Autonomic Dysfunction among Migraineurs with and without Complaints of Orthostatic Intolerance: Evidence for Small Fiber Nerve Damage

Background and Objective: Migraineurs often complain of orthostatic intolerance (OI), and its recognition is vital to appropriate treatment. This study attempts to identify and characterize autonomic dysfunction, comparing a sample of migraineurs with OI with a sample of migraineurs without OI. Methods: In a prospective cohort study, we examined one migraine sample complaining of OI for > 6 months (Group 1) and another group without OI (Group 2), using a 70-degree, 45-minute head-up passive tilt-table (HUT45) test, electrocardiographic R-R interval measurements during deep breathing, blood pressure and heart rate monitoring during Valsalva and release, QSART, and skin biopsy for nerve fiber density. We compared results with standard, 10-minute head-up passive tilt-table (HUT10) results to determine which test promoted greater sensitivity, specificity and diagnostic accuracy. Descriptive statistics were computed for each group, defined by the presence or absence of OI. We conducted several receiver operating characteristic analyses to determine whether certain clinical characteristics were predictive of symptoms of OI. Results: Thirty-nine Group 1 and 22 Group 2 subjects were studied and were similar demographically. Thirty eight of 39 (97.4%) Group 1, versus 15/22 (68.2%) Group 2 subjects, manifested abnormal HUT45 results, a significant difference (p=0.002). The HUT45 showed higher sensitivity (0.59; 95% CI: 0.42-0.74) than the standard 10-minute tilt-table test (HUT10) for all expressions of OI (0.31; 95% CI: 0.17-0.48). No differences in autonomic laboratory or skin biopsy findings distinguished the groups. We detected biopsy-proven small fiber neuropathy in 22/39 (56.4%) Group 1 and 10/22 (45.5%) Group 2 subjects. Discussion and Conclusions: In migraineurs, OI is an expression of autonomic dysfunction. We found evidence for a peripheral autonomic deficit on skin biopsy in 45% or more of both groups of migraineurs. Extending the head-up tilt table test to 45-minutes increases diagnostic sensitivity, spares patients misdiagnosis and unnecessary testing, and satisfies the principle of ecological validity.

Improvement of hyperadrenergic postural orthostatic tachycardia syndrome (POTS) with methylated B vitamins in the setting of a heterozygous COMT Val158Met polymorphism

A middle-aged woman was diagnosed with postural orthostatic tachycardia syndrome based on her clinical symptoms, elevated norepinephrine levels and positive tilt-table test. The patient was refractory to conventional treatment and improved only after she was treated with methylated B vitamins for her heterozygous catechol-O-methyltransferase Val158Met polymorphism.

What is a tilt table test and why is it performed during the investigation of syncope?

Falls are one of the most common reasons for patients to present to the emergency department. Syncope is a common cause of falls, which disproportionately affects older people. In most cases, syncope can be confirmed with a detailed history and simple bedside tests, but tilt table testing remains an invaluable diagnostic adjunct in more complex cases. Often misunderstood, the tilt table test is a useful way to reproduce a patient’s symptoms in a safe and controlled environment. The tilt table test is considered positive if the patient experiences symptoms associated with a drop in blood pressure or postural tachycardia. The test can support a diagnosis and can direct therapeutic interventions.

Intravenous Cyclophosphamide Treatment for Systemic Lupus Erythematosus with Severe Autonomic Disorders Confirmed by Head-Up Tilt Table Test: A Case Series

Autonomic disorders are common in patients with SLE, but the therapeutic strategy and methods for evaluating the effects of therapy have not been established. We describe the three cases of SLE patients who developed severe autonomic disorders as demonstrated by the head-up tilt table test (HUT). All three patients were treated by intensive immunosuppressive treatments including cyclophosphamide (IVCY); their HUT results all became negative. Our cases suggest that IVCY treatment can be a good therapeutic option for severe autonomic disorders in SLE patients. The HUT is a useful objective method for the diagnosis of and the evaluation of longitudinal therapeutic effects on autonomic disorders in SLE patients with orthostatic intolerance.

