Case · Presentation

At seven, fever and blindness. Today she finds it hard to speak and walk.

Jane T is 51, with no significant medical history and an active life — gardening, community volunteer work. Eight months ago she came to her primary care physician with severe fatigue, left‑sided facial weakness and bilateral sensorineural hearing loss, which progressed to the point of needing hearing aids.

Five days of intravenous steroids improved her symptoms markedly over several weeks, and she was diagnosed with CLIPPERS. A month later, while tapering, everything came back worse: progressive leg weakness, right‑sided appendicular ataxia and frequent falls, increasing difficulty speaking, tingling in the head and neck, persistent headaches, bilateral blurry vision.

On examination she is alert but fatigued, with left‑sided facial weakness, slurred speech, lower extremity weakness 3/5, right‑sided ataxia, sensory deficits in the head and neck, brisk reflexes and bilateral Babinski signs. Her gait is severely unstable.

Age at the first event

7 years

Since this episode began

8 months

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Case · Workup

MOG‑IgG 1:100. Clear positive.

Serum antibody testing returns MOG‑IgG clear positive at a titre of 1:100 on a cell‑based assay, with serum AQP4‑IgG negative. Cell‑based assays are the preferred method and serum the recommended specimen; live assays offer the highest sensitivity and specificity, fixed assays are acceptable alternatives, and ELISA is not recommended (Banwell, et al. 2023).

Today’s MRI shows an overall decrease in the prominence of the lesions seen six months ago, the brainstem enhancement has resolved, and no new areas of enhancement have developed. Those earlier images showed multiple areas of increased T2/FLAIR signal in the subcortical white matter, midbrain and pons, some enhancing.

CSF shows mild lymphocytic pleocytosis and elevated protein, without oligoclonal bands. The autoimmune panel, infectious testing — including HIV, syphilis and Lyme — and the paraneoplastic antibody panel were all negative.

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Case · Decision

What is the diagnosis?

Relapsing brainstem and cerebellar deficits in a woman of 51, MOG‑IgG clear positive, AQP4‑IgG negative, no oligoclonal bands, lesions that resolved. Choose one.

• ACLIPPERS
• BMultiple sclerosis
• CNMOSD
• DMOGAD
• ESarcoidosis

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Case · Verdict

The lesions cleared. MS lesions do not.

• ACLIPPERSRuled outThe label she arrived with. Her initial steroid response fits, but CLIPPERS is confined to the pons and adjacent brainstem, while her lesions extend into the subcortical white matter and midbrain. MOG‑IgG positivity is not seen in CLIPPERS, and improvement followed by worsening suggests a relapsing demyelinating disorder (Tobin WO, et al. 2017).
• BMultiple sclerosisRuled outMS does not typically present with MOG‑IgG. Her lesions resolved over time, where MS lesions usually persist and accumulate, and the absence of CSF oligoclonal bands — common in MS, rare in MOGAD — points away (Flanagan, et al. 2024).
• CNMOSDRuled outMOGAD and AQP4‑IgG NMOSD separate on serum biomarkers; dual positivity is extremely rare. She is AQP4‑IgG negative. NMOSD typically brings severe optic neuritis and longitudinally extensive transverse myelitis with irreversible damage, not brainstem predominance with lesion resolution (Flanagan, et al. 2024).
• DMOGADCorrectShe meets all three criteria. A core clinical demyelinating event — brainstem and cerebellar deficits. A clear positive MOG‑IgG by cell‑based assay on serum, which needs no additional supporting features. And better diagnoses excluded (Banwell, et al. 2023).
• ESarcoidosisRuled outNeurosarcoidosis can involve the brainstem, but it typically causes meningeal enhancement, periventricular involvement or a diffuse granulomatous process, none of which are on her MRI. It does not cause MOG‑IgG positivity, and no systemic manifestations are reported (Ungprasert, et al. 2019).

See what settles it

Case · Evidence

Titres fall. The clock was already running.

Diagnosis requires three things (Banwell, et al. 2023): a core clinical demyelinating event, a positive MOG‑IgG by cell‑based assay on serum, and the exclusion of better diagnoses, including multiple sclerosis.

• 01A clear positive stands alone. It requires no additional supporting features. A low positive requires AQP4‑IgG seronegativity and at least one supporting clinical or MRI feature — as does a positive without a reported titre (Banwell, et al. 2023).
• 02Timing changes the answer. Low‑positive results are more commonly associated with a longer time from onset to sampling. In a cohort tested within 6 months of onset, titres declined progressively: by 6 months about 25% returned a low positive, and by 12 months 50% returned a negative (Forcadela et al, 2023). Jane was sampled at about 8 months.
• 03The childhood episode was the first attack. Fever, dysarthria, bilateral vision loss and unilateral weakness at 7, resolving with steroids, points to an inflammatory demyelinating process — and it had not been fully explored at the time.
• 04Getting the name right is the treatment. There are no FDA‑approved therapies for MOGAD (Redenbaugh V and Flanagan EP, 2022), and relapse affects up to 70% of patients with longer follow‑up (Trewin BP, et al, 2024). Delays lead to misdiagnosis, inappropriate treatment and prolonged progression (Santoro, et al. 2023).

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