Time trends, frequency, characteristics and prognosis of short-duration transient global amnesia.

BACKGROUND AND PURPOSE: Transient global amnesia (TGA) is characterized by a sudden onset of anterograde amnesia lasting up to 24 h. One major differential for TGA is transient epileptic amnesia, which typically lasts < 1 h. However, TGA can also be short in duration and little is known about the time trends, characteristics and prognosis of TGA cases lasting < 1 h. METHODS: We compared the clinical features of TGA ascertained in two independent cohort studies in Oxfordshire, UK [Oxford cohort 1977-1987 versus Oxford Vascular Study (OXVASC) 2002-2018] to determine the time trends of clinical features of TGA. Results were validated in another independent contemporary TGA cohort in Italy [Northern Umbria TGA registry (NU) 2002-2018]. We compared the risk factors, clinical features and long-term prognosis (major cardiovascular events, recurrent TGA and seizure/epilepsy) of patients presenting with episodes lasting < 1 h versus those lasting ≥ 1 h. RESULTS: Overall, 639 patients with TGA were included (114 Oxford cohort, 100 OXVASC, 425 NU). Compared with the original Oxford cohort, there were more cases with TGA lasting < 1 h in OXVASC [32 (32.0%) vs. 9 (8.8%)] and NU (11.8% vs. 8.8% in Oxford cohort). In both OXVASC and NU, patient age, vascular risk factors and clinical features were largely similar between those with TGA lasting < 1 h versus those lasting ≥ 1 h. Moreover, there was no difference in the long-term risk of seizure/epilepsy or major cardiovascular events between TGA lasting < 1 h versus TGA lasting ≥ 1 h. CONCLUSIONS: Short-duration TGA episodes (<1 h) were not uncommon and were more frequent than in earlier studies. The clinical features and long-term prognosis of short-duration TGA did not differ from more typical episodes lasting ≥ 1 h.

Subclinical vestibular dysfunction in migraineurs without vertigo: A Clinical study.

OBJECTIVES: This observational study aimed to investigate the presence of potential vestibular system subclinical dysfunction among migraineurs without a history of vertigo and dizziness compared with healthy controls. METHODS: Patients diagnosed with episodic migraine with and without aura were enrolled. All patients and healthy controls underwent vestibular examination using the following conventional tests: sitting position, Pagnini-McClure's, Dix-Hallpike's, head hanging, video head impulse, subjective visual vertical, Romberg, Fukuda, and caloric vestibular stimulation by Fitzgerald-Hallpike's tests. Nystagmus and angular velocity of the slow phase during culmination phase was analyzed by video-nystagmography. RESULTS: Overall, 33 patients (76% female, 7 with aura and 26 without aura; mean age (mean ± SD): 29.1 ± 4.3 years) and 22 controls (33% female, mean age: 30.8 ± 9.4 years) were enrolled. There were no statistically significant differences in demographic features between patients and controls. Caloric vestibular stimulation test results were found to differ among patients and controls. In particular, right and left angular velocity (AV) were highly correlated one another (r = 0.88, P < .001). Right AV (53.0 ± 6.7 vs 44.0 ± 9.6) and left AV (54.3 ± 5.3 vs 43.3 ± 9.0) were statistically higher in migraineurs as compared to controls (P < .001). Also right V-HIT (1.1 ± 0.1 vs 0.8 ± 0.4) and left V-HIT (1.1 ± 0.1 vs 0.7 ± 0.2) were statistically higher in migraineurs compared to controls (P < .001). CONCLUSION: Our findings suggest a subclinical alteration of vestibular pathway in migraineurs who have never complained vertigo or postural imbalance. This finding supports the hypothesis of a vestibular-cerebellar dysfunction in migraineurs, particularly among those with aura.

Early management of patients with medication-overuse headache: results from a multicentre clinical study.

