Evaluation of retinal nerve fiber layer,ganglion cell layer and macular changes in patients with migraine

The aim of this study was to investigate retinal nerve fiber layer (RNFL), ganglion cell layer (GCL) thickness, macular changes (central subfield thickness (CST), cube average thickness (CAT), cube volume (CV) in patients with migraine using spectral-domain optical coherence tomography (OCT) and to assess if there was any correlation with white matter lesions (WML). In this prospective case–control study, RNFL, GCL thickness and macular changes of 19 migraine patients with aura (MA), 41 migraine without aura (MO) and 60 age- and gender-matched healthy subjects were measured using OCT device. OCT measurements were taken at the same time of the day to minimize the effects of diurnal variation. The average, inferior and superior quadrant RNFL thickness were significantly thinner in patients with migraine (p = 0.017, p = 0.010, p = 0.048). There was also a significant difference between patients with and without aura in the mean and superior quadrant RNFL thickness (p = 0.02, p = 0.043).While there was a significant thinning in CST and CAT in patients with migraine (p = 0.020), there were no significant difference in GCL measurements (p = 0.184). When the groups were compared to the control group, there were significant differences between MA and the control group regarding average, superior and inferior quadrant RNLF thickness (p < 0.001, p = 0.025, p < 0.001). On the other hand, there were significant differences between MO and the control group regarding average and inferior faces (p = 0.037, p = 0.04). When OCT measurements were evaluated according to the frequency of attacks, CST and GCL thickness were significantly thinner in patients who had more than four attacks a month (p = 0.024, p = 0.014). In patients with WML, only CV measurements were significantly thinner than migraine patients without WML (p = 0.014). The decreased RNFL, CST, CAT and CV of the migraine patients might be related to the vascular pathology of the disease. Because WML was not correlated with the same measurements except CV, we think that further studies are needed to evaluate the etiopathologic relationship between OCT measurements and WML in migraine patients.     

The efficacy of lymphatic drainage and traditional massage in the prophylaxis of migraine: a randomized,controlled parallel group study

This study aimed at examining the efficacy of lymphatic drainage (LD) and traditional massage (TM) in the prophylactic treatment of migraine using controlled prospective randomized clinical trial of 64 patients (57 women, 45 ± 10 years) with migraine with and without aura. Patients were randomized into three groups: LD (n = 21); TM (n = 21); waiting group (WG, n = 22). After a 4-week-baseline, a treatment period of 8 weeks was applied followed by a 4-week observation period. The patients filled in a headache diary continuously; every 4 weeks they filled in the German version of the CES-D and the German version of the Headache Disability Inventory. The main outcome measure was migraine frequency per month. At the end of the observation period, the number of migraine attacks and days decreased in the LD group by 1.8 and 3.1, respectively, in the TM group by 1.3 and 2.4, and in the WG by 0.4 and 0.2, respectively. The differences between LD and WG were significant (p = 0.006 and p = 0.015, respectively) as well as the differences between TM und WG (p = 0.042 and p = 0.016, respectively). There was a significant decrease in the amount of analgesic intake in the LD group compared to the two other groups (p = 0.004). TM and LD resulted in a reduction of migraine attack frequency. The analgesic intake only decreased significantly during LD intervention. Useful effects were identified for LD and TM as compared to WG for the prophylaxis of migraine. LD was more efficacious in some parameters than TM.     

Intranasal sumatriptan for acute migraine attacks: a systematic review and meta-analysis

We performed this systematic review and meta-analysis to evaluate the tolerability and efficacy of intranasal sumatriptan, a selective serotonin agonist, compared to placebo or other migraine therapeutics for the treatment of acute migraine attacks. We searched PubMed, SCOPUS, Embase, and Cochrane CENTRAL for relevant randomized controlled trials (RCTs). Data were extracted from eligible studies and pooled as risk ratios (RR), using RevMan software. We performed subgroup and meta-regression analyses for different doses and treatment endpoints. Sixteen RCTs (n = 5925 patients) matched our inclusion criteria. The overall effect-estimate showed that intranasal sumatriptan was superior to placebo in terms of pain relief (RR = 1.70, 95% CI [1.31, 2.21], p < 0.0001) and headache relief (RR = 1.58, 95% CI [1.35, 1.84], p < 0.00001) at 2 h. Although sumatriptan was superior to placebo in terms of headache relief at 30 min (RR = 1.31, 95% CI [1.08, 1.59], p = 0.005), no significant difference was found between both groups in terms of the frequency of pain-free participants at 30 min (RR = 1.18, 95% CI [0.49, 2.88], p = 0.71). Subgroup analysis and meta-regression models showed that increasing the dose of sumatriptan reduced the time needed for headache relief; however, this clinical improvement with higher doses was associated with more frequent adverse events in comparison to smaller doses. In conclusion, intranasal sumatriptan is effective for the treatment of acute migraine attacks. However, it was associated with a six-fold increase in the risk of taste disturbance, compared to the placebo. Future RCTs are recommended to provide head-to-head comparison of different administration routes and drug formulations of sumatriptan.     

