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

TL;DR

This review updates the understanding of movement disorders and eye movement issues in Whipple’s disease, emphasizing their importance for early diagnosis and treatment.

Contribution

The study provides an updated systematic review with new cases and highlights the increased recognition of oculomasticatory myorhythmia in CNS-Whipple’s disease.

Findings

Supranuclear gaze palsy was the most common oculomotor abnormality in 58% of cases.

Oculomasticatory myorhythmia was identified in 25% of cases, higher than previously reported.

MRI showed abnormalities in 87% of cases, and brain PAS staining had the highest diagnostic yield.

Abstract

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.

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.

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.

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.

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