BACKGROUND AND PURPOSE: Educational intervention has proved to be effective in reducing drug abuse in uncomplicated medication-overuse headache (MOH). This ancillary of the SAMOHA multicentre study aimed to assess any differences in phenotypic characteristics, type and amount of drugs overused, and comorbidities between patients with MOH who responded to simple advice and those who did not. METHODS: Demographic and clinical headache data of the last 3 months before enrollment of patients were collected and patients were then asked to fill out a daily headache diary for 4 weeks. Patients were then divided into two subgroups, i.e. those with confirmed MOH continued in the study [randomized (R) group], whereas those who did not still show any features of MOH dropped out of the study. RESULTS: A total of 88 (67.7%) patients still met the inclusion criteria after the baseline 4 weeks (R group). Conversely, 42 (32.3%) patients dropped out of the study. A detailed analysis of those who dropped out revealed that only 34 were not randomized at visit 2 because they no longer satisfied the inclusion criteria for MOH [screening failures (SF) group]. The SF group was significantly younger and had fewer years of migraine history than the R group. Moreover, the SF group had a significantly shorter history of chronicity compared with the R group. CONCLUSIONS: Our findings suggest that in MOH trials, after an educational session, an observational period is needed in order to confirm the diagnosis of MOH and to avoid overestimation of the effect of other treatments used to manage MOH. Future research should focus mainly on those patients with MOH who do not respond to simple advice and with unsuccessful withdrawal.

Epilepsy in hemiplegic migraine: Genetic mutations and clinical implications.

Objective We performed a systematic review on the comorbidities of familial/sporadic hemiplegic migraine (F/SHM) with seizure/epilepsy in patients with CACNA1A, ATP1A2 or SCN1A mutations, to identify the genotypes associated and investigate for the presence of mutational hot spots. Methods We performed a search in MEDLINE and in the Human Gene Mutation and Leiden Open Variation Databases for mutations in the CACNA1A, ATP1A2 and SCN1A genes. After having examined the clinical characteristics of the patients, we selected those having HM and seizures, febrile seizures or epilepsy. For each gene, we determined both the frequency and the positions at protein levels of these mutations, as well as the penetrance of epilepsy within families. Results Concerning F/SHM-Epilepsy1 (F/SHME1) and F/SHME2 endophenotypes, we observed a prevalent involvement of the transmembrane domains, and a strong correlation in F/SHME1 when the positively charged amino acids were involved. The penetrance of epilepsy within the families was highest for patients carrying mutation in the CACNA1A gene (60%), and lower in those having SCN1A (33.3%) and ATP1A2 (30.9%) mutations. Conclusion Among the HM cases with seizure/epilepsy, we observed mutational hot spots in the transmembrane domains of CACNA1A and ATP1A2 proteins. These findings could lead to a better understanding of the pathological mechanisms underlying migraine and epilepsy, therein guaranteeing the most appropriate therapeutic approach.

Optimizing the long-term management of chronic migraine with onabotulinumtoxinA in real life.

INTRODUCTION: Management of chronic migraine is challenging. OnabotulinumtoxinA (OBT-A) is the only medication licensed for prevention of chronic migraine, and has been widely adopted in clinical practice. Limited data is available on its long-term use. Areas covered: Data from controlled trials are combined with available data on the long-term use of OBT-A in real-life studies, with information obtained in a recent survey among Italian headache centers, and the clinical experience of the authors. Six areas were identified as relevant to patients with chronic migraine: 1) definition of responders to OBT-A; 2) management of responders to OBT-A; 3) optimal timing of prophylaxis with OBT-A; 4) position of OBT-A in prevention of chronic migraine; 5) management of medication overuse, and 6) patient education. Expert commentary: This review provides an update on the latest evidence regarding the long-term use of OBT-A in chronic migraine and analyzes the critical issues in the decision-making process that emerge from the analysis of the literature and routine practice. A treatment algorithm is proposed for the adoption in the daily practice.

Psychopathological comorbidities in medication-overuse headache: a multicentre clinical study.