Efficacy of frovatriptan versus other triptans in the acute treatment of menstrual migraine: pooled analysis of three double-blind,randomized, crossover,multicenter studies

The objective of this study was to review the efficacy and safety of frovatriptan (F) versus rizatriptan (R), zolmitriptan (Z) and almotriptan (A), in women with menstrually related migraine (IHS criteria) through a pooled analysis of three individual studies. Subjects with a history of migraine with or without aura were randomized to F 2.5 mg or R 10 mg (study 1), F or Z 2.5 mg (study 2), and F or A 12.5 mg (study 3). The studies had an identical multicenter, randomized, double-blind, crossover design. After treating three episodes of migraine in no more than 3 months with the first treatment, patients had to switch to the next treatment for other 3 months. 346 subjects formed intention-to-treat population of the main study; 280 of them were of a female gender, 256 had regular menses and 187 were included in the menstrual migraine subgroup analysis. Rate of pain free at 2, 4 and 24 h was 23, 52 and 67 % with F and 30, 61 and 66 % with comparators (P = NS). Pain relief episodes at 2, 4 and 24 h were 37, 60 and 66 % for F and 43, 55 and 61 % for comparators (P = NS). Rate of recurrence was significantly (P < 0.05) lower under F either at 24 h (11 vs. 24 % comparators) or at 48 h (15 vs. 26 % comparators). Number of menstrual migraine attacks associated with drug-related adverse events was equally low (P = NS) between F (5 %) and comparators (4 %).     

Allergens might trigger migraine attacks

Migraine is a common primary headache disorder. The mechanisms underlying the onset of a migraine attack are not completely understood. Environmental changes and a number of other factors could induce migraine attacks. The aim of this study was to investigate the relationship between the frequency of migraine attacks and allergens. Migraine patients without aura, and healthy individuals similar in age and gender without a history of headache and allergy were prospectively included in the study. The duration of migraine, the frequency of migraine attacks, the medication history, and the symptoms during attacks were questioned. Migraine disability assessment score (MIDAS) and visual analog scale (VAS) scores were obtained. Allergen extracts including dust, fungi, insect, animal epithelium, pollens, and food allergens were applied for allergy tests. 49 migraine patients and 49 healthy individuals were enrolled in the study. There was no significant difference in terms of age and gender. The median migraine disease duration, the number of attacks in a month, and the duration of attacks were, respectively, 5.5 years (1–44), 4 (1–10) day/month, and 24 (4–72) h. The mean MIDAS grade was 2.45 ± 0.14 (1–4), and mean VAS score was 7.89 ± 0.27 (4–10). The positivity of allergy tests was 55.1 % (27/49) in the migraine group and 32.7 % (16/49) in the control group (p < 0.05). The allergy tests were positive for house dust, red birch, hazel tree, olive tree, nettle, and wheat. The frequency of migraine attacks was higher in allergy-test-positive patients than in negative ones in the migraine group (p = 0.001). The migraine patients who had frequent attacks should be examined for allergies.     

