Spinal Cord Involvement in Neurosarcoidosis: A Case of Longitudinally Extensive Transverse Myelitis at Disease Onset

ABSTRACT

Acute‐onset neurological deficits in otherwise healthy individuals warrant a broad differential diagnosis. Neurosarcoidosis presenting as longitudinally extensive transverse myelitis is rare, mimicking demyelinating, infectious, or neoplastic disorders. Early recognition, histopathological confirmation, and timely immunosuppressive therapy are crucial. Further research is mandatory in optimizing treatment regimens, especially for refractory neurosarcoidosis cases.

1. Introduction

Sarcoidosis is a multisystem granulomatous disorder, with spinal involvement seen in < 1% of cases. Its manifestations may include cauda equina syndrome, radiculopathy, syringomyelia, cord atrophy, arachnoiditis, myelopathy, or transverse myelitis [1]. We present a challenging case of a 35‐year‐old male presenting with longitudinally extensive transverse myelitis (LETM) diagnosed with neurosarcoidosis (NS), highlighting the diagnostic complexity of this condition.

2. Case History

A 35‐year‐old African American male, with a past medical history significant for hypertension, hyperlipidemia, gastroesophageal disease, and esophagitis (LA grade B), presented as a transfer from an outside hospital for sudden onset bilateral lower extremity weakness. The patient was admitted to the outside hospital with a 1‐month history of back pain, left‐predominant leg weakness, numbness, unintentional 60‐pound weight loss in 1 month and recurrent falls. His symptoms began when he was discharged from the hospital for H. pylori Gastritis 1 month ago. The neurological examination revealed brisk deep tendon reflexes and a sustained ankle clonus.

3. Investigations and Treatment

Outside hospital imaging with Magnetic Resonance Imaging (MRI) of the brain revealed a small remote insult in the left frontal operculum. The Lumbar spine MRI was unremarkable. Neurosurgery was consulted, who recommended further imaging. MRI C‐Spine was also unremarkable but the MRI of the thoracic spine showed a longitudinally extensive T2 hyperintensity with enhancement from vertebrae T1–T11, concerning for an intramedullary tumor versus transverse myelitis (Figure 1). At the T5/6 level, evidence of a right‐sided disc herniation measuring 3–4 mm in the AP dimension impressing upon the right ventral thoracic spinal cord was also visualized (Figure 2). Cerebrospinal fluid (CSF) analysis revealed pleocytosis with a lymphocytic predominance, elevated protein level (135 mg/dL) and a negative meningitis/encephalitis panel. HIV and RPR were negative. A Computed Tomography (CT) chest/abdomen/pelvis showed left perihilar lymphadenopathy versus a lesion measuring 5 cm × 2 cm with a mass effect on the bronchi. Subsequently, a biopsy of the left upper lobe lymph nodes with endobronchial ultrasound (EBUS) was non‐diagnostic, resulting negative for malignancy or granulomas and > 90% macrophages. An infectious process was ruled out from the bronchoalveolar lavage (BAL). Since surgical intervention could worsen the neurologic deficits, Neurology recommended initiation of intravenous methylprednisolone (IVMP) followed by a prednisone taper over the next 6 months. After an initial improvement, his weakness began to worsen, resulting in his transfer to a tertiary care center for consideration of more advanced treatments, intravenous immunoglobulin (IVIG), and plasmapheresis. A repeat CSF analysis revealed reduced pleocytosis, improved protein level (102 mg/dL), normal glucose (71 mg/dL), no oligoclonal bands and a negative demyelinating panel (Aquaporin–4, Myelin Oligodendrocyte Glycoprotein Antibodies), arguing against a demyelinating etiology. Repeat MRI thoracic spine revealed interval enlargement of previously noted areas of abnormal enhancement from T1–T11 and interval increased intramedullary signal abnormality infiltrating the thoracic spinal cord (Figure 3). Given initial improvement in symptoms with IVMP, his weakness was thought to be related to an autoimmune process, so he was initiated on plasmapheresis. After five doses of plasmapheresis, a positron emission tomography scan (PET) revealed intensely hypermetabolic mediastinal and left supraclavicular lymphadenopathy, along with a solid nodular lesion in the left upper lobe. Repeat BAL and biopsy with EBUS was suggestive of well‐formed granulomas with central necrosis in two lymph nodes, consistent with infections, neoplasms, or allergens.

FIGURE 1.

Sagittal T2‐weighted MRI showing expansile hyperintensity and enhancement from T1–T11 with cord edema.

FIGURE 2.

3–4 mm Disc herniation impressing upon the right ventral thoracic spinal cord in enhanced T2‐weighted MRI axial view.

FIGURE 3.

Sagittal T2‐weighted MRI showing expansion of thoracic spine hyperintensity with interval increased cord edema post initial treatment.

