Evaluation of the applicability of weak shoulder and arm sparing signs in amyotrophic lateral sclerosis by multiple neurologists and neurology residents: A single-center study
Abstract
Introduction/Aims
Amyotrophic lateral sclerosis (ALS) exhibits selective muscle weakness. The weak shoulder and arm sparing signs, assessed by a single experienced neurologist, have been reported to be superior to previous signs in sensitivity and specificity. However, it is unknown whether the same results are observed when assessed by multiple neurologists.
Methods
Subjects were retrospectively identified from our department's inpatient database from 2014 to 2023. Medical Research Council (MRC) scores of the deltoid (Del), biceps brachii (BB), triceps brachii (TB), and first dorsal interosseous (FDI) muscles were evaluated. The weak shoulder sign was defined as positive when Del was weaker than BB and TB. The arm sparing sign was defined as positive when both Del and FDI were weaker than BB and TB. Sensitivity was analyzed in all ALS patients and in subgroups based on the region of symptom onset, presence or absence of upper motor neuron (UMN) signs, and the Japanese ALS Severity Classification.
Results
Seventy-one patients with ALS were identified. Eight neurologists and three neurology residents evaluated each patient's MRC scores. The weak shoulder and arm sparing signs were observed in 72% and 48% of patients, respectively, with no significant difference in sensitivity across patient subgroups.
Discussion
The weak shoulder and arm sparing signs showed high and moderate sensitivity, respectively, consistent with a previous report, even when evaluated by multiple examiners. This expands the clinical utility and increases the reliability of these signs, potentially contributing to accurate ALS diagnosis when combined with other clinical features and objective assessments.
Abbreviations
-
- ALS
-
- amyotrophic lateral sclerosis
-
- ALSFRS-R
-
- ALS Functional Rating Scale-revised version
-
- BB
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- biceps brachii
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- CSA
-
- cervical spondylotic amyotrophy
-
- Del
-
- deltoid
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- FDI
-
- first dorsal interosseous
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- LMN
-
- lower motor neuron
-
- MMT
-
- Manual Muscle Testing
-
- MRC
-
- Medical Research Council
-
- TB
-
- triceps brachii
-
- UMN
-
- upper motor neuron
1 INTRODUCTION
Despite advances in diagnostic techniques, the role of the neurological examination in the diagnosis of amyotrophic lateral sclerosis (ALS) remains central.1 The need for early diagnosis of ALS has increased over the years as early multidisciplinary care has improved patients' quality of life,2 and oral treatment with edaravone has become available for early-stage ALS.3
In general, muscle weakness in ALS is not uniform, and various signs of selective muscle involvement, such as split hand syndrome (dissociated small hand muscle atrophy),4 have been reported to help in the diagnosis. Among these signs, the weak shoulder and arm sparing signs, reported in 2022, were superior to previous signs in sensitivity and specificity.5 However, that report was based on an examination by a single experienced neurologist.
Manual muscle testing (MMT) is a quick and flexible method of evaluating muscle strength. However, the test is subjective, and results may depend on the examiner's experience.6 Therefore, it is unclear whether weak shoulder and arm sparing signs have the same high diagnostic performance when evaluated by multiple neurologists.
We believe that many of our ALS patients also exhibited weak shoulder and arm sparing signs. We aimed to determine the sensitivity of these signs when performed by multiple examiners with varying clinical experience.