Addenbrooke’s cognitive examination test for brief cognitive assessment of adolescents suffering from migraine with aura

The aim of this study was to assess the role of the Addenbrooke’s cognitive examination test (ACE-R) in the evaluation of cognitive status in migraineurs interictally. A total of 44 adolescent patients and 44 healthy controls, matched by age and gender, have undergone ACE-R testing. Migraineurs were additionally questioned about migraine aura features and presence of higher cortical dysfunctions (HCD) during an aura. According to the questionnaire results, patients were subsequently divided into HCD and Non-HCD group. ACE-R scores of migraine patients were significantly lower than in healthy controls (93.68 ± 3.64 vs 96.91 ± 2.49; t = 4.852, p < 0.001). Also, subscores of memory and verbal fluency were significantly higher in the control population. There was no correlation of HCD occurrence with cognitive examination score, although Non-HCD subgroup achieved better score (93.13 ± 3.91 vs 94.29 ± 3.30; t = 1.053, p = 0.298). Findings have shown that migraineurs get lower ACE-R test scores, with a tendency to have a poorer outcome in more complex aura. Also, our study has revealed that the ACE-R test is an easily administered test for brief assessment of cognitive status in migraineurs. Future perspectives could be further evaluation of ACE-R test in larger sample size and the impact of migraine with aura on cognitive function in adolescents.     

Migraine attacks in the pharmacy: a survey in Piedmont,Italy

Headache patients often consult a pharmacist in an attempt to obtain momentary pain relief without having been given any previous expert advice. A specific questionnaire was distributed to the pharmacies in order to assess the patterns of use and dispensing of analgesic medications to the headache patient who turns to the pharmacist for relief of a painful attack. This study aimed at identifying migraine patients who self-medicated, with further end points including whether these patients shared any particular clinical characteristics, the most common type of analgesic medications used, and what, if anything, was recommended by the pharmacist; lastly, which health care professional, if any, routinely managed the patient’s headaches. A total of 9,100 questionnaires were distributed to the pharmacies and the complete 3,065 were included in the database. The ID Migraine Screener Test was used to classify subjects into 4 groups: “Definite migraine” (3/3 positive answers: n = 1,042; 34 %), “Probable migraine” (2/3: n = 969; 31.6 %), “Unlikely migraine” (1/3: n = 630; 20.5 %), and “Other headaches” (0/3: n = 424; 13.8 %). Only Definite and Probable migraines (n = 2,011) are considered in this paper. Amongst the drugs usually taken by the patients, NSAIDs were more common in the Probable migraine group (60.7 %) than in the Definite migraine (44.7 %) group (p < 0.001). On the contrary, triptans were more commonly used by the Definite migraine group (42.9 %) than the Probable migraine (23.7 %) group (p < 0.001), and combination drugs were preferentially (p < 0.001) chosen by the Definite (13.8 %) rather than the Probable migraine group (8.7 %). A total of 29.2 % of respondents reported that for the management of their headaches, they did not avail themselves of any type of professional healthcare, such as their general practitioner, a headache specialist, or a Headache Center.     

Functional neuroimaging in migraine

Migraine can be accompanied by some gastrointestinal (GI) disorders. In this study, we aimed to investigate the relationship between migraine and tension-type headache (TTH) and different lower and upper GI disorders as well as non-alcoholic fatty liver (NAFLD) and cholelithiasis. This cross-sectional study included 1574 overweight and obese participants who were referred to the Obesity Research Center of Sina Hospital, Tehran, Iran. The diagnosis of migraine and TTH was made by an expert neurologist based on the international classification of headache disorders-III β (ICHD III β). GI disorders, including irritable bowel syndrome (IBS), constipation, heartburn, dyspepsia, non-alcoholic fatty liver (NAFLD), and cholelithiasis, were diagnosed by a gastroenterology specialist. The overall mean age of participants was 37.44 ± 12.62. A total of 181 (11.5%) migraine sufferers (with and without aura) and 78 (5%) TTH subjects were diagnosed. After adjusting for potential confounders by multivariable regression models, migraine had significant association with IBS (OR = 5.16, 95% CI = 2.07–12.85, P = 0.000), constipation (OR = 3.96, 95% CI = 2.25–6.99, P = 0.000), dyspepsia (OR = 4.12, 95% CI = 2.63–6.45, P = 0.000), and heartburn (OR = 5.03, 95% CI 2.45–10.33, P = 0.000), while the association between migraine and NAFLD was marginally significant (OR = 2.03, 95% CI = 0.98–4.21, P = 0.055). Furthermore, the prevalence of NAFLD (OR = 2.93, 95% CI 1.29–6.65, P = 0.010) and dyspepsia (OR = 4.06, 95% CI = 2.24–7.34, P = 0.000) was significantly higher in TTH patients than the headache-free group. These findings show an association between GI disorders and primary headaches especially migraine and are, therefore, of value to the management of migraine and TTH. Further studies should investigate the etiology of the relationship between all subtypes of primary headaches and GI disorders.     

