Clinically accessible tools for documenting the impact of orthostatic intolerance on symptoms and function in ME/CFS

1Introduction

Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) affects as many as 2.5 million people in the United States. ME/CFS is a debilitating disease with a significant unmet medical need that creates enormous burdens for patients, caregivers, the healthcare system and society [1]. Because fatigue is one of the most common complaints in primary care, as part of the differential diagnosis of ME/CFS it is critical to describe the severity and impact of fatigue on physical function. The fatigue observed in ME/CFS patients is typically more severe, more devastating and of longer duration than the fatigue level observed in other disorders characterized by fatigue. There is sufficient evidence that ME/CFS, where by the definition of fatigue persists for more than 6 months, is a serious illness that results in significant degradation or destruction of the ability to retain pre-illness levels of daily functioning (occupation, education, personal and social activity) [1]. The fatigue of ME/CFS is described by patients as “exhaustion, weakness, a lack of energy, feeling drained, an inability to stand for even a few minutes, an inability to walk even a few blocks without exhaustion, and an inability to sustain an activity for any significant length of time” [2]. This type of fatigue can make it hard to sustain even minor daily activities such as changing clothes, toileting or even speaking [2]. Therefore, not only the severity of fatigue as a symptom, but also the impact of fatigue on function should be assessed when making a diagnosis of ME/CFS.

Orthostatic stress worsens fatigue and cognitive function in many patients with ME/CFS [3, 4]. Orthostatic intolerance (OI) is defined as the development of symptoms upon assuming and maintaining upright postures that are alleviated by recumbency [5, 6]. “Symptoms of orthostatic intolerance are those caused primarily by 1) cerebral under-perfusion (such as lightheadedness, near-syncope or syncope, impaired concentration, headaches, and dimming or blurring of vision), or 2) sympathetic nervous system activation (such as forceful beating of the heart, palpitations, tremulousness, and chest pain), and 3) other common signs and symptoms of orthostatic intolerance such as fatigue, a feeling of weakness, intolerance to low-impact exercise, nausea, abdominal pain, facial pallor, nervousness, and shortness of breath.” [6]. Symptoms of OI are exacerbated by prolonged periods of upright posture and various daily experiences such as exercise, warm environments or large meals. Circumstances in daily life that can easily exacerbate OI include standing in line, grocery shopping, hot weather, overheated rooms, hot showers or baths and even sitting to eat a meal.

Clinicians should document patients’ symptoms and function in order to determine the impact of illness on the performance of daily activities and occupational responsibilities. A medical record that documents impaired function caused by ME/CFS is crucial for patients who need to claim Social Security Disability. A major barrier to disability support relates to the absence of ME/CFS in the Social Security List of Impairments, although there is a Social Security Regulation (SSR-14-1) that explains how impairments of ME/CFS constitute a determinable condition [7]. Regardless of disability status, the ability to measure impaired function is an important aspect of diagnosis, treatment, and assessment of treatment outcomes [7].

Our clinical experience with over 1,000 ME/CFS patients has indicated that their disease severity can be gauged by hours of upright activity which we define as time with feet on the floor over a 24-hour period. Severely ill ME/CFS patients reported 0 to 4 hours with their feet on the floor while moderately ill patients reported having their feet on the floor for 5 to 8 hours. This observation led us to explore which ME/CFS symptoms were associated with an upright activity. In this study, subjects were asked to report hours of upright activity (HUA) by estimating the hours per day spent in the following 4 positions over the past week: 1) hours upright (standing, walking, running), 2) hours sitting with feet on the floor, 3) hours reclining or sitting with feet elevated and, 4) hours lying down (includes sleeping). We also used a standardized orthostatic questionnaire to evaluate how being in upright positions affected daily activities and the severity of symptoms. We found that both assessment tools can be easily administered and are effective at documenting the impact of orthostatic intolerance on symptom severity and daily activities in ME/CFS patients.

