Clinical Reasoning: Longitudinally Extensive Spinal Cord Lesions in a Middle-aged Man

Section 1

An immunocompetent 47-year-old man presented with a five-month history of worsening lower limb weakness. Initially, he noticed numbness and weakness in the left leg and had slight gait difficulty. Over the next 5 months, the symptoms progressed to the right leg, to the point of being unable to walk. Two weeks ago, he also developed neck pain, urinary retention, and constipation. The pain was severe and persistent, radiating into the shoulders and lumbosacral region. One week before, he experienced intermittent fever. On physical examination, he was alert and oriented, with a temperature of 38.2°C and nuchal rigidity. Cranial nerves were intact. The strength and tone of upper limbs were normal. Lower limb strength was rated 0/5 bilaterally, with decreased muscle tone. Deep tendon reflexes of the upper limbs were rated 2+. Lower limbs were areflexic. Abdominal reflexes were bilaterally absent. Babinski sign was present bilaterally. There was no ankle clonus. Sensation to pinprick and vibration were diminished below the sternal angle, suggesting a T2 sensory level.

Section 2

Progressive lower limb weakness, sphincter dysfunction, and T2 sensory level are classic features of myelopathy. Longitudinally, the neck pain, T2 sensory level, absence of abdominal reflexes, and flaccid paralysis in lower limbs suggested involvement of the cervical, thoracic, and lumbosacral segments. Transversely, impaired structures may include anterior horns (areflexic lower limbs), posterior funiculus (diminished vibratory sensation), corticospinal tracts (presence of Babinski sign), posterior horn, and spinothalamic tracts (diminished sensation to pinprick). Temporally, because this patient has a chronic deteriorating course, disorders that worsen rapidly such as spinal cord infarction or disc herniation were less likely. Taken together, longitudinally extensive transverse myelopathy with a chronic deteriorating course should be considered at this stage. Differential diagnoses include infection, neoplasms, sarcoidosis, spinal arteriovenous fistula, demyelination, and metabolic disorders. The initial investigation approach should include routine screenings for these etiologies, as well as CSF analysis and enhanced cerebrospinal MRI.

Blood tests were notable for increased inflammatory markers and positive syphilis antibodies (eTable 1, links.lww.com/WNL/B734). Pulmonary CT and ECG were unremarkable. Enhanced brain and spinal cord MRI revealed longitudinally extensive lesions involving the cervical, thoracic, and lumbosacral spinal cord. The spinal cord was compressed, slightly hypointense on T1-weighted images, and hyperintense on T2-weighted images. The lesions were posterior to the spinal cord, iso-to hyperintense on T1-weighted images and hypointense on T2-weighted images, with well-defined borders and homogeneous enhancement (Figure 1). On lumbar puncture, CSF pressure was 390 mmH₂O. Less than 2 mL of yellow-colored CSF was collected because of hypercoagulability. CSF profiling showed pleocytosis (total cell count 120*10^6/L, a white blood cell count 12*10^6/L, polynuclear cells 60%), significant protein elevations (5.56 g/L), decreased glucose levels (1.6 mmol/L), a positive TPHA test, and a negative rapid plasma reagin test. Blood, urine, and stool cultures detected no bacteria or fungi, nor did the result of CSF next-generation sequencing.

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Figure 1 Spinal Cord MRI

(A-C) Cervical T1WI, T2WI, and enhanced spinal cord MRI. (D–F) Thoracic T1WI, T2WI, and enhanced spinal cord MRI. (G–I) Lumbosacral T1WI, T2WI, and enhanced spinal cord MRI.

Section 3

The ascending sensory disturbance, late-onset sphincter dysfunctions, significantly elevated CSF protein levels, and unique spinal MRI findings suggested an intradural-extramedullary lesion extending through multiple segments. In addition, the CSF hyperproteinosis, xanthochromia, and hypercoagulability indicated Froin syndrome, which together with the CSF pleocytosis and hypoglycorrhachia are highly suggestive of infectious or neoplastic disorders.

