Amyloidosis refers to a spectrum of disorders characterized by abnormal extracellular deposition of misfolded amyloid proteins in various tissues and organs, including the central nervous system. Cerebral amyloid angiopathy (CAA) is a subtype in which amyloid-β (Aβ) peptides accumulate in central nervous system (CNS) vasculatures.

Spinal cord amyloid angiopathy (SCAA) is an extremely rare condition characterized by amyloid deposition in the blood vessels of the spinal cord. These deposits can damage blood vessels, impair spinal cord perfusion, and lead to neurological deficits. Progressive neurological symptoms such as muscle weakness, numbness, and loss of coordination may develop. In severe cases, extensive deposition can cause compression, leading to spinal cord injury and paralysis.

We report a case of SCAA in a 31-year-old woman who presented with progressive dysesthesia and weakness in the right extremities. Magnetic resonance imaging (MRI) and positron emission tomography (PET) findings initially suggested an intramedullary tumor. However, histological examination revealed amyloid angiopathy. This report highlights the importance of considering amyloid angiopathy in the differential diagnosis of spinal cord lesions.

A 31-year-old woman was referred to the neurosurgery department with worsening dysesthesia and weakness in the right extremities. Two years earlier, she had been diagnosed with transverse myelitis of the cervical spinal cord after presenting with tingling sensations in both arms. Her symptoms improved following treatment with gabapentin and steroids. Initial MRI of the cervical spine demonstrated an ill-defined intramedullary lesion in the right posterolateral side of the spinal cord at the C6-T1, accompanied by mild swelling and minimal gadolinium (Gd) enhancement (Fig. 1A, B).

Approximately one year later, after a period of symptomatic improvement, the patient became pregnant. During pregnancy, tingling sensations in her right hand recurred and were accompanied by progressive weakness in the right hand and leg (grade 4). Follow-up MRI revealed an ill-defined, eccentric, expansile lesion in the right posterior spinal cord at the C6-T1 level. The lesion remained non-enhancing on Gd-enhanced images but had significantly increased in size compared with the previous study (Fig. 1C, D).

Because an intramedullary glioma was suspected, an 18F-fluorodeoxyglucose-PET (FDG-PET) scan was performed. The lesion demonstrated marked hypermetabolism at the C6-T1 level, suggesting a malignant intramedullary spinal cord tumor or an active inflammatory lesion (Fig. 2). No abnormal hypermetabolic lesions were detected elsewhere.

To establish a definitive diagnosis, a biopsy and partial resection were performed through a posterior approach with laminoplastic laminectomy at C6-7. The lesion appeared firm and grayish and lacked clear boundaries from the adjacent healthy spinal cord tissue. Only partial resection was performed to minimize the risk of postoperative neurological complications.

Immediately after surgery, the patient’s neurological status remained unchanged. With subsequent steroid therapy and pregabalin administration, motor strength in the right extremities gradually improved (right hand: grade 5; right leg: grade 5). However, paresthesia in the right hand persisted without significant improvement.

At the 3-year follow-up, she continued to receive medication for persistent hand paresthesia. Neurological examination and MRI findings remained stable (Fig. 1E, F), and she remained independent in activities of daily living.

Pathological examination revealed diffuse demyelination of the spinal cord without evidence of neoplasia. Prominent infiltration of lipid-laden histiocytes and amorphous proteinaceous deposition within the vascular walls—predominantly in small- to medium-sized vessels— were observed consistent with SCAA. Tissue sections were stained with Congo red, Luxol fast blue, and Masson’s trichrome. Congo red staining demonstrated amyloid within the vascular walls, Luxol fast blue staining revealed demyelination, and Masson’s trichrome staining highlighted amorphous proteinaceous material (Fig. 3).

Further evaluation for systemic or familial amyloidosis included brain MRI, serum free kappa (κ) and lambda (λ) light chain analysis, β2-microglobulin and α-microglobulin measurements, transthyretin (TTR) gene testing, and serum amyloid A. Serum amyloid A (AA) levels were increased (13.0 mg/L), whereas other laboratory results were within normal limits. No evidence of systemic amyloidosis or multiple myeloma was observed. Family history revealed no evidence of hereditary amyloidosis.

CAA represent a heterogeneous group of biochemically and genetically diverse disorders of the CNS. These disorders are characterized by deposition of Aβ peptides within vascular walls, particularly in small arteries and capillaries of the meninges and the cerebral and cerebellar cortices. CAA has traditionally been considered as a disease confined to the brain parenchyma and most commonly affects posterior brain regions¹⁰⁾. It rarely involves vessels within the white matter and shows little association with hypertension or arteriosclerosis¹⁾.

CAA are classified according to the type of deposited amyloid protein: (1) Aβ-type (sporadic); (2) amyloid light-chain (AL) angiopathy; (3) AA amyloid angiopathy; and (4) ATTR amyloid angiopathy. The most common form is sporadic CAA (Aβ-type), in which Aβ peptides accumulate within the vascular walls. Because Aβ peptides are produced during normal metabolic processes, their accumulation increases with age²⁾. Although sporadic CAA is generally not considered a strongly genetic disorder, the ε4 allele of apolipoprotein E has been identified as a risk factor⁵⁾.

