Fatigue, sleep-wake pattern, depressive and anxiety symptoms and body-mass index: analysis in a sample of episodic and chronic migraine patients.

Migraine clinical presentation and life-time course can be highly heterogeneous, with a subgroup of patients developing chronic migraine; moreover, migraine clinical spectrum is expanded by the association with different coexisting conditions and interictal dysfunctions. The aim of this study was to systematically evaluate migraine clinical features, daily functioning parameters, sleep pattern, presence of depressive-anxiety symptoms and body mass index (BMI) in a sample of 75 episodic and 75 chronic migraine without aura patients. Migraine-related disability, fatigue, daily sleepiness, subjective sleep quality, anxiety and depressive symptoms were, respectively, evaluated using the following questionnaires: Fatigue Severity Scale (FSS), Epworth Sleepiness Scale, Pittsburgh Sleep Quality Index (PSQI), Generalized Anxiety Disorder 7-item Scale (GAD-7), Patient Health Questionnaire 9-item Scale (PHQ-9). Mean FSS score (p < 0.001), PSQI score (p = 0.015), GAD-7 score (p = 0.019), PHQ-9 score (p < 0.001) and BMI score (p = 0.012) were significantly higher in chronic compared to episodic migraineurs. Additionally, a correlation analysis carried out in the total sample of 150 migraine patients documented a statistically significant, positive correlation between monthly frequency of migraine attacks and FSS score (p < 0.001), PSQI score (p = 0.006), GAD-7 score (p = 0.019), PHQ-9 score (p < 0.001) and BMI score (p = 0.049). Data from the present report seem to expand the concept of migraine as a continuum or spectrum, with greater occurrence of fatigue, poor sleep quality, anxiety-depressive symptoms and higher BMI score in chronic compared to episodic migraine patients; further investigation is certainly necessary to better define the biological basis and mechanisms associated with migraine transformation from episodic to chronic pattern.

Preferential occurrence of attacks during night sleep and/or upon awakening negatively affects migraine clinical presentation.

It is well known that migraine attacks can preferentially occur during night sleep and/or upon awakening, however the possible implications of this timing on migraine clinical presentation remain unclear. The aim of this study was to assess the possible consequences of sleep-related migraine (defined as ≥ 75% of migraine attacks occurring during night sleep and/or upon awakening) on the migraine clinical picture (i.e. migraine-related disability, attack severity, use of symptomatic drugs), subjective sleep quality, excessive daytime sleepiness and fatigue. Two hundred consecutive migraine without aura patients were enrolled; patients with comorbid disorders or chronic medication use were excluded. 39% of the migraineurs included in the study received a diagnosis of sleep-related migraine. The mean frequency of migraine attacks (days per month) did not significantly differ between the patients with and those without sleep-related migraine, whereas migraine-related disability (p<0.0001), mean attack severity (p<0.0001), and monthly intake of symptomatic drugs (p<0.0001) were significantly higher in patients with migraine preferentially occurring at night-time and/or upon awakening. Subjective sleep quality and excessive daytime sleepiness did not differ significantly between the two groups, whereas fatigue was significantly more present in the patients with sleep-related migraine (p=0.0001). These data seem to support the hypothesis that patients with sleep-related migraine represent a subset of individuals with a more severe and disabling clinical presentation of migraine and greater impairment of daily functioning, as suggested by the higher degree of fatigue. Migraineurs with night-time attacks Preferential occurrence of attacks during night sleep and/or upon awakening negatively affects migraine clinical presentation also showed a greater use of symptomatic drugs, possibly related to delayed use of symptomatic treatment. The identification of subtypes of patients with a higher disability risk profile could have crucial implications for individually tailored management of migraine patients.

Evidences of Reduced Antioxidant Activity in Patients With Chronic Migraine and Medication-Overuse Headache.

