Limits...
Demyelinating disease and anti-N-methyl-D-aspartate receptor immunoglobulin G antibodies: a case report.

Waschbisch A, Kallmünzer B, Schwab S, Gölitz P, Vincent A, Lee DH, Linker RA - BMC Res Notes (2014)

Bottom Line: Anti-N-methyl-D-aspartate receptor immunoglobulin G antibodies directed against the GluN1 subunit are considered highly specific for anti-N-methyl-D-aspartate receptor encephalitis, a severe clinical syndrome characterized by seizures, psychiatric symptoms, orofacial dyskinesia and autonomic dysfunction.Here we report a 33 year old Caucasian male patient with clinically definite multiple sclerosis who was found to be positive for anti-N-methyl-D-aspartate receptor antibodies.Rituximab therapy was initiated.

View Article: PubMed Central - PubMed

Affiliation: Department of Neurology, Friedrich-Alexander University of Erlangen, Schwabachanlage 6, 91054 Erlangen, Germany. Anne.Waschbisch@uk-erlangen.de.

ABSTRACT

Background: Anti-N-methyl-D-aspartate receptor immunoglobulin G antibodies directed against the GluN1 subunit are considered highly specific for anti-N-methyl-D-aspartate receptor encephalitis, a severe clinical syndrome characterized by seizures, psychiatric symptoms, orofacial dyskinesia and autonomic dysfunction.

Case presentation: Here we report a 33 year old Caucasian male patient with clinically definite multiple sclerosis who was found to be positive for anti-N-methyl-D-aspartate receptor antibodies. Rituximab therapy was initiated. On the 18 months follow-up visit the patient was found to be clinically stable, without typical signs of anti-N-methyl-D-aspartate receptor encephalitis.

Conclusion: Our findings add to the growing evidence for a possible association between anti-N-methyl-D-aspartate receptor encephalitis and demyelinating diseases.

Show MeSH

Related in: MedlinePlus

Magnetic resonance imaging. MR FLAIR imaging demonstrates multiple hyperintense lesions suggestive of multiple sclerosis (A-C, E). One of the lesions (arrow) was found to be Gadolinium (Gd) enhancing on T1 scans (D, F).
© Copyright Policy - open-access
Related In: Results  -  Collection

License 1 - License 2
getmorefigures.php?uid=PMC4307172&req=5

Fig1: Magnetic resonance imaging. MR FLAIR imaging demonstrates multiple hyperintense lesions suggestive of multiple sclerosis (A-C, E). One of the lesions (arrow) was found to be Gadolinium (Gd) enhancing on T1 scans (D, F).

Mentions: Cranial MRI on admission demonstrated multiple T2 hyperintense lesions (periventricular, juxtacortical, infratentorial), one of them with gadolinium enhancement (Figure 1). Upon comparison to the MRI six years before, an obvious increase of the lesion load was noted. Visually evoked potentials showed prolonged latencies in both eyes. CSF analysis revealed a borderline pleocytosis (5 cells/μl, 95% lymphocytes). The IgG index (1.3) indicated intrathecal IgG synthesis. A polyspecific intrathecal immunoglobulin synthesis against rubella, varicella and herpes simplex virus but not measles (MRZH reaction) was detected. Oligoclonal bands were found to be positive in serum and cerebrospinal fluid with additional bands in the CSF. Blood work and urine testing were unremarkable without evidence of chronic infection (syphilis, borreliosis, HIV, HBV and HCV), vitamin B12 deficiency or systemic autoimmune disease (ANA, ENA, ANCA, RF, dsDNA and anti-phospholipid antibodies, ACE). The patient was diagnosed with relapsing remitting MS according to the revised McDonald criteria [2] and received a glucocorticoid pulse (5 days, methylprednisolone 1 g/day i.v.) followed by complete recovery. 3 weeks later he returned complaining of new-onset paroxysmal tingling and cramping in his left hand and was found to have tonic spasms that responded well to another course of glucocorticoids and intermittent low dose carbamazepine therapy. Given the higher incidence of tonic spasms in neuromyelitis optica compared to MS [3] we decided to test for aquaporin-4 (AQ4) autoantibodies before initiation of immunomodulatory therapy. Serum samples were sent to an accredited commercial laboratory with long-standing experience (Stöcker Laboratories, Euroimmun AG, Lübeck) that employs a biochip to test for AQ4 autoantibodies in a cell based assay. This biochip consists of a mosaic of fixed human embryonal kidney 239 cells each expressing different recombinant antigens (AQ4, Glu1 NMDAR, AMPAR, GABA-bR, LGI, CASPR2, Amphiphysin, GAD, Hu, Ri, Yo, Tr, MAG, Myelin, Ma/Ta, Glycine receptor) in addition to frozen sections of rat hippocampus and cerebellum. The patient turned out to be AQ4 autoantibody negative but surprisingly IgG directed against the NR1 subunit of the NMDAR (titre 1:100) was detected and confirmed by a typical staining pattern on rat brain. Control testing with an independent serum sample yielded the same result. A third serum sample was sent to a second laboratory (A. Vincent, Imunology Laboratory, Churchill Hospital, Oxford, GB) and confirmed the results and titres.Figure 1


Demyelinating disease and anti-N-methyl-D-aspartate receptor immunoglobulin G antibodies: a case report.