4. Differential Diagnosis

Differentials included tuberculosis, sarcoidosis or other granulomatous diseases or malignancy. The tumor board excluded malignancy with testicular ultrasound and dermatologic evaluation. Infectious workup including Tuberculosis QuantiFERON, histoplasmosis and blastomycosis testing was negative. Serum Angiotensin Converting Enzyme and 1,25–vitamin D levels were normal. Further review of initial MRI thoracic spine revealed “Trident sign” (Figure 4), a characteristic finding of neurosarcoidosis. Per Neurosarcoidosis consortium consensus Group [2] criteria, the presence of non‐caseating granulomas in an extra‐neural site establishes the probable diagnosis of neurosarcoidosis, although occasional granulomas with coagulative necrosis may also occur. In the absence of infectious or malignant causes, a presumptive diagnosis of neurosarcoidosis was made.

FIGURE 4.

Contrast enhanced T1‐weighted MRI axial view revealing Trident sign at T4–T7 level.

5. Outcome and Follow‐Up

The patient was initiated on mycophenolate mofetil (MMF), in addition to high‐dose steroids, followed by a prednisone taper, by rheumatology. Post‐discharge repeat MRI scans showed a stable size of the lesion. Unfortunately, his weakness worsened to complete paralysis involving the right lower extremity while still on prednisone. He was diagnosed with refractory neurosarcoid myelitis and initiated on infliximab. The patient's motor function did not improve post infliximab infusions and he became wheelchair bound.

6. Discussion

Sarcoidosis is a multisystem granulomatous disorder with an annual incidence of 10 in 100,000 individuals in the United States. Its epidemiology varies globally, influenced by differences in age, sex, and race [3]. The disease occurs up to four times more frequently in African American individuals and women although emerging epidemiologic data suggests a contribution of genetics. Common symptoms include fatigue, fever, cough, unintentional weight loss as nonspecific symptoms occurring in about one third of the population, and extra‐thoracic involvement is frequently observed.

Neurosarcoidosis (NS) occurs in approximately 5%–16% of sarcoidosis cases, presenting as cranial or peripheral neuropathy, aseptic meningitis or psychiatric symptoms. LETM as a presentation is a rare finding, occurring only in 0.43%–1% of the patients with sarcoidosis [4]. It mimics other inflammatory or non‐inflammatory neurological conditions such as multiple sclerosis (MS), neuromyelitis optica (NMO), arteriovenous fistulas, spinal cord tumors, and sometimes even occurs without other systemic symptoms of sarcoidosis, like our patient, further complicating clinical recognition.

The diagnosis of NS remains largely presumptive but is strengthened when one or more of the following are identified: radiologic signs of sarcoidosis, evidence of systemic involvement, histologically confirmed noncaseating granulomas, sarcoidosis signs in bronchoalveolar lavage fluid (BALF) including a lymphocytic profile with elevated CD4:CD8 ratio and thorough exclusion of other causes of granulomatous inflammation. While no sensitive or specific biomarkers for diagnosis and prognosis exist, supportive markers include serum ACE levels, human leukocyte antigen types, and CD4 Vα2.3+ T cells in BALF [2], which reflects a T‐helper–cell–mediated granulomatous response. Necrotizing sarcoid granulomas are a rare variant and must be considered when infections have been excluded [5].

The patients presenting with incidental or asymptomatic mediastinal lymphadenopathy require close monitoring, but prompt initiation of steroids and immunomodulatory drugs remains the mainstay of sarcoidosis management, especially in extra‐pulmonary involvement [4]. Refractory NS warrants the administration of TNF‐alpha inhibitors, as supported by a recent Delphi survey [6] and several other single center studies [7, 8, 9]. The treatment response is monitored by physical examination and MRI, with consideration of infectious complications, in cases of clinical decline. Our patient had significant decline from his baseline; however, his followup MRIs revealed stable disease.

7. Conclusion

Sarcoidosis with multisystem involvement should allow an interdisciplinary approach to coordinate complex care and decision‐making. Evidence‐based guidelines for sarcoidosis presenting as LETM recommend high doses of steroids in combination with various immunosuppressive agents; however, further multicenter randomized controlled trials are needed for optimal management.

Author Contributions

Areeb Tiwana: conceptualization, writing – original draft, writing – review and editing. Vicky Elias Nahra: supervision, writing – review and editing. Muhammad Adeel Hassan: writing – review and editing.

Funding

The authors have nothing to report.

Ethics Statement

The authors have nothing to report.

Consent

Written Informed consent was obtained from the patient for the publication of this case report and any images, which can be made available to journal editor upon request. All efforts were made to ensure patient anonymity and confidentiality.

Conflicts of Interest

The authors declare no conflicts of interest.

Data Availability Statement

The data that support the findings of this study are available from the corresponding author upon reasonable request.