BACKGROUND AND PURPOSE: In medication-overuse headache (MOH) patients, the presence of psychopathological disturbances may be a predictor of relapse and poor response to treatment. This multicentre study aimed to assess the occurrence of psychopathological disorders in MOH patients by comparing the incidence of psychopathological disturbances with episodic migraine (EM) patients and healthy controls (HC). METHODS: The psychopathological assessment of patients and HC involved the administrations of the Beck Depression Inventory, the Beck Anxiety Inventory, the Modified Mini International Neuropsychiatric Interview (M-MINI), the Yale-Brown Obsessive Compulsive Scale (Y-BOCS) and the Leeds Dependence Questionnaire. RESULTS: The MOH, EM and HC groups (88, 129 and 102 subjects, respectively) differed significantly from each other for the presence of moderate/severe anxiety, whereas mood disorder and depression were revealed in similar proportions for both MOH and EM patients. By stratifying the M-MINI questionnaire results according to the number of psychiatric disorders, it was found that MOH patients had a more complex profile of psychiatric comorbidity. Furthermore, clinically relevant obsessive-compulsive disturbances for abused drugs assessed by Y-BOCS appeared to be more represented in the MOH group, whilst the prevalence of this trait in the EM group was comparable to that of HC (12.5%, 0.8% and 0%, respectively). CONCLUSIONS: Our study indicates the multiple presence of psychopathological comorbidities in patients with MOH. In light of this, it is recommended that the assessment of the psychopathological profile be included in an evaluation of MOH patients, allowing the clinician to more rapidly start an appropriate behavioural treatment, which would greatly improve MOH management.

Balance control impairment induced after OKS in patients with vestibular migraine: an intercritical marker.

The aim of the study was to assess the effects of optokinetic stimulation (OKS) on vestibular postural control in migraine patients with recurrent vertigo. 15 patients with vestibular migraine (VM) were enrolled in a posturographic study in eyes open (OE) and eyes closed (CE) condition. The tests were performed between attacks of headache and vertigo at three different time: before, during, and 60 min after OKS. Data of patients with VM were compared with those obtained from two control groups matched for sex and age (15 for each group): (a) normal subjects not suffering from migraine without history of recurrent vertigo (N group); (b) subjects suffering from migraine with no history of recurrent vertigo (M group). Mean sway path velocity and sway area were analyzed. OKS increased the instability in all groups during the stimulus, and both the velocity and area values were higher in M and VM group. However, there was not significant difference between these two groups when stability was examined in OE condition before, during and after OKS stimulation. Conversely, in CE condition a significant greater instability was induced after OKS stimulation only in VM. In particular, post-stimulus values were significantly higher than the pre-stimulus one only in this group, while no significant difference was observed in other groups. A spatial analysis of the sway area evidenced that the instability induced by the OKS in VM group occurred along the direction of OKS. We suggest that this enhanced instability observed after OKS during the intercritical period may be considered an useful marker to support the diagnostic definition of VM in the absence of other vestibular signs.

Lower urinary tract symptoms and urodynamic dysfunction in clinically isolated syndromes suggestive of multiple sclerosis.

BACKGROUND AND PURPOSE: Urinary symptoms associated with multiple sclerosis (MS) are common and negatively impact on quality of life, representing a considerable psychosocial and economic burden, often requiring care and hospitalization. Although the importance of identifying and adequately treating urinary symptoms in MS is now well recognized, there is no information, to date, about the real prevalence and impact of bladder symptoms in patients with clinically isolated syndromes (CISs) suggestive of MS. METHODS: The aim of the present study was to investigate, in a cohort of patients with a diagnosis of CIS suggestive of MS, the prevalence of urinary tract symptoms, their impact on quality of life measures and their association with functional urodynamic dysfunctions. Patients underwent a complete neurological and urological visit, urodynamic investigation and the MSQoL-54 questionnaire. RESULTS: Twenty-eight consecutive patients presenting with CISs were enrolled in the study; 53.6% of CIS patients reported urinary symptoms, 46.7% reporting irritative symptoms, 33.3% both irritative and obstructive symptoms and 20% obstructive symptoms alone. Urodynamic abnormalities were observed in 57.1% of the CIS patients. In 17.9% of the CIS patients urodynamic dysfunctions were asymptomatic. The presence of urinary symptoms was associated with lower scores on specific quality of life domains, particularly in women with obstructive symptoms. CONCLUSIONS: A high prevalence of urinary symptoms and urodynamic dysfunctions in patients with CISs and an association of urinary symptoms with quality of life measures were found. These results highlight the importance of identifying and optimally treating urinary symptoms also at the very early stages of MS.

