronic head pain or, alternatively, as an expression of hypothalamic response to stress due to chronic pain. A potential role for orexin-A in driving drug seeking in MOH patients through activation of stress pathways in the brain can also be hypothesized.

Endocannabinoids in platelets of chronic migraine patients and medication-overuse headache patients: relation with serotonin levels.

BackgroundChronic migraine (CM) and medication-overuse headaches (MOH) are well-recognized disabling conditions affecting a significant portion of the headache population attending centers specialized in treating headaches. A dysfunctioning of the serotonergic system has been demonstrated in MOH and CM patients. Here we report on our assessment of the dysfunctioning of the endocannabinoid system as a potential underlying factor in pathogenic mechanisms involved in CM and MOH.MethodTo test the hypothesis of an impairment in the endocannabinoid system in patients with MOH and CM and to assess its relationship with any disruption of the serotonergic system, we determined the levels of the two main endogenous cannabinoids, anandamide (AEA) and 2-acylglycerol (2-AG), in platelets of 20 CM patients, 20 MOH patients and 20 control subjects and also measured the platelet serotonin levels in the same patients.ResultsWe found that 2-AG and AEA levels were significantly lower in MOH patients and CM patients than in the control subjects, without significant differences between the two patient groups. Serotonin levels were also strongly reduced in the two patient groups and were correlated with 2-AG levels, with higher values for MOH patients.ConclusionThese data support the potential involvement of a dysfunctioning of the endocannabinoid and serotonergic systems in the pathology of CM and MOH. These systems appear to be mutually related and able to contribute to the chronification of both CM and MOH.

NF‐κB activity and iNOS expression in monocytes from internal jugular blood of migraine without aura patients during attacks

This study investigated nuclear factor-kappa B (NF-κB) activity by electrophoresis mobility gel shift assay and IκBα expression by Western blot analysis in monocytes obtained from serial samples of internal jugular venous blood taken from seven migraine patients without aura during attacks. Inducible nitric oxide synthase (iNOS) expression was also assessed by reverse transcription-polymerase chain reaction. An increase in NF-κB activity peaked 2 h after attack onset. This was accompanied by a transient reduction in IκBα expression. Up-regulation of iNOS was evident at 4 h, maintained at 6 h and reduced at the end of the attack. These findings substantiate the hypothesis of transitory delayed inflammation, as suggested by the animal model, and suggest the possibility of using therapeutic approaches to target NF-κB transcription in the treatment of migraine.

Clinical-biochemical correlates of migraine attacks in rizatriptan responders and non-responders.

The present study was aimed at verifying the clinical characteristics of a typical attack in 20 migraine patients, 10 responders and 10 non-responders to rizatriptan, and at investigating any differences in the levels of neuropeptides of the trigeminovascular or parasympathetic systems [calcitonin gene-related peptide (CGRP), neurokinin A (NKA) and vasoactive intestinal peptide (VIP) measured by radio-immunoassay methods in external jugular blood] between responders and nonresponders. In all responders to rizatriptan, pain was unilateral, severe, and pulsating, and in five of them at least one sign suggestive of parasympathetic system activation was recorded. Five patients who were non-responders to rizatriptan referred bilateral and non-pulsating pain, even though severe in most of them. CGRP and NKA levels measured before rizatriptan administration were significantly higher in responders than in non-responders (P < 0.0001 and P < 0.002, respectively). In the five patients with autonomic signs among rizatriptan responders, detectable VIP levels were found at baseline. One hour after rizatriptan administration, a decrease in CGRP and NKA levels was evident in the external jugular venous blood of rizatriptan responders, and this corresponded to a significant pain relief and alleviation of accompanying symptoms. VIP levels were also significantly reduced at the same time in the five patients with autonomic signs. After rizatriptan administration, CGRP and NKA levels in non-responder patients showed less significant variations at all time points after rizatriptan administration compared with rizatriptan responders. The present study, although carried out on a limited number of patients, supports recent clinical evidence of increased trigeminal activation associated with a better triptan response in migraine patients accompanied by parasympathetic activation in a subgroup of patients with autonomic signs. In contrast, the poor response seems to be correlated with a lesser degree of trigeminal activation, lower variations of trigeminal neuropeptides after triptan administration, and no evidence of parasympathetic activation at baseline.

Language disturbances as a side effect of prophylactic treatment of migraine.

Background.— Language disturbances have been previously described as word‐finding difficulties in epileptic patients. These disturbances have been recently reported in migraineurs in treatment with topiramate but they have never been defined and assessed in these patients with the aid of neuropsychological testing.

An open-label pilot study on the efficacy and tolerability of levetiracetam in the prophylaxis of migraine

AbstractA preliminary, open label study was conducted on 20 patients with migraine without aura and with high headache frequency to assess the efficacy and tolerability of the new antiepileptic drug levetiracetam. Patients were treated with levetiracetam for three months. The drug was started at a dose of 500 mg and slowly increased within 10 days to the target dose of 2000 mg/day. After 3 months of treatment, 11 (57.9%) of 19 patients who completed the study had a reduction of at least 50% in headache frequency. The intensity of migraine attacks was significantly reduced as was the use of symptomatic drugs. A 3-month carry-over effect was found in about two-thirds of the 11 patients reporting a positive treatment response. Levetiracetam was well tolerated and no patient discontinued the drug due to side effects. This preliminary study supports the potential role of levetiracetam as a new preventive treatment for migraine without aura. The promising results obtained should be confirmed by further research with a double-blind controlled design.

Application of the ICHD-II criteria to the diagnosis of primary chronic headaches via a computerized structured record.

Background.—The authors recently developed a software program designed to analyze clinical data from patients affected by primary headache. The program is based exclusively on the International Classification of Headache Disorders 2nd edition (ICHD‐II) criteria. This software examines all the diagnoses of primary headaches on the basis of the variables needed to fulfill these mandatory criteria.

Application of the 1988 International Headache Society diagnostic criteria in nine Italian headache centers using a computerized structured record.

Background.—The actual application of the current International Headache Society (IHS) diagnostic criteria in clinical practice has not been investigated thoroughly.