Waschbisch A, Kallmünzer B, Schwab S, Gölitz P, Vincent A, Lee DH, Linker RA - BMC Res Notes (2014)

Magnetic resonance imaging. MR FLAIR imaging demonstrates multiple hyperintense lesions suggestive of multiple sclerosis (A-C, E). One of the lesions (arrow) was found to be Gadolinium (Gd) enhancing on T1 scans (D, F).
© Copyright Policy - open-access
Related In: Results  -  Collection

License 1 - License 2
Show All Figures
getmorefigures.php?uid=PMC4307172&req=5

Fig1: Magnetic resonance imaging. MR FLAIR imaging demonstrates multiple hyperintense lesions suggestive of multiple sclerosis (A-C, E). One of the lesions (arrow) was found to be Gadolinium (Gd) enhancing on T1 scans (D, F).
Mentions: Cranial MRI on admission demonstrated multiple T2 hyperintense lesions (periventricular, juxtacortical, infratentorial), one of them with gadolinium enhancement (Figure 1). Upon comparison to the MRI six years before, an obvious increase of the lesion load was noted. Visually evoked potentials showed prolonged latencies in both eyes. CSF analysis revealed a borderline pleocytosis (5 cells/μl, 95% lymphocytes). The IgG index (1.3) indicated intrathecal IgG synthesis. A polyspecific intrathecal immunoglobulin synthesis against rubella, varicella and herpes simplex virus but not measles (MRZH reaction) was detected. Oligoclonal bands were found to be positive in serum and cerebrospinal fluid with additional bands in the CSF. Blood work and urine testing were unremarkable without evidence of chronic infection (syphilis, borreliosis, HIV, HBV and HCV), vitamin B12 deficiency or systemic autoimmune disease (ANA, ENA, ANCA, RF, dsDNA and anti-phospholipid antibodies, ACE). The patient was diagnosed with relapsing remitting MS according to the revised McDonald criteria [2] and received a glucocorticoid pulse (5 days, methylprednisolone 1 g/day i.v.) followed by complete recovery. 3 weeks later he returned complaining of new-onset paroxysmal tingling and cramping in his left hand and was found to have tonic spasms that responded well to another course of glucocorticoids and intermittent low dose carbamazepine therapy. Given the higher incidence of tonic spasms in neuromyelitis optica compared to MS [3] we decided to test for aquaporin-4 (AQ4) autoantibodies before initiation of immunomodulatory therapy. Serum samples were sent to an accredited commercial laboratory with long-standing experience (Stöcker Laboratories, Euroimmun AG, Lübeck) that employs a biochip to test for AQ4 autoantibodies in a cell based assay. This biochip consists of a mosaic of fixed human embryonal kidney 239 cells each expressing different recombinant antigens (AQ4, Glu1 NMDAR, AMPAR, GABA-bR, LGI, CASPR2, Amphiphysin, GAD, Hu, Ri, Yo, Tr, MAG, Myelin, Ma/Ta, Glycine receptor) in addition to frozen sections of rat hippocampus and cerebellum. The patient turned out to be AQ4 autoantibody negative but surprisingly IgG directed against the NR1 subunit of the NMDAR (titre 1:100) was detected and confirmed by a typical staining pattern on rat brain. Control testing with an independent serum sample yielded the same result. A third serum sample was sent to a second laboratory (A. Vincent, Imunology Laboratory, Churchill Hospital, Oxford, GB) and confirmed the results and titres.Figure 1

Bottom Line: Anti-N-methyl-D-aspartate receptor immunoglobulin G antibodies directed against the GluN1 subunit are considered highly specific for anti-N-methyl-D-aspartate receptor encephalitis, a severe clinical syndrome characterized by seizures, psychiatric symptoms, orofacial dyskinesia and autonomic dysfunction.Here we report a 33 year old Caucasian male patient with clinically definite multiple sclerosis who was found to be positive for anti-N-methyl-D-aspartate receptor antibodies.Rituximab therapy was initiated.

View Article: PubMed Central - PubMed

Affiliation: Department of Neurology, Friedrich-Alexander University of Erlangen, Schwabachanlage 6, 91054 Erlangen, Germany. Anne.Waschbisch@uk-erlangen.de.

ABSTRACT

Background: Anti-N-methyl-D-aspartate receptor immunoglobulin G antibodies directed against the GluN1 subunit are considered highly specific for anti-N-methyl-D-aspartate receptor encephalitis, a severe clinical syndrome characterized by seizures, psychiatric symptoms, orofacial dyskinesia and autonomic dysfunction.

Case presentation: Here we report a 33 year old Caucasian male patient with clinically definite multiple sclerosis who was found to be positive for anti-N-methyl-D-aspartate receptor antibodies. Rituximab therapy was initiated. On the 18 months follow-up visit the patient was found to be clinically stable, without typical signs of anti-N-methyl-D-aspartate receptor encephalitis.

Conclusion: Our findings add to the growing evidence for a possible association between anti-N-methyl-D-aspartate receptor encephalitis and demyelinating diseases.

Show MeSH
Related in: MedlinePlus