Autonomic Dysfunction from Diagnosis to Treatment.

Autonomic disorders can present with hypotension, gastrointestinal, genitourinary symptoms, and heat intolerance. Diabetes is the most common causes of autonomic failure, and management should focus on glucose control to prevent developing autonomic symptoms. The most prevalent cause of dysautonomia, or autonomic dysfunction, is Postural Orthostatic Tachycardia Syndrome (POTS). Autonomic testing characterizes causes for nonspecific symptoms but is not necessary in patients with classic presentations. Treatment for autonomic dysfunction and failure focus on discontinuing offending medications, behavioral modification, and pharmacologic therapy to decrease symptom severity. Autonomic failure has no cure; therefore, the focus remains on improving quality of life.

Phenoconversion in pure autonomic failure: a multicentre prospective longitudinal cohort study.

We aimed to describe the clinical features of patients with pure autonomic failure (PAF) preceding phenoconversion that could be useful as predictive markers for advancing α-synuclein-associated neurodegeneration of the brain. Patients diagnosed with PAF were evaluated at 8 Centers (7-US based and 1 European) and enrolled in a longitudinal observational cohort study (NCT01799915). Subjects underwent detailed assessments of motor, sleep, olfactory, cognitive, and autonomic function and were followed prospectively to determine whether they developed parkinsonism or dementia for up to 10 years. We identified incident cases of Parkinson disease (PD), dementia with Lewy bodies (DLB), or multiple system atrophy (MSA) and computed hazard ratios for phenoconversion as functions of clinical features. A total of 209 participants with PAF with a median disease duration of 6 years (IQR: 3-10) were enrolled. Of those, 149 provided follow-up information at an office or telemedicine visit. After a mean follow-up duration of 3 years, 48 (33%) participants phenoconverted (42% to PD, 35% to DLB, and 23% to MSA). Faster phenoconversion from study enrollment to any diagnosis was associated with urinary and sexual dysfunction [HR 5.9, 95%CI: 1.6-22, and HR: 3.6, 95%CI: 1.1-12] followed by subtle motor signs [HR: 2.7, 95%CI: 1.2-6], trouble swallowing [HR 2.5, 95%CI: 1.4-4.5], and changes in speech [HR:2.4, 95%CI:1.1-4.8] at enrollment. Subjects reporting deterioration of handwriting were more likely to phenoconvert to PD (HR: 2.6, 95%CI: 1.1-5.9, ) and those reporting difficulty handling utensils were more likely to phenoconvert to DLB (HR: 6.8, 95%CI: 1.2-38). Patients with a younger age of PAF onset [HR: 11, 95%CI: 2.6-46], preserved olfaction [HR: 8.7, 95%CI: 1.7-45], anhidrosis [HR: 1.8, 95%CI: 1-3.1, p=0.042], and severe urinary problems [HR 1.6, 95%CI: 1-2.5, p=0.033] were more likely to phenoconvert to MSA. The best autonomic predictor of PD was a blunted heart rate increase during the tilt-table test (HR: 6.1, 95%CI: 1.4-26). Patients with PAF have an estimated 12% (95% CI: 9%-15%) per year annual risk following study entry of phenoconverting to a manifest CNS synucleinopathy.

Symptoms of postural orthostatic tachycardia syndrome in pregnancy: a cross-sectional, community-based survey.