Patients with reflex syncope have a higher prevalence of atrial fibrillation than general population which is predicted by the type of the tilt table test response

Introduction Reflex syncope is the result of an imbalance between the sympathetic and parasympathetic nervous system. The autonomic nervous system has been associated to some forms of atrial fibrillation (AF). Objective The aim of this study was to assess the prevalence of AF in patients with reflex syncope and a positive tilt table test and to identify the type of tilt test response in patients with AF in comparison to patients without AF. Methods We retrospectively studied consecutive patients that underwent a tilt table test at our institution between 2016 and 2019. We selected those patients with a positive test. Patients with an implanted pacemaker at the time of the tilt test and patients followed in a different institution were excluded. Previous diagnoses of AF episodes were assessed. We analysed the clinical characteristics and the tilt table test results according to previous history of AF. Results We studied 49 patients with a positive tilt test. Seven (14.3%) patients had previously diagnosed paroxysmal AF at the time of the tilt table test. Patients with AF were older, had more frequently hypertension, and the tilt test response was more frequently a vasodepressor than mixed or cardioinhibitory response (71.4% vs. 28.6%) (Table). In univariate analysis, age and hypertension were associated with AF, respectively, OR 1.08 (95% CI 1.01–1.17), p=0.034 and OR 10.80 (95% CI 1.19–98.36), p=0.035. A vasodepressor response was also associated with AF (OR 6.25, 95% CI 1.06–36.74, p=0.043). Conclusions Patients with reflex syncope and a positive tilt table test had a higher prevalence of AF than the general population. A vasodepressor response was associated with AF as were age and hypertension, demonstrating the possible impact of the autonomic nervous system and the multifactorial nature of AF. FUNDunding Acknowledgement Type of funding sources: None.

Interesting presentation of a broad complex tachycardia during the head up tilt table test

Broad complex tachycardia (BCT) during head up tilt test (HUTT) is infrequent. Electrophysiology Study (EPS) plays an important part in further differentiation of BCT. We present a case of BCT during HUTT in a patient presenting with presyncope which later on EPS with 3D mapping was diagnosed as ventricular tachycardia. This case highlights the unusual occurrence of BCT during HUTT, the differential diagnosis of BCT and the utility of EPS to reliably identify the type and origin of BCT.

Electrocardiographic Patterns in Patients with Neurally Mediated Syncope

The baseline electrocardiogram (ECG) is less informative in neurally mediated syncope (NMS) than in arrhythmic syncope. However, some of the ECG patterns present in NMS can have diagnostic and prognostic value in such patients. Electrocardiographic documentation of a syncopal spell and thus identification of the ECG changes can be performed during tilt table test (TTT) or during prolonged ECG monitoring. This work reviews the specific ECG patterns in NMS, which are primarily related to the cardioinhibitory reflex. In addition, there are other ECG findings present in patients with NMS that are being analyzed, such as increased heart rate variability as well as specific QRS voltage patterns. In addition to the diagnostic and prognostic value, these ECG patterns in NMS may help improving the selection of patients for pacemaker implant.

The Diagnostic Value of Cardiac Deceleration Capacity in Vasovagal Syncope

Background: Increased parasympathetic activity is thought to play important roles in syncope events of patients with vasovagal syncope (VVS). However, direct measurements of the vagal control are difficult. The novel deceleration capacity (DC) of heart rate measure has been used to characterize the vagal modulation. This study aimed to assess vagal control in patients with VVS and evaluate the diagnostic value of the DC in VVS. Methods: Altogether, 161 consecutive patients with VVS (43±15 years; 62 males) were enrolled. Tilt table test was positive in 101 and negative in 60 patients. Sixty-five healthy subjects were enrolled as controls. DC and heart rate variability in 24-hour ECG, echocardiogram, and biochemical examinations were compared between the syncope and control groups. Results: DC was significantly higher in the syncope group than in the control group (9.6±3.3 versus 6.5±2.0 ms, P <0.001). DC was similarly increased in patients with VVS with a positive and negative tilt table test (9.7±3.5 and 9.4±2.9 ms, P =0.614). In multivariable logistic regression analyses, DC was independently associated with syncope (odds ratio=1.518 [95% CI, 1.301–1.770]; P =0.0001). For the prediction of syncope, the area under curve analysis showed similar values when comparing single DC and combined DC with other risk factors ( P =0.1147). From the receiver operator characteristic curves for syncope discrimination, the optimal cutoff value for the DC was 7.12 ms. Conclusions: DC>7.5 ms may serve as a good tool to monitor cardiac vagal activity and discriminate VVS, particularly in those with negative tilt table test.