Treatment with telmisartan,a long-acting angiotensin II receptor blocker,prevents migraine attacks in Japanese non-responders to lomerizine

Lomerizine, calcium channel blocker, is the most used medication for migraine prophylaxis in Japan. The effectiveness of this drug is reported as 50–75%. Telmisartan is angiotensin II receptor blockers which plasma half-life is 24 h. We examined whether telmisartan has preventative benefits in lomerizine non-responsive migraineurs. Lomerizine non-responders received telmisartan (20 mg/day) for 3 months after the investigation period of 3 months. Blood pressure, frequency of headache days/month, headache severity, and doses of triptans and analgesics were analyzed by Wilcoxon signed rank test. Thirty-three migraineurs (25 women and 8 men) participated in this study. Seven patients had migraine with aura and 26 patients had migraine without aura. Mean age (SD) was 46.6 (10.3) years. Mean duration (SD) of migraine was 20.4 (12.5) years. Headache severity exhibited mild degree in 5 patients, moderate degree in 9 patients and severe degree in 19 patients. Mean frequency (SD) of headache days was 10.9 (8.5) days/month. Mean usage (SD) of triptans was 4.8 (5.1) tablets/month and that of analgesics was 15.2 (22.2) tablets/month. Five patients (15%) had hypertension. Telmisartan administration had benefits in 30 patients (90%). This medication significantly decreased frequency of headache days (P < 0.01) and headache severity (P < 0.01). Doses of triptans were reduced at one-third (P < 0.05) and those of analgesia at one-fifth after telmisartan treatment (P < 0.01). After telmisartan, mean (SD) of systolic blood pressure was significantly decreased (P < 0.05). The present study supported that telmisartan treatment had preventive effects in 90% of lomerizine non-responders. Telmisartan non-responders (10%) exhibited chronic migraine and long migraine duration.     

Unilateral cranial autonomic symptoms in patients with migraine

The aim of this study is to investigate the frequency of unilateral cranial autonomic symptoms during migraine attacks, and to compare the clinical characteristics of migraine patients with and without unilateral cranial autonomic symptoms. One hundred and eighty-six consecutive patients with episodic migraine attacks were prospectively included. Cranial autonomic symptoms of the patients occurred during headache, frequency, duration, severity and character of headache, disease duration, presence of aura, laterality of headache, accompanying symptoms, relation of migraine attacks with menstruation, lesions detected on magnetic resonance images, and family history of migraine were recorded. The patients with and without unilateral cranial autonomic symptoms during headache were compared in terms of above-mentioned parameters. Seventy-seven (41.4 %) patients were observed to develop unilateral cranial autonomic symptoms during migraine attack. Disease duration was longer in the patients with unilateral cranial autonomic symptoms than in those without (p = 0.045). Headache was unilateral in 83.1 % of the patients with unilateral cranial autonomic symptoms (p = 0.001). Pure menstrual or menstrually related migraine attacks were more common in the patients with unilateral cranial autonomic symptoms (p = 0.043) and is thought that menstruation-related hormonal factors might have a triggering role on the trigeminal-autonomic reflex pathway. The longer disease duration in patients with unilateral cranial autonomic symptoms might be associated with the activation of pathophysiological mechanisms that cause cranial autonomic symptoms in time. Frequent unilateral pain in migraine patients with unilateral cranial autonomic symptoms is likely to indicate that the development of autonomic symptoms may share common mechanisms with the pathogenesis of trigeminal autonomic cephalalgias.     