A magnetization transfer study of mild and advanced Parkinson's disease.

BACKGROUND AND PURPOSE: Magnetization transfer ratio (MTR) technique has identified brain changes in grey and white matter in Parkinson's disease (PD), even in the early phase. However, how these tissue changes differ along the course of the illness is still unclear. This study was aimed at investigating how MTR values change from mild PD (PD1) to patients with advanced PD (PD2). METHODS: We measured MTR values by region of interest, in 11 PD1, 11 PD2 and 10 healthy age-matched subjects. RESULTS: Compared with controls, patients with PD1 exhibited a significant MTR reduction in substantia nigra pars compacta, substantia nigra pars reticulata, putamen, periventricular white matter and parietal white matter. In addition to the changes observed in PD1, the PD2 group exhibited a significant MTR reduction in caudate, pons, frontal white matter and lateral thalamus. CONCLUSION: These results suggest that MTR might reflect morphological changes induced by the disease in distinct brain areas at different stages.

Safety and efficacy of natalizumab in children with multiple sclerosis.

OBJECTIVE: To describe the effect of natalizumab in the treatment of subjects with active multiple sclerosis (MS) treated before the age of 18 years. METHODS: Nineteen pediatric subjects with MS (mean age 14.6 +/- 2.2 years, mean number of attacks 5.2 +/- 1.9 during the pretreatment phase of 27.7 +/- 19.7 months, median pretreatment Expanded Disability Status Scale score [EDSS] 2.5, range 1.0-5.0) were treated with natalizumab at the dose of 300 mg every 28 days. After treatment initiation, patients were reassessed clinically every month; brain MRI was performed at baseline and every 6 months. RESULTS: Patients received a median number of 15 infusions (range 6-26). A transient reversible worsening of preexisting symptoms occurred in 1 subject during and following the first infusion. All the patients remained relapse-free during the whole follow-up. The median EDSS decreased from 2.5 to 2.0 at the last visit (p < 0.001). EDSS remained stable in 5 cases, decreased by at least 0.5 point in 6 cases, and decreased by at least 1 point in 8 cases. At baseline, the mean number of gadolinium-enhancing lesions was 4.1 (range 1-20). During the follow-up, no gadolinium-enhancing lesions were detected (p = 0.008); 3 patients developed new T2-visible lesions at month 6 scan but the overall number of T2 lesions remained stable during the subsequent follow-up. Transient and mild side effects occurred in 8 patients. CONCLUSIONS: Natalizumab was well-tolerated in all subjects. A strong suppression of disease activity was observed in all subjects during the follow-up. CLASSIFICATION OF EVIDENCE: This study provides Class IV evidence that natalizumab, 300 mg IV once every 28 days, decreased EDSS scores in pediatric patients with MS over a mean treatment period of 15.2 months.

Aortic stiffness and pulse wave reflection in young subjects with migraine: A case-control study.

BACKGROUND: Migraine has been associated with an increased risk for ischemic stroke and other cardiovascular (CV) events, including angina, myocardial infarction, and CV death, but the mechanisms that link migraine to CV disease remain uncertain. We hypothesized that aortic pulse wave velocity (PWV), a direct measure of aortic stiffness and an independent predictor of stroke and CV disease, may be increased in young migraineurs with no overt CV disease or major CV risk factors. METHODS: We studied 60 subjects with migraine (age 33 ± 8 years, 85% women, blood pressure 119/74 ± 11/9 mm Hg) and 60 age-, sex-, and blood pressure-matched healthy control subjects. In all participants, carotid-femoral PWV and aortic augmentation index were determined by applanation tonometry. Cases and controls were free from overt CV disease, diabetes, and major CV risk factors. RESULTS: Subjects with migraine had a higher aortic PWV (7.6 ± 1.2 vs 6.4 ± 1.1 m × s(-1), p < 0.001) and aortic augmentation (heart rate-adjusted augmentation index, 0.17 ± 0.13 vs 0.08 ± 0.15, p < 0.001) than matched control subjects. Migraine patients with aura (n = 17) had higher aortic PWV than those without aura (n = 43; 8.2 ± 1.2 vs 7.4 ± 1.1 m × s(-1), p = 0.027). Age, mean arterial pressure as a measure of distending pressure, and migraine (all p < 0.05) independently predicted aortic PWV when a consistent number of CV risk factors was simultaneously controlled for. CONCLUSIONS: Migraine is independently associated with increased aortic stiffness and enhanced pressure wave reflection. This finding, obtained in young subjects without major CV risk factors, may represent one possible mechanism underlying the increased CV risk in migraine patients.