OBJECTIVE: To evaluate the relationship between postural orthostatic tachycardia syndrome (POTS) and pregnancy. DESIGN: Cross-sectional survey. SETTING: International. SAMPLE: A total of 8941 female patients with a diagnosis of POTS. METHODS: Data from the survey were analysed using descriptive measures and stratified for comparisons. MAIN OUTCOME MEASURES: Symptom course of POTS during pregnancy. Secondary outcomes included pregnancy loss, POTS onset during pregnancy and the impacts of a comorbid diagnosis of Ehlers-Danlos syndrome or an autoimmune disorder on symptoms during pregnancy. RESULTS: Overall, 40.8% (n = 3652) of participants reported one or more pregnancies. Most participants experienced worsening of symptoms in the first (62.6%) and third (58.9%) trimesters and 3 months after pregnancy (58.7%), and 81.1% experienced worsening symptoms at any point in their pregnancy. Most participants with worsening symptoms in the first trimester also experienced worsening symptoms in the second (61.6%) and third (68.1%) trimesters, but if they improved in the first trimester then this improvement persisted in the second and third trimesters. Of participants who reported that POTS was triggered by a specific event (41.3%), 8.1% reported pregnancy as the trigger for the onset. CONCLUSIONS: Postural orthostatic tachycardia syndrome symptoms in the first trimester of pregnancy may help predict symptom course throughout the duration of pregnancy. Some individuals may experience an initial onset of POTS during pregnancy. This novel information may guide clinicians in counselling patients with POTS who are planning pregnancy.

Gender Disparities in the Career of Neurology Researchers.

BACKGROUND AND OBJECTIVES: To assess gender disparities in neurology researcher careers in the United States. METHODS: A 34-question survey was distributed to 4,644 US-based American Academy of Neurology members who self-identified as researchers in 2020 addressing the following domains: research and funding, scholarly activities, coronavirus disease 2019 (COVID-19) effect, and local institutional climate. RESULTS: A total of 700 (15%) individuals completed the survey (women, n = 231; men, n = 426), with 71% White and >80% conducting research. Women respondents were significantly younger than men, more likely to be assistant professors (32% vs 21%), and less likely to be full professors (18% vs 39%). Compared with men, women received equivalent grants and research support and had comparable or additional formal research training and mentorship. Women had less middle author publications (mean 5.8 [SD 9.2] vs mean 8.2 [SD 11.8], p = 0.03) compared with men but similar first or last author publications (mean 4.3[5.4] vs 6.1 [9.8], p = 0.05). A lower proportion of women presented research at grand rounds or at a national/international conference compared with men (58% vs 69%, p = 0.01). Women spent more time in nonprofessional responsibilities, were less satisfied with their work-life balance, and were less likely to agree with statements addressing equity/diversity and institutional climate. Respondents shared their concerns regarding how the pandemic was affecting neurology research careers, with a higher proportion of women reporting that family responsibilities affected research activities and lead to delayed submission of non-COVID-19-related manuscripts. DISCUSSION: Our survey of US-based neurology researchers demonstrated continued gender-based disparities in academic rank, manuscript authorship, and invited speaking engagements, although funding opportunities and access to additional training were equivalent. Women were less likely than men to agree that neurology departments support diversity and equity and that the institutional climate was inclusive and transparent. The pandemic had affected both genders in research, but areas were different for women related to family responsibilities. This article also highlights additional areas of research and areas for intervention to improve and reduce gender disparities among neurology researchers.

Management of Orthostatic Hypotension in the Hospitalized Patient: A Narrative Review.

Orthostatic hypotension is a frequent cause of falls and syncope, impairing quality of life. It is an independent risk factor of mortality and a common cause of hospitalizations, which exponentially increases in the geriatric population. We present a management plan based on a systematic literature review and understanding of the underlying pathophysiology and relevant clinical pharmacology. Initial treatment measures include removing offending medications and avoiding large meals. Clinical assessment of the patients' residual sympathetic tone can aid in the selection of initial therapy between norepinephrine "enhancers" or "replacers." Role of splanchnic venous pooling is overlooked, and applying abdominal binders to improve venous return may be effective. The treatment goal is not normalizing upright blood pressure but increasing it above the cerebral autoregulation threshold required to improve symptoms. Hypertension is the most common associated comorbidity, and confining patients to bed while using pressor agents only increases supine blood pressure, leading to worsening pressure diuresis and orthostatic hypotension. Avoiding bedrest deconditioning and using pressors as part of an orthostatic rehab program are crucial in reducing hospital stay.

Management Strategies for Comorbid Supine Hypertension in Patients with Neurogenic Orthostatic Hypotension.