Migraine causes retinal and choroidal structural changes: evaluation with ocular coherence tomography

Few studies have evaluated whether the retina is involved in migraine through the evaluation of retinal nerve fiber layer (RNFL) examined with ocular coherence tomography (OCT) with conflicting results. Aim of this case–control study is to evaluate the retina and the choroid in migraine. Patients having migraine with aura (MwA) or without aura (MoA) and chronic migraine (CM) were evaluated. Age- and sex-matched normal subjects were selected as healthy controls (HC). Patients and HC were examined with OCT. RNFL, ganglion cell layer (GCL), foveal thickness (FT), choroidal thickness (CT) and total macular volume (TMV) were calculated for right eyes (RE) and left eyes (LE). Seventy-seven patients (62 women; 80.5%), 21 MoA, 12 MwA, 44 CM and 42 HC were enrolled in the study. Patients compared to HC had a significant reduction of RNFL (RE: 91.2 ± 9.2 vs 99.3 ± 7.5 μm; p < 0.001. LE: 93.3 ± 8.7 vs 100.2 ± 6.5 μm; p < 0.001). GCL (RE: 80.6 ± 6.4 vs 86.9 ± 2.1 μm; p < 0.0001. LE: 81.5 ± 5.7 vs 87.1 ± 2.6 μm; p < 0.0001) and CT (RE: 286.4 ± 31.4 vs 333.2 ± 3.1 μm; p < 0.0001. LE: 287.2 ± 31.6 vs 334.5 ± 4.1 μm; p < 0.0001) were thinner in patients compared to HC. Moreover, CM showed reduction of RNFL and of GCL compared to the other migraineurs. Finally, we found a significant inverse correlation between RNFL thickness and total number of headache attacks per months. Our data suggest the involvement of retina and choroid in migraineurs, especially in the CM group. Although migraine is an episodic and recurrent disease, its chronic nature might cause permanent structural abnormalities involving not only the brain, but also the retina.     

Frovatriptan versus zolmitriptan for the acute treatment of migraine: a double-blind,randomized, multicenter,Italian study

The objective of this study is to assess patients’ satisfaction with migraine treatment with frovatriptan (F) or zolmitriptan (Z), by preference questionnaire. 133 subjects with a history of migraine with or without aura (IHS criteria) were randomized to F 2.5 mg or Z 2.5 mg. The study had a multicenter, randomized, double-blind, cross-over design, with each of the two treatment periods lasting no more than 3 months. At the end of the study, patients were asked to assign preference to one of the treatments (primary endpoint). The number of pain-free (PF) and pain-relief (PR) episodes at 2 h, and number of recurrent and sustained pain-free (SPF) episodes within 48 h were the secondary study endpoints. Seventy-seven percent of patients expressed a preference. Average score of preference was 2.9 ± 1.3 (F) versus 3.0 ± 1.3 (Z; p = NS). Rate of PF episodes at 2 h was 26% with F and 31% with Z (p = NS). PR episodes at 2 h were 57% for F and 58% for Z (p = NS). Rate of recurrence was 21 (F) and 24% (Z; p = NS). Time to recurrence within 48 h was better for F especially between 4 and 16 h (p < 0.05). SPF episodes were 18 (F) versus 22% (Z; p = NS). Drug-related adverse events were significantly (p < 0.05) less under F (3 vs. 10). In conclusion, our study suggests that F has a similar efficacy of Z, with some advantage as regards tolerability and recurrence.     

Do bilateral and unilateral greater occipital nerve block effectiveness differ in chronic migraine patients?

We aimed to compare the effectiveness of bilateral and unilateral block application in chronic migraine patients and whether there were differences in their effectiveness retrospectively. In chronic migraine patients undergoing Greater occipital nerve (GON) block, mean number of days with pain per month before and after block, mean duration of pain in attacks (in hours), and mean Visual Analog Scale (VAS) in attack and pain severity were recorded from files. The patients underwent one block a week for the first 1 month, thereafter one block a month according to GON block protocol used by our institute. Of 41 patients included in the study, 23 underwent unilateral block (group 1) and 18 underwent bilateral block (group 2). In both groups, number of days with migraine decreased significantly in 2 and 3 months as compared to pre-block treatment (P < 0.001). Mean duration of headache decreased in group 2 during treatment (P < 0.001). In group 1, mean duration of headache also decreased but did not differ significantly (P = 0.051). Mean severity of migraine decreased significantly differ in group 1 in 2, 3 months as compared to pre-block treatment (P < 0.001). No differences were observed in frequency, severity and duration of headache between groups during 3-month treatment period. GON block is effective in chronic migraine and bilateral application is no superior over unilateral application.     