Underdiagnosis and undertreatment of migraine in Italy: a survey of patients attending for the first time 10 headache centres.

The aim of this study was to asses the clinical features, pattern of healthcare and drug utilization of migraine patients attending 10 Italian headache centres (HC). Migraine is underdiagnosed and undertreated everywhere throughout the world, despite its considerable burden. Migraine sufferers often deal with their problem alone using self-prescribing drugs, whereas triptans are used by a small proportion of patients. All patients attending for the first time 10 Italian HCs over a 3-month period were screened for migraine. Migraine patients underwent a structured direct interview about previous migraine diagnosis, comorbidity, headache treatments and their side-effects and healthcare utilization for migraine. Patient satisfaction with their usual therapy for the migraine attack was evaluated with the Migraine-Assessment of Current Therapy (ACT) questionnaire. The quality of life of migraine patients was assessed by mean of Short Form (SF)-12 and Migraine-Specific Quality of life (MSQ) version 2.1 questionnaires. Of the 2675 patients who attended HCs for the first time during the study period, 71% received a diagnosis of migraine and the first 953 subjects completed the study out of 1025 patients enrolled. Only 26.8% of migraine patients had a previous diagnosis of migraine; 62.4% of them visited their general practitioner (GP) in the last year, 38.2% saw a specialist for headache, 23% attended an Emergency Department and 4.5% were admitted to hospital for migraine; 82.8% of patients used non-specific drugs for migraine attacks, whereas 17.2% used triptans and only 4.8% used a preventive migraine medication. Triptans were used by 46.4% of patients with a previous diagnosis of migraine. About 80% of migraine patients took over-the-counter medications. The Migraine-ACT revealed that 60% of patients needed a change in their treatment of migraine attacks, 85% of whom took non-specific drugs. Both the MSQ version 2.1 and the SF-12 questionnaires indicated a poor quality of life of most patients. Migraine represents the prevalent headache diagnosis in Italian HCs. Migraine is still underdiagnosed in Italy and migraine patients receive a suboptimal medical approach in our country, despite the healthcare utilization of migraine subjects being noteworthy. A cooperative network involving GPs, neurologists and headache specialists is strongly desirable in order to improve long-term migraine management in Italy.

A 1H magnetic resonance spectroscopy study in patients with obstructive sleep apnea.

BACKGROUND AND PURPOSE: Repeated episodes of hypoxia, hypercapnia and transient blood pressure elevation in obstructive sleep apnea syndrome (OSAS) may damage neutral structures and induce cerebral metabolic impairment. This study aimed to determine the impact of OSAS on cerebral metabolites measured by (1)H magnetic resonance spectroscopy ((1)H -MRS). METHODS: Twenty OSAS patients underwent standard overnight polysomnography and (1)H-MRS separately. Proton volumes of interest (VOIs) were placed in frontal and midtemporal regions bilaterally. RESULTS: Significantly lower values of the N-acetylaspartate (NAA)/creatine (Cr) ratio were found in frontal regions (P < 0.004) compared with 20 age-matched control subjects. A significant increase in the myo-inositol (Ins)/Cr ratio was evident bilaterally in temporal and frontal regions (P < 0.00002 and P < 0.04). Choline (Cho)/Cr ratio values were also significantly greater in temporal regions (P < 0.00001). A significant negative correlation (r = -0.51, P < 0.03) was found between the apnea-hypopnea index (AHI) and NAA/Cr ratio in the frontal regions of OSAS patients. CONCLUSIONS: Reduction in the NAA/Cr ratio in frontal regions of OSAS patients could be related to neural loss. Increase in the Cho/Cr ratio in temporal regions and Ins/Cr ratio in both frontal and temporal regions could be interpreted as evidence of membrane breakdown and reactive gliosis, respectively, consequent to repeated episodes of hypoxia in OSAS.

