MOGAD Optic Neuritis Mis-Classified as CLIPPERS


Video Presentation


Myelin oligodendrocyte glycoprotein (MOG) is targeted in auto-immune neuropathies of the central nervous system (CNS). Anti-MOG antibodies (MOG-ab) are associated with demyelinating disorders, including optic neuritis (ON), as part of MOG-ab disease (MOGAD). Overlapping signs and symptoms with other auto-immune neuropathies complicates diagnosis. Chronic lymphocytic inflammation with pontine perivascular enhancement responsive to steroids (CLIPPERS) is a rare non-demyelinating disorder affecting the brainstem, pons, cerebellum, and spinal cord, further complicating accurate MOGAD diagnosis. MOGAD and CLIPPERS have characteristic magnetic resonance imaging (MRI) lesions and are steroid-responsive. We report a MOGAD patient with mono-phasic ON misclassified as CLIPPERS.

Case Description:
A 63-year-old woman presented with headache, ocular pain, and bilateral vision loss. Physical evaluation revealed brainstem abnormalities and bilateral ON. The patient received intravenous corticosteroids followed by an oral taper. The patient subsequently reported slightly improved vision bilaterally with no progressive vision loss.

MRI noted increased fluid-attenuated inversion recovery (FLAIR) signal in optic nerves, chiasm, and ponto-medullary junction, with enhancement in the pons and chiasm, a pattern characteristic of CLIPPERS. The patient was MOG-ab seropositive. Cerebrospinal fluid (CSF) protein was also noted to be elevated (61 mg/dL), as occurs in one third of MOGAD cases.

High-dose corticosteroid therapy was continued and tapered over 9-months. Subsequent MRI was inconsistent with CLIPPERS. Ocular mobility, visual field, and vision were noted to improve, with no new symptoms developing. Vision remains stable two years following initial presentation, despite a recurrent episode of ON after 18-months. Steroid-responsiveness supports a MOGAD diagnosis.

In adults with MOGAD, ON is the most common neurological symptom and typically involves the anterior optic pathway. Symptoms are often bilateral and result from optic nerve inflammation and optic nerve lesions. Patients may experience acute vision loss with eye pain, afferent pupillary defect, and/or visual field abnormalities. CLIPPERS presents with ponto-cerebellar dysfunction.

MOGAD and other auto-immune neuropathies, have distinct biological origins and responsiveness to steroids, should not be relied upon as a single means of diagnosis. Disease-specific antibodies are the diagnostic standard. In the case of CLIPPERS wherein a definitive biomarker has not yet been identified, antibody-independent biomarkers such as plasma metabolite may support the molecular distinction of phenotypically overlapping diseases and contribute to future monitoring and diagnosis.

MRI patterns of MOG-ab ON include hyper-intensities of the anterior portions of the optic nerve. Clinical and imaging features were consistent with a demyelinating process and met criteria for MOG-ab ON, however, pontine lesions suggested the possibility of CLIPPERS. Characteristic imaging patterns with CLIPPERS include punctate gadolinium enhancement within the pons. MOGAD, however, may also cause pontine lesions and thus is a better unifying diagnosis in the presence of ON.

Differential diagnosis of patients with ON should include MOGAD and prompt testing for disease-specific antibodies. These results in concert with diagnostic imaging, responsiveness to treatment, history of present illness, and existing disability, may provide a complete diagnostic picture. Additional research must be done to elucidate the pathogenesis of MOGAD to optimize diagnosis and treatment.