Reconceptualizing autonomic function testing in migraine: a systematic review and meta-analysis.

BACKGROUND: Autonomic nervous system (ANS) testing has aided in our ability to evaluate autonomic dysfunction in migraine patients. We reviewed the literature in multiple databases which investigate ANS function in migraine patients and healthy subjects. METHODS: This systematic review and meta-analysis examined the respective deep breathing, Valsalva manoeuvre, orthostatic and isometric challenge results, using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) and Meta-analyses of Observational Studies in Epidemiology (MOOSE) statements. RESULTS: Seven articles met all inclusion criteria. Fixed-effects meta-analysis showed migraine patients (n = 424), collectively, had lower interictal autonomic test results compared with healthy controls (n = 268). In detail, this was true for the standardized mean difference (g) of deep breathing (g= -0.32; 95% confidence interval (CI) -0.48, -0.16), orthostatic challenge (g= -0.28; 95% CI -0.44, -0.13) and isometric challenge (g= -0.55; 95% CI -0.71, -0.39) and for the difference of means (MD) of the Valsalva ratio (MD = -0.17; 95% CI -0.23, -0.10). CONCLUSIONS: Interictal ANS dysfunction can be identified in migraine patients when compared to healthy controls. These findings indicate the importance to evaluate ANS function in migraine patients - especially, as migraine-specific prophylactic therapies (such as anti-calcitonin gene-related peptide (CGRP) antibodies) may affect the function of the ANS.

Triptans and vascular comorbidity in persons over fifty: Findings from a nationwide insurance database - A cohort study.

OBJECTIVE: To gather information about prescription of triptans and to evaluate whether vascular comorbidity differs in users and nonusers of triptans over the age of 50 years. BACKGROUND: Beyond the age of 50 years, migraine is still common-yet the incidence of vascular disorders increases. Triptans, medications for treating migraine attacks, are vasoconstrictive drugs and contraindicated in persons with vascular disorders. METHODS: Based on a nationwide insurance database from 2011, we compared the prescription of vascular drugs (identified by Anatomical Therapeutic Chemical codes), vascular diagnoses and hospitalizations, between triptan users greater than 50 years and a matched control group. RESULTS: Of the 3,116,000 persons over 50 years, 13,833 (0.44%) had at least one triptan prescription; 11,202 (81%) were women. Thirty percent of the triptan users (13,833/47,336 persons) were over 50 years. Of those over 50 years, 6832 (49.4%) had at least one vascular drug and 870 (6.3%) had at least one inpatient vascular diagnosis; 15.7% (2166 of 13,833 users) overused triptans. We compared triptan-users to 41,400 nonusers, using a 1:3 match. In triptan-users, prescriptions of cardiac therapies and beta blockers were significantly more common (odds ratio [OR] = 1.35, 95% confidence interval [CI] = 1.24-1.47 and OR = 1.19, 95% CI = 1.14-1.25, respectively); whereas prescriptions of calcium channel blockers and renin/angiotensin inhibitors were significantly less common (OR = 0.82, 95% CI = 0.76-0.88 and OR = 0.75, 95% CI = 0.72-0.79, respectively). The prescriptions of antihypertensive, diuretic, and antilipidemic drugs as well as platelet inhibitors and direct thrombin inhibitors did not differ in users and nonusers. Triptan users had significantly more hospital stays (OR = 1.39, 95% CI = 1.33-1.45); however, the number of days spent in the hospital and more importantly the frequency of inpatient vascular diagnoses did not differ statistically significantly between the two groups. CONCLUSION: In persons over 50 years of age, a prescription of triptans is common. Vascular comorbidity is comparable in users and nonusers of triptans showing that triptans are prescribed despite vascular comorbidity and suggesting that triptan use does not increase vascular risk in patients with migraine over the age of 50 years. Nevertheless, regular evaluation for contraindications against triptans and for vascular risk factors is recommended in this age group.

Monoclonal Antibodies against Calcitonin Gene-Related Peptide for Migraine Prophylaxis: A Systematic Review of Real-World Data.

OBJECTIVE: To perform a systematic review of real-world outcomes for anti-CGRP-mAbs. METHODS: Following the PRISMA guidelines, we searched PubMed for real-world data of erenumab, galcanezumab, fremanezumab, or eptinezumab in patients with migraines. RESULTS: We identified 134 publications (89 retrospective), comprising 10 pharmaco-epidemiologic and 83 clinic-based studies, 38 case reports, and 3 other articles. None of the clinic-based studies provided follow-up data over more than one year in more than 200 patients. Findings suggest that there are reductions in health insurance claims and days with sick-leave as well as better treatment adherence with anti-CGRP-mAbs. Effectiveness, reported in 77 clinic-based studies, was comparable to randomized controlled trials. A treatment pause was associated with an increase in migraine frequency, and switching to another antibody resulted in a better response in some of the patients. Adverse events and safety issues were addressed in 86 papers, including 24 single case reports. CONCLUSION: Real-world data on anti-CGRP-mAbs are limited by retrospective data collection, small patient numbers, and short follow-up periods. The majority of papers seem to support good effectiveness and tolerability of anti-CGRP-mAbs in the real-world setting. There is an unmet need for large prospective real-world studies providing long-term follow-ups of patients treated with anti-CGRP-mAbs.

