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|NI FEATURE: FACING ADVERSITY…TOMORROW IS ANOTHER DAY! - LETTER TO EDITOR
|Year : 2017 | Volume
| Issue : 5 | Page : 1131-1134
Neurosarcoidosis-induced longitudinal extensive transverse myelitis
Sushilkumar S Gupta1, Shyam Shankar1, Evan Stein2, Sina Khasani3
1 Department of Internal Medicine, Maimonides Medical Center, Brooklyn, New York, USA
2 Department of Radiology, Maimonides Medical Center, Brooklyn, New York, USA
3 Department of Neurology, Maimonides Medical Center, Brooklyn, New York, USA
|Date of Web Publication||6-Sep-2017|
Sushilkumar S Gupta
Department of Internal Medicine, Maimonides Medical Center, 4802 10th Avenue, Brooklyn, New York
Source of Support: None, Conflict of Interest: None
|How to cite this article:|
Gupta SS, Shankar S, Stein E, Khasani S. Neurosarcoidosis-induced longitudinal extensive transverse myelitis. Neurol India 2017;65:1131-4
Longitudinal extensive transverse myelitis (LETM) is a rare inflammatory disorder causing damage to the spinal cord with varying degrees of motor, sensory, and/or autonomic dysfunction. LETM is defined as a lesion that extends over three or more vertebral segments, located centrally in the spinal cord. LETM is a characteristic feature of and one of the diagnostic criteria for neuromyelitis optica (NMO); however, it can also be seen with infections involving the spinal cord and with autoimmune disorders such as systemic lupus erythematous, Sjogren syndrome, multiple sclerosis, and sarcoidosis.,
Neurosarcoidosis usually presents with other forms of sarcoidosis, but in 1% of the cases, it can present as an isolated lesion, which makes the diagnosis more difficult during the preliminary stages. It can affect the central nervous system – the brain, spinal cord, peripheral nerves, and the muscles. LETM is a rare consequence of neurosarcoidosis.
A 53-year old male patient presented to the emergency room with complaints of sudden onset of urine retention for 1 day and 15 pounds of unintentional weight loss since the last 3 months. His past medical history was significant for hypertension and peripheral vascular disease, which was managed with a calcium channel blocker. He denied any history of fever, dyspnea, night sweats, and motor or sensory deficits. The routine laboratory investigations were unremarkable except for elevated blood urea nitrogen (BUN) [41 mg/dl] and creatinine (2.5 mg/dl). The patient was admitted with a preliminary diagnosis of acute renal failure possibly secondary to obstructive uropathy. He had a urine output of 2400 ml after Foley catheterization. The renal ultrasonography was negative for hydronephrosis.
The next morning, the patient developed bilateral lower extremity weakness with a power of 0/5 bilaterally. Magnetic resonance imaging (MRI) with intravenous (IV) gadolinium administration of the thoracic and lumbar spine showed an abnormal hyperintense signal intensity in the spinal cord from T3 to T12 region with associated cord expansion, suggestive of LETM [Figure 1]. Pulse dose of 1 g IV methylprednisone was instituted for 5 days. Inflammatory marker panel including rheumatoid factor, anti-double stranded deoxyribonucleic acid (ds-DNA), lupus anticoagulant, cytoplasmic antineutrophil cytoplasmic antibodies (c-ANCA), perinuclear antineutrophil cytoplasmic antibodies (p-ANCA), and beta 2 glycoprotein were all negative, as was the anti-aquaporin 4 antibody. The infection panel was negative for human immunodeficiency virus (HIV), human T-lymphotropic virus (HTLV) 1 and 2, and treponemal antibody. Blood and urine cultures were also negative. Cerebrospinal fluid analysis (CSF) revealed a cell count of 104 cells/μl with lymphocytic pleocytosis (96%), normal glucose level, elevated protein (85 mg/dl), and elevated immunoglobin G level (136.6 mg/dl). CSF angiotensin converting enzyme (ACE) was not detectable. The CSF was sterile, and its cytology was negative for cryptoccocal antigen, Lyme disease, enterovirus, and West-Nile virus. Oligoclonal bands were absent. Serum angiotensin-converting enzyme (ACE) and calcium levels were normal.
|Figure 1: Sagittal T1-weighted (a), T2-weight (b), and short-tau inversion recovery (STIR) T2-weighted (c) imaging demonstrate a longitudinally extensive spinal cord lesion (LESCL) extending from T3 to T12 with confluent hyperintense signal intensity and mild cord expansion (arrow). Subcarinal soft tissue which is iso-intense to muscle on T1 weighted imaging and hyperintense on T2 weighted imaging can also be seen (arrow head)|
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Due to poor neurological response to high dose steroids and no available definitive diagnosis, plasmapheresis (PLEX) was initiated. Five cycles of PLEX were completed with no significant improvement. Computed tomography (CT) of the chest showed subcarinal and mediastinal lymphadenopathy. Due to his extended stay in the hospital and no significant improvement in his medical condition, the patient requested to be discharged and was followed-up as an outpatient.
