| Description |
A fifty-one-year-old man in good health presented with painless, right-sided visual deficits described as green-brown blotches, progressing to blurry vision and wavy lines in bilateral visual fields. Visual acuities were 20/50 OD, 20/25 OS. Ishihara plate scores were 5/8 OD and 8/8 OS. Automated perimetry demonstrated bilateral inferior arcuate visual field defects. Slit-lamp exam demonstrated anterior vitreous cells bilaterally. Funduscopy showed bilateral optic disc edema with telangiectasias. There was capillary leakage in both optic discs on fluorescein angiography. MRI of brain and orbits showed contrast enhancement of both optic nerve heads. The patient was initiated on IV methylprednisolone 1000 mg/day for 3 days, with partial visual improvement. He was discharged on high-dose oral steroids (60 mg daily) with taper, but self discontinued due to side effects after 2 weeks, resulting in symptom recurrence three weeks later. Visual deficits worsened to involve bilateral lower quadrants. The patient reported symptoms of disabling orthostatic dizziness. He had mild sleep apnea, but began experiencing nighttime insomnia, daytime somnolence and sleep-related twitching movements in his extremities. Slit-lamp exam continued to show vitreous cells. Funduscopy demonstrated largely resolved optic nerve edema, with interval left temporal pallor development, with telangiectatic vessels extending off the left optic nerve. OCT showed bilateral ganglion cell thinning. Neurological exam demonstrated new subtle torsional nystagmus in down and right gaze, diffuse hyperreflexia and ataxic and abnormal tandem gait. Serological testing was negative/normal for ANA, ACE, SSA/B, RF, ANCA, hepatitis B & C, HIV, Lyme, tuberculosis, syphilis, aquaporin-4 and MOG antibodies. CSF evaluation demonstrated normal opening pressure, 4 nucleated cells with lymphocytic predominance and elevated protein of 82 mg/dl, without oligoclonal bands. CSF cytology and infectious screens were negative. Whole-body PET-CT was unrevealing. Left testicular ultrasound demonstrated hyperechogenic foci suggestive of burned-out tumor or a prior inflammatory process. Orchiectomy did not demonstrate malignant tissue. |
| History |
CSF indirect immunofluorescence assay was positive for IgLON5 (Immunoglobulin-like cell adhesion molecule-5) antibodies at 1:8 titer, confirmed by cell-based assay. After completion of a subsequent steroid taper, given symptomatic progression, the patient's treatment regimen was escalated to monthly intravenous cyclophosphamide infusions (750 mg/m2 body surface area) for 6 doses, followed by maintenance on mycophenolate mofetil (1000 mg twice daily). The patient subsequently experienced improvement in neurologic and ophthalmologic symptoms, with stable exam. IgLON5 is a neuronal cell-surface antigen. Neuropathologic examination of brains from patients with IgLON5-targeted antibodies demonstrated neuronal loss and gliosis, with accumulation of hyperphosphorylated tau in the hypothalamus and brainstem tegmentum, up to the upper cervical cord. MRI T2 hyperintensities in the same areas early in the disease course suggest IgLON5-mediated inflammation in these regions. There is mounting evidence that while IgLON5-related disease in the subacute period resembles other autoimmune CNS neurologic disorders, if left untreated, it appears to develop into a tauopathy-predominant neurodegenerative condition. IgLON5 autoantibodies possibly interfere with the internal cytoskeletal network, leading to neuronal dysfunction and neurodegeneration. Thus far, the reported clinical spectrum includes sleep disorders with parasomnia and sleep breathing difficulties, a bulbar syndrome including dysphagia, sialorrhea, stridor/acute respiratory insufficiency, gait and movement disorders including hyperkinesis, chorea and a syndrome resembling progressive supranuclear palsy. Per our knowledge, there is no prior report of IgLON-5 antibody positivity accompanied by bilateral optic neuritis or a testicular mass. However, in recent conversations with colleagues at the Mayo clinic, an as-yet unpublished series of these patients has been identified. The current case would therefore represent the index case of an emerging neuroimmunologic condition of neuro-ophthalmic interest. |
| References |
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