BACKGROUND: Migraine is a complex multifactorial, neurobiological disorder, whose pathogenesis is not fully understood, nor are the mechanisms associated with migraine transformation from episodic to chronic pattern. A possible role of impaired oxidative mitochondrial metabolism in migraine pathogenesis has been hypothesized, and increased levels of peripheral markers of oxidative stress have been reported in migraine patients, although the literature data are limited and heterogeneous. OBJECTIVES: The aim of this cross-sectional study was to determine plasmatic levels of advanced oxidation protein products, ferric-reducing antioxidant power and total plasmatic thiol groups, all plasmatic markers related to oxidative stress, in a sample of chronic migraine patients and medication-overuse headache, compared to a control group of healthy subjects. METHODS: Thirty-three patients with a diagnosis of both chronic migraine and medication-overuse headache (International Classification of Headache Disorders,3rd edition, beta version) and 33 healthy, headache-free subjects were enrolled. Patients with comorbid/coexisting conditions were excluded, as well as patients in treatment with migraine preventive drugs. Plasmatic levels of advanced oxidation protein products, ferric-reducing antioxidant power, and total thiol groups were determined in migraine patients and controls; moreover, oxidative stress biomarkers were compared in migraine patients with triptan compared to non-steroidal anti-inflammatory drug overuse. RESULTS: The statistical analysis showed significantly lower levels of ferric-reducing antioxidant power and total plasmatic thiol groups, both expression of antioxidant power, in patients with chronic migraine and medication-overuse headache compared to controls (respectively, ferric antioxidant power median [interquartile range] 0.53 [0.22] vs 0.82 [0.11] mmol/L, P < .001; total thiol groups 0.25 [0.08] vs 0.51 [0.11] µmol/L, P < .001). Moreover, no statistically significant differences in oxidative stress biomarkers were detected between patients with triptan and nonsteroidal anti-inflammatory drug overuse. CONCLUSIONS: The data from the present study suggest that antioxidant capacity is lower in chronic migraine patients and medication-overuse headache compared to healthy headache-free subjects, with no differences between patients with triptan or nonsteroidal anti-inflammatory drug overuse. Further investigation is certainly necessary in order to define the causal or consequential role of an imbalance between pro-oxidants and antioxidant defenses in migraine pathogenesis and "chronification" and the possible therapeutic implications in clinical practice.

Migraine features in migraineurs with and without anxiety-depression symptoms: a hospital-based study.

BACKGROUND: Migraine, anxiety and depression often coexist. A "neurolimbic" model of migraine has been recently proposed accounting for a dynamic influence of pain, mood and anxiety on the migraine disease. However, very few data exist concerning clinical migraine features in patients reporting anxiety-depression symptoms. OBJECTIVE: Aim of our study was to test differences in clinical migraine features between migraineurs with anxiety-depression symptoms and migraineurs without ones. MATERIALS AND METHODS: We recruited 200 consecutive migraineurs. Other primary headaches comorbidity and migraine prophylaxis were exclusion criteria. Each patient was interviewed following a structured questionnaire including general features about migraine, triggers, allodynia. Anxiety and depression symptoms were evaluated in each patient by two brief self-reported scales: the generalized anxiety disorder 7-item scale (GAD-7) and the Patient Health Questionnaire 9-item scale (PHQ-9). A cut-off of 5 in both the GAD-7 and the PHQ-9 was considered positive for the presence of anxiety-depressive symptoms. RESULTS: One hundred and one patients (51.5%) had anxiety-depression symptoms (GAD-7 and PHQ-9 ≥ 5). They reported a more headaches/month (p = 0.004), higher number of triggers (p < 0.001), and were more allodynic (p = 0.005). In a binary logistic regression model triggers and allodynia made a unique statistical contribution on reporting anxiety-depression symptoms. CONCLUSION: Our results showed that the presence of anxiety-depression symptoms affects migraine clinical presentation. They are associated with enhanced migraine triggers susceptibility, more ictal allodynic symptoms as well as more headaches/month. An altered sensation in migraineurs with anxiety-depression symptoms could be a result of a lower pain threshold and an increased cortical excitability in a broader context of a neurolimbic dysfunction.

A clinical and laboratory study evaluating the profile of cytokine levels in relapsing remitting and secondary progressive multiple sclerosis.

The main aim of the study was to evaluate levels of cytokines IL-1ra, IL-2, IL-4, IL-6, IL-8, IL-10, IL-12, IL-17, TNF-alfa, TGB-beta1 and IFN-gamma in 30 patients with relapsing remitting (RRMS) compared to 30 secondary progressive multiple sclerosis (SPMS) in a peripheral blood sample. Statistical analysis showed significant higher levels of IL-17 and INF-gamma, which are cytokines with pro-inflammatory properties, and lower levels of TGF-beta1, a molecule with immunosuppressant activity, in RRMS compared to SPMS. These results underline the existence of a different cytokines dysregulation in RRMS compared to SPMS phases with higher pro-inflammatory activity in RRMS.

Clinical features associated with ictal osmophobia in migraine.

Olfactory hypersensitivity may occur during migraine attacks and has been found to be very specific for this form of headache. Aim of this study was to investigate if migraineurs with ictal osmophobia have particular clinical features comparing to patients without ictal osmophobia. We recruited 200 consecutive migraineurs. Other primary headaches comorbidity and migraine prophylaxis were exclusion criteria. Each patient was interviewed following a structured questionnaire including general features about migraine, depression and anxiety symptoms. Migraine triggers both spontaneously and selecting from a specific list. Allodynia during the migraine attack was measured using the Allodynia symptoms check-list 12 (ASC-12). Eighty four (42 %) patients are non-osmophobic vs. 116 patients (58 %) who are osmophobic. After a logistic regression analysis, pain intensity (OR 1.391; p = 0.008) and anxiety (OR 1.099; p = 0.047) were significantly higher while aura (OR 0.421; p = 0.028) is less frequent in osmophobic migraineurs. We found significant differences in clinical features of osmophobic patients in respect to non-osmophobic ones. Ictal osmophobia seems being related to a broader sensorial hypersensitivity that could lead to a more florid clinical presentation.