2 METHODS
2.1 Subjects
Patients initially admitted for the diagnosis of ALS and diagnosed with ALS between 2014 and 2023 were identified from our department's inpatient database. Their clinical and electrodiagnostic records were retrospectively reviewed. Inclusion criteria were (1) a diagnosis of or suspicion of ALS during our initial clinical and electrodiagnostic evaluations; (2) exclusion of other diseases by appropriate ancillary tests; and (3) follow-up information confirming the diagnosis of ALS by reaching endpoints (death, mechanical ventilation, tracheostomy, or gastrostomy) or definite inexorable progression not due to other causes. Patients were excluded if their final diagnosis was other than ALS. Each patient was reclassified at the time of this study according to the Gold Coast Criteria1 based on clinical signs and electrophysiological examination results at admission. Patients who did not meet the criteria at admission were included if the diagnosis of ALS was confirmed at follow-up. The duration of illness, region of symptom onset, and grade of the Japan ALS Severity Classification on admission were also evaluated. (The Japanese ALS severity classification7 score ranges from 1 to 5: [1] able to work or perform housework; [2] independent living but unable to work; [3] requiring assistance for eating, excretion, or ambulation; [4] presence of respiratory insufficiency, difficulty in coughing out sputum or dysphagia; and [5] using a tracheostomy tube, tube feeding, or tracheostomy positive pressure ventilation.) Although this severity grade is not a quantitative measure of ALS severity, it was evaluated because of its importance in treatment selection. Data on the ALS Functional Rating Scale-revised version (ALSFRS-R) score at admission could not be collected because many patients did not have sufficient data.
This study was approved by the Ethics Committee of Akita University (Approval No. 3091), and informed consent was obtained from the subjects in the form of an opt-out on the website.
2.2 Medical Research Council scores
Multiple neurologists and neurology residents evaluated each patient's Medical Research Council (MRC) scores on admission. The residents were supervised by neurologists on how to perform MMT. MRC scores assessed independently by the residents were also used as data.
We evaluated the side muscles that were more severely affected by measuring the MRC scores of the deltoid (Del), biceps brachii (BB), triceps brachii (TB), and first dorsal interosseous (FDI) muscles. The MRC score was graded according to the standard method. However, we used a modified scale for muscles unaffected by gravity.8 We scored using a plus or minus suffix (such as 4+ or 4−), but they were rounded to an integer. For example, 4+ was rounded up to 5, and 4- was rounded down to 3. The final classification system had six levels of integers 0–5. Individual muscle MRC scores were used to assess signs of selective muscle involvement. One muscle was defined as weaker than another if there was a difference of one or more in the MRC scores of the two muscles.
2.3 Definition of “weak shoulder” and “arm sparing” signs
In defining these two signs, we have accurately referenced definitions from previous studies.5 A muscle was judged to be weaker than a muscle group composed of two muscles when the former was weaker than both two latter muscles or was weaker than one and no stronger than the other. When Del was weaker than the arm muscle group BB and TB, the “weak shoulder” sign was judged to be positive. When both Del and FDI were weaker than the arm muscle group BB and TB, the “arm sparing” sign was judged to be positive.
2.4 Statistical analysis
Patients with a lack of MRC scores necessary to determine the weak shoulder and arm sparing signs were excluded from the analysis. The MRC scores of the two muscles were compared using the sign test. The sensitivity was determined by the number of patients presenting with weak shoulder and arm sparing signs. Comparisons between different patient groups, classified by region of symptom onset, presence or absence of upper motor neuron (UMN) signs, and Japan ALS Severity Classification grade, were made using the chi-squared test. The duration of illness was compared between the two groups (positive and negative for each sign) using the Mann–Whitney U test, as the data were not normally distributed.
Authors became aware of these signs in 2022, after the publication of the previous study. The sensitivity of these signs for patients up to 2021 was also assessed.
p < .05 was considered statistically significant. Statistical analyses were performed using Excel (version 16.79.2, Microsoft Corp, Redmond, Washington) and EZR (version 4.3.2, Saitama Medical Center, Jichi Medical University).
3 RESULTS
3.1 Patients
A total of 71 ALS patients were identified, including 46 men and 25 women. The mean age of the patients was 69.4 ± 10.8 years (range: 39–88). Symptom onset manifested in different regions: bulbar (n = 13), upper limb (n = 37), lower limb (n = 18), and respiratory (n = 3). The Gold Coast criteria were fulfilled by 97% (n = 69) of patients. Of the two patients who did not meet the Gold Coast criteria, one had lower motor neuron (LMN) signs meeting the criteria in fewer than two body regions without accompanying UMN signs, while the other had UMN signs in one body region and LMN signs in another. The mean disease duration at admission was 14.7 ± 11.9 months (range: 2–70, median: 10). The mean Japan ALS Severity Classification grade was 2.6 ± 1.2 (range: 1–5, median: 3).
