Overlapping demyelinating syndromes and anti–N‐methyl‐D‐aspartate receptor encephalitis

Abstract

Objective To report the clinical, radiological, and immunological association of demyelinating disorders with anti-N-methyl-D-aspartate receptor (NMDAR) encephalitis. Methods Clinical and radiological analysis of a cohort of 691 patients with anti-NMDAR encephalitis. Determination of antibodies to NMDAR, aquaporin-4 (AQP4) and myelin oligodendrocyte glycoprotein (MOG) was performed using brain immunohistochemistry and cell-based assays. Results Twenty-three of 691 patients with anti-NMDAR encephalitis had prominent MRI and/or clinical features of demyelination. Group 1 included 12 patients in whom anti-NMDAR encephalitis was preceded or followed by independent episodes of NMO-spectrum disorder (5 cases, 4 anti-AQP4-positive), or brainstem or multifocal demyelinating syndromes (7 cases, all anti-MOG-positive). Group 2 included 11 patients in whom anti-NMDAR encephalitis occurred simultaneously with MRI and symptoms compatible with demyelination (5 AQ4-positive, 2 MOG-positive). Group 3 (136 controls) included 50 randomly selected patients with typical anti-NMDAR encephalitis, 56 with NMO, and 30 with multiple sclerosis: NMDAR-antibodies were detected only in the 50 anti-NMDAR patients, MOG-antibodies in 3/50 anti-NMDAR and 1/56 NMO patients, and AQP4-antibodies in 48/56 NMO and 1/50 anti-NMDAR patients (p<0.0001 for all comparisons with Groups 1 and 2). Most patients improved with immunotherapy, but compared with anti-NMDAR encephalitis the demyelinating episodes required more intensive therapy and resulted in more residual deficits. Only 1/23 NMDAR patients with signs of demyelination had ovarian teratoma compared with 18/50 anti-NMDAR controls (p=0.011) Interpretation Patients with anti-NMDAR encephalitis may develop concurrent or separate episodes of demyelinating disorders, and conversely patients with NMO or demyelinating disorders with atypical symptoms (e.g., dyskinesias, psychosis) may have anti-NMDAR encephalitis.

Infectious and Autoantibody-Associated Encephalitis: Clinical Features and Long-term Outcome

“…[32][33][34] There were some patients with $2 etiologic associations (Supplemental Table 4), and these patients provide a challenge for diagnosis and illustrate the overlap between infectious and autoantibodyassociated syndromes. 32,[35][36][37][38] There were notable etiologic absences in this cohort, such as no Mycobacterium tuberculosis encephalitis. Unlike in the United Kingdom, 5 Mycobacterium tuberculosis is rare in Australian children.…”

Therapeutic Approach to the Management of Pediatric Demyelinating Disease: Multiple Sclerosis and Acute Disseminated Encephalomyelitis

“…A small percentage (≤ 10 %) of patients with ADEM will experience a biphasic course, with a subsequent second attack of ADEM-termed multiphasic ADEM [15,26]. Rarely, ADEM may be followed by monophasic or recurrent optic neuritis and may also precede or follow a diagnosis of anti-N-methyl-D-aspartate (NMDA) receptor encephalitis [27,28].…”

Antecedent anti-NMDA receptor encephalitis in two patients with multiple sclerosis

“…2 An overlap has recently been recognised between anti-NMDAR encephalitis and inflammatory demyelinating disorders, particularly neuromyelitis optical spectrum disorder (NMOSD). 3 We describe two patients with an initial presentation consistent with anti-NMDAR encephalitis who have subsequently developed relapsing-remitting multiple sclerosis (MS). The cases described build on the three existing reports of anti-NMDAR encephalitis occurring in patients with established MS. [4][5][6] These cases outline patients with relapsing-remitting MS who had developed encephalopathy.…”

“…2 In a recent large series of 691 patients with anti-NMDAR encephalitis, 3.3% had clinical and/or imaging evidence of a demyelinating disorder, usually with features suggestive of NMOSD (longitudinally-extensive transverse myelitis, bilateral optic neuritis) and most (18 out of 23) had anti-AQP4 or anti-MOG antibodies. 3 In half of cases the demyelinating events were concurrent with the anti-NMDAR encephalitis and half were disseminated in time. 3 An unanswered question is whether the overlap between anti-NMDAR encephalitis and the idiopathic inflammatory demyelinating disorders represents a chance occurrence or whether they may be mechanistically linked.…”

“…3 In half of cases the demyelinating events were concurrent with the anti-NMDAR encephalitis and half were disseminated in time. 3 An unanswered question is whether the overlap between anti-NMDAR encephalitis and the idiopathic inflammatory demyelinating disorders represents a chance occurrence or whether they may be mechanistically linked. The reported frequency of NMOSD in patients with anti-NMDAR encephalitis in the series described above would argue against chance alone, although, any association is in part clouded by the high rate of co-morbid autoimmune disorders in patients with NMOSD.…”