2Methods

3Results

The characteristics of subjects are shown in Table 1. The demographics and baseline vitals of the ME/CFS subjects were similar to HCs. The majority of subjects were Caucasian (HC 92% and ME/CFS 96%, p = 0.54). The average HUA was 6.2 hours (95% CI±1.09) in ME/CFS and 13.36 hours (95% CI±0.57) in HCs. The average duration of illness in ME/CFS was 14.67 years (95% CI±4.21). Among HUA subgroups (Table 2), the duration of illness in ME/CFS subjects with ≥5 HUA was 13.4 years (95% CI±2.57) and 17.8 years (95% CI±7.07) with <5 HUA (p = 0.41). The employment rate was 76% in HCs and 32% in ME/CFS, p = 0.001. Furthermore, none of the <5 HUA ME/CFS subjects were employed compared to 44% of the ≥5 HUA ME/CFS subjects (p = 0.03).

Orthostatic intolerance had a profound effect on all daily activities for ME/CFS subjects. All 6 upright activity items of the OIDAS were significantly different (p < 0.0001) between ME/CFS and HCs (Table 3). Interestingly, there were no differences in OIDAS scores between <5 HUA and ≥5 HUA ME/CFS groups with both experiencing similar levels of interference in daily upright activities involving standing or walking. There were significant differences in the types of OI symptoms experienced by the <5 and ≥5 HUA ME/CFS subjects (Table 4). Specifically, <5 HUA ME/CFS subjects had more problems with vision (p = 0.04), more weakness (p = 0.04) and more trouble concentrating (p = 0.04) compared to ≥5 HUA ME/CFS subjects. There were no significant differences in dizziness, lightheadedness, feeling faint, or blackout, fatigue and head/neck discomfort.

OIQ is the combined score of OIDAS (possible 60) and OISA (possible 40) to equal a total score of possible 100. Total OIDAS and OISA scores between HCs and ME/CFS showed clear differences (Table 5); OIDAS: HC 5.08, MECFS 25.32, p < 0.001; OISA: HC 6.72, MECFS 33.88, p < 0.001). The total OIQ scores were significantly different between <5 HUA and ≥5 HUA groups with the <5 HUA ME/CFS subjects having higher (worse) OIQ scores (p = 0.04).

Table 6 compares the study subjects based on OIQ scores and employment status. ME/CFS subjects that were employed had on average 8.62 HUA while ME/CFS subjects who were not working had on average 5.06 HUA (p = 0.001). The OIQ scores were significantly higher for unemployed ME/CFS subjects (63.82) compared to employed ME/CFS subjects (49.38) (p = 0.04). The unemployed ME/CFS subjects reported significantly higher OISA scores than the employed group (p = 0.05), while there was no significant difference in total OIDAS scores (employed group: 22.13, unemployed group: 26.82, p = 0.11).

4Discussion

Lightheadedness, headache, fatigue, weakness, heart palpitations, and exercise intolerance are some of the symptoms of orthostatic intolerance. Various physiological irregularities can underlie orthostatic symptoms including postural orthostatic tachycardia syndrome and orthostatic hypotension [10]. While questions still exist concerning the exact role of orthostatic intolerance in ME/CFS, increasing evidence shows substantial comorbidity [11]. Indeed, the Institute of Medicine report on clinical diagnostic criteria for ME/CFS lists orthostatic intolerance as one of the core diagnostic features of the illness [1]. Head-up tilt table testing and continuous heart rate monitoring are used in the research of OI, however, neither are modalities readily available to clinicians. Our goal was to use simple assessments to determine the impact of orthostatic symptoms and daily activities in ME/CFS patients to show the utility of HUA and OIQ for ME/CFS patients.

Clinical observation of ME/CFS patients at the Bateman Horne Center over the past 15 years indicates that patients who report more time in bed or reclining and less time with feet on the floor (e.g., sitting at a desk or table, standing, walking) were more severely ill. This observation was borne out by this study. ME/CFS subjects had significantly less HUA and significantly higher OIQ scores compared to HCs. This means that all upright postures –sitting with feet on the floor, standing, walking, running –exacerbate orthostatic intolerance and cause patients’ orthostatic symptoms to flare. Patients report that can it take days for symptoms to subside following prolonged upright activity, and recovery requires them to lie down, elevate legs and feet, and rehydrate. Further, patients that have been sick for many years have learned to mitigate or prevent OI symptoms by managing energy expenditure (pacing), and especially, minimizing or avoiding exertion that keeps them in an upright position for longer than they know they can tolerate. This may help explain why ME/CFS subjects reported similar interference with daily activities due to OI on the OIDAS despite differences in HUA (<5 or ≥5).