AL amyloid angiopathy results from systemic accumulation of immunoglobulin light chains and is associated with plasma cell dyscrasia such as multiple myeloma. Serum AA is increased in AA amyloid angiopathy and is identified in the vasculature of multiple organs. ATTR amyloid angiopathy (non-Aβ peptide angiopathy) is a hereditary form that particularly affects the heart. In the present case, no evidence of systemic or familial disease was identified.

Familial forms of amyloid angiopathy are typically associated with mutations in the amyloid precursor protein (APP) gene, which encodes the precursor of Aβ peptide. In these cases, symptoms usually appear systemically in the early stages. Abnormal APP processing leads to increased production of Aβ peptides—particularly Aβ40—resulted in accelerated deposition within vascular walls. APP mutation analysis was not available at our institution.

CAA cannot be diagnosed solely based on clinical characteristics¹²⁾. Histopathological examination remains essential for definitive diagnosis. Microscopically, Aβ fibrils and non-fibrillar Aβ proteins accumulate around smooth muscle cells in the arterioles and deposit in the lamina densa^1,14). Degeneration of the tunica media causes vessel wall cracking (“double-barrel” appearance) and para-vascular blood leakage⁸⁾. Congo-red staining of vascular walls is the primary diagnostic tool for histological confirmation of amyloid deposition in aggregated form¹⁶⁾. Additional stains used in the diagnosis of amyloid angiopathy include Luxol fast blue, Masson trichrome, Thioflavin, Daylon stain (direct fast scarlet)¹¹⁾.

In symptomatic patients, damaged cerebral blood vessels can lead to blood leakage, intracerebral hemorrhage, dementia, or cerebral infarction. Behavioral changes, headaches, or seizures may also occur in cases of CAA-related inflammation, which is thought to represent an autoimmune response to amyloid deposits^7,15).

Amyloid angiopathy of the nervous system most commonly involves the brain and is exceedingly rare in the spinal cord. Only a few cases have been reported in the literature. Tokuda et al.¹³⁾ reported an autopsy case of SCAA in a 71-year-old woman with cerebral AA who died from recurrent cerebral hemorrhage; vascular amyloid deposits were found in leptomeningeal vessels of the cerebellum and spinal cord. Hart et al.⁴⁾ described a case of Aβ protein deposit in a surgically removed vascular malformation in the intradural, extra-parenchymal space at T11-12. Yamada et al.¹⁷⁾ identified vascular amyloid deposit in one of 123 spinal cord autopsies. Kiuru et al.⁶⁾ reported a familial case of amyloidosis involving the spinal cord, corresponding to the Finnish-type, autosomal dominant, and systemic, corresponding to gelsolin mutation (G654A or G654T). Postmortem examinations revealed congophilic amyloid deposits in both the cerebral cortex and spinal cord.

Amyloid deposits within neural tissues can also occur in the form of amyloidomas, which consist of aggregates of amyloid fibrils derived from soluble proteins undergoing conformational changes. Primary amyloidoma represents a solitary mass of amyloid protein without systemic amyloidosis and can be found in various tissues, including bone, skin, lymph nodes, cerebrum, and spine. Histologically, it is characterized by extracellular deposition of an amorphous, eosinophilic, glassy substance¹³⁾. Spinal amyloidomas are rare³⁾. They also differ from the present case because they normally form localized masses that compress the spinal cord. In contrast, our case demonstrated diffuse vascular deposition without mass formation⁹⁾.

The present case differs from previously reported cases in several aspects. SCAA was confined to a localized spinal cord segment (C6-T1), with no evidence of brain involvement or systemic disease. The patient was young and had no family history of amyloidosis, and TTR gene testing revealed no mutations. Importantly, MRI and histological confirmation were obtained in a living patient rather than postmortem. The MRI showed that the lesion mimicked an intramedullary tumor or acute inflammation of the spinal cord and demonstrated marked hypermetabolism on FDG-PET imaging. The elevated FDG uptake (SUVmax 17.0) may reflect an inflammatory response surrounding amyloid deposition rather than the amyloid material itself. Such findings have never been reported previously. Initially, the lesion was misdiagnosed as a malignant tumor or active myelitis. The size of the lesion increased during the first two years after first presentation but remained stable during the subsequent three years of follow-up. Although no hemorrhagic events have occurred, the risk remains and warrants careful long-term monitoring. This is a very rare description of a single lesion confined to the spinal cord along with laboratory, radiological, and clinical findings.

We describe a rare case of solitary SCAA without evidence of systemic or familial disease. MRI and PET data mimicked those of an intramedullary tumor or inflammatory lesion. Because the clinical presentation and disease course differ from those typically associated with amyloid angiopathy, further studies and accumulation of similar cases are necessary. Amyloid angiopathy should be considered in the differential diagnosis of spinal cord lesions with similar clinical and radiological features.