A 73-Year-Old Man Presenting with Shoulder Muscle Pain and a Diagnosis of Guillain-Barré Syndrome

Introduction

Guillain-Barré syndrome (GBS) is a type of acute autoimmune-mediated paralytic polyneuropathy [1]. Relevant research indicates that the global incidence rate of GBS is 0.4–2.5 per 100 000 population. With each additional 10 years of age, the risk of developing the condition increases by 20%, and the incidence rate is higher in males than in females [2]. GBS includes various subtypes, including acute inflammatory demyelinating polyneuropathy (AIDP), acute motor axonal neuropathy (AMAN), acute motor and sensory axonal neuropathy (AMSAN), and Miller-Fisher syndrome (MFS). Among these, AIDP is the most common and typical subtype of GBS [3]. According to diagnostic criteria such as those from the National Institute of Neurological Disorders and Stroke (NINDS) and the Brighton criteria for GBS, most GBS patients experience antecedent events such as upper respiratory or gastrointestinal infections within the 4 weeks prior to onset of the disease. Furthermore, the condition typically reaches its peak severity within 2 weeks, with nearly all patients experiencing peak symptoms within 4 weeks [4]. Currently, intravenous immunoglobulin therapy and plasma exchange are widely used worldwide to control the progression of GBS and reduce disability. However, even when standard immunotherapy is employed, there is still a mortality rate of approximately 5%, and up to 20% of patients are unable to walk independently 1 year after onset of the disease [1].

Early diagnosis is crucial for treatment and prognosis of GBS. GBS typically presents with symmetric progressive limb weakness and decreased or absent tendon reflexes as the primary symptoms. Onset often begins in the distal extremities and, in some cases, patients experience paralysis. Some patients also exhibit varying degrees of facial or bulbar muscle weakness, and in severe cases, weakness of the neck and respiratory muscles can occur, leading to breathing difficulties [5]. However, there is a subset of patients whose clinical presentation is entirely different from the above symptoms, showing significant heterogeneity, which may lead clinicians to consider alternative diagnoses and potentially result in treatment delays [6].

Pain is a frequently overlooked symptom in GBS, yet it can be a significant clinical feature. In some cases, pain precedes weakness or other neurological symptoms, making early diagnosis challenging [7]. In the past few decades, studies from multiple countries have reported various types of GBS and its diverse presentation, with pain as an initial symptom. Clinical reports have indicated that the location and nature of pain in GBS patients vary, including localized muscle pain, back pain, headaches, and even generalized joint pain and neuropathic pain (such as burning or knife-like pain) [8–17]. These clinical features suggest that pain may serve as a key clue for the early diagnosis of GBS. Therefore, pain should be considered an important and often overlooked clinical manifestation of GBS, especially in the early stages of the disease, where it can influence clinical judgment and lead to delays in appropriate treatment.

Pain is under-reported or not considered a key symptom in GBS because it often lacks specificity and can mimic other common conditions, such as musculoskeletal disorders. Clinicians may focus on the more prominent motor symptoms, overlooking pain as a diagnostic indicator. Additionally, patients might not emphasize pain during consultations, or it may be attributed to benign causes, leading to underdiagnosis. However, studies have shown that 33.3% of GBS patients experienced pain in the 2 weeks prior to onset, and the pain was positively associated with cerebrospinal fluid protein concentration [18]. This under-recognition contributes to diagnostic delays or incorrect judgment. Highlighting pain’s role, especially when it precedes other symptoms, is crucial for clinicians to consider GBS in their differential diagnoses and to initiate timely treatment.

The presence of pain, particularly shoulder muscle pain, as an initial symptom of GBS, is uncommon and may lead clinicians to consider alternative diagnoses, as was the case with the patient discussed in this report. This report is of a 73-year-old man presenting with shoulder muscle pain and a diagnosis of Guillain-Barré syndrome.

