Background

Brainstem and cerebellar involvement are recognized to occur in myelin-oligodendrocyte-glycoprotein-antibody-associated-disorder (MOGAD) and the clinical syndrome can be severe. However, data on brainstem and cerebellar involvement in MOGAD is limited.

Objectives

To determine the frequency and characteristics of brainstem/cerebellar involvement in MOGAD versus aquaporin-4-IgG-seropositive-neuromyelitis-spectrum-disorder (AQP4-IgG-NMOSD) and multiple sclerosis (MS).

Methods

In this observational study, we retrospectively identified 185 Mayo Clinic MOGAD patients and included those with: 1) characteristic MOGAD phenotype; 2) MOG-IgG seropositivity by live-cell-based-assay; 3) brainstem/cerebellar MRI lesion(s). We compared clinical, MRI and cerebrospinal fluid (CSF) characteristics of symptomatic brainstem/cerebellar attacks in MOGAD to AQP4-IgG-NMOSD (n=30) and MS (n=30).

Results

Brainstem/cerebellum involvement occurred in 62/185 (34%) MOGAD patients of which 39/62 (63%) had accompanying brainstem/cerebellum symptoms/signs. Ataxia (45%) and diplopia (26%) were common manifestations. The median age in years (range) in MOGAD of 24 (2–65) was younger than MS at 36 (19–65) and AQP4-IgG-NMOSD at 45 (6–72)(P<.05). Isolated brainstem/cerebellar attacks in MOGAD (9/39[23%]) were less frequent than MS (22/30[73%]; p<0.05) but not significantly different from AQP4-IgG-NMOSD (14/30[47%]; p=0.07). Diffuse middle cerebellar peduncle MRI-lesions favored MOGAD (17/37[46%]) over MS (3/30[10%]; P<0.05) and AQP4-IgG-NMOSD (3/30[10%]; p<0.05), while diffuse medulla, pons or midbrain MRI-lesions occasionally occurred in MOGAD and AQP4-IgG-NMOSD but never in MS. CSF oligoclonal bands were similarly rare in MOGAD (2/30[7%]) and AQP4-IgG-NMOSD (1/22[5%]; p>0.99) but common in MS (17/22[77%]; p<0.05). Expanded-disability-status-scale-score (EDSS) and brainstem/cerebellar functional-system-scores (FSS) at nadir and recovery did not significantly differ between the groups.

Conclusions

Brainstem/cerebellar involvement is common in MOGAD but usually occurs as a component of a multifocal CNS attack rather than in isolation. We identified clinical, CSF, and MRI attributes that can help discriminate MOGAD from AQP4-IgG-NMOSD and MS.

Background

Antibodies against myelin oligodendrocyte glycoprotein (MOG-IgG) are a biomarker of MOG-IgG associated disorder (MOGAD), a CNS demyelinating disease that disproportionately affects the optic nerves as optic neuritis (ON). MOG-IgG ON is usually associated with pain and is often steroid responsive, but details of this in a large cohort are lacking.

Objectives

To investigate whether timing of steroid treatment affects the rate and extent of visual recovery in a large cohort of MOGAD patients and examine the temporal relation of eye pain to visual loss.

Methods

We included consecutive patients evaluated by the neuro-ophthalmology departments at 5 centers from January 2017 to April 2020. Patients fulfilling the following criteria were included: (1) clinically documented history of ON; (2) serum positivity for MOG-IgG by live cell-based-assay. The details of each ON attack was recorded, including presence of eye pain, days of eye pain prior to the onset of vision loss, nadir of visual acuity loss, type of acute treatment, time to treatment, time to recovery, and final visual acuity after each attack.

Results

A total of 221 ON attacks in 115 patients with one or more episodes of MOG-IgG ON were included. The average age at the initial ON onset was 36.8 (SD 19.3); 71 (62%) were female. Eye pain was present in 171/193 (89%) of attacks with data collected on eye pain. Among 98 attacks with available temporal data, the pain began a mean of 4.2 (SD 4.2) days prior to the vision loss. Early steroid therapy administered to 9 patients (6 with MRI optic nerve enhancement; 3 had clinical ON but no MRI) with eye pain but lacking vision loss had resolution of eye pain and never developed vision loss.

Among 37 ON attacks treated with intravenous methylprednisolone (IVMP) within 2 days of onset of vision loss, the average time to recovery was 1.9 days (SD 3.1) compared to 12.1 days (SD 12.1) in 84 ON attacks treated later than 2 days (p<0.001). Those treated within 2 days had less severe visual acuity (VA) loss at time of treatment (mean LogMAR VA 0.62, SD .77) compared to those treated later than 2 days (mean LogMAR VA 1.6, SD 0.9), p<0.001, and also had a better final VA after IVMP (mean LogMAR VA 0.05, SD 0.11) compared to those treated later than 2 days (LogMAR VA 0.26, SD 0.57), p=0.034.

Conclusions

The observational findings that early IVMP leads to faster recovery and better outcomes and that pain precedes vision loss in the majority of MOG-IgG ON attacks suggests there may be a therapeutic window for steroid treatment that reduces the risk of permanent deficits.