A Patient With Encephalomyeloradiculoneuropathy Exhibiting a Relapsing-Remitting Clinical Course: Correlation of Serum and Cerebrospinal Fluid Anti-Neutral Glycosphingolipids Antibodies With Clinical Relapse

Abstract

Several patients who had a progressive clinical course involving both the central and peripheral nervous systems have been reported, but the diagnostic marker has been remained uncertain. More recently, such patients were reported to have namely "encephalomyeloradiculoneuropathy (EMRN)" associated with anti-neutral glycosphingolipid (GSL) antibodies. These antibodies were reported to disappear from the serum in the recovery phase, but whether this finding applies to the cerebrospinal fluid (CSF) remains uncertain. We describe a 67-year-old man with EMRN in whom we measured anti-neutral GSL antibodies in serial serum and CSF samples. During the disease course, the optical densities of the positive band against the background intensity ratio (-<0.3; ±≥0.3 to <0.6; +≥0.6 to <1.0; 2+≥1.0 to <2.0; 3 +≥2.0) for serum and CSF anti-lactosylceramide (LacCer) antibodies were found to be as follows: 2+ and 1+ at the first admission, ± and - when the consciousness level improved after immunotherapy, - and 1+ at clinical relapse, and ± and - when the consciousness level improved after immunotherapy. This is the first time to document that clinical relapse occurred in EMRN, and at this time the negative anti-LacCer antibodies in CSF after the first course of immunotherapy turned positive, but this was not seen in serum samples.

Keywords: antibody; encephalomyeloradiculoneuropathy; encephalopathy; glycosphingolipids; lactosylceramide; myelopathy; neuropathy.

Figure 1

Thoracic magnetic resonance imaging (MRI). T2-weighted thoracic MRI showed abnormal high signals in the spinal cord (A–C). After 5 months, the high signals were diminished on the follow-up thoracic MRI (D,E).

Figure 2

Clinical course and serum and cerebrospinal fluid anti-lactosylceramide antibodies.

Figure 3

Serial Far-Eastern blot analyses. Neutral glycosphingolipids (GSLs), such as lactosylceramide, glucosylceramide, and galactosylceramide (GalCer) were applied onto thin-layer chromatography plates (TLC plates) to obtain the respective pure neutral GSLs, and they were developed as described previously (4). The separated neutral GSLs were transferred to a regular polyvinylidene difluoride membrane (PVDF membrane) with a thermal blotter (ATTO, Tokyo, Japan). The positive band(s) were detected with a chemiluminescence detection system (4). The separated GSLs were probed with serum from a healthy volunteer [(1): negative control] and with serum from a patient with encephalomyeloradiculoneuropathy [(2): positive control]. Panel (3) shows the separated GSLs from the patient at the following multiple time-points: serum at the first admission, cerebrospinal fluid (CSF) at the first admission, serum at the second admission, CSF at the second admission, serum after final immunotherapy, and CSF after final immunotherapy. Positive bands were detected with serum and CSF from the patient at the first admission and CSF from the patient at the second admission. A positive band was weakly detected with serum from the patient after final immunotherapy. Sera and CSF are usually 1,000- and 5-times diluted with the antibody reaction buffer, respectively. Lactosylceramide and glucosylceramide were applied to (a) lane, whereas GalCer was applied to each (b) lane of the TLC plates.