Movement Disorders and Oculomotor Abnormalities in Whipple's Disease: An Updated Systematic Review.

Introduction: Whipple's disease (WhD) is a rare multisystemic infection caused by Tropheryma whipplei, with central nervous system (CNS) involvement seen in up to 50% of cases. Neurological symptoms may precede systemic features or occur in isolation. Movement disorders (MDs) and oculomotor abnormalities, especially oculomasticatory myorhythmia (OMM) and oculofacioskeletal myorhythmia (OFSM), are of a high diagnostic importance but remain underrecognized. This systematic review aims to update our understanding of MDs in CNS-WhD, building on a 2018 review. Methods: A systematic search of MEDLINE, EMBASE, and Cochrane Library was performed for English-language human studies published between 01/2017-05/2025. Search terms targeted WhD and MDs. Titles, abstracts and full-text were screened in Rayyan.ai, by two independent reviewers. Results: We added 19 articles (22 new cases) to the 100 articles (146 cases) from the previous report, making up a total of 168 CNS-WhD patients with MDs or oculomotor abnormalities. Supranuclear gaze palsy (SGP) was the most common sign (58%), followed by myorhythmia and ataxia (40% each). Pathognomonic OMM/OFSM were identified in 25% of cases, higher than previously reported. MRI showed abnormalities in 87% of cases, and brain tissue PAS staining had the highest diagnostic yield, although mostly performed post-mortem. Treatment with ceftriaxone followed by Trimethoprim-Sulfamethoxazole remained common, though doxycycline-hydroxychloroquine use has increased. MDs improved in 53% of cases. Conclusion: Oculomotor abnormalities and MDs, especially SGP and OMM/OFSM/other myorhythmia, are key diagnostic clues in CNS-WhD, even in the absence of systemic symptoms. Greater diagnostic awareness is essential to improve outcomes of this life-threatening, but treatable, condition.