Objective:

To describe a case of IgLON5 disease presenting with a PSP-like phenotype, underscoring the importance of antibody testing in atypical parkinsonian syndromes. 

Background:

IgLON5 disease is a rare neuroimmune disorder caused by antibodies against the neuronal cell-adhesion protein IgLON5, resulting in concurrent antibody-mediated neuroinflammation and tau-related degeneration. Its close clinical resemblance to progressive supranuclear palsy (PSP) often results in diagnostic delay. Early recognition is essential, as some patients demonstrate meaningful response to immunotherapy.  

Design/Methods:

NA

Results:

A 76-year-old patient presented with one year of progressive gait and postural instability characterized by shuffling steps, frequent falls, and symmetric bradykinesia and rigidity. He endorsed hypophonia, dysphagia, drooling, and his spouse reported dream enactment behaviors consistent with REM sleep behavior–like features. Neurologic examination revealed vertical gaze limitation, frontal release signs, reduced blink rate, and symmetric rigidity with bradykinesia. MRI brain was unremarkable, and DAT scan showed no presynaptic dopaminergic deficit. CSF analysis demonstrated mildly elevated protein (57 mg/dL) and was positive for IgLON5 antibodies, confirming autoimmune etiology. The patient received intravenous methylprednisolone (1 g daily for 5 days) and five plasma-exchange sessions with mild short-term improvement. He was discharged on mycophenolate mofetil, with rituximab planned if progression continued. At three-month follow-up, gait stability had modestly improved but remained fluctuating, consistent with partial treatment response. 

Conclusions:

IgLON5 disease can closely mimic PSP, presenting with axial rigidity, vertical gaze palsy, gait freezing, and bulbar dysfunction but lacking dopaminergic denervation. Detection of IgLON5 antibodies in serum or CSF should be pursued in atypical or treatment-responsive PSP phenotypes, as early immunotherapy may alter the clinical course.