In: Journal of Neuroinflammation, 13 (2016), Nr. 281. pp. 1-23. ISSN 1742-2094

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PDF, English Download (1MB) | Lizenz: MOG-IgG in NMO and related disorders: a multicenter study of 50 patients. Part 3: Brainstem involvement - frequency, presentation and outcome by Jarius, Sven ; Kleiter, Ingo ; Ruprecht, Klemens ; Asgari, Nasrin ; Pitarokoili, Kalliopi ; Borisow, Nadja ; Hümmert, Martin W. ; Trebst, Corinna ; Pache, Florence ; Winkelmann, Alexander ; Beume, Lena-Alexandra ; Ringelstein, Marius ; Stich, Oliver ; Aktas, Orhan ; Korporal-Kuhnke, Mirjam ; Schwarz, Alexander ; Lukas, Carsten ; Haas, Jürgen ; Fechner, Kai ; Buttmann, Mathias ; Strobl, Judith ; Zimmermann, Hanna ; Brandt, Alexander U. ; Franciotta, Diego ; Schanda, Kathrin ; Paul, Friedemann ; Reindl, Markus ; Wildemann, Brigitte underlies the terms of Creative Commons Attribution 3.0 Germany

Abstract

Background: Myelin 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. Objective: To investigate the frequency, clinical and paraclinical features, course, outcome, and prognostic implications of brainstem involvement in MOG-IgG-positive ON and/or myelitis. Methods: Retrospective case study. Results: Among 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). Conclusions: Brainstem 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.