Association of anti-calcitonin gene-related peptide with other monoclonal antibodies for different diseases: A multicenter, prospective, cohort study.

BACKGROUND AND PURPOSE: Although there is extensive evidence about the safety of monoclonal antibodies against calcitonin gene-related peptide (anti-CGRP mAbs) in combination with traditional drugs, scarce data are available on the safety of their combination with other mAbs. This study aimed to evaluate the 6-month effectiveness and tolerability of anti-CGRP mAbs in combination with other mAbs for different diseases. METHODS: Patients included in the Italian Headache Registry and treated concomitantly with an anti-CGRP mAb and another mAb were included. Effectiveness outcomes for migraine included reduction from baseline of monthly headache days (MHDs), Migraine Disability Assessment (MIDAS) score, Headache Impact Test-6 (HIT-6) scores, and Patients' Global Impression of Change (PGIC) scale. Adverse events (AEs) were recorded. RESULTS: Thirty-eight patients were included. In 27 patients (71.1%), the anti-CGRP mAb was added to a previously ongoing mAb. Nine patients (23.7%) discontinued one of the two mAbs before the end of treatment (seven discontinued the anti-CGRP mAb and two the other mAb). One patient discontinued for AEs. Anti-CGRP mAbs were discontinued due to ineffectiveness (n = 5, 55.5%) and one each (11.1%) for clinical remission and lost to follow-up. MHDs significantly decreased from baseline to 3 months (p < 0.0001) and 6 months (p < 0.001), as did the MIDAS and the HIT-6 scores at 3 and 6 months (p < 0.001). For anti-CGRP mAbs, 27.4% of patients reported PGIC ≥ 5 at 3 months and 48.3% at 6 months. Mild AEs associated with introduction of a second mAb were detected in six patients (15.8%). CONCLUSIONS: In this real-world study, anti-CGRP mAbs showed safety and effectiveness when administered concomitantly with other mAbs.

Comparison of the Effect of Tanacethum Parthenium, 5-Hydroxy Tryptophan, and Magnesium (Aurastop) versus Magnesium Alone on Aura Phenomenon and Its Evolution.

None of the clinical trials on migraine conducted thus far have focused on the possibility to modulate the phenomenon of aura. Furthermore, whether proper management of aura results in a better control of the headache phase has been poorly investigated. In the setting of a single-center, pilot, clinical trial, we aimed at comparing the effects of Aurastop (a combination of tanacetum parthenium (150 mg extracted at 0.8% = 1.2 mg di of active parthenolide), griffonia simplicifoila (20 mg of 5-hydroxy tryptophan), and magnesium (185 mg of magnesium pidolatum)) with those of magnesium alone (2.25 grams/tablet, corresponding to 184 mg of Mg++) in the treatment of acute attacks of migraine with aura. Between June 2017 and June 2018, 50 consecutive patients (27/23 male/female; mean age, 31 [18-57] years) with at least 3 episodes of aura per year were included (t 0). Participants were instructed to keep track of the following 4 episodes of migraine with aura (t 1) and invited to assume (1) a tablet of Aurastop at the beginning of the following 2 episodes of aura and (2) a magnesium tablet alone at the occurrence of the third and fourth aura attacks. Forty-eight patients (96.0%) had >50% reduction in aura duration when treated with Aurastop vs. 7 patients (14.0%) when treated with magnesium alone (p < 0.001); 48 patients (96.0%) had >50% reduction of aura-related disability when receiving Aurastop vs. 5 patients (10.0%) when treated with magnesium alone (p < 0.001); however, patients receiving Aurastop did not need to take pain killers in 35% of aura attacks vs. 3% when assuming magnesium (p < 0.001). These results support the hypothesis that Aurastop might be effective in interfering with the phenomenon of aura and provide evidence that the clinical benefit attributable to this combination of molecules might be greater than that obtained with single compounds of proven effect on the biology of migraine.

Prevalence of headache attributed to aeroplane travel in headache outpatient populations: An Italian multicentric survey.