Biopsy of the subcarinal lymph nodes showed noncaseating granulomas consistent with sarcoidosis [Figure 2] and [Figure 3]. The biopsy was negative for malignancy, gram stain, and acid fast bacilli stain. After the biopsy results were obtained, multiple attempts were made to contact the patient but he never responded and was lost to follow-up.
|Figure 2: Subcarinal lymph node biopsy shows non caseating granuloma, hematoxylin and eosin stained confluent sarcoid granulomata pattern (black arrows). Tissue shows occasional multinuclear giant cells, mononuclear phagocytes, and lymphocytes. No necrosis was present|
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Sarcoidosis is a multiorgan disease that affects approximately 10% of the patients as neurosarcoidosis. The peak incidence of neurosarcoidosis is between 30 and 50 years of age; the female patients tend to be more affected as compared to the male ones., Worldwide, the African–American population is affected more than the Caucasian, followed by the Scandinavian population. Approximately 25% of the patients may be diagnosed with neurosarcoidosis during an autopsy, which reveals that there is a high likelihood that asymptomatic or misdiagnosed patients may be missed at their initial presentation.
The diagnosis of neurosarcoidosis is difficult because radiologic, laboratory, and clinical presentations are nonspecific, which can be seen in a variety of neurological anomalies. Neurosarcoidosis is more commonly associated with other forms of sarcoidosis but in 1% of instances, it only affects the nervous system. It can present as an intraparenchymal lesion, a spinal cord lesion or as a myopathy depicting a neuromuscular pathology. Spinal cord lesions usually present with gait disturbance, bladder-and-bowel dysfunction, weakness, or sensory deficit. Radiological studies are essential in providing the initial clue to the diagnosis. In an acute presentation, MRI scans show a hyperintense signal intensity and cord expansion, whereas chronic cases show cord atrophy. The other diagnostic work-up includes CSF and serum ACE level analyses. Elevated protein count and cell count are the most commonly reported abnormalities in patients with neurosarcoidosis. Studies have shown that serum ACE level does not correlate well with disease activity due to its low sensitivity and the presence of genetic polymorphism., An active disease can be defined by the presence of granulomas in the body. Biopsy of the lesion or lymph node remains the gold standard method for diagnosis. Zajicek et al., have developed the diagnostic classification system for neurosarcoidosis. This classification is accepted globally by neurologists and helps to distinguish it into “definite,” “probable,” and “possible,” as shown in [Table 1].
|Table 1: Diagnostic criteria and disease classification of neurosarcoidosis|
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The mainstay of the management of neurosarcoidosis includes high dose corticosteroids. They act mainly by suppression of interferon gamma, tumor necrosis factor α, and other important inflammatory cytokines that are responsible for the formation of a sarcoid granuloma. At present, there are no fixed guidelines available to determine the dose and duration of corticosteroid use. The treatment is individualized based on the severity and the signs and symptoms of the disease. As in the case presented here, neurosarcoidosis may be refractory to corticosteroids, and additional anti-sarcoid agents may need to be considered. They can also be used in patients who develop side effects of corticosteroids or as a corticosteroid sparing agent. These agents include mycophenolate mofetil, methotrexate, cyclophosphamide, and anti-TNF-α agents such as infliximab.,, Infliximab is used as a final resort when other corticosteroid sparing agents do not show much benefit. Mycophenolate mofetil has been the most successful agent compared to other medications for the management of neurosarcoidosis. It is a prodrug of mycophenolic acid, which reversibly inhibits inosine monosphosphate dehydrogenase in purine synthesis, a critical factor for the growth of B and T lymphocytic cells. Routine hematology and biochemistry investigations are required to monitor the potential side effects. Although these drugs have shown promising results in case reports and small case series, more prospective trials would be required to validate their efficacy.
The goal of presenting this case is to emphasize the importance of recognizing this rare manifestation of neurosarcoidosis as well as to provide appropriate therapy early in the course to prevent the development of debilitating disorders. A thorough work-up screening for other inflammatory disorders, such as neuromyelitis optica, and infectious causes should be done. Potential adverse effects should be considered while selecting immunosuppressants for management.
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Conflicts of interest
There are no conflicts of interest.
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[Figure 1], [Figure 2], [Figure 3]