Case Report

A 73-year-old Chinese man initially sought medical attention at our hospital’s outpatient clinic for severe left shoulder muscle pain. After a medical consultation, it was determined that he had a cold and diarrhea 1 week ago, and his symptoms improved after taking over-the-counter cold medication. At the time of the visit, apart from the left shoulder muscle pain, the patient did not experience any other discomfort. The physician conducted a detailed range of motion assessment of the patient’s shoulder joints. The results indicated that both active and passive shoulder joint ranges of motion were essentially normal, with no joint swelling, significant joint stiffness, movement limitations, or clicking sounds during activity. Cervical spine magnetic resonance imaging (MRI) showed marginal osteophytes at the vertebral bodies, and disc protrusions at the C3/4 to C6/7 intervertebral levels; however, no abnormalities were found in the spinal cord morphology or adjacent tissues. No signs of degenerative changes were observed in the shoulder joints, such as joint space narrowing, osteophyte formation, or cartilage degeneration. Therefore, the doctor initially diagnosed the patient with cervical spondylosis and administered acupuncture treatment to the patient’s neck acupoints. Two days later, the patient returned for a follow-up appointment and reported that the left shoulder muscle pain had not significantly improved. He also reported experiencing gradual numbness and weakness in both upper limbs, decreased sensation in the right upper limb, and weakened grip strength in both hands, with no abnormalities noted in the lower limbs. Given the progressive worsening of his condition, further diagnosis and treatment were deemed necessary, and he was advised to be admitted to the hospital on the same day.

When the patient was transferred from the outpatient clinic to our hospital ward, he was alert, with clear and fluent speech. He experienced continuous pain in his left shoulder, numbness and weakness in both upper limbs, reduced sensation in the right upper limb, and weak grip strength in both hands. Range of motion testing, stability examinations, and palpation showed that active and passive movements of the shoulder joints were within normal limits. There were no obvious dislocations or subluxations, and no joint deformities, joint instability, crepitus, or specifically localized pain points during shoulder movements. He had a history of hypertension and myocardial infarction. On the day of admission, the electrocardiogram (ECG) results showed sinus rhythm, indicating signs of an old myocardial infarction, but the current ECG was normal with no typical changes of an acute myocardial infarction. The serum myocardial enzyme spectrum results were all within the normal range. Upon physical examination, the patient exhibited a strength of 4/5 in the proximal muscles of both upper limbs, 2/5 in the distal muscles of both upper limbs, and 5/5 in both lower limbs. The patient showed asymmetry in facial expression, with the right corner of the mouth rising less than the left during a smile, and a shallower forehead wrinkle on the right side. When he stuck out his tongue, the tip deviated to the right, indicating partial cranial nerve dysfunction. The tendon reflexes were normal in both the elbows and wrists of the upper limbs, as well as in the knees and ankles of the lower limbs. Sensory examination revealed hypersensitivity to touch and pain in the upper limbs, while the sensory function in the lower limbs remained normal. The Babinski sign was negative, and no other pathological signs were observed.

On the third day of admission, he reported worsening pain in the left shoulder and upper left arm, which persisted and was not alleviated. No symptoms of chest tightness, shortness of breath, chest pain, or back pain were observed. Additionally, since admission, the patient’s symptoms of limb numbness and weakness further intensified. Deep tendon reflexes in both the upper and lower limbs became diminished, and sensory examination revealed a blunting of touch and pain sensation. Muscle strength in the left lower limb decreased to grade 3, while that in the right lower limb had weakened to grade 2. The patient had difficulty urinating. Relevant laboratory tests showed elevated level of immunoglobulin A (IgA) at 5.340 g/L (reference range: 0.700–4.000) and immunoglobulin E (IgE) at 434.000 IU/mL (reference range: 0.000–100.000). Considering the evolving symptoms and possibility of Guillain-Barré syndrome, which was suspected at that time, immediate immunotherapy with intravenous immunoglobulin (IVIG) was administered. As he showed rapid clinical improvement, a re-evaluation of the cervical MRI was not performed. Gabapentin was prescribed to manage pain symptoms, and a urinary catheter was inserted to address urinary difficulties. Oxygen therapy was administered. To further confirm the diagnosis, a lumbar puncture was performed to obtain cerebrospinal fluid for analysis, and electro-myography (EMG) testing was conducted. The cerebrospinal fluid analysis revealed an opening pressure of 110 mmH2O. The white blood cell count in the cerebrospinal fluid was 0, and the cerebrospinal fluid micro total protein (CSF-MITP) was elevated at 0.70 g/L (reference range: 0.08–0.43 g/L). The EMG results indicated peripheral nerve damage in both upper limbs, with decreased sensory conduction amplitudes in both the median and ulnar nerves. The motor conduction study revealed reduced conduction velocities and decreased amplitudes in these nerves. Needle electromyography showed signs of acute denervation in the distal muscles of the upper limbs. Additionally, F-waves were absent, and H-reflexes were not elicitable, further supporting the diagnosis. The serum tests showed that the GM1 antibody was positive. Additional diagnostic evaluation was performed to rule out other potential causes. Brain MRI revealed softening lesions in the basal ganglia, thalamus, and corpus callosum, without the presence of new lesions. Based on the progression of symptoms and the results of diagnostic tests, a definitive diagnosis of Guillain-Barré syndrome was made.

