Faculty Bibliography

Physicians who specialize in autonomic disorders think in terms of orthostasis, synapses, catecholamines, ganglionopathies, and baroreflexes. Patients, on the other hand, inhabit a world of streaming, downloads, hashtags, tweets, and blogs. In an increasingly digital era, if we are to communicate effectively with patients, we must understand their language, including that of social media. The cultural revolution of social media opens new opportunities for autonomic medicine. First, social media can direct patients to specialists who have the expertise to evaluate and treat their disorders when such expertise is not available locally. Listing contact information on reputable dysautonomia websites is an effective way to facilitate these connections, as is creating practice websites to showcase unique expertise and resources. Secondly, online platforms can empower the patient population through education. In clinical practice, we see how frequently patients turn to the Internet for medical information. However, search engines alone are inadequate because of the sheer volume of available information, much of which is unmonitored. Patients can quickly be led down a path of misinformation about their particular condition. Dr. Google is frequently wrong. Moreover, it takes on average 2.5 clicks to get from a headache to a brain tumor. As experts in the field, we have an obligation to participate online in the translation and dissemination of accurate medical information. It is important to consider the demographics of the target audience and how best to reach them, be it Facebook, Twitter, Instagram or Snap Chat. By doing this we can assist patients in understanding their autonomic disorders and managing their symptoms. Thirdly, social media can be an important tool for research. Social media platforms can be used to recruit research subjects with rare disorders and as a tool to promote the need for research funding from the public. Social media is undoubtedly an effective way to spread news and can be used to disseminate new knowledge arising from research, which allows patients to keep abreast of current breakthroughs. Lastly, social media can be leveraged to raise public awareness about autonomic disorders and their treatment, build community, share experiences, and engage patient groups in partnership

Introduction: Patients with afferent or efferent lesions in the arterial baroreflex pathways can have orthostatic hypotension, but only those with afferent lesions have stress-induced paroxysmal hypertension. The effect of these different abnormalities on circadian blood pressure (BP) and heart rate (HR) profiles has not been systematically compared.
Method(s): We prospectively collected 24-h ambulatory BP and HR recordings in 50 patients with afferent lesions (6 acquired and 44 developmental due to familial dysautonomia). We compared this with recordings obtained in 51 patients with efferent lesions (40 with Lewy body disorders and 11 with multiple system atrophy). A similar number of patients in both groups were taking fludrocortisone (25 %) and midodrine (37 %). Thirty-six percent of patients with afferent lesions were taking clonidine. Differences in age, medications, and diagnosis were used as co-variants.
Result(s): Patients with afferent lesions were younger, had lower average 24-h, daytime, and nighttime systolic (p<0.0001, p = 0.0002, p<0.0001) and diastolic blood pressures (p = 0.006, p = 0.085, p = 0.0001). However, with age as a covariant, these differences were not significant. HR was consistently higher in patients with afferent lesions (p<0.0001). Variability of both diastolic BP (STD 19.35.9 vs. 12.63.9 mmHg, p<0.0001) and HR (STD 11.53.5 vs. 8.54.2 bpm, p = 0.0003) were higher in patients with afferent lesions, and this was still significant with age and clonidine use as co-variants. Patients with afferent lesions had at least one diastolic hypertensive surge that was higher than those captured in patients with efferent lesions (11625 vs. 10516 mmHg, p = 0.009). Nighttime BP dipping (i.e., a fall >10 %) was present in 46 % patients with afferent lesions and only in 19 % of those with efferent lesions. Excluding patients taking clonidine did not change the significance of the results.
Conclusion(s): Patients with afferent lesions of the baroreflex have higher variability in BP and HR over a 24-h period than those with efferent lesions. Unstable blood pressure is a known risk factor for target organ damage. As these patients frequently have early onset renal disease, prospective trials to reduce blood pressure variability are warranted

Autoimmune autonomic ganglionopathy (AAG) is a rare condition characterized by acute-onset generalized autonomic failure. Some of these patients also develop severe sensory and motor deficits. Droxidopa, an oral norepinephrine precursor, has been previously reported as effective treatment of neurogenic orthostatic hypotension (nOH) in one patient with AAG. Here we report our experience using droxidopa to treat symptomatic nOH in 3 patients with suspected AAG. Patient #1 (35-year-old woman) presented with acute-onset recurrent syncope, urinary retention, constipation, dry mouth, and decreased sweating, but no motor or sensory deficits. Patient #2 (11 year-old boy) and patient #3 (43-year-old woman) presented with similar autonomic deficits as well as severe impairment in all sensory modalities, but patient #3 also had severe generalized muscle weakness and had been initially diagnosed with Guillain-Barre syndrome. In all three patients, autonomic testing showed severe nOH confirmed by absent phase IV blood pressure overshoot after release of the Valsalva strain and very low or undetectable plasma norepinephrine levels. Ganglionic acetylcholine receptor antibodies were not detected in any patient. Droxidopa increased blood pressure and improved symptoms in all three patients. After 1 year, patient #1 is still receiving droxidopa 200 mg three times/day with normalization of standing BP, and continued symptomatic improvement. During the initial droxidopa titration, patients #2 and #3 experienced nausea, abdominal pain, and severe hypertension (>180 mmHg) with dosages > 200 mg. Both have now been receiving 100 mg once/day for a year with improvement in orthostatic tolerance and BP, no side effects and no supine hypertension. In conclusion, droxidopa substantially increased blood pressure standing and reduced symptoms of orthostatic hypotension in adult and pediatric patients with suspected acute autonomic ganglionopathy