BACKGROUND: To assess the prevalence of headache attributed to aeroplane travel (AH) in patients referred to Italian Headache Centres. MATERIAL AND METHOD: 869 consecutive patients visiting six Italian headache centres during a 6 month-period (October 2013 to March 2014) were enrolled in the survey. Among them, 136 (15.6%) had never flown and therefore were excluded from the study. The remaining 733 patients (f = 586, m = 147; age 39.1 ± 17.3) were asked about the occurrence of headache attacks during flight; those who answered the question positively filled in a detailed questionnaire that allowed the features of the attacks to be defined. RESULTS: Headache attacks during the flight was reported by 34/733 subjects; four presented attacks fulfilling ICHD-3 beta (1) criteria for migraine without aura and therefore were not further considered. The features of the remaining 30 (4.0%; m = 18, f = 12, age 36.4 ± 7.3) completely fulfilled the ICHD-3 beta criteria for AH. In more detail, the pain was unilateral (fronto-orbital: n = 23; fronto-parietal: n = 7; without side-shift: n = 25, with side-shift: n = 5), lasting up to 30 min in 29 subjects. All the patients reported the pain as very severe or unbearable and landing as the phase of travel in which the attack appeared. In four cases, a postictal, milder, dull headache could last up to 24 hours. Accompanying symptoms were present in eight cases (restlessness: n = 5; conjunctival injection and tearing: n = 2; restlessness + ipsilateral conjunctival injection and tearing: n = 1). The fear of experiencing further attacks negatively affected the propensity for future flights in 90.0% of subjects (n = 27). In all the patients, AH onset did not coincide with the first flight experience. Concomitant migraine without aura was diagnosed in 24, tension-type headache in four, migraine without aura + tension-type headache in two cases; none suffered from cluster headache. Five subjects reported AH on each flight, 20 in > 50% of flights, five occasionally. Despite the severe intensity of the pain, only one third of this sample spontaneously reverted to a pharmacological treatment; the most useful strategy combines a decongestant nasal spray plus the intake of a simple analgesic 30 min before the estimated attack. Spontaneous manoeuvres were applied by 18 patients (Valsalva-like: n = 12; compression: n = 2; both manoeuvres: n = 4), more often without significant improvement. These data confirm our previous finding on the clinical features of AH. CONCLUSION: AH was found in 4.0% of a multicentre, large sample of patients with flight experiences. Although limited to a sample of patients followed in six Italian headache centres, to the best of our knowledge these are the first epidemiological data on AH gathered by direct interview. If properly investigated, AH seems to be a not infrequent condition, which, when diagnosed, could probably be prevented in many cases.

Association of brain amyloidosis with pro-inflammatory gut bacterial taxa and peripheral inflammation markers in cognitively impaired elderly.