3.2 Examiners
One of eight neurologists or three neurology residents evaluated each patient's MRC scores on admission. The neurologists had a median of 5 years of experience (interquartile range: 3–9, range: 0–16) at the time of evaluation, with a mean of 5.92 ± 4.29 years. The neurologists included specialist and non-specialist doctors, with 45 of the 71 patients assessed by specialists. The three neurology residents were in their first year and trained in neurology for 1–2 months.
3.3 Weak shoulder and arm sparing signs in ALS patients
We were able to use data from 65 patients for the analysis of the weak shoulder sign and 56 patients for the arm sparing sign (Figure 1).
Table 1 summarizes the results of the weak shoulder and arm sparing signs in ALS patients. The sensitivity of the weak shoulder sign was 72% of the total ALS patient population, whereas the sensitivity of the arm sparing sign was 48% of the patients. The statistical significance was confirmed using the sign test.
| Weak shoulder (sensitivity) | p valuea | Arm sparing (sensitivity) | |
|---|---|---|---|
| Between Del and BB/TB | |||
| All ALS patients | 47/65 (72%) | <.0001 | 27/56 (48%) |
| Region of symptom onset | |||
| Bulbar | 10/13 (77%) | <.05 | 5/11 (45%) |
| Upper limb | 24/33 (73%) | <.0001 | 16/28 (57%) |
| Lower limb | 11/16 (69%) | <.01 | 4/14 (29%) |
| UMN signs | |||
| Positive | 41/58 (71%) | <.0001 | 23/49 (47%) |
| Negative | 6/7 (88%) | <.05 | 4/7 (57%) |
| Japan ALS Severity Classification | |||
| 1 and 2 | 22/31 (71%) | <.001 | 14/29 (48%) |
| 3–5 | 25/34 (74%) | <.0001 | 13/27 (48%) |
- Abbreviations: ALS, amyotrophic lateral sclerosis; BB, biceps brachii; Del, deltoid; FDI, first dorsal interosseous; NS, not significant; TB, triceps brachii, UMN, upper motor neuron.
- a Sign test.
In an analysis of patients up to 2021, before we recognized these signs, the sensitivity of the weak shoulder sign was 74% (40/54 patients) and that of the arm sparing sign was 49% (23/47 patients).
Regarding the region of symptom onset, the weak shoulder sign showed high sensitivity in the bulbar, upper limb, and lower limb groups. The arm sparing sign showed moderate sensitivity in the bulbar and upper limb groups. Of three patients with respiratory onset (not shown in the table), both weak shoulder and arm sparing signs were found in two.
The chi-square test showed no statistically significant associations between the region of symptom onset (bulbar, upper limb, lower limb) and either the weak shoulder sign (p = .886) or the arm sparing sign (p = .215).
The number of patients without UMN signs was small, but sensitivity was not reduced in those without UMN signs. The chi-square test showed no statistically significant associations between UMN signs and either the weak shoulder sign (p = 0.695) or the arm sparing sign (p = 0.919).
The analysis results by the Japan ALS Severity Classification grade showed that two signs in the grades 1 and 2 groups, defined as early stage, showed the same level of sensitivity as all the patients with ALS. The chi-square test showed that these signs were not significantly associated with the Japan ALS Severity Classification (grades 1 and 2 vs. grades 3–5) (p = 1.0 for both signs).
The Mann–Whitney U test revealed no significant relationship between the duration of illness and the presence of the weak shoulder sign (p = .329) or the arm sparing sign (p = .669).
4 DISCUSSION
This study showed that the weak shoulder and arm sparing signs are notable features in a substantial proportion of ALS patients, even when clinically evaluated by multiple neurologists and neurology residents.
In a previous study,5 the weak shoulder and arm sparing signs in ALS patients were compared with other signs of selective involvement, and their specificity for cervical spondylotic amyotrophy (CSA), which is common in Japan,9 and multifocal motor neuropathy was discussed. The sensitivity of the weak shoulder sign was higher than that of the conventional signs (split hand, split finger, split hand plus, split elbow). The sensitivity of the arm sparing sign was not significantly different from split hand and split finger, but the arm sparing sign was found in only 2% of patients with CSA and was useful in diagnosing ALS.