Infections that can form long segmental abscesses or granulomas in the subdural space need to be considered. Tuberculosis, fungus, and brucella were excluded as the exposure history, and relevant pathogen tests were negative. The patient was positive for TPHA in both serum and CSF, suggesting neurosyphilis. Antisyphilitic treatment with penicillin was indicated. However, the spinal MRI findings of our patient were very uncommon for neurosyphilis. Pathologically, intradural-extramedullary syphilitic myelopathy is most likely caused by syphilitic gumma.¹ The MRI findings typically present as short-segment T2 hyperintensities, with nodular or ring-like enhancement.^2,-,6 The “flip-flop” sign, an enhanced lesion shown as hypointense signals on T2-weighted images, and the “candle guttering” sign, a flame-like enhancement of the spinal parenchyma beneath the pia mater, were thought to be characteristic.^4,5 Our patient's MRI lacked most of the above features.

The avid contrast enhancement on MRI and CSF changes prompt the consideration of intradural-extramedullary neoplasms. Neurofibroma, lymphoma, myxopapillary ependymoma, and spinal metastasis are not very likely, although they can cause long segmental lesions with clear margination and enhancement. Their lesions are usually hypointense on T1-weighted images and hyperintense on T2-weighted images.^7,8 Other neoplasms, such as melanotic schwannomas and extraosseous Ewing sarcoma, cannot be excluded because they can seem hyperintense on T1-weighted images and hypointense on T2-weighted images.^7,9 Confirmatory diagnosis requires a biopsy.

Other diagnoses were less likely. Sarcoidosis can cause CSF changes similar to those in our patient. However, sarcoidosis typically presents as longitudinally extensive transverse myelitis with dorsal subpial enhancement.¹⁰ Intradural-extramedullary sarcoidosis is uncommon and seldom solely presents as myelopathy. Our patient lacked multisystemic manifestations such as hepatomegaly and hilar lymphadenopathy. The angiotensin converting enzyme levels and pulmonary CT were also unremarkable.

Spinal arteriovenous fistula (sAVF) can occur in the intradural-extramedullary space, spanning multiple continuous segments. Nevertheless, CSF glucose levels are often normal in sAVF. Spinal cord edema and tortuous vessels typically seem as diffuse hyperintensities and perimedullary flow voids on T2-weighted images, with linear, heterogeneous, or diffuse patchy enhancement.¹¹ The CSF profiling and absence of flow void signals in our patient argued against sAVF.

The normal brain MRI, spared optic nerves, and negative antibodies excluded primary progressive multiple sclerosis and neuromyelitis optica spectrum disorder. The normal vitamin B12 and copper levels ruled out subacute combined degeneration and copper deficiency.

Section 4

To further distinguish between infection and neoplasm, whole-body PET/CT and spinal cord biopsy were indicated. The 18F-FDG-PET/CT indicated slightly increased intraspinal FDG uptake (SUVmax = 8.6) (Figure 1D). He underwent the surgery of laminectomy and spinal cord mass resection at the C6-T1 level. The tumor was 46*14*8 mm in size, projecting in the subarachnoid space and destroying the dorsal spinal cord. Histopathology showed small round blue cells microscopically. Immunostaining was positive for NKX2.2, CD56, CD99, synaptophysin, and Ki67 (50%) (Figure 2). Molecular analysis detected a MALAT-CYSLTR1 fusion protein and variants in oncogenic genes including PTCH1, TERT, CREBBP, SPEN, and STK11. The diagnosis of extraosseous Ewing sarcoma (ES) was confirmed.

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Figure 2 Histopathology and Immunostaining

(A) Hematoxylin and eosin staining showed small round blue cells (magnification ×200). Immunostaining was positive for (B) CD99, (C) NKX2.2, (D) CD56, (E) synaptophysin, and (F) Ki67 (magnification ×200).