Patients on hemodialysis may have various osteoarticular complications. Hemodialysis-associated amyloidosis is a common osteoarticular complication affecting patients undergoing long-term hemodialysis.¹ The condition shows the deposition of amyloid fibrils, especially in the synovia of joints and tendons and in subchondral bone. The most common clinical manifestations are carpal tunnel syndrome and arthropathy of the shoulders, knees, hips, and axial skeleton, which can cause neurologic symptoms and pain.² Destructive spondyloarthropathy can occur in patients on long-term hemodialysis, but localized amyloid deposits in the spine are uncommon.³ The management of spinal amyloidosis requires active local resection and stabilization of the spine, depending on the extent of the invasion. We report a case of cervical myelopathy apparently caused by amyloid deposits at the C1-4 level in a patient with chronic kidney disease who had been on hemodialysis for about 25 years.

A 69-year-old male patient presented with pain and progressive gait disturbances in both upper and lower extremities for more than one year. He underwent a total thyroidectomy 40 years earlier. He started receiving hemodialysis 25 years ago and was diagnosed with gastric cancer 22 years ago and underwent gastrectomy. He also received surgical relief for bilateral carpal tunnel syndrome in his wrists. In a left shoulder MRI performed 6 years ago, a space occupying lesion about 5.4 cm sized with T1 and T2 low signal intensity was identified in the subacromial-subdeltoid bursa, and it was thought to be a deposition disease such as amyloidosis caused by long-term hemodialysis (Fig. 1). He underwent periodic carpal tunnel injections for both wrists and intra-articular shoulder injections for shoulder pain.

Figure 1. Coronal T1 (A) and T2 (B) weighted left shoulder MRI shows a space occupying lesion with T1 (A, arrow) and T2 (B, arrow) low signal intensity in the subacromial-subdeltoid bursa, thought to be a deposition disease such as amyloidosis caused by complication of long-term hemodialysis.

When hospitalized, he complained of neuropathic pain in both upper and lower extremities with numeric rating scale (NRS) scores of 8-9 and visual analog scale (VAS) scores of 8. A motor function examination was performed. A score of 5 in the Medical Research Council (MRC) grading system indicates normal power. The right upper extremity was measured as MRC grade 2-3, and the left upper extremity could not be accurately examined due to severe pain. Both lower extremities were measured as MRC grade 3. He complained of hypesthesia and hypoalgesia below the C4 level, which was graded as C3 ASIA D. He showed generalized hyperreflexia in all four extremities. Deep anal pressure sensation and voluntary anal contraction were intact, and the bulbocavernosus reflex was normal. Both shoulders appeared enlarged. He was able to perform outdoor walking and activities of daily living (ADL) independently before the onset of symptoms. However, when he was admitted to the hospital, he needed moderate to maximal assistance with ADL, especially eating, dressing, and grooming, and he could walk with a quad-cane with moderate assistance. The initial Berg Balance Scale (BBS) score was 4, and the Spinal Cord Independence Measure (SCIM) score was 38. The patient was right-handed, and the Jebsen Taylor Hand Function test (JTHFT) could not be performed due to severe pain and stiff hands.

Cervical spine magnetic resonance imaging (MRI) showed slightly high T1 and T2 heterogeneous low signal intensity space-occupying lesions in the atlantoaxial joint, posterior aspect of C4, odontoid process, and posterior aspect of the C2-3 level (Fig. 2). There was combined bony osteolysis in the left lateral aspect of the atlas and direct extension of a soft tissue lesion in both the paravertebral and prevertebral aspects of the C1-2 level. Severe bilateral facet joint degenerative changes and similar signal intensity change space-occupying lesions were noted on both sides at the C4-5 level, seemed to be indicating amyloidosis, which was likely related to long-standing hemodialysis. Cervical myelopathy at the C3-C4 level was identified. Also, ossified yellow ligaments were observed on both sides at the T10-11 level on thoracic spine MRI, and it is thought to be another involvement of amyloidosis (Fig. 3).

Figure 2. Sagittal T1 (A), T2 (B), and axial T2 (C and D) weighted cervical spine MRI shows space-occupying lesions in the atlantoaxial joint (A, arrow), posterior aspect of odontoid process (B, arrow), and posterior aspect at the C2-3 level (C, arrow). Also, internal cord signal intensity change was identified at the C3-C4 level (D, arrow). MRI: magnetic resonance imaging.

Figure 3. Sagittal T2 weighted thoracic spine MRI shows ossification of yellow ligaments on both sides at the T10-11 level (arrow) probably associated with involvement of amyloidosis. MRI: magnetic resonance imaging.

Electrodiagnostic examinations, including nerve conduction study (NCS), somatosensory and motor evoked potential (SEP and MEP) study, and needle electromyography (EMG) were performed. In sensory NCS, bilateral median nerves showed absent response. In motor NCS, right median nerve showed absent response, and left median nerve showed decreased amplitude and slowed conduction velocity. The SEP study showed severe dysfunction starting from both the upper extremities to the somatosensory cortex and moderate dysfunction starting from both the lower extremities to the somatosensory cortex. The MEP study showed severe dysfunction starting from the motor cortex to both the upper extremities, and moderate dysfunction starting from the motor cortex to both the lower extremities. Needle EMG showed increased insertional activity, abnormal spontaneous activity, polyphasic motor unit action potential (MUAP) and decreased interference pattern in both abductor pollicis brevis muscles. These electrophysiologic findings are suggestive of bilateral carpal tunnel syndrome with bland scale of 6 on the right side and bland scale of 5 on the left side. Also, when considered together with imaging studies, it is compatible with cervical myelopathy, clinically.