Plasmatic oxidative stress biomarkers in multiple sclerosis: relation with clinical and demographic characteristics.

OBJECTIVES: In multiple sclerosis (MS) oxidative injury likely plays a major role in disease progression and in damaging tissue in the central nervous system (CNS), although with different mechanisms in the initial and the progressive disease stages. We compared the biomarker levels of plasmatic oxidative stress in patients with relapsing remitting (RR) and secondary progressive (SP) MS in order to correlate biomarker levels with demographic and clinical variables. DESIGN AND METHODS: We included 60 consecutive MS patients (30 with RR-MS and 30 with SP-MS) and a control group of 81 healthy subjects. All patients underwent clinical assessment, including disability, fatigue and sleepiness evaluations and blood sample collection for advanced oxidation protein products (AOPPs), plasmatic ferric reducing ability (FRA) and thiol group dosage. RESULTS: Plasmatic AOPPs were significantly higher while FRA and thiol levels were lower in MS patients compared to healthy controls. No difference was found in oxidative stress biomarker values in RR and SP-MS patients. However, in patients with "active" disease, FRA levels and thiol groups (expression of antioxidant power) were significantly lower. No significant correlation was found with demographic and clinical characteristics of patients, including age, disease duration, disability, fatigue, and daytime sleepiness. CONCLUSIONS: Plasmatic AOPPs, FRA and thiol groups show oxidative damage and reduced antioxidant capability in MS. Although their power to characterize different courses of the disease is limited, they seem to be related to disease activity.

Evidence of increased restless legs syndrome occurrence in chronic and highly disabling migraine.

The existence of an association between migraine and restless legs syndrome (RLS) has recently been reported, although the possible implications of this for migraine clinical presentation remain poorly understood. The objectives of this study were to determine RLS frequency in a population of migraineurs compared with healthy subjects and to assess RLS occurrence in episodic versus chronic migraine patients; the relationship between migraine-related disability and RLS comorbidity was also evaluated. Two hundred and seventy-seven consecutive migraineurs (ICHD-II, 2004) were enrolled and compared with 200 controls; migraine was episodic in 175 and chronic in 102 patients. RLS (IRLSSG criteria, 2003) was present in 22.7% of the total sample of migraineurs and in 7.5% of the controls (p<0.0001). RLS occurred significantly more frequently in chronic compared with episodic migraineurs (34.3% vs 16%, respectively, p=0.0006); a significant association between RLS diagnosis and moderate-severe migraine-related disability was also documented (p=0.0003). In conclusion, the results of the present study not only confirm the higher occurrence of RLS in migraine patients compared with the general population, but also suggest that RLS (the condition itself, or the disruption of sleep patterns often found in patients affected by RLS) might affect migraine clinical presentation, being associated with chronic and highly disabling migraine. These findings could have important therapeutic and prognostic implications in clinical practice.

Sleep-related migraine occurrence increases with aging.

A preferential occurrence of attacks at night-time or during early morning is documented in migraine without aura, suggesting a relationship between migraine and sleep and an impairment of circadian rhythms. The objective of this study was to verify the occurrence of sleep-related migraine in a large sample of migraineurs divided in different age groups and to evaluate the possible role of physiological variables (i.e., aging, gender) and comorbidities (i.e., psychiatric diseases). 734 patients (519 women and 215 males), aged 21-70 years, fulfilling IHS criteria (2004) for migraine without aura, were enrolled. The population was divided into five groups according to decades of life and it was evaluated the percentage of sleep-related migraine (at least 75% migraine attacks occurring during night sleep and/or upon awakening) in the different age groups. Headache clinical diary, Pittsburgh Sleep Quality Index and Beck Depression Inventory were also used. The preferential emergence of attacks during night sleep and/or upon awakening progressively increased with aging, without gender predilection; the percentage of patients with sleep-related migraine was: 16% between 20 and 30 years, 27% between 31 and 40 years, 38% between 41 and 50 years, 45% between 51 and 60 years, and 58% between 61 and 70 years, respectively. Poor sleep quality and depression did not account for night-time and/or awakening migraine collocation. These data suggest the main role of aging in order to favor nocturnal/early morning emergence of migraine without aura and support the hypothesis of an involvement of impaired chronobiological mechanisms and sleep regulation.