After continuous IVIG treatment for 5 days, the patient’s condition improved. At the time of discontinuation, there was noticeable improvement in the patient’s limb mobility. The muscle strength in both upper limbs had increased from grade 2 to grade 4, whereas in both lower limbs, it had improved to grade 3. The grip strength in the right hand also improved, although the left hand still had limited grip strength. The left shoulder muscle pain significantly improved, and he was able to urinate independently. After the patient was admitted, continuous acupuncture therapy has been administered to address pain and limb mobility symptoms (for both upper limbs, LI4, PC6, LI10, LI11, LI14, LI15, HT1, LU5, and GB20; for both lower limbs, ST34, SP10, ST36, ST37, ST39, GB34, SP9, SP6, KI3, and LR3). After discontinuing immunotherapy, and continuing acupuncture treatment for 1 more week, the patient’s upper limb muscle strength recovered to grade 5, and the lower limb muscle strength also improved from grade 3 to level 5. The left shoulder muscle pain was significantly reduced, and no abnormalities were found in relevant laboratory tests. EMG results indicated improvement in the peripheral nerve damage. As a result of this progress, the patient was successfully discharged from the hospital (for the timeline of the disease course, see Figure 1).

Discussion

This case report highlights the importance of recognizing atypical presentations of GBS to ensure timely and accurate diagnosis, ultimately improving patient outcomes. Specifically, it underscores that GBS can initially present with isolated muscle pain, such as severe shoulder muscle pain, which may lead clinicians to consider alternative diagnoses and delay appropriate treatment if not carefully evaluated.

The patient, a 73-year-old man, initially presented with severe left shoulder muscle pain without other neurological symptoms, which is an uncommon initial manifestation of GBS. This atypical presentation led to an initial diagnosis of cervical spondylosis. However, the subsequent development of progressive limb weakness, numbness, and cranial nerve involvement shifted the diagnostic consideration towards GBS.

The typical presentation of GBS may not pose a diagnostic challenge; however, overlooking atypical symptoms can often lead to missed diagnoses and delayed treatment. While the clinical diagnosis of GBS can be supported by additional tests such as cerebrospinal fluid analysis and nerve conduction studies, which can be helpful for patients with atypical symptoms or diagnostic uncertainty, these tests primarily serve as a means to rule out other diagnoses and may not promptly identify the disease [19]. Therefore, summarizing and accumulating knowledge regarding atypical symptoms is crucial for clinicians to make accurate disease assessments. Throughout the course of GBS, pain symptoms can manifest either as the disease progresses or, in some cases, precede the weakness symptoms [20]. This complex presentation of GBS makes its diagnosis challenging.

