MOG-IgG in NMO and related disorders: a multicenter study of 50 patients. Part 3: Brainstem involvement - frequency, presentation and outcome

Abstract

BackgroundMyelin oligodendrocyte glycoprotein antibodies (MOG-IgG) are present in a subset of aquaporin-4 (AQP4)-IgG-negative patients with optic neuritis (ON) and/or myelitis. Little is known so far about brainstem involvement in MOG-IgG-positive patients.ObjectiveTo investigate the frequency, clinical and paraclinical features, course, outcome, and prognostic implications of brainstem involvement in MOG-IgG-positive ON and/or myelitis.MethodsRetrospective case study.ResultsAmong 50 patients with MOG-IgG-positive ON and/or myelitis, 15 (30 %) with a history of brainstem encephalitis were identified. All were negative for AQP4-IgG. Symptoms included respiratory insufficiency, intractable nausea and vomiting (INV), dysarthria, dysphagia, impaired cough reflex, oculomotor nerve palsy and diplopia, nystagmus, internuclear ophthalmoplegia (INO), facial nerve paresis, trigeminal hypesthesia/dysesthesia, vertigo, hearing loss, balance difficulties, and gait and limb ataxia; brainstem involvement was asymptomatic in three cases. Brainstem inflammation was already present at or very shortly after disease onset in 7/15 (47 %) patients. 16/21 (76.2 %) brainstem attacks were accompanied by acute myelitis and/or ON. Lesions were located in the pons (11/13), medulla oblongata (8/14), mesencephalon (cerebral peduncles; 2/14), and cerebellar peduncles (5/14), were adjacent to the fourth ventricle in 2/12, and periaqueductal in 1/12; some had concomitant diencephalic (2/13) or cerebellar lesions (1/14). MRI or laboratory signs of blood-brain barrier damage were present in 5/12. Cerebrospinal fluid pleocytosis was found in 11/14 cases, with neutrophils in 7/11 (3-34 % of all CSF white blood cells), and oligoclonal bands in 4/14. Attacks were preceded by acute infection or vaccination in 5/15 (33.3 %). A history of teratoma was noted in one case. The disease followed a relapsing course in 13/15 (87 %); the brainstem was involved more than once in 6. Immunosuppression was not always effective in preventing relapses. Interferon-beta was followed by new attacks in two patients. While one patient died from central hypoventilation, partial or complete recovery was achieved in the remainder following treatment with high-dose steroids and/or plasma exchange. Brainstem involvement was associated with a more aggressive general disease course (higher relapse rate, more myelitis attacks, more frequently supratentorial brain lesions, worse EDSS at last follow-up).ConclusionsBrainstem involvement is present in around one third of MOG-IgG-positive patients with ON and/or myelitis. Clinical manifestations are diverse and may include symptoms typically seen in AQP4-IgG-positive neuromyelitis optica, such as INV and respiratory insufficiency, or in multiple sclerosis, such as INO. As MOG-IgG-positive brainstem encephalitis may take a serious or even fatal course, particular attention should be paid to signs or symptoms of additional brainstem involvement in patients presenting with MOG-IgG-positive ON and/or myelitis.

Clinical characteristics and prognosis of myelin oligodendrocyte glycoprotein antibody-seropositive paediatric optic neuritis in China

“…In another study, similar to our results, MOG-Abs were detected in 21 of 37 patients (56.8%) with an acute episode of PON at 6 paediatric hospitals in Germany and Austria 17. The presence of serum MOG-Abs has been proposed to indicate a specific subtype of ON, as it is becoming clear that this biomarker is associated with specific disease features and may be a novel serodiagnostic biomarker of demyelination 18. Zhou et al 13 tested the serum of 47 Chinese children patients and determined that among them, 13 (27.7%) were AQP4-Ab-positive; however, MOG-Abs were not tested for in this study.…”

Myelin Oligodendrocyte Glycoprotein: Deciphering a Target in Inflammatory Demyelinating Diseases

“…Results from these studies are shown in Table 4 and Figure 1. We have identified 26 studies which fulfilled these criteria (50, 55, 56, 109–116, 119, 121, 126, 130, 132, 134, 137, 141, 147, 148, 152, 156, 158, 165, 174). Only 13 of these studies included a control group with 50 or more individuals and only 5 studies included more than 100 controls (Table 4).…”

Pediatric Optic Neuritis: What Is New

“…During the 4-year follow-up, 9 (8%) children fulfilled criteria for MS (18). Thus, normal MRI and a CSF profile do not preclude the possibility of an MS diagnosis in the future, but the likelihood is low.…”

“…CSF OCBs were detected in 12.5% of children with recurrent optic neuritis (10). The frequency of anti-MOG antibodies in children with recurrent optic neuritis is not known, whereas 13 of 37 (35%) adults with recurrent ON had MOG-IgG positivity (18). …”