The pathway leading from amyloid-ß deposition to cognitive impairment is believed to be a cornerstone of the pathogenesis of Alzheimer's disease (AD). However, what drives amyloid buildup in sporadic nongenetic cases of AD is still unknown. AD brains feature an inflammatory reaction around amyloid plaques, and a specific subset of the gut microbiota (GMB) may promote brain inflammation. We investigated the possible role of the GMB in AD pathogenesis by studying the association of brain amyloidosis with (1) GMB taxa with pro- and anti-inflammatory activity; and (2) peripheral inflammation in cognitively impaired patients. We measured the stool abundance of selected bacterial GMB taxa (Escherichia/Shigella, Pseudomonas aeruginosa, Eubacterium rectale, Eubacterium hallii, Faecalibacterium prausnitzii, and Bacteroides fragilis) and the blood expression levels of cytokines (pro-inflammatory cytokines: CXCL2, CXCL10, interleukin [IL]-1ß, IL-6, IL-18, IL-8, inflammasome complex (NLRP3), tumor necrosis factor-alpha [TNF-α]; anti-inflammatory cytokines: IL-4, IL-10, IL-13) in cognitively impaired patients with (n = 40, Amy+) and with no brain amyloidosis (n = 33, Amy-) and also in a group of controls (n = 10, no brain amyloidosis and no cognitive impairment). Amy+ patients showed higher levels of pro-inflammatory cytokines (IL-6, CXCL2, NLRP3, and IL-1ß) compared with both controls and with Amy- patients. A reduction of the anti-inflammatory cytokine IL-10 was observed in Amy+ versus Amy-. Amy+ showed lower abundance of E. rectale and higher abundance of Escherichia/Shigella compared with both healthy controls (fold change, FC = -9.6, p < 0.001 and FC = +12.8, p < 0.001, respectively) and to Amy- (FC = -7.7, p < 0.001 and FC = +7.4, p = 0.003). A positive correlation was observed between pro-inflammatory cytokines IL-1ß, NLRP3, and CXCL2 with abundance of the inflammatory bacteria taxon Escherichia/Shigella (rho = 0.60, p < 0.001; rho = 0.57, p < 0.001; and rho = 0.30, p = 0.007, respectively) and a negative correlation with the anti-inflammatory E. rectale (rho = -0.48, p < 0.001; rho = -0.25, p = 0.024; rho = -0.49, p < 0.001). Our data indicate that an increase in the abundance of a pro-inflammatory GMB taxon, Escherichia/Shigella, and a reduction in the abundance of an anti-inflammatory taxon, E. rectale, are possibly associated with a peripheral inflammatory state in patients with cognitive impairment and brain amyloidosis. A possible causal relation between GMB-related inflammation and amyloidosis deserves further investigation.

Assessment of the Incremental Diagnostic Value of Florbetapir F 18 Imaging in Patients With Cognitive Impairment: The Incremental Diagnostic Value of Amyloid PET With [18F]-Florbetapir (INDIA-FBP) Study.

IMPORTANCE: Cerebral amyloidosis is a key abnormality in Alzheimer disease (AD) and can be detected in vivo with positron emission tomography (PET) ligands. Although amyloid PET has clearly demonstrated analytical validity, its clinical utility is debated. OBJECTIVE: To evaluate the incremental diagnostic value of amyloid PET with florbetapir F 18 in addition to the routine clinical diagnostic assessment of patients evaluated for cognitive impairment. DESIGN, SETTING, AND PARTICIPANTS: The Incremental Diagnostic Value of Amyloid PET With [18F]-Florbetapir (INDIA-FBP) Study is a multicenter study involving 18 AD evaluation units from eastern Lombardy, Northern Italy, 228 consecutive adults with cognitive impairment were evaluated for AD and other causes of cognitive decline, with a prescan diagnostic confidence of AD between 15% and 85%. Participants underwent routine clinical and instrumental diagnostic assessment. A prescan diagnosis was made, diagnostic confidence was estimated, and drug treatment was provided. At the time of this workup, an amyloid PET/computed tomographic scan was performed, and the result was communicated to physicians after workup completion. Physicians were asked to review the diagnosis, diagnostic confidence, and treatment after the scan. The study was conducted from August 5, 2013, to December 31, 2014. MAIN OUTCOMES AND MEASURES: Primary outcomes were prescan to postscan changes of diagnosis, diagnostic confidence, and treatment. RESULTS: Of the 228 participants, 107 (46%) were male; mean (SD) age was 70.5 (7) years. Diagnostic change occurred in 46 patients (79%) having both a previous diagnosis of AD and an amyloid-negative scan (P < .001) and in 16 (53%) of those with non-AD diagnoses and an amyloid-positive scan (P < .001). Diagnostic confidence in AD diagnosis increased by 15.2% in amyloid-positive (P < .001; effect size Cohen d = 1.04) and decreased by 29.9% in amyloid-negative (P < .001; d = -1.19) scans. Acetylcholinesterase inhibitors and memantine hydrochloride were introduced in 61 (65.6%) patients with positive scan results who had not previously received those drugs, and the use of the drugs was discontinued in 6 (33.3%) patients with negative scan results who were receiving those drugs (P < .001). CONCLUSIONS AND RELEVANCE: Amyloid PET in addition to routine assessment in patients with cognitive impairment has a significant effect on diagnosis, diagnostic confidence, and drug treatment. The effect on health outcomes, such as morbidity and mortality, remains to be assessed.