PURPOSE OF REVIEW: In autonomic failure, neurogenic orthostatic hypotension (nOH) and neurogenic supine hypertension (nSH) are interrelated conditions characterized by postural blood pressure (BP) dysregulation. nOH results in a sustained BP drop upon standing, which can lead to symptoms that include lightheadedness, orthostatic dizziness, presyncope, and syncope. nSH is characterized by elevated BP when supine and, although often asymptomatic, may increase long-term cardiovascular and cerebrovascular risk. This article reviews the pathophysiology and clinical characteristics of nOH and nSH, and describes the management of patients with both nOH and nSH. RECENT FINDINGS: Pressor medications required to treat the symptoms of nOH also increase the risk of nSH. Because nOH and nSH are hemodynamically opposed, therapies to treat one condition may exacerbate the other. The management of patients with nOH who also have nSH can be challenging and requires an individualized approach to balance the short- and long-term risks associated with these conditions. Approaches to manage neurogenic BP dysregulation include nonpharmacologic approaches and pharmacologic treatments. A stepwise treatment approach is presented to help guide neurologists in managing patients with both nOH and nSH.

Local Passive Heat for the Treatment of Hypertension in Autonomic Failure.

Background Supine hypertension affects a majority of patients with autonomic failure; it is associated with end-organ damage and can worsen daytime orthostatic hypotension by inducing pressure diuresis and volume loss during the night. Because sympathetic activation prevents blood pressure (BP) from falling in healthy subjects exposed to heat, we hypothesized that passive heat had a BP-lowering effect in patients with autonomic failure and could be used to treat their supine hypertension. Methods and Results In Protocol 1 (n=22), the acute effects of local heat (40-42°C applied with a heating pad placed over the abdomen for 2 hours) versus sham control were assessed in a randomized crossover fashion. Heat acutely decreased systolic BP by -19±4 mm Hg (versus 3±4 with sham, P<0.001) owing to decreases in stroke volume (-18±5% versus -4±4%, P=0.013 ) and cardiac output (-15±5% versus -2±4%, P=0.013). In Protocol 2 (proof-of-concept overnight study; n=12), we compared the effects of local heat (38°C applied with a water-perfused heating pad placed under the torso from 10 pm to 6 am) versus placebo pill. Heat decreased nighttime systolic BP (maximal change -28±6 versus -2±6 mm Hg, P<0.001). BP returned to baseline by 8 am. The nocturnal systolic BP decrease correlated with a decrease in urinary volume (r=0.57, P=0.072) and an improvement in the morning upright systolic BP (r=-0.76, P=0.007). Conclusions Local heat therapy effectively lowered overnight BP in patients with autonomic failure and supine hypertension and offers a novel approach to treat this condition. Future studies are needed to assess the long-term safety and efficacy in improving nighttime fluid loss and daytime orthostatic hypotension. Registration URL: https://www.clinicaltrials.gov; Unique identifiers: NCT02417415 and NCT03042988.

Long-COVID postural tachycardia syndrome: an American Autonomic Society statement.

COVID-19 is a global pandemic that has had a devastating effect on the health and economy of much of human civilization. While the acute impacts of COVID-19 were the initial focus of concern, it is becoming clear that in the wake of COVID-19, many patients are developing chronic symptoms that have been called Long-COVID. Some of the symptoms and signs include those of postural tachycardia syndrome (POTS). Understanding and managing long-COVID POTS will require a significant infusion of health care resources and a significant additional research investment. In this document from the American Autonomic Society, we outline the scope of the problem, and the resources and research needed to properly address the impact of Long-COVID POTS.

Postural orthostatic tachycardia syndrome is associated with significant employment and economic loss.