ME/CFS is debilitating and causes extreme limitations in a person’s ability to accomplish even the most mundane of daily activities, including sitting upright at the dining table, standing to make a salad, taking a shower, driving a car, grocery shopping and cleaning the house. So, the 67% unemployment rate in our ME/CFS study subjects is not surprising. The data showed that ME/CFS subjects who were able to work had an average HUA of 8.62 a day in contrast to unemployed ME/CFS subjects who had an average HUA of 5 a day. Recall that the OIDAS score was not different between <5 and ≥5 HUA ME/CFS subjects. Even though a person with ME/CFS maintains employment status, it should not be assumed that they can sustain normal work productivity without accommodations, normal physical function, or even the ability to engage in routine activities after work hours. If moderately ill ME/CFS patients spend all of their hours of upright activity at work, they often have nothing left for home, family, self-care and social activities. Therefore, clinicians should carefully consider each patient’s orthostatic symptom severity and actual upright activity tolerance as it relates to performance in the workplace.

A recent paper described the importance of documenting medical disability in ME/CFS and the importance of documenting a reduction in the ability to carry out daily or work-related activities because of their disease [7]. The medical record documenting impaired physical function caused by ME/CFS is crucial for patients who need to claim Social Security disability due to the absence of ME/CFS within the Social Security List of Impairment [12]. There is a Social Security Regulation (SSR-14-1) that explains how impairments of ME/CFS constitute a determinable condition [13]. Both HUA and OIQ are simple assessments that can be used by the physician to document the impact of ME/CFS on physical function and daily activities. This documentation is not only useful for disability, but it is also essential for the effective diagnosis, treatment and ongoing management of ME/CFS patients [7]. ME/CFS is a multi-system illness, so simply assessing the presence of fatigue or OI is not enough to address the full clinical presentation and symptom severity. Clinicians must comprehensively assess all of the patient’s major symptoms, including frequency, severity, and contribution to impaired physical function. This study focused on tools to recognize impaired function (HUA) and the presence of orthostatic intolerance; both are core clinical manifestations and possibly the most commonly overlooked aspects of ME/CFS illness. These tools can lead to better medical documentation, diagnosis and management as well as justification for engaging in more time-consuming objective measurements of OI such as the 10 minute Lean Test or Tilt Table testing.

In this study the relationship between self-reported hours of upright activity and the severity of orthostatic intolerance as assessed by a validated questionnaire was examined. We found that fewer hours of upright activity correlated with more severe orthostatic intolerance, which in turn increased the likelihood of being unemployed or underemployed. There are few studies demonstrating the assessment of symptoms and daily limitations of physical function in ME/CFS as described in this report. The ability to assess impairment and orthostatic symptom severity is meaningful and can be used as a tool for clinicians in the care of their ME/CFS patients. These results can also be used for educating patients about the importance of managing orthostatic intolerance in order to help improve daily function.

This study is limited by its relatively small sample size, enrollment of ME/CFS subjects from a single clinic, and the inclusion of only female subjects. The OHQ was developed and validated for orthostatic hypotension and the validity and reliability of this questionnaire for assessing orthostatic intolerance in ME/CFS is not known. The self-report of HUA is also a study limitation. However, the results of this small study showed stark differences between HCs and ME/CFS subjects on almost all measures, indicating that HUA is a valuable measure for ME/CFS and has inspired us to develop devices that objectively and passively measure HUA. Further study is required to validate these findings in a larger, more diverse population, including men, with consideration of stage/duration of illness and the presence of comorbid conditions.

Conflict of interest

None to report.