뇌졸중

https://doi.org/10.35827/cp.2020.19.1.23

접수일 : 2019 년 9 월 6 일 , 게재승인일 : 2019 년 10 월 2 일 책임저자 : 김우진 , Department of Rehabilitation, Epworth Rehabili-

tation, Epworth Healthcare, 50 Burwood Road, Hawthorn, VIC 3122, Australia

Tel: 61-3-9415-5760, Fax: 61-3-9415-5607 E-mail: cyctaz@hanmail.net

뇌졸중 후 복합부위통증증후군에서 부위별 위상각을 이용한 평가

인제대학교 해운대 백병원 재활의학교실

, 호주 엡워스 병원 재활의학과

박세흠¹ㆍ김우진²ㆍ조근열¹ㆍ권준구¹

Application of Segmental Phase Angle for Assessment of Post-Stroke Complex Regional Pain Syndrome

Se-Heum Park, M.D.

, Woo-Jin Kim, M.D., Ph.D.

, Geun-Yeol Jo, M.D., Ph.D.

and Jun-Koo Kwon, M.D.

1

Department of Rehabilitation Medicine, Inje University Haeundae Paik Hospital, Busan, Korea,

2

Department of Rehabilitation, Epworth Rehabilitation, Epworth Healthcare, Hawthorn, VIC, Australia

Our objective is to evaluate the applicability of segmental phase angle (PhA) via bioelectrical impedance analysis (BIA) for post-stroke complex regional pain syndrome (CRPS). Due to its noninvasiveness and convenience, various studies have used BIA in clinical conditions. We measured segmental PhA in 4 patients at the time of CRPS diagnosis and repeated 4 weeks after 2 weeks of steroid pulse therapy. In 3 cases, the affected-to-unaffected ratio of the upper limb PhA decreased at the time of diagnosis. In 2 cases with improvement of more than 5 points in the CRPS severity score (CSS), increased ratios were observed. In other 2 cases with improvement of less than 4 points in the CSS, no remarkable changes in the ratios were found. We suggest that the segmental PhA can be helpful in assessment of post-stroke CRPS and its recovery. (Clinical Pain 2020;19:23-27)

Key Words: Stroke, Electric impedance, Complex regional pain syndrome

INTRODUCTION

Post-stroke complex regional pain syndrome (CRPS) has been identified as a phenomenon that develops in hemi- plegic patients with stroke.

Although the symptoms of CRPS are frequently reported in the hemiplegic limb of pa- tients with stroke, the diagnosis of post-stroke CRPS is not common.

In recent years, there has been a significant progress in understanding CRPS. The Budapest diagnostic criteria, which has a sensitivity and a specificity of 0.99 and 0.79, respectively, is used for diagnosis.

However, it is a clin- ically derived diagnostic criteria based on observed and pa- tient-reported signs and symptoms and there is no gold standard for the diagnosis of CRPS.

Therefore, there is

an increasing need for more objective and feasible tools for diagnosis of CRPS.

Phase angle (PhA) measured by the bioelectrical im- pedance analysis (BIA) has been used as a parameter for cellular health, as it reflects the cellularity, cell membrane integrity, and cell function.

Various studies have shown the inverse relationship between PhA and inflammation.

As the pathophysiology of early phase CRPS involves acute local inflammation resulting in tissue damage, a decrease in PhA is predicted.

Meanwhile, steroid therapy is a pathophysiology-ori- ented therapy that has clinical trial evidence for CRPS.

Through their anti-inflammatory action, steroid reduces the neurogenic inflammation in the acute period and prevent neuropathic pain.

Therefore we can hypothesize an in- crease in PhA may reflect symptomatic recovery following steroid therapy for CRPS.

In this case report, we investigated the feasibility of seg-

mental PhA for diagnosing post-stroke CRPS and monitor-

ing CRPS following the steroid therapy. As PhA is known

to be affected by age, sex, nutritional status, and body mass

index, we used the ratio of PhA on the affected side to that

Fig. 1. Description of the BIA measurement protocol. After the patient had maintined a supine position for 10 minutes, the ground surface was wiped with an alcohol swab and the BIA

measurement was performed. Fig. 2. Example of raw data of BIA measurement.

on the unaffected side to minimize the influence of these factors on the measurements.

CASE REPORT

Hemiplegic stroke patients referred to the Rehabilitation Medicine department and diagnosed with post-stroke CRPS in the affected limb were investigated from March 2018 to August 2018. When stroke patients with no significant trauma history presented with pain in the affected limb, other causes mimicking post-stroke CRPS including central pain, spasticity related pain, and musculoskeletal disorders associated with hemiparesis were excluded through phys- ical examination and imaging studies. This was followed by physical examination and assessment for the Budapest criteria. Patients who met the Budapest criteria, underwent a 3-phase bone scan to confirm CRPS. Demographic data, medical history, and segmental PhA data of the 4 patients with post-stroke CRPS were gathered after obtaining an in- formed consent. Following the diagnosis, the routine re- habilitation program and stroke medication continued.

