Isolated Neck Extensor Myopathy Associated with Sarcopenia

Abstract

A 64-year-old woman with low body weight presented for treatment because of a 1-month history of progressively worsening headdrop. A physical examination revealed isolated weakness in the neck extensor muscles. Short T1 inversion recovery sequences revealed localized high signal intensity in the bilateral splenius capitis muscles, and needle electromyography revealed myopathic changes. Isolated neck extensor myopathy (INEM) secondary to sarcopenia was diagnosed. Steroid therapy was administered, which resulted in a significant improvement in the dropped head syndrome. This case highlights the importance of evaluating sarcopenia in patients who present with dropped head, and considering steroid treatment for INEM associated with inflammatory findings.

Introduction

Isolated neck extensor myopathy (INEM) is characterized by localized cervical extensor myopathy, which manifests as dropped head syndrome (DHS) without generalized symptoms (1). INEM has been frequently reported in elderly individuals (1,2). Immunotherapy and surgical interventions have also been reported as potential treatment strategies for INEM (1-4). Nevertheless, the exact pathogenesis of INEM, as well as its established risk factors and optimal treatment strategies, remain unclear. In addition, specific diagnostic criteria for INEM are lacking.

We herein report a patient with INEM associated with sarcopenia who demonstrated significant clinical improvement with steroid therapy. This case elucidates the potential pathogenesis of INEM and enhances our understanding of the disease.

Case Report

A 64-year-old woman presented with a 1-month history of progressively worsening headdrop. She had been leaning forward because of lower back pain that preceded the onset of head drop. However, she did not experience any infection before the onset of headdrop. Her medical history included mild cervical spondylosis and shingling. The patient had a slender build (height, 151 cm; weight, 32.6 kg; body mass index, 14.3) and exhibited a dropped head posture (Fig. 1A). A physical examination revealed isolated weakness of the neck extensor muscles, which was quantified as a manual muscle testing (MMT) score of 2. Cervical spinal mobility and normal muscle tone were maintained. No additional muscle weakness was observed. Tendon reflexes were normal, and pathological reflexes were not observed. In addition, symptoms indicative of parkinsonism and myasthenic fatigability were not detected.

Figure 1.

(A) X-ray image showing dropped head. (B) Short T1 inversion recovery (STIR) sequence of the neck showing localized high-signal intensity in both splenius capitis muscles (white arrows). (C) Needle electromyography image showing low amplitude and polyphasic motor unit potentials. (D) Sagittal T2-weighted cervical spine magnetic resonance imaging (MRI) scan revealing mild intervertebral disc herniations at the C3 to C6 levels without spinal deformities or abnormal intramedullary signals. (E) Axial image of the C5/C6 level shows no evidence of foraminal stenosis (yellow arrows).

Blood test results revealed a creatine kinase (CK) level of 331 U/L. Inflammatory markers, including the white blood cell count (4,500 /μL), C-reactive protein level (0.11 mg/dL), and erythrocyte sedimentation rate (6 mm), were within normal limits. Thyroid function test results, including free T3, free T4, and thyroid-stimulating hormone levels, were also within normal ranges. Tests for antibodies against thyroglobulin, thyroid peroxidase, the acetylcholine receptor, muscle-specific tyrosine kinase, and aminoacyl-tRNA synthetase yielded negative results. The bone mineral density of the femoral neck, assessed using dual X-ray absorptiometry, was 0.468 g/cm² (52% of the mean for young adults), leading to a diagnosis of osteoporosis. Short T1 inversion recovery sequence of the neck revealed a localized high signal intensity within the bilateral splenius capitis muscles (Fig. 1B). An electrophysiological examination and repetitive nerve stimulation tests did not show waning; however, needle electromyography identified myopathic changes in the paraspinal muscles at the C7 level (Fig. 1C). Needle electromyography of the right biceps brachii revealed no abnormalities. Cervical magnetic resonance imaging (MRI) revealed slight intervertebral disc herniation at the C3-C6 levels; however, spinal deformities, abnormal signals within the cord, and foraminal stenosis were not observed (Fig. 1D, E).