CSF proteome analysis in multiple sclerosis patients by two-dimensional electrophoresis.

BACKGROUND AND PURPOSE: In recent years, different approaches have been used to investigate changes of cerebrospinal fluid (CSF) proteome in patients affected by multiple sclerosis (MS) with the aim to identify protein markers with potential diagnostic or prognostic value. Because of the lack of standardization of current proteomic techniques, contrasting results were achieved until now in different laboratories. In this study, we compare CSF proteome of 10 relapsing-remitting MS (RR-MS) patients, 11 patients with clinically isolated syndrome (CIS), and 10 control subjects without neurological or systemic diseases. METHODS: The differential expression of CSF proteins amongst these cohorts of patients was investigated by using two-dimensional electrophoresis and mass spectrometry. RESULTS AND CONCLUSIONS: We found an overexpression of IgG free kappa light chain protein in both CIS and RR-MS patients, compared with control subjects and an increased expression of an apolipoprotein E isoform in RR-MS patients, compared with CIS and control groups. Our results confirm the presence of CSF proteome changes in MS patients. Future research should be aimed to investigate the role of these candidate CSF markers in larger cohorts of CIS and MS patients.

Abnormalities in the cerebrospinal fluid levels of endocannabinoids in multiple sclerosis.

OBJECTIVE: Endocannabinoids (eCBs) play a role in the modulation of neuroinflammation, and experimental findings suggest that they may be directly involved in the pathogenesis of multiple sclerosis (MS). The objective of our study was to measure eCB levels in the cerebrospinal fluid (CSF) of patients with MS. PATIENTS AND METHODS: Arachidonoylethanolamine (anandamide, AEA), palmotylethanolamide (PEA), 2-arachidonoylglycerol (2-AG) and oleoylethanolamide (OEA) levels were measured in the CSF of 50 patients with MS and 20 control subjects by isotope dilution gas-chromatography/mass-spectrometry. Patients included 35 patients with MS in the relapsing-remitting (RR) form of the disease, 20 in a stable clinical phase and 15 during a relapse, and 15 patients with MS in the secondary progressive (SP) form. RESULTS: Significantly reduced levels of all the tested eCBs were found in the CSF of patients with MS compared to control subjects, with lower values detected in the SP MS group. Higher levels of AEA and PEA, although below those of controls, were found in the CSF of RR MS patients during a relapse. Higher levels of AEA, 2-AG and OEA were found in patients with MRI gadolinium-enhancing (Gd+) lesions. DISCUSSION: The present findings suggest the presence of an impaired eCB system in MS. Increased CSF levels of AEA during relapses or in RR patients with Gd+ lesions suggest its potential role in limiting the ongoing inflammatory process with potential neuroprotective implications. These findings provide further support for the development of drugs targeting eCBs as a potential pharmacological strategy to reduce the symptoms and slow disease progression in MS.

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.

Degradation of endocannabinoids in chronic migraine and medication overuse headache.

Chronic migraine (CM) is frequently associated with medication overuse headache (MOH). The endocannabinoid system plays a role in modulating pain including headache and is involved in the common neurobiological mechanism underlying drug addiction and reward system. Anandamide (AEA) and 2-arachidonoylglycerol are the most biologically active endocannabinoids, which bind to both central and peripheral cannabinoid receptors. The level of AEA in the extracellular space is controlled by cellular uptake via a specific AEA membrane transporter (AMT), followed by intracellular degradation by the enzyme AEA hydrolase (fatty acid amide hydrolase, FAAH). AMT and FAAH have also been characterized in human platelets. We assayed the activity of AMT and of FAAH in platelets isolated from four groups of subjects: MOH, CM without MOH, episodic migraine and controls. AMT and FAAH were significantly reduced in CM and MOH, compared to either controls or episodic migraine group. This latter finding was observed in both males and females with CM and MOH. Changes observed in the biochemical mechanisms degrading endogenous cannabinoids may reflect an adaptative behaviour induced by chronic headache and/or drug overuse.