BACKGROUND: Postural orthostatic tachycardia syndrome (POTS) is a debilitating form of chronic orthostatic intolerance that primarily affects women and causes substantial impairment in quality of life and function. Yet, there is minimal literature describing the employment and economic consequences of POTS. We explored these aspects of the POTS patient experience through a self-reported study designed using community-based participatory research principles. METHODS AND RESULTS: A comprehensive questionnaire, including employment and economic consequences, was developed in partnership with Dysautonomia International, a patient advocacy organization. The POTS community engaged in all stages of the research design and analysis. Participants were recruited through Dysautonomia International's website and social media channels. The analysis included 5,556 adult (age ≥18 years) participants with a physician-confirmed diagnosis of POTS. The majority of participants were female (95%). Forty-eight per cent of participants reported employment during the three months prior to the survey, and of these participants, 66.8% would work greater hours if not for illness limitations. Over two-thirds (70.5%) of participants have lost income due to POTS symptoms, with 36.0% of the total cohort losing more than $10,000 USD in the 12 months prior to the survey. Almost all (95%) participants reported POTS-related out-of-pocket medical expenses since diagnosis, with 51.1% of participants spending $10,000 USD or more. CONCLUSIONS: This is the largest study reporting the employment and economic challenges experienced by individuals with POTS. Exposure of these challenges emphasizes the need for earlier diagnosis and improved therapeutic strategies to reduce the negative individual and societal consequences of this disorder.

Symptom Presentation and Access to Medical Care in Patients With Postural Orthostatic Tachycardia Syndrome: Role of Sex.

BACKGROUND: Postural orthostatic tachycardia syndrome (POTS) is a chronic form of orthostatic intolerance that primarily impacts female patients of childbearing age. The role of sex differences in POTS is not well understood. We sought to identify sex differences in diagnosis, symptoms, comorbidities, and treatments in female and male patients diagnosed with POTS. METHODS: A comprehensive survey was designed in partnership by Dysautonomia International (East Moriches, NY) and Vanderbilt University Medical Center (Nashville, TN). Patients were recruited through Dysautonomia International's website and social media channels. The survey was delivered online through a secure research data capture database. Responses were analyzed according to biological sex. Continuous variables are presented as median (25th percentile-75th percentile), and categorical variables are presented as number and proportion of participants. RESULTS: A total of 8919 patients reported a physician diagnosis of POTS and were included in this analysis. The majority of respondents were female (93.7%). Female and male patients experienced misdiagnosis at similar rates (76.2% vs 74.9%, P = 0.5) and saw a similar number of doctors before diagnosis (5 [3-8] vs 5 [3-8], P = 0.9). Despite these similarities, diagnostic delay was longer for female, compared with male, patients (1.50 [0.25-5.25] years vs 0.92 [0.08-2.91] years, P < 0.001). CONCLUSIONS: Despite the primarily female demographic of POTS patients, female patients experience more challenges with diagnosis than male patients. Increased awareness and recognition of POTS may help to reduce the diagnostic challenges in both female and male patients, and improve treatment and management for individuals living with this debilitating disorder.

CONTEXTE: Le syndrome de tachycardie orthostatique posturale (STOP) est une forme chronique d'intolérance orthostatique qui touche principalement les femmes en âge de procréer. L'incidence du sexe sur le STOP n'est pas bien comprise. Nous avons cherché à déterminer les différences entre les sexes en ce qui a trait au diagnostic, aux symptômes, aux comorbidités et aux traitements chez les patients féminins et masculins ayant reçu un diagnostic de STOP. MÉTHODOLOGIE: Une enquête exhaustive a été conçue en partenariat par Dysautonomia International (East Moriches, NY, États-Unis) et le Vanderbilt University Medical Center (Nashville, TN, États-Unis). Les patients ont été recrutés par l'entremise du site Web de Dysautonomia International et des médias sociaux. L'enquête a été réalisée en ligne au moyen d'une base de données sécurisée de saisie de données de recherche. Les réponses ont été analysées en fonction du sexe biologique. Les variables continues sont présentées sous forme de médiane (25e percentile-75e percentile), et les variables nominales sont présentées sous forme de nombre et de proportion de participants. RÉSULTATS: Au total, 8 919 patients ont signalé un diagnostic de STOP établi par un médecin et ont été inclus dans cette analyse. La majorité des répondants étaient des femmes (93,7 %). Les patients de sexe féminin et masculin ont été mal diagnostiqués dans des proportions similaires (76,2 % vs 74,9 %, p = 0,5) et ont vu un nombre similaire de médecins avant le diagnostic (5 [3-8] vs 5 [3-8], p = 0,9). Malgré ces similitudes, le retard de diagnostic était plus long chez les femmes que chez les hommes (1,50 [0,25-5,25] an contre 0,92 [0,08-2,91] an, p < 0,001). CONCLUSIONS: Même si les patients atteints de STOP sont principalement des femmes, ces dernières ont plus de difficultés à recevoir un diagnostic que les hommes. Une meilleure connaissance et reconnaissance du STOP peut contribuer à réduire les problèmes liés au diagnostic chez les patients féminins et masculins, et à améliorer le traitement et la prise en charge des personnes atteintes de ce trouble débilitant.

