Clinical Reasoning: A 70-year-old man with rapid stepwise paraparesis and sensory loss

Section 1

A 70-year-old man with a history of cardioembolic stroke, hypertension, hyperlipidemia, peripheral vascular disease, and recently diagnosed myelodysplastic syndrome presented to an outside facility with acute sensory loss in the left buttock and lower extremity without weakness. Spine MRI demonstrated nonenhancing T2-hyperintense lesions in the upper thoracic cord and conus medullaris. MRI brain showed areas of nonspecific T2-hyperintensity. CSF revealed 20 total nucleated cells (TNC)/µL; 11,000 red blood cells (RBC)/µL; normal glucose, protein, and immunoglobulin G (IgG) index; 0 unique CSF oligoclonal bands; negative Gram stain, herpes simplex virus (HSV) 1/2 PCR, and Borrelia PCR; cytology was normal. Pleocytosis was attributed to traumatic lumbar puncture (utilizing correction of 1 TNC/µL per 500 RBC/µL), and history was inconsistent with HSV or subarachnoid hemorrhage as a cause of elevated RBCs. Serum aquaporin-4-IgG was negative. Mild anemia and thrombocytopenia were apparent. He was discharged with a provisional diagnosis of demyelinating disease. Three weeks later, he developed acute paraparesis with bladder and bowel dysfunction within hours. Repeat MRI at the outside institution showed enlargement of the nonenhancing lesions in the upper thoracic cord, now longitudinally extensive (≥3 vertebral body segments), and the lower thoracic cord extending into the conus (figure, A and E). Given concern for progressive demyelination due to motor decline and expanding lesions, IV methylprednisolone was initiated. Despite treatment, his paraparesis worsened and he was transferred to our facility.

• Download figure
• Open in new tab
• Download powerpoint

Figure MRI findings

MRI approximately 9 days after initial presentation reveals more pronounced T2-hyperintense signal seen best on sagittal STIR sequencing at T3-4 (A, arrow) and the lower thoracic cord extending into the conus (E, arrow). After an additional 2 days, the upper and lower thoracic lesions continued to develop, with the T2-hyperintensity extending from T11 to the conus medullaris on sagittal imaging (B, highlighted by notched arrows) and T2-hyperintense signal throughout the central cord (F) becoming more apparent. Following steroids and plasma exchange treatment, there was marked progression of the lesions within the thoracic cord and conus (C, G) with new patchy gadolinium enhancement most prominent at the T12-L1 level on sagittal T1-weighted imaging (D, highlighted by the chevron) and axial cut (H).

Collateral history revealed 2 months of fatigue attributed to myelodysplastic syndrome, but no preceding infections, travel, or rashes. The patient was afebrile and hemodynamically stable. Neurologic examination demonstrated asymmetric flaccid paraparesis with plegia of the left lower extremity, saddle anesthesia, and loss of vibratory and pain sensation to the midthigh bilaterally with no truncal sensory level. He was areflexic in the lower extremities with mute plantar responses.

Section 2

Clinical features of severe flaccid paraparesis (despite weeks of symptoms), lower extremity hypoesthesia without associated truncal sensory level, and bladder/bowel dysfunction without upper motor neuron (UMN) signs localizes to the conus or cauda equina. In this case, the acuity and severity of the progressive conus syndrome as the predominant myelopathy finding likely obscured UMN findings from the upper thoracic lesion.

Approach to myelopathy requires careful focus on history, imaging, and CSF. A rapid worsening of deficits should prompt consideration of a compressive lesion (such as a herniated disc or hematoma), as it necessitates emergent surgical decompression. Vascular myelopathies are another category with rapid worsening; in an elderly patient with stepwise decline involving the conus, spinal dural arteriovenous fistula (sDAVF) should be considered, especially with worsening on steroids.¹ Early identification of sDAVF via magnetic resonance angiography (MRA) or conventional angiography improves outcomes.² The clinical course and conus involvement make this a consideration, although signal in the upper thoracic cord is unusual.

