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