Prevalence and demographic features of early-onset neurodegenerative dementia in Brescia County, Italy.

A few epidemiologic studies are available on the prevalence of early-onset Alzheimer disease (AD) and frontotemporal lobar degeneration (FTLD). The aim of this study was to establish in an Italian population, namely in Brescia County, the prevalence of early-onset neurodegenerative dementia, and how it is shared between AD and FTLD. A network among the participating centers has been established for 10 years. A standardized form was sent to be filled in for each patient. The census day was chosen as December 1, 2009. The prevalence of disease was calculated stratifying patients according to sex and diagnosis. On the census day, 175 patients in the whole population aged 45--65 years were enrolled into the study. The resulting overall prevalence of early-onset neurodegenerative dementia was found of 55.1 per 100,000 inhabitants (95%confidence interval, 47.0--63.4). A comparable prevalence between AD and FTLD was reported (25.5 and 29.6 per 100,000 inhabitants, respectively), and no differences in sex distribution were found both in AD and FTLD. The improvement of knowledge on early-onset neurodegenerative dementias allows us to reconsider its epidemiology and to rethink its impact on public polices. This would be crucial for defining the urgency of treatment approaches.

Functional serotonin 5-HTTLPR polymorphism is a risk factor for migraine with aura.

In the present work, we report that the functional serotonin transporter gene promoter (5-HTTLPR) polymorphism is involved in migraine pathogenesis. The distribution of 5-HTTLPR genotypes was significantly different in MA patients (S/S vs. S/L vs. L/L=32.7 vs. 42.3 vs. 25.0%), MO patients (18.5 vs. 39.1 vs. 42.4%) and CON (18.0 vs. 51.3 vs. 30.7%; chi-square test, p<0.05). In 5-HTTLPR S/S carriers, the odds ratio for MA risk was 2.60 (95% confidence interval [95%CI]=1.75-3.85) compared to CON, and it was 2.14 (95%CI=1.42-3.21) compared to MO. These data provide a further insight on the complex genotype-phenotype relationship involved in MA pathogenesis, and might eventually result in new and individualised prognostic and therapeutic measures.

Intraforaminal O(2)-O(3) versus periradicular steroidal infiltrations in lower back pain: randomized controlled study.

BACKGROUND AND PURPOSE: Reports about steroids and oxygen-ozone therapy to treat lower back pain have been increasing. The purpose of our study was to compare the clinical outcomes in patients treated with infiltrations of O(2)-O(3) gas or steroids at short-, medium-, and long-term follow-up. METHODS: A total of 306 patients (166 with primarily disk disease, 140 with nondisk vertebral disease) with acute or chronic low back and sciatic nerve pain received a CT-guided intraforaminal infiltration of an O(2)-O(3) gas mixture or an periradicular infiltration of steroids. Neurologists unaware of the type of treatment assessed the patients. RESULTS: At 1-week follow-up, most patients had a complete remission of pain, regardless of the treatment. At 6-month follow-up, differences in favor of O(2)-O(3) treatment were significant in patients with disk disease (P = .0021) but not in those without disk disease (P = .0992). Clinical outcomes were poor in 13 (15.1%) of 86 patients receiving O(2)-O(3) infiltration and in 18 (22.5%) of 80 patients receiving steroid injection (P = .2226). Among patients without disk disease, six (8.6%) of 70 patients receiving O(2)-O(3) infiltration but 21.4% of the patients receiving steroid injections had poor outcomes (P = .0332). CONCLUSION: Oxygen-ozone treatment was highly effective in relieving acute and chronic lower back pain and sciatica. The gas mixture can be administered as a first treatment to replace epidural steroids.