Postprandial hypotension in neurological disorders: systematic review and meta-analysis.

PURPOSE: Postprandial hypotension (PPH) has been associated with increased risk of syncope, falls, stroke, angina and mortality. As the majority of patients with PPH are asymptomatic, the diagnosis is often overlooked. The aim of this study was to perform a systematic review and meta-analysis of available scientific evidence on the likelihood of PPH in neurological diseases. METHODS: A systematic review of the literature (PubMed library, Cochrane Database for Systematic Reviews and Cochrane Central Register of Controlled Trials for results up to January 2017) identified 327 studies, of which 11 reported the frequency of PPH in patients with neurological diseases compared to healthy controls. These 11 studies were on patients with Parkinson's disease (PD; n = 6 studies), multiple system atrophy (MSA; n = 1), Alzheimer's disease (AD; n = 1) and diabetic neuropathy (DN; n = 2). RESULTS: The meta-analysis revealed that patients with neurological diseases had a significantly higher frequency of PPH than healthy controls [147/289 patients vs. 41/217 controls; odd ratio (OR) 5.23, 95% confidence interval (CI) 2.90-9.45, p < 0.00001]. For each of the four diseases, the respective patients had a significantly higher frequency of PPH than healthy controls (PD: 107/201 patients vs. 32/136 controls; OR 3.49, 95% CI 2.09-5.83, p < 0.0001; MSA: 19/27 patients vs. 0/24 controls; OR 89.55, 95% CI 2.65-3030.33, p = 0.01; AD: 7/10 patients vs. 6/23 controls; OR 6.61, 95% CI 1.28-34.14, p = 0.02; DN: 14/51 patients vs. 3/34 controls; OR 4.83, 95%CI 1.20-19.41, p = 0.03). CONCLUSION: The likelihood of having PPH is higher in patients with neurological diseases than in healthy controls. These findings should prompt further research focusing on the epidemiology and pathophysiology of PPH in different neurological diseases.

Differences in neurohumoral and hemodynamic response to prolonged head-up tilt between patients with high and normal standing norepinephrine forms of postural orthostatic tachycardia syndrome.

OBJECTIVE: To investigate the optimal timing for blood sample collection of catecholamines and the possible correlations between neurohumoral and hemodynamic responses to prolonged head-up tilt (HUT) in postural orthostatic tachycardia syndrome (POTS). METHODS: Nineteen patients underwent a 30-minute, 70° HUT test. Blood samples (norepinephrine (NE), epinephrine and dopamine) were taken in the 10th minute of supine, and 10th, 20th and 30th minutes of HUT. RESULTS: There were no significant differences in the proportion of high and normal standing NE patients in the different time points. Mean NE (nmol/L) values in 10th, 20th and 30th minute of HUT were 4.37, 4.87, and 4.35 in the high standing NE, and 2.49, 2.59 and 2.88 in the normal standing NE group. High standing NE patients had higher blood pressure (BP) during the first 6min of HUT (2nd minute after the HUT systolic BP (sBP): 118.29±15.65 vs. 95.70±13.43, p=0.004; diastolic BP (dBP): 78.71±6.68 vs. 65.10±9.04, p=0.003), while normal standing NE patients exhibited a drop in BP compared to resting values during the same time period. The normal standing NE group exhibited a progressive increase in norepinephrine values during the HUT. CONCLUSION: One blood sample taken at the 10th minute of HUT correctly identifies high and normal standing NE POTS patients, but a small number of patients (1 out of 19, 5.2%) can be misidentified. High and normal standing NE POTS patients display distinctly different neurohumoral and hemodynamic responses to HUT.

Hemodynamic profile and heart rate variability in hyperadrenergic versus non-hyperadrenergic postural orthostatic tachycardia syndrome.

OBJECTIVES: To investigate differences in hemodynamic profile between hyperadrenergic and non-hyperadrenergic postural orthostatic tachycardia syndrome (POTS) in response to head-up tilt test (HUTT). METHODS: Ten patients with hyperadrenergic and 33 patients with non-hyperadrenergic POTS underwent HUTT consisting of a 10-min supine phase and 30-min 70° tilted phase. Heart rate (HR), systolic and diastolic blood pressure (dBP), and heart rate variability (HRV) parameters of the two groups were compared. RESULTS: Hyperadrenergic patients had higher supine HR (82.6 ± 16.3 bpm vs. 73.8 ± 10.4 bpm, p=0.048). Supine HRV analysis showed significantly lower cardiac vagal activity and possible predominance of cardiac sympathetic activity in the hyperadrenergic group. Non-hyperadrenergic patients had lower dBP during the first four minutes of tilt. Furthermore, 60% of non-hyperadrenergic patients had lower average dBP in the 1st minute of tilted phase when compared to supine values, whereas only 2 of 10 hyperadrenergic patients exhibited the same response. Syncope or intolerable symptoms, causing early ending of HUTT, developed earlier in the non-hyperadrenergic group (8.9 ± 6.8 min vs. 21.2 ± 3.5 min, p=0.001). CONCLUSION: Hyperadrenergic and non-hyperadrenergic type of POTS seem to have distinctly different response to HUTT. SIGNIFICANCE: This study has shown significant differences in hemodynamic response to HUTT between hyperadrenergic and non-hyperadrenergic type of POTS indicating possible differences in their pathophysiology.