Chapter 29 - Clinical neurophysiology of postural tachycardia syndrome

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Abstract

Postural tachycardia syndrome (POTS) is one of several disorders of orthostatic intolerance (OI). It is defined by the development of symptoms of cerebral hypoperfusion or sympathetic activation and a sustained heart rate increment of 30 beats/min or more (40 beats/min for teenagers) within 10 min of standing or head-up tilt in the absence of orthostatic hypotension; the standing heart rate is often 120 beats/min or higher. POTS is approximately five times more common in women than men. This heterogeneous syndrome is caused by several pathophysiologic mechanisms (limited autonomic neuropathy, hyperadrenergic state, hypovolemia, venous pooling, deconditioning), which are not mutually exclusive. Anxiety and somatic hypervigilance play significant roles in POTS. Common comorbidities include visceral pain and dysmotility, chronic fatigue and fibromyalgia, migraine, joint hypermobility, mitral valve prolapse, and inappropriate sinus tachycardia. Patients with suspected POTS should undergo comprehensive cardiac and neurologic examinations and autonomic and laboratory tests to determine the most likely pathophysiologic basis of OI. The objectives of POTS management are to (1) increase the time that patients can stand, perform daily activities, and exercise and (2) avoid syncope. Management involves nonpharmacologic (fluid and salt loading, physical countermaneuvers, compression garments, exercise training) and pharmacologic (β-blockers, pyridostigmine, fludrocortisone, midodrine) approaches.

Introduction

Postural tachycardia syndrome (POTS) is one of several disorders of orthostatic intolerance (OI), including neurocardiogenic or vasovagal syncope and neurogenic orthostatic hypotension (nOH). OI is defined as symptoms of cerebral hypoperfusion or sympathetic activation that develop with upright posture and are relieved with recumbency. POTS is defined as a symptomatic and sustained heart-rate increment of 30 beats/min or more within 10 min of standing or head-up tilt in the absence of OH; the standing heart rate is often 120 beats/min or higher (Freeman et al., 2011; Sheldon et al., 2015). An orthostatic increment of 30 beats/min exceeded the 99th percentile of 271 control subjects aged 10–83 years (Low et al., 1997). For individuals aged 12–19 years, the required increment is at least 40 beats/min (Freeman et al., 2011; Singer et al., 2012). Diagnostic criteria have not been established for younger children.

The current definition of POTS focuses on symptoms and heart-rate increment induced by postural changes. The focus on orthostatic tachycardia is appropriate because an excessive rise in heart rate is the earliest and most consistent of the readily measured indices of OI (Streeten, 1987).

Section snippets

Demographics

The typical age of presentation is between 15 and 50 years (Schondorf and Low, 1993; Thieben et al., 2007). Early studies suggested men and women were affected equally (Fouad et al., 1986; Hoeldtke et al., 1989), but the preponderance of more recent work has shown an overrepresentation of women (Rosen and Cryer, 1982; Schondorf and Low, 1993; Low et al., 1994; Thieben et al., 2007) at a ratio of approximately 5:1.

Symptoms

Symptoms of cerebral hypoperfusion that may occur with any of the OI disorders include lightheadedness, dizziness, presyncope, blurred vision, generalized weakness, and cognitive difficulties. Symptoms of sympathoexcitation include palpitations, chest pain, shortness of breath, tremulousness, nausea, diarrhea, pallor, sweating, and coldness of the extremities. Approximately one-third of patients with POTS also experience posturally triggered vasovagal syncope (Al-Shekhlee et al., 2008).

Clinical Examination

The neurologic examination in patients with POTS is normal, with rare exception. Supine and standing vital signs will show an excessive heart-rate increment without blood pressure drop, though pulse pressure may be excessively reduced. Palpating the radial pulse may become more difficult with continued standing or with the performance of a Valsalva maneuver (Flack sign). Prolonged standing may also be associated with coldness, blueness, or swelling of the hands and feet (Streeten, 1987).

Pathophysiology

POTS is not one disorder but rather a heterogeneous syndrome resulting from several distinct pathophysiologic mechanisms that are not mutually exclusive (Sandroni et al., 1999; Jacob et al., 2000; Stewart and Montgomery, 2004; Nickander et al., 2005; Medow and Stewart, 2007; Garland et al., 2007b; Carew et al., 2009; Low et al., 2009; Parsaik et al., 2012). The main POTS mechanisms are impaired sympathetically mediated vasoconstriction in the lower limbs (neuropathic POTS), excessive cardiac

Comorbidities

Many patients with POTS have additional chronic conditions. These comorbidities may include visceral hypersensitivity, gastrointestinal dysmotility, chronic fatigue, insomnia, fibromyalgia, headaches, joint hypermobility, mitral valve prolapse (MVP), and inappropriate sinus tachycardia (IST).

Differential Diagnosis

In addition to the causes of OI already discussed (anxiety/panic, CFS, fibromyalgia, EDS, MVP), the differential diagnosis of POTS also includes nOH, constitutional OI, cerebrospinal fluid (CSF) leak, and median arcuate ligament syndrome.

Evaluation

The evaluation of a patient suspected of having POTS is necessarily multidisciplinary and should begin with a complete history and physical examination. The history should focus on the timing of onset and progression of orthostatic symptoms, presence of nonorthostatic symptoms, precipitating and aggravating factors, fluid and caffeine intake, level of physical activity and standing time, response to previously attempted treatments, and current drug therapy (Low et al., 2009; Mathias et al., 2011

Management

The objectives of POTS management are to (1) increase the time that patients can stand, perform daily activities, and exercise and (2) avoid syncope. Management involves nonpharmacologic (Table 29.3) and pharmacologic (Table 29.4) approaches. Patient education about POTS is fundamental and should include review of potential aggravating or precipitating factors of orthostatic and exercise intolerance. Few treatments have been subjected to the rigor of randomized clinical trials, and consensus is

Prognosis

Data are limited on the long-term prognosis of POTS. In one large cross-sectional study that used a validated autonomic symptom profile at initial evaluation and a structured autonomic questionnaire at prospective follow-up at least 18 months later, 80% of patients were improved, 90% were able to return to work, and 60% were functionally normal (Sandroni et al., 1999). Salt supplementation and β-blockers were the most efficacious therapies. In another prospective follow-up study, 70% of

Future Directions

Recent work has shown not only impaired quality of life measures but also increased thoughts of suicide in patients with POTS (Pederson and Brook, 2017). Such findings highlight the importance of further elucidating the causes and mechanisms of POTS, as well as ongoing work to develop more effective treatments.

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