Characteristics of hypertrophic pachymeningitis in patients with granulomatosis with polyangiitis

Hypertrophic pachymeningitis (HP) is an important neurologic complication of granulomatosis with polyangiitis (GPA, formerly Wegener’s granulomatosis). The aim of this study is to investigate the clinical features, radiological findings, and diagnostic pitfalls of GPA-related HP. A retrospective chart review was performed to screen patients diagnosed with GPA at Samsung Medical Center between 1997 and 2016. Neurologic manifestation, laboratory findings, neuroimaging data, and clinical course were evaluated in all patients. Characteristics of patients with HP were compared to those of patients without HP. Sixty-five patients with GPA were identified. Twenty-five of these patients had central nervous system involvement. HP (N = 9, 36%) was the second most common radiologic finding. Other neurologic findings included stroke (N = 7, 28%) and granulomatous disease (N = 10, 40%). Patients with HP had lower incidences of systemic manifestations (N = 2, 22.2% vs. N = 38, 67.9%, p = 0.013 in the lung and N = 1, 11.1% vs. N = 28, 50.0%, p = 0.030 in the kidney) than those without HP. Six patients with GPA-related HP were MPO-ANCA positive (66.7%) and two had PR3-ANCA (22.2%). Most of the patients with HP presented with headache (N = 8, 88.9%) at a rate that is similar to those of primary headache disorders (migraine, tension-type, and stabbing) and other secondary headache disorders (postural type and meningitis). Patients with HP rarely had neurologic deficits (N = 3, 37.5%). Different clinical or radiologic features may be observed in GPA-related HP. Early recognition and accurate diagnosis of GPA-related HP are needed in addition to neuroimaging findings.     

ApoA1, ApoJ and ApoE Plasma Levels and Genotype Frequencies in Cerebral Amyloid Angiopathy

The involvement of apolipoproteins, such as the ApoE4 isoform, in Alzheimer’s disease (AD) and cerebral amyloid angiopathy (CAA) highlights the fact that certain lipid carriers may participate in soluble β-amyloid (Aβ) transport. Our general aim was to characterize the soluble levels of the apolipoproteins apoE, apoA1 and apoJ/clusterin and their genotype status in patients with CAA. We analyzed the genotypes frequency of APOA1 (rs5069, rs670), CLU (rs11136000, rs1532278, rs7012010, rs9331888) and APOE (rs429358, rs7412) in a cohort of patients with CAA-associated intracerebral hemorrhage (ICH) (n = 59) and compared the results with those from hypertension-associated ICH (n = 42), AD patients (n = 73) and controls (n = 88). In a subgroup of patients, we also determined the plasma concentrations of apoE, apoA1 and apoJ/clusterin. We found increased plasma apoJ/clusterin levels in CAA patients compared to AD patients or controls after adjusting for sex and age (CAA vs. controls, p = 0.033; CAA vs. AD, p = 0.013). ApoA1 levels were not altered between groups, although a strong correlation was observed between plasma Aβ(1-40) and apoA1 among CAA patients (r = 0.583, p = 0.007). Regarding plasma apoE concentration, a robust association between circulating levels and genotype status was confirmed (p < 0.001). Whereas the APOE4 frequency was higher in AD (p < 0.001) and CAA (p = 0.013), the APOA1 and CLU genotypes were not different among groups. In the CAA cohort, the risk-linked CLU variant (C) rs11136000 was associated with white matter hyperintensities (p = 0.045) and the presence of lobar microbleeds (p = 0.023) on MRI. In summary, our findings suggest that apoA1 may act as a physiological transporter of Aβ(1-40) and that apoJ/clusterin appears to be a chaperone related to distinctive lesions in CAA brains.     

Frovatriptan vs. other triptans for the acute treatment of oral contraceptive-induced menstrual migraine: pooled analysis of three double-blind,randomized, crossover,multicenter studies