Restless legs syndrome is increased in postural orthostatic tachycardia syndrome.

STUDY OBJECTIVES: Postural orthostatic tachycardia syndrome (POTS) and restless legs syndrome (RLS) are both characterized by sleep disturbance along with autoimmune/inflammatory features and autonomic dysfunction. However, to our knowledge, there has been no direct study looking at the prevalence of RLS in patients with POTS patients compared with healthy participants (controls). METHODS: Ninety-six physician-diagnosed patients with POTS (89 female and 7 male) and 130 controls (99 female and 31 male) were administered the Cambridge Hopkins questionnaire. Participants who were diagnosed with probable or definite RLS on the Cambridge Hopkins questionnaire were then contacted to determine the severity of RLS with the International Restless Legs Scale. RESULTS: More patients with POTS (15 of 96; 15.6%) than controls (6 of 130; 4.6%) were diagnosed with probable or definite RLS on the Cambridge Hopkins questionnaire (P = .0048). A sensitivity analysis with only female respondents yielded similar results. RLS severity was in the moderate range (12.23 ± 9.22). CONCLUSIONS: There is a higher prevalence of RLS in patients with POTS patients compared with controls. This association may have to do with shared increased inflammatory/autoimmune load and autonomic dysfunction.

Management of Neuropathic Pain in Polyneuropathy.

PURPOSE OF REVIEW: Many polyneuropathies cause significant neuropathic pain, resulting in substantial morbidity and reduced quality of life. Appropriate management is crucial for maintaining quality of life for patients with painful polyneuropathies. The US Food and Drug Administration (FDA) has only approved one new drug for painful diabetic neuropathy in the past decade, a topical capsaicin patch that was initially approved for the treatment of postherpetic neuralgia in 2009. Gabapentinoids and serotonin norepinephrine reuptake inhibitors (SNRIs) continue to have an advantage in safety profiles and efficacy. Other antiepileptic medications remain second-line agents because of fewer studies documenting efficacy. RECENT FINDINGS: This article reviews recent literature on complementary and pharmacologic therapies for the management of painful polyneuropathies. Exercise has emerged as an important therapeutic tool and may also improve the underlying polyneuropathy in the setting of obesity, metabolic syndrome, and diabetes. SUMMARY: The approach to management of painful polyneuropathies is multifactorial, using both pharmacologic and nonpharmacologic measures to improve pain severity and patient quality of life.

Idiopathic distal sensory polyneuropathy: ACTTION diagnostic criteria.

OBJECTIVE: To present standardized diagnostic criteria for idiopathic distal sensory polyneuropathy (iDSP) and its subtypes: idiopathic mixed fiber sensory neuropathy (iMFN), idiopathic small fiber sensory neuropathy (iSFN), and idiopathic large fiber sensory neuropathy (iLFN) for use in research. METHODS: The Analgesic, Anesthetic, and Addiction Clinical Trial Translations, Innovations, Opportunities and Networks (ACTTION) public-private partnership with the Food and Drug Administration convened a meeting to develop consensus diagnostic criteria for iMFN, iSFN, and iLFN. After background presentations, a collaborative, iterative approach was used to develop expert consensus for new criteria. RESULTS: An iDSP diagnosis requires at least 1 small fiber (SF) or large fiber (LF) symptom, at least 1 SF or LF sign, abnormalities in sensory nerve conduction studies (NCS) or distal intraepidermal nerve fiber density (IENFD), and exclusion of known etiologies. An iMFN diagnosis requires that at least 1 of the above clinical features is SF and 1 clinical feature is LF with abnormalities in sensory NCS or IENFD. Diagnostic criteria for iSFN require at least 1 SF symptom and at least 1 SF sign with abnormal IENFD, normal sensory NCS, and the absence of LF symptoms and signs. Diagnostic criteria for iLFN require at least 1 LF symptom and at least 1 LF sign with normal IENFD, abnormal sensory NCS, and absence of SF symptoms and signs. CONCLUSION: Adoption of these standardized diagnostic criteria will advance research and clinical trials and spur development of novel therapies for iDSPs.

