By Jai S. Perumal, MD
Assistant Professor of Neurology, Weill Cornell Medical College
Dr. Perumal reports she receives grant/research support from Genzyme Corp., and is on the speakers bureau for Biogen Idec, Genzyme Corp., Acorda Therapeutics, and Teva Pharmaceuticals.
SYNOPSIS: Based on a retrospective analysis of 71 patients with an neuromyelitis optica spectrum disorder (n = 37) or sarcoidosis (n = 34), whose initial presentation was longitudinally extensive transverse myelitis (≥ 3 vertebral segments), the authors report clinical, radiologic, and laboratory findings that help distinguish one from the other.
SOURCE: Flanagan EP, Kaufmann TJ, Krecke KN, et al. Discriminating long myelitis of neuromyelitis optica from sarcoidosis. Ann Neurol 2016:79:437-447.
Neuromyelitis optica (NMO) is an inflammatory disease of the central nervous system that preferentially affects the optic nerves and spinal cord. NMO spectrum disorder (NMOSD) is diagnosed in patients with optic neuritis or transverse myelitis who have the NMO IgG antibody. The typical longitudinally extensive (≥ 3 vertebral segments) spinal cord lesions in NMOSD help differentiate this condition from multiple sclerosis along with other clinical, radiologic, and laboratory features. But transverse myelitis in the context of other immune-mediated diseases like sarcoidosis, systemic lupus erythematosus, and Sjogren’s disease can have a very similar appearance to NMOSD. Sarcoidosis can mimic NMOSD and is often an underdiagnosed cause of longitudinally extensive transverse myelitis, especially since the initial or the only clinical presentation of sarcoidosis can be myelopathy. The authors undertook a study to examine clinical, radiologic, and laboratory features that can help distinguish sarcoidosis from NMOSD.
Adult patients (≥ 18 years of age) who had a diagnosis of NMOSD or sarcoidosis and whose initial presentation was longitudinally extensive transverse myelitis were included in the study. Thirty-seven NMOSD and 34 sarcoidosis patients were included in the analysis. NMOSD was diagnosed if 1) the first myelitis was characterized by a T2 hyperintensity that spanned ≥ 3 vertebral segments; 2) there was seropositivity for NMO IgG ab (AQP4 Ab); and 3) there were adequate clinical data. Sarcoidosis was diagnosed if 1) the first myelitis was characterized by a T2 hyperintensity that spanned ≥ 3 vertebral segments; 2) there was pathological confirmation of sarcoidosis at time of myelitis; and 3) there were adequate clinical data. Similarities and differences in demographics, clinical presentations, radiologic features, and laboratory findings were analyzed.
Statistically significant clinical and laboratory findings that were more likely to indicate NMOSD were female sex, presence of optic neuritis, episodes of intractable nausea and vomiting, paroxysmal tonic spasms, and coexisting systemic autoimmunity, either clinical or serologic. Similarly, findings that were more suggestive of sarcoidosis were presence of constitutional symptoms, longer median time to worst deficit during an acute event, and longer time from onset of symptoms to diagnosis. Although cerebrospinal fluid (CSF) pleocytosis and elevated protein were common in both, it was more suggestive of sarcoidosis. Hilar adenopathy was exclusive to sarcoidosis and seen in 73% of patients who had a CT of the chest. CSF hypoglycorrhachia and elevated angiotensin-converting enzyme also were seen exclusively in sarcoidosis patients but were seen only in 11% and 18% of patients, respectively. With regard to radiologic findings, the distribution of lesions in the spinal cord or the length of the individual lesions did not show a statistical difference between the two groups. However, subpial gadolinium enhancement and persistent gadolinium enhancement for more than two months were more common in sarcoidosis, while ring-enhancement was more common in NMOSD, than in sarcoidosis.
Among the 34 patients who were confirmed as having sarcoidosis, the initial diagnosis was sarcoidosis in 32%; in the others, one or more of the following causes for the transverse myelitis, in decreasing order of frequency were NMOSD, transverse myelitis not otherwise specified, tumor, and multiple sclerosis. Among the 37 NMOSD patients, the initial diagnosis was one or more of the following: NMOSD in 22, transverse myelitis not otherwise specified in eight, tumor in three, multiple sclerosis in three, and gastrointestinal disease in one.
The authors concluded that sarcoidosis can present initially with longitudinally extensive transverse myelitis, and these patients often are misdiagnosed as having NMOSD or idiopathic transverse myelitis. This could potentially explain the delay in diagnosing sarcoidosis compared to NMOSD, due to a lack of specific or sensitive serologic or CSF markers and the need for pathological confirmation before making a diagnosis of sarcoidosis. They have shown factors that are more suggestive of sarcoidosis vs. NMOSD that can raise clinical suspicion and initiation of appropriate workup, including imaging and biopsy, that can lead to the correct diagnosis. A correct diagnosis is important, because the clinical course and treatment of sarcoidosis is different from NMOSD.
Sarcoidosis is one of the causes of longitudinally extensive transverse myelitis along with NMOSD. The initial presentation of sarcoidosis can be transverse myelitis, and a diagnosis of sarcoidosis is frequently made after a delay or is missed in patients with longitudinally extensive transverse myelitis. Often, sarcoidosis is wrongly attributed to NMOSD or one of the other inflammatory conditions. The authors have shown clinical, radiologic, and laboratory findings that are more suggestive of sarcoidosis than of NMOSD. Since the disease course and treatment of these conditions are different, it is important for clinicians to be clinically vigilant to factors that are more suggestive of one diagnosis vs. the other so that the correct diagnosis can be made in a timely fashion and appropriate treatment initiated.