Oral contraceptive-induced menstrual migraine (OCMM) is a particularly severe form of migraine triggered by the cyclic hormone withdrawal. To review the efficacy of frovatriptan vs. other triptans, in the acute treatment of OCMM through a pooled analysis of three individual randomized Italian studies. With or without aura migraineurs were randomized to frovatriptan 2.5 mg or rizatriptan 10 mg (study 1), frovatriptan 2.5 mg or zolmitriptan 2.5 mg (study 2), frovatriptan 2.5 mg or almotriptan 12.5 mg (study 3). All studies had a multicenter, randomized, double-blind, crossover design. After treating 1–3 episodes of migraine in 3 months with the first treatment, patients switched to the other treatment for the next 3 months. In this analysis, the subset of 35 of the 280 women of the intention-to-treat population taking combined oral contraceptives and experiencing a migraine attack during the withdrawal phase, were analyzed. The proportion of pain free and pain relief at 2 h were 25 and 51 % with frovatriptan and 28 and 48 % with comparators (p = NS). At 24 h, 71 and 83 % of frovatriptan-treated patients and 60 and 76 % of comparator-treated patients were pain free (p < 0.05 between treatments) and had pain relief (p = NS), respectively. Relapse at 24 and 48 h was significantly (p < 0.05) lower with frovatriptan (17 and 21 %) than with the comparators (27 and 31 %). Our results suggest that, due to its sustained antimigraine effect, frovatriptan may be particularly suitable for the management of OCMM than other triptans.     

Sympathetic cardiovascular and sudomotor functions are frequently affected in early multiple sclerosis

Objective

The aim of this study was to determine the prevalence of autonomic dysfunction using the composite autonomic scoring scale (CASS) and heart rate variability (HRV) in patients with clinically isolated syndrome (CIS) and to correlate autonomic dysfunction with other measures of MS disease activity.

Methods

CASS, HRV and plasma catecholamines during supine and tilted phase were performed in 104 CIS patients. MRI findings were analyzed for total number of lesions and the presence of brainstem and cervical spinal cord lesions.

Results

Autonomic dysfunction (CASS >1) was present in 59.8 % of patients, parasympathetic dysfunction in 5 %, sympathetic in 42.6 % and sudomotor in 32.7 % of patients. Patients with autonomic dysfunction on CASS had lower level of norepinephrine in the supine position compared to patients without autonomic dysfunction (1.06 ± 0.53 vs. 1.37 ± 0.86, p = 0.048). The CASS score showed positive correlation with s-HF (r = 0.226, p = 0.031), s-SDNN (r = 0.221, p = 0.035), t-HF (r = 0.225, p = 0.032), and t-HFnu (r = 0.216, p = 0.04), and a negative correlation with t-LF/HF (r = ?0.218, p = 0.038). More patients with MRI brainstem lesions had a positive adrenergic index (p = 0.038). Patients with MRI brainstem lesions also had a lower t-SDNN (26.2 ± 14.2 vs. 32 ± 13.3, p = 0.036) and a lower t-LF (median 415.0 vs. 575.5, p = 0.018) compared to patients without these lesions. Patients with adrenergic index ≥1 had a significantly higher standing heart rate compared to patients with an adrenergic index of 0 (96 ± 13.5 vs. 90 ± 12, p = 0.032).

Conclusion

Autonomic (primarily sympathetic) dysfunction is present in a large proportion of early MS patients and it seems to be related to brainstem involvement.

     

Peripheral nerve diffusion tensor imaging as a measure of disease progression in ALS

Clinical trial design in amyotrophic lateral sclerosis (ALS) remains hampered by a lack of reliable and sensitive biomarkers of disease progression. The present study evaluated peripheral nerve diffusion tensor imaging (DTI) as a surrogate marker of axonal degeneration in ALS. Longitudinal studies were undertaken in 21 ALS patients studied at 0 and 3 months, and 19 patients at 0, 3 and 6 months, with results compared to 13 age-matched controls. Imaging metrics were correlated across a range of functional assessments including amyotrophic lateral sclerosis functional rating scale revised (ALSFRS-R), lower limb muscle strength (Medical Research Council sum score, MRCSS-LL), compound muscle action potential amplitudes and motor unit number estimation (MUNE). Fractional anisotropy was reduced at baseline in ALS patients in the tibial (p < 0.05), and peroneal nerve (p < 0.05). Fractional anisotropy and axial diffusivity declined in the tibial nerve between baselines, 3- and 6-month scans (p < 0.01). From a functional perspective, ALSFRS-R correlated with fractional anisotropy values from tibial (R = 0.75, p < 0.001) and peroneal nerves (R = 0.52, p = 0.001). Similarly, peroneal nerve MUNE values correlated with fractional anisotropy values from the tibial (R = 0.48, p = 0.002) and peroneal nerve (R = 0.39, p = 0.01). There were correlations between the change in ALSFRS-R and tibial nerve axial diffusivity (R = 0.38, p = 0.02) and the change in MRCSS-LL and peroneal nerve fractional anisotropy (R = 0.44, p = 0.009). In conclusion, this study has demonstrated that some peripheral nerve DTI metrics are sensitive to axonal degeneration in ALS. Further, that DTI metrics correlated with measures of functional disability, strength and neurophysiological measures of lower motor neuron loss.     