Our review of previous reports on Guillain-Barré syndrome with pain as the initial symptom [8–17,21–25] showed that the age distribution of patients with Guillain-Barré syndrome-related pain is broad. The initial onset of pain can occur in various parts of the body, including the head, back, abdomen, waist, and legs. Furthermore, pain presents in various forms such as throbbing, stabbing, and cutting sensations [8,22]. These diverse pain symptoms often lead to incorrect judgment by healthcare professionals, resulting in off-target initial clinical treatment plans. Similarly, in the cases reported in this article, the patients exhibited a novel pain symptom, pain in the left shoulder muscle. In the absence of other symptoms, this presentation can be initially diagnosed as cervical spondylosis. Therefore, in the diagnostic process of GBS, it is important to pay special attention to pain symptoms as they may present in unique and unexpected ways.

In addition to the need to pay special attention to pain symptoms in the clinical diagnosis of GBS, research into the potential underlying mechanisms of this pain is also crucial. Current studies have proposed several hypotheses regarding these mechanisms: some research suggests that the pain is related to the immune-mediated inflammatory response in the peripheral nerves, where the release of cytokines and other inflammatory mediators sensitizes nociceptors (pain receptors) in the peripheral nerves. Other studies indicate that during the autoimmune process there can be direct damage to the myelin and sensory nerve axons, leading to ectopic discharges and spontaneous pain [3,26]. Furthermore, the disruption of normal nerve conduction due to demyelination may result in abnormal sensory processing in the central nervous system, which could also play a role in the development of pain. Recent research has also suggested that certain autoantibodies, such as anti-ganglioside antibodies, can cause pain by directly interacting with sensory nerve fibers [27]. Moreover, central sensitization may significantly contribute to pain in GBS. Continuous abnormal input from damaged peripheral nerves can heighten the excitability of neurons in the dorsal horn of the spinal cord, intensifying pain perception [28]. Additionally, immune-mediated damage to specific nerve fibers, such as A-delta and C fibers responsible for pain transmission, can lead to neuropathic pain symptoms. Inflammatory cytokines like TNF-α and IL-6 released during the immune response may further sensitize nociceptors, amplifying pain signals [29]. Understanding these specific physiological mechanisms is crucial for effective pain management in GBS patients.

Furthermore, we also observed that in the previously reported cases, pain management primarily relied on opioids, nonsteroidal anti-inflammatory drugs (NSAIDs), and nerve-suppressing medications. Some reports did not mention specific pain management measures. Although these analgesic medications provide some relief from pain, they also carry the risk of dependency and have inevitable adverse effects. Therefore, the management of pain in GBS requires further optimization and the development of scientifically sound standards. In the case reported in this article, in addition to gabapentin, the patient received acupuncture therapy throughout treatment. At the time of discharge, the patient experienced significant relief from pain and limb weakness symptoms. Acupuncture, as a low-cost, low-risk, and convenient treatment modality, has gained international recognition for its effectiveness in managing pain. It has shown significant therapeutic benefits in the treatment of pain associated with various medical conditions [30,31]. However, there is currently limited literature on the use of acupuncture for pain management in GBS patients. Further clinical observation and exploration are needed to better understand its potential in treating GBS-related pain. We also noticed that our patient developed hyponatremia as his condition progressed. Upon admission, his blood sodium level was 142.2 mmol/L (reference range: 136.0–145.0 mmol/L). However, during the hospital stay, blood sodium level gradually decreased, reaching a minimum of 130.5 mmol/L. The patient was instructed to increase salt intake, after which blood sodium levels began to recover. Previous studies have indicated that blood sodium levels are closely related to the severity and prognosis of GBS [32,33]. This suggests that increased attention should be paid to blood sodium levels during GBS treatment. In addition, the patient mentioned experiencing symptoms of a cold and diarrhea during the initial consultation. However, during the later stages of diagnosis and treatment, no stool culture was performed, which we acknowledge as a limitation in this case report. This is an important consideration for clinical management, and a stool culture should be included to rule out potential infections that could be linked to the onset of GBS.

Conclusions

This report highlights that deep muscle pain can be a symptom of Guillain-Barré syndrome. Recognizing such atypical presentations is crucial for timely diagnosis and effective management. This case provides a clinical basis for the diagnosis of atypical GBS and offers insights into pain management in GBS.