Splanchnic Venous Compression Enhances the Effects of ß-Blockade in the Treatment of Postural Tachycardia Syndrome.

Background Splanchnic venous pooling induced by upright posture triggers a compensatory increase in heart rate (HR), a response that is exaggerated in patients with postural tachycardia syndrome. To assess whether abdominal compression attenuates orthostatic tachycardia and improves symptoms, 18 postural tachycardia syndrome patients (32±2 years) were randomized to receive either abdominal compression (40 mm Hg applied with an inflatable binder ≈2 minutes before standing) or propranolol (20 mg) in a placebo-controlled, crossover study. Methods and Results Systolic blood pressure, HR, and symptoms were assessed while seated and standing, before and 2 hours postdrug. As expected, propranolol decreased standing HR compared with placebo (81±2 versus 98±4 beats per minute; P<0.001) and was associated with lower standing systolic blood pressure (93±2 versus 100±2 mm Hg for placebo; P=0.002). Compression had no effect on standing HR (96±4 beats per minute) but increased standing systolic blood pressure compared with placebo and propranolol (106±2 mm Hg; P<0.01). Neither propranolol nor compression improved symptoms compared with placebo. In 16 patients we compared the combination of abdominal compression and propranolol with propranolol alone. The combination had no additional effect on standing HR (81±2 beats per minute for both interventions) but prevented the decrease in standing systolic blood pressure produced by propranolol (98±2 versus 93±2 mm Hg for propranolol; P=0.029), and significantly improved total symptom burden (-6±2 versus -1±2 for propranolol; P=0.041). Conclusions Splanchnic venous compression alone did not improve HR or symptoms but prevented the blood pressure decrease produced by propranolol. The combination was more effective in improving symptoms than either alone. Splanchnic venous compression can be a useful adjuvant therapy to propranolol in postural tachycardia syndrome. Registration URL: https://www.clini​caltr​ials.gov; Unique identifier: NCT00262470.

Autonomic function testing in the COVID-19 pandemic: an American Autonomic Society position statement.

COVID-19 is a global pandemic that is wreaking havoc with the health and economy of much of human civilization. In this document from the American Autonomic Society, we identify the potential risks of exposure to patients, physicians, and allied healthcare staff. We provide guidance for conducting autonomic function testing safely in this environment.

Initiation of droxidopa during hospital admission for management of refractory neurogenic orthostatic hypotension in severely ill patients.

Orthostatic hypotension (OH) is a common cause of hospitalization, particularly in the elderly. Hospitalized patients with OH are often severely ill, with complex medical comorbidities and high rates of disability. Droxidopa is a norepinephrine precursor approved for the treatment of neurogenic OH (nOH) associated with autonomic failure that is commonly used in the outpatient setting, but there are currently no data regarding the safety and efficacy of droxidopa initiation in medically complex patients. We performed a retrospective review of patients started on droxidopa for refractory nOH while hospitalized at Vanderbilt University Medical Center between October 2014 and May 2017. Primary outcome measures were safety, change in physician global impression of illness severity from admission to discharge, and persistence on medication after 180-day follow-up. A total of 20 patients were identified through chart review. Patients were medically complex with high rates of cardiovascular comorbidities and a diverse array of underlying autonomic diagnoses. Rapid titration of droxidopa was safe and well tolerated in this cohort, with no cardiovascular events or new onset arrhythmias. Supine hypertension requiring treatment occurred in four patients. One death occurred during hospital admission due to organ failure associated with end-stage amyloidosis. Treating physicians noted improvements in presyncopal symptoms in 80% of patients. After 6 months, 13 patients (65%) continued on droxidopa therapy. In a retrospective cohort of hospitalized, severely ill patients with refractory nOH, supervised rapid titration of droxidopa was safe and effective. Treatment persistence was high, suggesting that symptomatic benefit extended beyond acute intervention.

