Bedside Assessment of Autonomic Dysfunction in Multiple System Atrophy

History taking

In MSA, autonomic dysfunction is typically severe, begins early in the disease course and affects multiple domains.

Neurogenic orthostatic hypotension and urogenital dysfunction represent core MSA diagnostic features [1, 3]. Symptoms suggestive of orthostatic intolerance such as syncope, light-headedness, blurred/darkened vision, troubles concentrating, neck, shoulder (so called “coat-hanger”) and low-back pain, typically develop upon standing and improve after sitting or lying down. Such symptoms are often reported after large meals, pointing towards post-prandial hypotension, and may be exacerbated by levodopa intake.

Lower urinary tract symptoms (LUTS) are common features already at early MSA stages. History taking should therefore address both storage (urinary urgency, frequency, urge incontinence, and nocturia) and voiding disturbances (hesitancy, incomplete bladder emptying, poor and intermittent urine stream). Unexplained erectile dysfunction in men younger than 60 is another suggestive MSA red flag. Stridor is a high-pitched inspiratory sound, which is highly distinctive of MSA. Mimicking stridor with the physician’s voice or using audio recordings may enable caregivers recognizing it (an audio recording of stridor can be found under [4]).

Patient-reported outcomes tools and rating scales (Table 1) can assist physicians in the systematic assessment of autonomic complaints and in quantifying their burden and impact on quality of life. Self-completed blood pressure and bladder diaries may provide additional real-life information. Their use is particularly recommended in those low-resources contexts, where access to second-level examinations (e.g., tilt-table and other cardiovascular autonomic function tests, 24-hour ambulatory blood pressure measurements and urodynamic studies) is limited.

Physical examination

In people with suspected MSA, the neurological examination is often biased towards its core motor features. Nonetheless, a careful physical examination may disclose cold, discolored hands and feet (Fig. 1A–C) showing delayed capillary refill after digital pressure (Fig. 1D). The so-called “cold hands and cold feet sign” indicates insufficient sympathetic control over cutaneous blood vessels and represents an important MSA red flag [3, 5]. Skin examination may disclose further indirect signs of impaired sweating, such as dry and chapped skin. Both stridor and inspiratory sighs may be heard during the examination.

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Fig. 1

Vasomotor disturbances affecting hands (“cold hands” –A, B) and feet (“cold feet” –C, D) in a 62-year-old lady with a 4-year history of MSA. Delayed capillary refill after digital pressure can be observed in panel D.

Bedside assessments

The standing test is a simple and cost-effective tool to screen for orthostatic hypotension (OH) at bedside. It is performed with an arm-cuff sphygmomanometer by measuring supine-to-standing heart rate (HR) and blood pressure (BP) changes 1, 3, and 5 (or 10) minutes upon standing. The test indicates classic OH in case of a sustained BP fall ≥20 mmHg systolic and/or ≥10 mmHg diastolic within 3 minutes upon standing. Prolonging the orthostatic challenge beyond 3 minutes may disclose delayed OH. Delayed OH is considered a beginning form of OH, which may progress to classic OH over time [3]. Since OH may often remain asymptomatic (a, to date not fully understood phenomenon called “hypotensive unawareness” [6, 7]), actively screening for OH is particularly important in patients with recurrent unexplained falls. The calculation of the neurogenic-OH (nOH) ratio, i.e., the ratio between the increase in heart rate and the fall in systolic BP upon standing, may help differentiating neurogenic from non-neurogenic causes of OH [8]. This ratio cannot be applied to patients, whose heart rate is influenced by other factors like cardiac arrhythmia, pacemakers or β-blocker therapy [9]. The diagnostic accuracy of both the standing test and the nOH ratio is however suboptimal, especially in milder forms of cardiovascular autonomic failure. These bedside tests should be therefore intended as screening measures to identify those patients, who may benefit from referral to specialized centers for tilt test and other cardiovascular autonomic function tests. A negative standing test does not also completely rule out nOH, so that patients with a strong clinical suspicion should be equally referred for an in-depth autonomic assessment.

In subject reporting urinary complaints, urinary tract infections should be ruled out first by means of urine dipsticks. Post-void bladder ultrasound or in-and-out catheterization may point out voiding disturbances in case of a residual post-void urine volume >100 ml and identify patients with an indication for urodynamic studies [3].

Patient consent

We declare that written informed consent for both video/picture recording and their publication was obtained from the patient and can be provided upon request; all information has been managed confidentially and in accordance to current European data protection and privacy regulations. No patient-related information enabling subject's identification is disclosed. The Innsbruck Ethical Committee approved the case report (EK Nr: 1233/2021).