Although the patient refused a muscle biopsy because of its invasive nature, our examination results allowed the exclusion of various causes of DHS, including Parkinson's disease, myasthenia gravis, motor neuron disease, and metabolic disorders. INEM was clinically suspected, and sarcopenia was diagnosed based on the Asian Working Group for Sarcopenia 2019 criteria (5). A sarcopenia evaluation indicated the following results: calf circumference, 26.0 cm/25.5 cm; handgrip strength, 15 kg/17 kg; Strength, Assistance with walking, Rise from a chair, Climb stairs, Falls (SARC-F) questionnaire score, 4; height-adjusted muscle mass, 4.8 kg/m² (measured with bioimpedance); and five times sit-to-stand test, 22 s.

Oral prednisone (20 mg daily) was initiated as INEM treatment. Approximately 4 weeks after treatment initiation, the DHS gradually improved (Fig. 2A). Slight weakness of the neck extensor muscles (MMT score, 4) persisted, neck MRI no longer detected abnormal signals (Fig. 2B), and needle electromyography showed myopathic changes (Fig. 2C). Oral prednisone was gradually tapered over the course of seven months. After discontinuation, recurrence was not observed for approximately six months. Regarding osteoporosis treatment, intervention with bisphosphonates was postponed until after the completion of ongoing dental procedures. Although anti-signal recognition particles and anti-3-hydroxy-3-methylglutaryl coenzyme A reductase antibodies in this patient were not assessed, the clinical course was not suggestive of immune-mediated necrotizing myopathy (IMNM). Consequently, the patient was diagnosed with INEM.

Figure 2.

After steroid treatment, (A) dropped head (X-ray), (B) high signal intensity (magnetic resonance imaging), and (C) myogenic changes (needle electromyography) improved.

Discussion

Previous reports have documented cases of INEM associated with various diseases, including Parkinson's disease, cervical spondylosis, and osteoporosis (1,6,7). In the present case, sarcopenia was suspected to have contributed to the development of INEM. Sarcopenia is a chronic condition characterized by a decline in skeletal muscle mass, strength, and function and is commonly recognized as a consequence of aging. A previous study found that the prevalence of sarcopenia in patients with DHS was higher than that in healthy controls (6); however, the association between sarcopenia and INEM remains unclear.

The pathological features of sarcopenia include muscle fiber atrophy and accumulation of interstitial fibrous tissue (8), which leads to the loss of tissue elasticity. Our patient met the criteria for sarcopenia, indicating the potential for reduced tissue elasticity. In addition, factors that contribute to INEM may include kyphotic postural changes and loss of tissue elasticity in the cervical paraspinal musculature (1). In the present case, muscle impairment was considered the result of excessive and sustained loading of the cervical extensor muscles, which lost tissue elasticity due to sarcopenia. The impaired cervical extensor muscles in this case may have experienced further loading triggered by the forward leaning posture, resulting in a dropped head.

Furthermore, the muscle regeneration and remodeling processes associated with sarcopenia cause persistent muscle inflammation (9), which may exacerbate the load on muscles with reduced tissue elasticity. Muscle biopsy results have identified nonspecific inflammation in some patients with INEM (10). In the present case, the high signal intensity observed on neck MRI may have indicated inflammation. Moreover, the number of cases, including the present case, that responded to steroid therapy early during the course of the disease (11) supports the involvement of inflammation in the pathogenesis of INEM. Despite the shared pathophysiological features of sarcopenia and INEM, including loss of tissue elasticity and systemic inflammation, reports on the relationship between INEM and sarcopenia are lacking; therefore, sarcopenia may be underestimated in the context of INEM.