Factors associated with distal symmetric polyneuropathies in adult Zambians: A cross-sectional, observational study of the role of HIV, non-antiretroviral medication exposures, and nutrition.

BACKGROUND: Non-antiretroviral (ART) drug exposures and poor nutrition may be important modifiable risk factors for distal symmetric polyneuropathies (DSP) in sub-Saharan Africa. METHODS: We conducted a cross-sectional study of DSP prevalence and factors associated with DSP among clinic attendees in urban and rural Zambia. All participants underwent neurologist-performed examination. Laboratory investigations seeking comorbid risk factors for DSP were performed for DSP cases. RESULTS: We identified 31/137 (22.6%) HIV+ and 21/177 (11.9%) HIV- DSP cases. DSP prevalence did not differ by urbanicity, although rural participants were significantly more likely to have one asymptomatic DSP sign. Low dietary diversity, history of syphilis, history of tuberculosis, and prior metronidazole and ciprofloxacin use were associated with DSP amongst HIV+ cases, while age and education were associated with DSP in HIV- participants (all p-values < 0·05). In a multivariate logistic regression model, HIV (p = 0·0001) and age (p < 0·0001), and ciprofloxacin exposure (p = 0·01) remained independently associated with DSP. While diabetes was rare, supoptimal micronutrients levels were common among DSP cases regardless of HIV status. CONCLUSIONS: While HIV infection is strongly associated with DSP in Zambia, history of non-ART drug exposures and low dietary diversity are also important determinants of DSP in HIV+ individuals. Treatable micronutrient deficiencies were common.

Orthostatic heart rate changes in patients with autonomic failure caused by neurodegenerative synucleinopathies.

OBJECTIVE: Blunted tachycardia during hypotension is a characteristic feature of patients with autonomic failure, but the range has not been defined. This study reports the range of orthostatic heart rate (HR) changes in patients with autonomic failure caused by neurodegenerative synucleinopathies. METHODS: Patients evaluated at sites of the U.S. Autonomic Consortium (NCT01799915) underwent standardized autonomic function tests and full neurological evaluation. RESULTS: We identified 402 patients with orthostatic hypotension (OH) who had normal sinus rhythm. Of these, 378 had impaired sympathetic activation (ie, neurogenic OH) and based on their neurological examination were diagnosed with Parkinson disease, dementia with Lewy bodies, pure autonomic failure, or multiple system atrophy. The remaining 24 patients had preserved sympathetic activation and their OH was classified as nonneurogenic, due to volume depletion, anemia, or polypharmacy. Patients with neurogenic OH had twice the fall in systolic blood pressure (SBP; -44 ± 25 vs -21 ± 14 mmHg [mean ± standard deviation], p < 0.0001) but only one-third of the increase in HR of those with nonneurogenic OH (8 ± 8 vs 25 ± 11 beats per minute [bpm], p < 0.0001). A ΔHR/ΔSBP ratio of 0.492 bpm/mmHg had excellent sensitivity (91.3%) and specificity (88.4%) to distinguish between patients with neurogenic from nonneurogenic OH (area under the curve = 0.96, p < 0.0001). Within patients with neurogenic OH, HR increased more in those with multiple system atrophy (p = 0.0003), but there was considerable overlap with patients with Lewy body disorders. INTERPRETATION: A blunted HR increase during hypotension suggests a neurogenic cause. A ΔHR/ΔSBP ratio < 0.5 bpm/mmHg is diagnostic of neurogenic OH. Ann Neurol 2018;83:522-531.