In noncompressive myelopathies, inflammatory etiologies are a common consideration. Multiple sclerosis is unlikely given the patient's age, rapidly progressive deficits, longitudinally extensive lesions, and negative oligoclonal bands. With a longitudinally extensive lesion, aquaporin-4-IgG seropositive neuromyelitis optica spectrum disorder (NMOSD), myelin oligodendrocyte glycoprotein (MOG)–IgG myelitis, and neurosarcoidosis should be considered. CSF in these processes often reveals a lymphocytic pleocytosis, though this is not unique to these disorders and additional testing is required to identify the distinct process. Clinicians should have a low threshold for checking aquaporin-4-IgG via cell-based assay (CBA), particularly if lesions are longitudinally extensive with patchy or ring-like contrast enhancement.³ MOG-IgG myelitis (evaluated via serum CBA) is a consideration with conus involvement and faint/no contrast enhancement.⁴ Seronegative NMOSD is rare and an alternative etiology is often discovered when investigated thoroughly.^3,4 Neurosarcoidosis is characterized by avid gadolinium enhancement (typically dorsal subpial predominant) and inflammatory CSF, making this diagnosis unlikely.¹ Isolated paraneoplastic myelopathies are rare, typically presenting as tractopathy with progressive course.⁵ Autoimmune connective tissue diseases such as lupus with myelitis are rare, and unlikely without systemic manifestations. Idiopathic transverse myelitis is a diagnosis of exclusion with criteria, which are not met here given decline >21 days.⁶ Arachnoiditis is considered with a progressive cauda equina syndrome, but there was no predisposing history or characteristic imaging.

An acute, stepwise presentation is atypical for intramedullary neoplastic etiologies without hemorrhage, such as glioma or ependymoma, and lack of enhancement makes most neoplasms including intramedullary spinal cord lymphoma unlikely.^1,7 However, intravascular lymphoma (IVL) can present as an acute myelopathy with preferential conus involvement, encephalopathy, or stroke-like symptoms without contrast enhancement on initial MRI.⁸

Intraparenchymal infectious causes of myelopathy to consider include viral etiologies (for example, HIV, varicella-zoster virus [VZV], HSV 1/2, West Nile virus [WNV]) and specific bacterial etiologies (Borrelia, syphilis). This category is unlikely without typical exposures, supportive systemic findings, and an unremarkable CSF.

Section 3

Repeat spine MRI demonstrated worsening nonenhancing T2-hyperintense lesions in the thoracic spinal cord (figure, B and F) with possible leptomeningeal enhancement around the conus and cauda equina. MRI brain revealed stable T2-hyperintensities consistent with previous ischemic changes. MRA showed no evidence of sDAVF. Repeat lumbar puncture revealed the following: 2 TNC/µL, protein 76 mg/dL, glucose 60 mg/dL, 2 oligoclonal bands (normal), and normal IgG index. Pertinent negative CSF testing included WNV serology, VZV PCR, Epstein-Barr virus PCR, cytology, and flow cytometry. Syphilis and HIV serologies were negative. Serum lactate dehydrogenase (LDH) was elevated at 435 U/L. Repeat serum aquaporin-4-IgG (CBA), MOG-IgG (CBA), paraneoplastic autoantibody, and CSF paraneoplastic autoantibody evaluation were pending.

With no evidence of sDAVF on MRA and final serologic evaluations pending, empiric immunotherapy was reinitiated with 5 days of IV methylprednisolone followed by plasma exchange (PLEX). Mild improvement was seen after PLEX treatments; however, MOG-IgG and other antibody testing returned negative.

Question for consideration:

1. Given the inadequate response to empiric treatment and lack of evidence for an immune-mediated myelopathy, what additional studies should be considered?

GO TO SECTION 4

Section 4

PET-CT scan was obtained to search for malignancy, or less likely sarcoidosis. This revealed 2 cutaneous fluorodeoxyglucose avid soft tissue nodules on the right shoulder but no hilar adenopathy to suggest sarcoidosis. Ultrasound-guided aspiration of the first nodule demonstrated cells positive for CD20, multiple myeloma oncogene 1, and myelocytomatosis oncogene, consistent with diffuse large B-cell lymphoma (DLBCL). Bone marrow biopsy revealed hypercellular marrow without lymphoma. Given the lymphoma nodule, conus lesion without enhancement, and elevated LDH, IVL was suspected. Therefore, an excisional biopsy of the second nodule was obtained, revealing foci of neoplastic CD20 and paired box protein 5–positive B cells adherent to the lumina of small arteries, consistent with IVL. A repeat MRI revealed worsening of the lesions (figure, C and G) with atypical enhancement, consistent with evolution of IVL (figure, D and H). The patient was initiated on chemotherapy with MR-CHOP (methotrexate, rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone). At discharge, lower extremity strength improved to antigravity bilaterally.