Immunotherapy is commonly administered to patients with INEM, but its efficacy varies significantly. Furthermore, the inflammatory findings vary among cases, suggesting that the pathophysiology of INEM is heterogeneous. Notably, focal myositis involving the neck extensor muscles is considered a form of inflammatory INEM (10). Because of the difficulty in clearly distinguishing focal myositis of the neck extensor muscles from INEM, it may be reasonable to consider focal myositis as part of the broader clinical spectrum of INEM. To further elucidate the pathophysiology and treatment of INEM in this broader context, we conducted a literature review including focal myositis. To our knowledge, only 19 cases of INEM with available clinical details of immunotherapy have been reported (1,2,7,10-16) (Table). Among the 13 cases, including the present case, that showed clinical improvement with immunotherapy, approximately half (7/13) exhibited inflammatory findings during MRI or pathological examinations. In the remaining patients (6/13) who benefited from immunotherapy despite the absence of inflammatory findings, MRI or pathological examinations were not performed, suggesting that the inflammatory findings in these cases may have been underestimated. Among the six patients who did not show clinical improvement with immunotherapy, only one (Case 9) failed to respond despite the presence of inflammatory findings. Notably, none of the patients with cervical spondylosis as a comorbidity (4/4), including Case 9, who underwent surgical intervention, responded to immunotherapy. This observation suggests that immunotherapy may be ineffective in treating myelopathy caused by mechanical stress. Consequently, immunotherapy appears to be particularly beneficial in cases with inflammatory findings and without mechanical compression factors, such as cervical spondylosis. Furthermore, some cases categorized as INEM may have an inflammatory pathology indistinguishable from focal myositis (17). Recognizing this possibility is essential to avoid missing opportunities for effective immunotherapy. Further prospective studies are required to evaluate the efficacy of immunotherapy for INEM.

Table.

Clinical Features of Cases with INEM Treated with Immunotherapy.

Case	Age/sex	Comorbidity	Duration*	Image analysis		Pathological analysis		Immunotherapy	Response***	Ref
				MRI	HIA**	Biopsy	Inflammation
1	81/F		3 months	-		+	-	Oral PSL	-	(12)
2	64/M	CS	1 week	+	NA	+	-	Oral PSL	-	(1)
3	84/F	CS	3 months	+	NA	+	-	Oral PSL	-	(1)
4	65/M	CS	2 months	+	NA	+	-	Oral PSL	-	(1)
5	80/F	Osteoporosis	4 months	-		+	+ (Inflammatory infiltrates composed of B and T lymphocytes)	mPSL, oral PSL, AZA	+	(7)
6	35/M		1 year	-		+	+ (Polymyositis showing inflammatory T lymphocytes)	Oral PSL	+	(13)
7	52/M		1 year	-		+	-	Oral PSL	-	(13)
8	54/F		7 months	+	+	+	+ (Myophagia and T-cell infiltrates)	Oral PSL	+	(10)
9	68/F	CS	1 month	+	+	+	-	Corticosteroids	-	(14)
10	74/M		2 months	+	+	+	+ (Perivascular and endomysial inflammatory infiltrates)	mPSL, oral PSL, AZA	+	(11)
11	78/F		5 years	-		+	-	Oral PSL, MMF	+	(15)
12	74/F		1 year	+	-	-		Oral PSL	+	(15)
13	66/M		7 months	-		+	-	Oral PSL, AZA	+	(15)
14	58/F		4 months	-		+	-	Oral PSL	+	(15)
15	69/F	PD	2 months	+	-	-		Oral PSL	+	(2)
16	74/F	PD	2 months	+	-	-		Oral PSL	+	(2)
17	77/F	PD	3 months	+	+	-		Oral PSL	+	(2)
18	44/F		2 months	+	+	-		Oral PSL	+	(16)
19 (Our case)	64/F	Sarcopenia	1 month	+	+	-		Oral PSL	+

*Duration from disease onset to the initiation of immunotherapy.