Steroid therapy regime was commenced, and the proto- col for steroid pulse therapy was as follow. Oral pre- dnisolone taken at a dose of 60 mg for 6 days, followed by 30 mg for 3 days, 15 mg for 3 days, 10 mg for 2 days,

and 5 mg for 1 day, finishing on day 15. To monitor the course of CRPS, we measured the CRPS severity score (CSS) at the time of CRPS diagnosis and 4 weeks after the steroid therapy.

Unlike the conventional BIAs for whole body composi- tion, the Inbody S10

(Inbody, Seoul, Korea) used in these case reports, measured each segment of the body composi- tion and enabled the comparisons between the left and the right extremities (Fig. 1, 2). The baseline segmental PhA was measured in all stroke patients at the time of transfer to the rehabilitation department. For patients who devel- oped post-stroke CRPS, the BIA measurements were re- peated for evaluation of segmental PhA of the affected and the unaffected limbs at the time of diagnosis with CRPS before the commencement of steroid therapy and four weeks after cessation of the steroid therapy.

Demographics and characteristics of the enrolled patients are summarized in Table 1. Three patients had experienced an ischemic stroke, while one patient had a hemorrhagic stroke. All patients presented with symptoms of CRPS, 4 to 7 weeks after the stroke episode. All 4 patients showed signs and symptoms such as allodynia, altered skin color, signs of hyperalgesia, skin color asymmetry, decreased range of motion (ROM), and sweating asymmetry. Two of the 4 patients showed signs and symptoms of edema in the hemiplegic limb. For every patient enrolled in this study, CRPS was confirmed according to the Budapest criteria and the 3-phase bone scan results.

Segmental PhA and the CSS of the patients are summar-

ized in Table 2. BIA was not measured in one of the pa-

Table 2. Segmental PhA Values of the Upper Limbs and CSS

　 Patient 1 Patient 2 Patient 3 Patient 4

Before diagnosis Unaffected side 5.2° 5.1° 5.0°

Affected side 5.8° 4.5° 4.7°

Ratio* 1.1 0.9 0.9

At diagnosis Unaffected side 4.7° 4.8° 5.0° 4.9°

Affected side 3.2° 3.7° 4.0° 3.6°

Ratio* 0.7 0.8 0.8 0.7

CSS 13 15 14 14

After treatment Unaffected side 5.1° 4.9° 5.8° 4.5°

Affected side 3.4° 4.3° 4.5° 4.3°

Ratio* 0.7 0.9 0.8 1.0

CSS 10 10 12 8

PhA: Phase angle, CSS: Complex regional pain syndrome severity score. *The ratio of the upper limb PhA value on the affected side to that on the unaffected side.

Table 1. Demographics and Characteristics of the Enrolled Patients

Patient 1 Patient 2 Patient 3 Patient 4

Sex Female Male Female Female

Age (years) 61 54 78 65

Brain lesion Left basal ganglia ICH Left MCA infarction Left MCA infarction Right MCA infarction

CRPS onset 4 weeks 6 weeks 7 weeks 7 weeks

Stroke medication AED

ARB

ASA AChEI

ASA ARB AChEI

ASA CCB AChEI Budapest criteria

Symptoms

Sensory ＋ ＋ ＋ ＋

Vasomotor ＋ ＋ ＋ ＋

Sudomotor/edema ＋ ＋ ＋ −

Motor/trophic − ＋ − ＋

Signs

Sensory ＋ ＋ ＋ ＋

Vasomotor ＋ ＋ ＋ ＋

Sudomotor/edema ＋ ＋ ＋ ＋

Motor/trophic ＋ ＋ ＋ ＋

CRPS: Complex regional pain syndrome, ICH: Intracerebral hemorrhage, MCA: Middle cerebral artery, AED: Antiepileptic drug, ASA:

Acetylsalicylic acid, ARB: Angiotensin receptor blocker, CCB: Calcium channel blocker, AChEI: Acetylcholinesterase inhibitor.

tients before CRPS as the patient showed CRPS symptoms immediately following transfer to our department.

When comparing the PhA ratios before and after the CRPS diagnosis in patients 1, 2, and 3, the PhA ratios were decreased at the time of CRPS diagnosis. The PhA ratio decreased from 1.1 to 0.7 in patient 1, 0.9 to 0.8 in patient

2, and 0.9 to 0.8 in patient 3. After the steroid therapy, the

CSS decreased by 3 and 2 points in patients 1 and 3, re-

spectively, whereas the CSS decreased by 5 and 6 points

in patients 2 and 4, respectively. In patients 1 and 3, the

PhA ratios remained unchanged after steroid therapy with

the PhA ratios of 0.7 and 0.8, respectively. In patients 2

and 4, the PhA ratios were increased after steroid therapy.

