A Baldi

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.

Risk of recurrent cerebrovascular events in patients with cryptogenic stroke or transient ischemic attack and patent foramen ovale: The FORI (Foramen Ovale Registro Italiano) study

Background: The optimal management of patients with cryptogenic ischemic stroke found to have a patent foramen ovale (PFO) at diagnostic workup remains unclear. The aims of this observational multicenter study were to evaluate: (1) the risk of recurrent cerebrovascular events in patients with cryptogenic minor ischemic stroke or transient ischemic attack (TIA) and PFO who either underwent percutaneous PFO closure or received only medical treatment, and (2) the risk factors associated with recurrent events. Methods: Consecutive patients (aged 55 years or less) with first-ever cryptogenic minor ischemic stroke or TIA and PFO were recruited in 13 Italian hospitals between January 2006 and September 2007 and followed up for 2 years. Results: 238 patients were included in the study (mean age 42.2 ± 10.0 years; 118 males); 117 patients (49.2%) received only antithrombotic therapy while 121 patients underwent percutaneous PFO closure (50.8%). Stroke as the qualifying event was more common in the medical treatment group (p = 0.01). The presence of atrial septal aneurysm and evidence of 20 bubbles or more on transcranial Doppler were more common in the PFO closure group (p = 0.002 and 0.02). Eight patients (6.6%) experienced a nonfatal complication during PFO closure. At the 2-year follow-up, 17 recurrent events (TIA or stroke; 3.6% per year) were observed; 7 of these events (2.9% per year) occurred in the percutaneous PFO closure group and 10 events (4.2% per year) in the medical treatment group. The rate of recurrent stroke was 0.4% per year in patients who underwent percutaneous closure (1 event) and 3.4% per year in patients who received medical treatment (8 events). On multivariate analysis, percutaneous closure was not protective in preventing recurrent TIA or stroke (OR = 0.1, 95% CI = 0.02–1.5, p = 0.1), while it was barely protective in preventing recurrent stroke (OR = 0.1, 95% CI = 0.0–1.0, p = 0.053). Conclusions: The results of this observational, nonrandomized study suggest that PFO closure might be superior to medical therapy for the prevention of recurrent stroke. Periprocedural complications were the trade-off for this clinical benefit. Controlled randomized clinical trials comparing percutaneous closure with medical management are required.

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.

Brain-derived neurotrophic factor in cerebrospinal fluid of patients with chronic daily headache: relationship with nerve growth factor and glutamate levels

Abstract Little has been done to investigate the biochemical basis of chronic daily headache (CDH). Our group has recently demonstrated an increase in the cerebrospinal fluid (CSF) levels of nerve growth factor (NGF) in CDH patients, supporting the involvement of this growth factor in the abnormal processing of head pain in this pathological condition. Other members of the neurotrophin family, especially brain-derived neurotrophic factor (BDNF), have been hypothesized as being involved in the development of chronic head pain in patients affected by CDH, but so far no data are available on this subject. BDNF, NGF and glutamate levels were determined in the CSF of 25 patients affected by CDH with a previous history of migraine. These levels were compared with those of a group of 20 control subjects, for whom the CSF examination and other instrumental investigations excluded diseases of the central and peripheral nervous systems. Significantly higher levels of BDNF, NGF and glutamate were found in CDH patients compared with control subjects (p<0.0001, p<0.0002 and p<0.001, respectively). A significant positive correlation emerged between CSF values of BDNF and those of NGF (r=0.61, p<0.001) and glutamate (r=0.44, p<0.025) in CDH patients. No significant differences were detected in BDNF, NGF and glutamate levels between CDH patients with analgesic overuse and those without. These results support the involvement of BDNF in CDH through the potentiation of glutamatergic transmission involved in the processing of head pain. The significant correlation between BDNF and NGF levels suggests that NGF-mediated up-regulation of BDNF in central sites involved in long-term sensitization plays a key role in persistent head pain in CDH patients.

Cluster headache in childhood and adolescence: One-year prevalence in an out-patient population

AbstractA multicenter one-year study was carried out on 6629 headache patients under 18 years of age, attending 27 centers and clinics devoted to headache in Italy to identify the prevalence of cluster headache (CH) in childhood and adolescence. Two male CH patients aged 9 and 17 years were identified. Their attacks fulfilled the IHS criteria for CH, and they were classified as having cluster headache with undetermined periodicity and episodic cluster headache, respectively. The one-year prevalence in this headache out-patient population under 18 years of age was calculated to be 0.03%. This value is smaller than that derived in the general population. This finding further confirms the rarity of early diagnosis of this primary disorder in childhood and adolescence, as demonstrated in other studies.

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 ICHD 2nd edition criteria for primary headaches with the aid of a computerised, structured medical record for the specialist

We tested the computerised, structured medical record by entering and analysing the consecutive clinical sheets of primary headaches in the episodic forms (200) and chronic headache (200) and the corresponding output diagnoses of patients attending our Headache Centre. A diagnosis of one of the primary headache forms was obtained in 67.9% of cases. A certain diagnosis of primary headache plus that of a probable form was obtained in 24.4% of cases (12.7% represented by chronic migraine (CM) or chronic tension–type headache (CTTH)+probable medicationoveruse headache). Only probable forms were diagnosed in the remaining 7.3% (as single probable diagnosis in 5.8% of cases or multiple diagnoses of probable forms in the remaining ones). The percentage of certain diagnoses mainly in the chronic headache group (28.4%), and to a lesser extent tension–type headache (6.5%), were obtained in 34.9% of cases. A certain diagnosis of one chronic form plus that of a probable form was obtained in 50.8% of cases (26.9% represented by probable medication–overuse headache). Only probable forms were diagnosed in 13.46% (as single probable diagnosis in 8.73% of cases or multiple diagnoses of probable forms in the remaining ones). In the other cases, the ICHD–II classification does not allow the diagnoses of CM, CTTH or probable forms and medicationoveruse headache because the mandatory criteria for the diagnoses are too stringent and do not reflect modifications of the headache pattern in relation to its chronicity. These preliminary results underscore the usefulness of a computerised device based on the ICHD 2nd edition for diagnostic purposes in tertiary centres dedicated to headaches in clinical practice as well as its relevance for research. This computerised device may help to validate the new diagnostic criteria and to answer some emerging questions from the application of the new classification version, the relevance of which should be verified in clinical practice.