Efficacy of dosing and re-dosing of two oral fixed combinations of indomethacin, prochlorperazine and caffeine compared with oral sumatriptan in the acute treatment of multiple migraine attacks: a double-blind, double-dummy, randomised, parallel group, multicentre study.

AIMS AND METHODS: In this double-blind, double-dummy, randomised, parallel group, multicentre study, the efficacy of dosing and re-dosing of a fixed combination of indomethacin, prochlorperazine and caffeine (Indoprocaf) was compared with encapsulated sumatriptan in the acute treatment of two migraine attacks. Additionally, in the group taking Indoprocaf, two different oral formulations were tested: effervescent tablets and encapsulated coated tablets. RESULTS: Of 297 patients randomised (150 assigned to Indoprocaf and 147 to sumatriptan), 281 were included in the intention-to-treat efficacy analysis. The initial dosing of Indoprocaf and sumatriptan was similarly effective with pain-free rates higher than 30% (95% CI of odds-ratio: 0.57-1.28) and headache relief rates of about 60% (95% CI of odds-ratio: 0.82-1.84) with both the drugs. The efficacy of re-dosing of Indoprocaf as rescue medication was more effective than that of sumatriptan with pain-free values of 47% vs. 27% in the total attacks with a statistically significant difference in the first migraine attack in favour of Indoprocaf. The efficacy of re-dosing to treat a recurrence/relapse was very high without differences between the drugs (pain-free: 60% with Indoprocaf and 50% with sumatriptan in the total attacks). Indoprocaf and sumatriptan were well-tolerated. CONCLUSION: The study demonstrated that the efficacy of the initial dosing of Indoprocaf was not higher than that of sumatriptan, but that the strategy to use the lowest effective dose as soon as the headache occurred, followed by a second dose if the headache has not relieved or to treat a relapse, was very effective, especially with Indoprocaf.

Production of brain-derived neurotrophic factor by mononuclear cells of patients with multiple sclerosis treated with glatiramer acetate, interferon-beta 1a, and high doses of immunoglobulins.

Sixty, relapsing remitting (RR) multiple sclerosis (MS) patients, who underwent treatment with glatiramer acetate (GA), interferon (IFN)-beta 1a, and immunoglobulins (Igs) (20 per treatment group), were assessed for levels of brain-derived neurotrophic factor (BDNF) in the supernatants of unstimulated and stimulated peripheral blood mononuclear cells (PBMCs) in the first year of treatment. Phytohemagglutinin (PHA), anti-OKT3 antibody, myelin basic protein (MPB) and GA were used as stimuli. Cytokine responses by ELISPOT and lymphoproliferative responses were also assessed. The GA-treated MS patient group showed a progressive increase in BDNF levels, from baseline to month three; thereafter, the levels remained stable and significantly greater compared with baseline and controls (ANOVA=P<0.001). IFN-beta 1a had no effect on BDNF production, whereas Igs induced a slight decrease (ANOVA=P<0.04). ELISPOT analysis revealed a significant decrease of IFN-gamma, an increase of interleukin (IL)-4 and IL-5 in GA-treated MS patients, and an increase of IL-10 in patients treated with IFN-beta 1a and GA. No significant correlation was found between BDNF secretion in the supernatants of PBMCs and cytokine response, lesional load, and measures of atrophy. Increased BDNF production related to GA treatment can have implications for understanding the mechanism of action of this immunomodulatory agent, in light of evidence suggesting its effects in promoting neuroprotective immunity in MS patients; however, a clinically measurable effect, especially in terms of an impact on actual disease progression, remains to be established.

NF-kappaB 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-kappaB) activity by electrophoresis mobility gel shift assay and IkappaBalpha 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-kappaB activity peaked 2 h after attack onset. This was accompanied by a transient reduction in IkappaBalpha 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-kappaB transcription in the treatment of migraine.