Assessments by multiple examiners with varying clinical experience in our institute yielded similar sensitivity to a previous study by a single experienced neurologist.5 Reproducibility in completely different settings increases the reliability of both studies and highlights the potential of these signs for widespread use in clinical practice. The consistency of sensitivity between multi-examiner and single-examiner studies suggests that these signs could be valuable in a multicenter study.
Importantly, both signs demonstrated consistent sensitivity in patients before we recognized these signs. In the previous study, a single experienced neurologist was aware of the presence of these signs long before publication, for the inevitable reason that they were the pioneers in discovering these signs.5 Our results up to 2021 eliminate any potential bias towards MMT that may arise from prior knowledge of these signs and support the usefulness and reliability of these signs.
Another finding is that the sensitivity was high regardless of the region of symptom onset. A detailed study of the order of region of lower motor neuron symptoms based on the ALSFRS-R revealed that symptom onset is most commonly in the upper or lower limbs, with bulbar onset the next most common. The second region of symptom appearance varied from case to case.10 The same trend was observed in the present study, and the sensitivity of the weak shoulder sign was high regardless of the region in which the first symptom appeared. This sign may help diagnose ALS regardless of the region of symptom onset.
The weak shoulder and arm sparing signs were equally useful in diagnosing patients with grades 1 and 2 of the Japanese ALS Severity Classification, where early use of edaravone is recommended. This suggests that these signs may aid in early ALS diagnosis and contribute to the control of disease progression.
This study has several limitations. First, MMT is a subjective assessment. Intraexaminer and interexaminer reproducibility between neurologists and residents was not assessed in this retrospective study. Second, we did not examine the specificity of these signs for CSA. This was due to the variability in diagnostic methods by multiple examiners and the tendency of neurologists at our institute to see atypical CSA cases that deviate from the characteristics of the general CSA population.11, 12
The mechanism of selective muscle involvement in ALS remains inconclusive.5 Hypotheses include higher oxidative stress and metabolic load on frequently used muscles,4 preferential involvement of muscles innervated by alpha motor neurons receiving direct corticomotoneuronal input,13, 14 and the “multifocal hits and local propagation” hypothesis based on abnormal electromyography findings in various spinal cord regions.15 In our study, there was no reduction in sensitivity in patients without UMN signs, which may be a small clue to the mechanism.
In conclusion, this study demonstrates the reproducibility of the weak shoulder and arm sparing signs evaluated by multiple examiners. These findings expand the clinical utility and increase the reliability of these signs, potentially contributing to accurate ALS diagnosis when combined with other clinical features and objective assessments.
AUTHOR CONTRIBUTIONS
Yui Sanpei: Conceptualization; formal analysis; investigation; methodology; validation; visualization; writing – original draft; writing – review and editing. Keita Yasuda: Writing – review and editing. Yoshiko Takahashi: Writing – review and editing. Akira Hanazono: Writing – review and editing. Masashiro Sugawara: Project administration; supervision; writing – review and editing. Katsunori Iijima: Writing – review and editing.
ACKNOWLEDGMENTS
The authors thank Dr. Sachiko Kamada and Homare Funasaka (Omagari Kosei Medical Center, Akita, Japan), Dr. Momoka Funasaka (Akita City Hospital, Akita, Japan), Dr. Masazumi Matsuda, Dr. Masaya Ogasawara, Dr. Wataru Kuroki, and Dr. Hinako Shimada (Akita University Hospital, Akita, Japan) for cooperating with this study.
CONFLICT OF INTEREST STATEMENT
The authors declare no conflicts of interest.
ETHICS STATEMENT
We confirm that we have read the Journal's position on issues involved in ethical publication and affirm that this report is consistent with those guidelines.
Open Research
DATA AVAILABILITY STATEMENT
The data that support the findings of this study are available from the corresponding author upon reasonable request.