**T2-weighted, fluid attenuated inversion recovery, or short T1 Inversion recovery sequences were used for evaluation.

***The presence of clinical symptom improvement through immunotherapy.

AZA: azathioprine, CS: cervical spondylosis, F: female, HIA: high-intensity area, INEM: isolated neck extensor myopathy, NA: not available, PD: Parkinson’s disease, PSL: prednisolone, M: male, MRI: magnetic resonance imaging, mPSL: methylprednisolone

DHS can be caused by a wide range of conditions, and the diagnosis of INEM requires the careful exclusion of other potential etiologies. Multiple system atrophy was excluded in the present case because of the absence of autonomic dysfunction, parkinsonism, and cerebellar ataxia. Parkinson's disease was excluded because of a lack of signs of parkinsonism. Myasthenia gravis was considered unlikely based on normal repetitive nerve stimulation test results. Endocrine and metabolic myopathies, such as hypothyroidism, hyperparathyroidism, Cushing's syndrome, and hypokalemia, were excluded because laboratory test results showed no abnormalities suggestive of these conditions. Iatrogenic causes, including drug-induced myopathies, were excluded based on the patient's medication history. Amyloidosis presenting with DHS is rare, and only two previous cases have been reported (18,19); the clinical course of our case, which included marked improvement with steroid therapy and the absence of subsequent deterioration, suggested that amyloidosis was unlikely. Among autoimmune myopathies associated with DHS, IMNM is of particular clinical importance. According to Allenbach et al., the mean serum CK level of patients with IMNM is 6,272 IU/L (standard deviation ±1,255 IU/L) (20). In our literature review, we found no reports of patients with IMNM and normal CK levels. Two cases of IMNM with dropped head as the primary symptom have been reported, both of which demonstrated elevated CK levels at the time of the initial evaluation (21,22). Furthermore, IMNM is typically characterized by subacute progression to generalized muscle involvement and exhibits limited responsiveness to steroid therapy (20). Our patient did not exhibit the characteristic features of IMNM; therefore, it was considered clinically unlikely. Moreover, the absence of a preceding infection and clinical signs suggestive of myositis, such as muscle pain, as well as postural changes attributable to compensation for lower back pain, further supported the likelihood that an autoimmune mechanism was not involved.

A biopsy is the most critical test used to detect myopathy. However, INEM does not exhibit any specific pathological changes, and some cases are diagnosed without a biopsy owing to its characteristic clinical features (2). We propose that clinically probable INEM be considered when patients with DHS, including our patient, have muscle weakness that is completely confined to the neck extensor muscles and suggestive biomarkers, such as high signal intensity in the corresponding muscles exhibited by MRI and myogenic changes exhibited by needle electromyography. Patients with probable INEM should be followed up closely to ensure that generalized muscle weakness does not develop.

Osteosarcoma that co-occurs with osteoporosis is known as osteosarcopenia. The risk of complications, such as falls and fractures, associated with osteosarcopenia is higher than that associated with either sarcopenia or osteoporosis alone (23). In the present case, osteosarcopenia may have contributed to an increased risk of INEM. However, as osteosarcopenia is a relatively new concept, further investigation is required to clarify its association with INEM.

Several limitations associated with the present study warrant mention. Since a muscle biopsy was not performed, the possibility of amyloidosis could not be entirely excluded. However, the clinical course did not support a diagnosis of amyloidosis. Biopsies should be actively considered when patients experience symptoms that extend beyond the neck region or when poor responsiveness to steroid therapy occurs. However, the patient refused to undergo this procedure. Certain autoantibodies, including anti-signal recognition particles and anti-hydroxy-3-methylglutaryl coenzyme A reductase antibodies were not evaluated. As a result, we could not definitively rule out autoimmune focal myositis, including IMNM. Although the clinical course of our case was not suggestive of IMNM, atypical presentations, including chronic progression or muscle weakness confined to the neck region, have been reported (20,21). We believe that comprehensive antibody testing should be strongly considered in patients who present with markedly elevated CK levels, symptom progression from the neck muscles to other regions, or resistance to steroid therapy.

Conclusion

We hypothesized that sarcopenia could be a risk factor for INEM because sarcopenia and INEM share common pathophysiology, including loss of tissue elasticity and systemic inflammation. Before diagnosing DHS, an evaluation should be performed to exclude sarcopenia, and steroid treatment should be considered for INEM associated with signs of inflammation. Further investigation is necessary to establish the pathogenesis and diagnostic criteria of INEM.

The authors state that they have no Conflict of Interest (COI).