Clinical Value of Neutrophil to Lymphocyte and Platelet to Lymphocyte Ratio After Aneurysmal Subarachnoid Hemorrhage

Background

Inflammation and thrombosis are associated with the pathogenesis of aneurysmal subarachnoid hemorrhage (aSAH) and neutrophil to lymphocyte ratio (NLR) and platelet to lymphocyte ratio (PLR) are emerging as novel inflammatory markers in stroke. We aimed to identify the association of NLR and PLR with delayed cerebral ischemia (DCI) and 3-month outcome after aSAH.

Methods

Two hundred and forty-seven patients diagnosed with aSAH within 24 h of symptoms onset were enrolled. Clinical, neuroradiological, laboratory, and follow-up data were collected from electronic database. Functional outcome was assessed by modified Rankin Scale. Admission NLR, PLR, and combined NLR-PLR associated with outcomes were evaluated by logistic regression analysis, and we used receiver operating characteristic curves to detect the overall predictive accuracy of these markers.

Results

Fifty-five (22.3 %) patients had unfavorable outcome and 47 (19 %) developed DCI. Both NLR and PLR were correlated with WFNS grade (ρ = 0.35[p < 0.001], ρ = 0.28[p < 0.001]) and modified Fisher grade (ρ = 0.25[p = 0.001], ρ = 0.28[p = 0.003]) and independently related to DCI (OR 2.18, 95 %CI 1.51–3.15, p = 0.016; OR 2.21, 95 %CI 1.61–3.32, p = 0.008) and functional outcome (OR 1.89, 95 %CI 1.52–3.17, p = 0.015; OR 1.77, 95 %CI 1.48–3.21, p = 0.018) at 3 months after aneurysm repair. They had comparable predictive ability in DCI occurrence (area under the curve [AUC] 0.65, 95 %CI 0.55–0.74, p = 0.002; AUC 0.68, 95 %CI 0.60–0.76, p < 0.001) and poor outcome (AUC 0.70, 95 %CI 0.63–0.77, p < 0.001; AUC 0.65, 95 %CI 0.58–0.72, p = 0.001). However, combination of the two indexes showed a better predictive value than each alone (AUC 0.73, 95 %CI 0.66–0.81, p < 0.001 for DCI; AUC 0.76, 95 %CI 0.70–0.83, p < 0.001 for poor outcome).

Conclusions

NLR and PLR as novel inflammatory biomarkers are independent predictors of DCI development and functional outcome after acute aSAH. When combined together, they may help to identify high-risk patients more powerfully.

     

Frovatriptan versus zolmitriptan for the acute treatment of migraine with aura: a subgroup analysis of a double-blind,randomized, multicenter,Italian study

Migraine with aura affects ~20–30 % of migraineurs and it is much less common than migraine without aura. The aim of this study was to compare the efficacy of frovatriptan 2.5 mg and zolmitriptan 2.5 mg in the treatment of migraine with aura. Analysis was carried out in a subset of 18 subjects with migraine with aura (HIS criteria) out of the 107 enrolled in a multicenter, randomized, double-blind, cross-over study. According to the study design, each patient had to treat three episodes of migraine in no more than 3 months with one drug, before switching to the other treatment. The rate of pain-free episodes at 2 h was significantly (p < 0.05) larger under frovatriptan (45.8 %) than under zolmitriptan (16.7 %). Pain free at 4 h, pain relief at 2 and 4 h and recurrent episodes were similar between the two treatments, while sustained pain-free episode was significantly (p < 0.05) more frequent during frovatriptan treatment (33.3 vs. 8.3 % zolmitriptan). Our study suggests that frovatriptan is superior to zolmitriptan in the immediate treatment of patients with migraine with aura, and it is capable of maintaining its acute analgesic effect over 48 h.