Because of the complication of long-standing hemodialysis-associated cervical myelopathy probably caused by amyloid deposition, laminoplasty was performed from C1 to C4, and laminectomy was performed from T10 to T11. Unfortunately, histological examination was not performed.

The patient was discharged to home two weeks after surgery and was admitted for rehabilitation. Comprehensive rehabilitative treatment was carried out. The patient received physical therapy for 2 hours and occupational therapy for 1 hour per day for 4 weeks. In physical therapy, strengthening exercises for both upper and lower extremities, dynamic standing balance training, and progressive gait training were performed. Occupational therapy to improve hand function impaired by cervical compression and ADL training, including feeding and personal hygiene, was performed.

The patient’s neurological condition gradually improved. The upper extremity motor power improved to MRC grade 3 on the right side and grade 4 on the left side. In the lower extremities, muscle power improved to MRC grade 4 on both sides. He needed minimal to moderate assistance for performing ADL, and he could walk with a quad-cane with minimal assistance. Neuropathic pain also showed improvement, with NRS scores of 4-5, VAS scores of 5 at the time of discharge. The BBS score was improved from 4 to 18, and the SCIM score was improved from 38 to 44. The JTHFT was still unable to perform due to stiff hands.

Amyloidosis is divided into primary and secondary, and focal, localized, or systemic deposits can appear. Hemodialysis-associated amyloidosis is a unique type of amyloidosis affecting patients undergoing long-term hemodialysis. It occurs secondarily to the deposition of β2-microglobulin and causes significant morbidity with potential mortality. β2-microglobulin tends to deposit in osteoarticular tissues, especially in large bones close to the joint space, synovial membrane, and carpal tunnel.^1,2,4 Physicians should be aware of hemodialysis-associated amyloidosis in long-term dialysis patients, with a reported incidence of 9∼18%.² The risk factors for dialysis-related amyloidosis include increasing age and duration of dialysis, the use of low-flux dialysis membranes, bioincompatible dialysis membranes, and lack of residual renal function.¹

Amyloidoma is a rare subset of amyloidosis and presents with focal amyloid deposition. Amyloidoma may appear in osteoarthritic spaces, but focal-localized amyloidoma is unusual, and spinal involvement is much rarer. Although cervical amyloidoma has been reported in primary amyloidosis, it is very rare in hemodialysis-associated amyloidosis. Spinal amyloidoma may present as a more aggressive malignant process but has a better prognosis with an earlier diagnosis. In patients with spinal amyloidoma, neurologic deficits are accompanied by pain when the vertebral body is involved. The management of spinal amyloidoma requires local excision and spinal stabilization, and symptomatic relief is seen after surgery. Accurate and prompt diagnosis is essential because disease involving the vertebral body is reversible. Delays in diagnosis can lead to serious sequelae.¹ Proper diagnosis, promptly planned surgery, and rehabilitation in our patient resulted in neurological and functional recoveries.

Amyloid deposits typically appear low signal intensity on T2-weighted MRI exam.⁵ In our patient, a space occupying lesion of T1 and T2 low signal intensity was identified in the subacromial-subdeltoid bursa, thought to be an amyloid deposit, in the left shoulder MRI performed 6 years ago. In cervical spine MRI, T2 heterogeneous low-signal intensity space-occupying lesions are identified in the atlantoaxial joint, posterior aspect of C4, odontoid process, and posterior aspect of the C2-3 level, and this is consistent with MRI findings of amyloid deposit, and clinical correlation is required.

We report the case of an end-stage renal disease patient who had been on hemodialysis for 25 years. Unusual cervical amyloidoma developed after long-term hemodialysis. The first symptom may mimic chronic uremic peripheral neuropathy,¹ so it should not be overlooked. The progression of amyloidosis can present as sudden motor weakness and neuropathic pain, which in our case was gradual and occurred over a year.

A biopsy is nearly always required for a definitive diagnosis. Unfortunately, in our case, this could not be confirmed because pathology was not performed. However, because histologic confirmation is not always possible and increased serum β2-microglobulin levels are not diagnostic, imaging findings combined with history and clinical findings are usually used to assess the involvement of dialysis-related amyloidosis.^6-8 Considering the history of shoulder involvement, carpal tunnel release surgeries, and MRI findings, a diagnosis of cervical myelopathy due to amyloidoma could be made, and treatment was performed accordingly.

We reviewed cases of spinal involvement due to amyloidosis in a long-term hemodialysis patient.^1,2 Commonly, patients were diagnosed with carpal tunnel syndrome. Unlike other cases, our patient also had amyloid deposits in the shoulder. While in the previously published case, symptoms appeared suddenly or subacute over a period of two months, in our case symptoms appeared more gradually over a year. Time courses can appear in various ways.

Long-term hemodialysis patients show a variety of neurologic complaints, and clinically, it is very important to recognize reversible complications. It is easy for clinicians to ignore these complaints and consider them to be peripheral neuropathy. Dialysis arthropathy, bone cysts, and recurrent carpal tunnel syndrome due to amyloid accumulation are well-known complications in long-term hemodialysis patients,⁹ and our patient also showed preceding carpal tunnel syndrome and shoulder arthropathy. Therefore, when patients with the above history show progressive or sudden weakness and neurologic symptoms, spinal cord compression caused by amyloidosis, which rarely occurs, should be considered.

This research was supported by the Soonchunhyang University Research Fund.