The PhA ratio increased from 0.8 to 0.9 in patient 2 and from 0.7 to 1.0 in patient 4 (Table 2).

DISCUSSION

Unlike the conventional CRPS patients, most of the post-stroke CRPS patients present with pain and limited ROM in the hemiparetic shoulder, wrist, and hand, sparing the elbow. This is reflected in the term “shoulder-hand syn- drome”.

In most of the cases, post-stroke CRPS occurred within 5 months after the stroke, with incidence as high as 70%.

However, post-stroke CRPS is easily overlooked, and often progresses to a chronic stage without inter- ventions such as corticosteroid treatment in the early phase of the disease.

Difficulty while diagnosing CRPS is asso- ciated with a lack of an objective method to confirm post-stroke CRPS and the sequelae associated with the pa- retic limb such as dependent hand edema, pain after shoulder subluxation, and spasticity, which are similar to the symptoms of CRPS.

The Budapest criteria is widely used in the diagnosis of CRPS.

According to the Budapest criteria, CRPS can be diagnosed if signs in more than 2 categories and symptoms in more than 3 categories from the 4 categories of sensory, vasomotor, sudomotor/edema, and motor/trophic are con- firmed in addition to continuous pain, and if these symp- toms cannot be explained by any other diagnosis.

However, the Budapest criteria relies on physical examina- tion and history records rather than objective test results and there is a high risk of overdiagnosis.

Several tools in- cluding X-rays, 3-phase bone scintigraphy, MRI, and ther- mography to aid in the diagnosis of CRPS have been studied.

However, such diagnostic methods are not al- ways utilized in all facilities and evidence for their added accuracy is still lacking.

Therefore, more convenient and objective test methods, which can help diagnose CRPS, are required.

Various studies have shown the clinical relevance and usefulness of PhA in a variety of diseases.

However, most of the studies utilized the whole body PhA values, and not the segmental PhA values. This approach does not enable comparisons between the left and the right sides. Hence, in diseases such as post-stroke CRPS that affect the body asymmetrically, segmental PhA analysis of each limb is

more feasible to compare the left and the right sides.

In these case reports, we found a decrease in the seg- mental PhA values of the affected limb and a decrease in the PhA ratios at the time of CRPS diagnosis. This finding is consistent with our hypothesis that the PhA value would decrease in the acute inflammatory phase of CRPS as PhA is affected by the inflammation. The CSS is based on 16 signs and symptoms and is used to assess the severity and monitor the course of CRPS.

In a study by Harden et al.,

the authors suggested that a decrease in the CSS by 4.9 points or greater indicates real improvement in CRPS symptomatology after intervention. In patients 1 and 3, de- creases in the CSS were less than 4.9 points and the PhA ratios showed no change after the steroid therapy.

However, in patients 2 and 4, decreases in the CSS were greater than 4.9 points and the PhA ratios were increased after therapy. The overall pattern of these findings supports the validity of the segmental PhA, especially the PhA ratio, in diagnosis and monitoring of post- stroke CRPS.

There are some limitations in these case reports. First, though we found changing patterns of PhA according to the clinical course of CRPS, we could not establish a cut-off PhA value for the diagnosis of post-stroke CRPS due to the small number of cases. A large-scale study should be conducted to establish the cut-off value for the diagnosis of post-stroke CRPS and to find statistical significance. Second, possible influence of the stroke medi- cation on PhA should be taken into account. In these case reports, patients took antiepileptic drug (levetiracetam), an- tihypertensive drug (losartan, telmisartan, amlodipine), cognition-enhancing drug (acetylcholinesterase inhibitor) and antiplatelet drug (acetylsalicylic acid) as stroke medications. To date, there are no reports on the associa- tion between these drugs and PhA. However, considering the relationship between PhA and inflammation, which is the main pathophysiology of early CRPS, anti-in- flammatory effects of acetylsalicylic acid may affect the PhA values at diagnosis of CRPS. Third, we studied the usefulness of PhA only in the acute phase of post-stroke CRPS. However, unlike other CRPS patients, early diag- nosis and treatment of post-stroke CRPS patients is im- portant, as it may interfere with stroke rehabilitation.

Therefore, the clinical usefulness of PhA in early diagnosis of post-stroke CRPS may be significant.

To our knowledge, this is the first attempt to test the ap-

plicability of the segmental PhA via BIA for unilateral CRPS in patients with stroke. Changes in the ratios of the upper limb PhA value on the affected side to that of un- affected side suggest that the segmental PhA via BIA can be considered as a useful adjunctive tool for assessment of post-stroke CRPS. Moreover, correlation between the changes in the PhA and the CSS following steroid therapy demonstrates usefulness of PhA as an objective method to assess the clinical improvement in post-stroke CRPS patients.

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