Background: Infusion of vasoactive agents in the assessment of orthostatic intolerance in the autonomic laboratory is controversial. The technique of lower body negative pressure (LBNP) was described two decades ago. LBNP exaggerates orthostatic stress by closely mimicking a physiologic stimulus, and has the advantage of being quickly reversible. However, it is not routinely used in clinical practice.
Objective(s): To describe our experience using LBNP in the clinical autonomic laboratory in patients with orthostatic intolerance of unclear origin.
Method(s): We used a customized airtight cover, sealed to a tilttable and to the subject at the level of the iliac crest. After 30 min of asymptomatic passive head-up tilt, LBNP was applied while the patient was still upright. Suction was briefly initiated at -20 mmHg for 1-min and then increased to -40 mmHg for the following 10-min. Blood pressure, heart rate and plasma catecholamines when supine, after 10-min of head up tilt, and during syncope or other paroxysmal event, were measured. Time from LBNP onset to episode was recorded.
Result(s): Fifteen subjects (8 men; aged 40 +/- 20 years, range: 12-75 years) were enrolled. During LBNP, 7 subjects developed typical vasovagal syncope (after 3.8 +/- 1.3 min of LBNP) with hypotension and bradycardia and marked increases in plasma levels of epinephrine and vasopressin. Six tolerated the procedure uneventfully. One patient became unresponsive and his head stooped forward but BP and HR remained stable without changes in plasma catecholamines. The remaining patient had flailing bilateral movements with no changes in consciousness, BP or HR, but a significant increase in plasma epinephrine levels. All patients recovered without sequelae.
Conclusion(s): LBNP is a useful technique in the differential diagnosis of patients with orthostatic intolerance of unclear origin and can be easily implemented in the clinical setting. In addition to its wellknown value to induce vasovagal syncope, this technique can also be useful to induce psychogenic episodes

The prodrug droxidopa increases blood pressure (BP) in patients with neurogenic orthostatic hypotension. The BP profile of droxidopa in neurogenic orthostatic hypotension patients (n = 18) was investigated using ambulatory BP monitoring. Following dose optimization and a washout period, 24-hour "off-drug" data were collected. "On-drug" assessment was conducted after 4-5 weeks of droxidopa treatment (mean dose, 444 mg, three times daily). Ambulatory monitoring off drug revealed that 90% of patients already had abnormalities in the circadian BP profile and did not meet criteria for normal nocturnal BP dipping. On treatment, both overall mean 24-hour systolic and diastolic BPs were higher compared to off drug (137/81 mm Hg vs. 129/76 mm Hg; P = .017/.002). Mean daytime systolic BP was significantly higher with droxidopa (8.4 +/- 3.1 mm Hg; P = .014). Although nocturnal BP was not significantly higher on droxidopa versus off treatment (P = .122), increases in nocturnal (supine) BP >/=10 mm Hg were observed in four cases (22%). Severe supine systolic hypertensive readings at night (>200 mm Hg) were captured in one case and only while on treatment. These data demonstrate that ambulatory BP monitoring is useful to evaluate the circadian BP profile after initiating treatment with a pressor agent.

Objective: To evaluate the cutaneous silent period (CSP) in patients with hereditary sensory and autonomic neuropathies (HSAN) type III (HSAN-III) with decreased pain perception and type IV (HSAN-IV) with complete insensitivity to pain. Background: Decreased pain perception is a cardinal feature of HSAN. The CSP, the electrophysiological equivalent of a withdrawal reflex from a painful stimulus, may help to evaluate A-delta fibers in patients with different types of HSAN. Methods: Twenty patients with HSAN-III, 3 patients with HSAN-IV and 24 age-matched healthy control subjects were evaluated. The CSP was recorded from voluntarily contracted thenar muscles while electrical pulses were given to the second finger at 75 and 90 mA intensities. The percentage of appearance, latency, and duration of CSP responses were quantified. Kruskal-Wallis test was used for between group comparisons. Results: Patients with HSAN-III and control subjects showed 100[percnt] of appearance of CSP for both intensities of stimulation. However, when compared to controls, patients with HSAN-III showed significantly longer latencies (75 mA: 79+/-11 versus 69+/-12, p=0.02; 90 mA: 74+/-8 versus 67+/-11, p=0.0001) and increased durations (75 mA: 54+/-21 versus 32+/-13, p=0.0001; 90 mA: 54+/-12 versus 43+/-17, p=0.04) for the two intensities of stimulation. Patients with HSAN-IV showed no CSP responses at both intensities of stimulation. Conclusions: Relatively preserved, albeit delayed and prolonged, CSP responses in HSAN-III are congruent with the clinical observation that these patients are able to perceive some forms of pain (e.g., sharp pain). We speculate that even a reduced population of A-delta fibers is sufficient to produce CSP in HSAN-III. In contrast, the absence of CSP in HSAN-IV, congruent with complete insensitivity to pain, suggests that these patients have no functional A-delta nociceptive fibers. CSP can be used as an efficient physiologic aid to discriminate between complete insensitivity to pain and dulled pain perception