Oculomasticatory myorhythmia (OMM) is a pathognomonic manifestation of Whipple’s disease (WD) of the central nervous system. It is characterized by smooth, continuous, slow (1-3 Hz), pendular, convergent-divergent nystagmus, concurrent contractions of the masticatory muscles, supranuclear vertical gaze palsy, and occasionally, rhythmic movements of the limbs (see video in Media below). It differs from other forms of pendular nystagmus in that it is smooth and continuous with a high amplitude and slow frequency. These eye movements may persist during sleep.
The term OMM is sometimes used interchangeably with oculo-facial-skeletal myorhythmia (OFSM). The two conditions are almost identical except that OFSM also involves rhythmic movements of the proximal and distal skeletal muscles. In fact, the term OFSM was first used in a case of OMM with skeletal muscle involvement. Both OMM and OFSM are pathognomonic for Whipple’s disease.
Pathogenesis & Epidemiology
Whipple’s disease is a rare systemic disorder that primarily affects the gastrointestinal system causing malabsorption, although it can affect any part of the body. It often presents with symptoms of weight loss, steatorrhea, arthralgia, fever, and sometimes, neurologic findings like dementia and somnolence. It is caused by the bacteria Tropheryma whipplei which predominantly infects macrophages of the small intestines. The specific findings of OMM are thought to be due to lesions in the midbrain and upper pons.
To date, only about 1000 cases have been reported in the literature. Up to nearly 40% of WD patients may demonstrate abnormal movements, including myoclonus, choreiform movements, and OMM. OMM is more common in men than women. This condition is incredibly uncommon so there is no accurate estimate of incidence, although some reports suggest that the incidence of OMM in patients with WD is around 20%.
As OMM is pathognomonic for WD, it is not necessary to have biopsy confirmation in order to treat empirically. Nonetheless, diagnosis of WD in the absence of OMM is made by duodenal or jejunal biopsy which will show PAS-positive “foamy” macrophages containing Gram positive bacilli. Additionally, it can be diagnosed via PCR assay for T. whipplei or using a FISH rRNA probe. WD is rare and generally only considered after other malabsorption, infectious, and systemic disorders have been ruled out. As a presentation of OMM is pathognomonic for WD, recognition can aid in quickly making a diagnosis.
Diagnosis of CNS Whipple's Disease (CNS WD) with or without OMM can be made in accordance with the guidelines proposed by Louis et al. in 1997:
Definite CNS WD
Must have any 1 of the following 3 criteria:
- OMM or OFSM
- Positive tissue biopsy
- Positive PCR analysis
Note: If histological or PCR analysis was not performed on CNS tissue, then the patient must also demonstrate neurological signs. If histological or PCR analysis was performed on CNS tissue, then the patient need not demonstrate neurological signs (i.e. asymptomatic CNS infection).
Oculopalatal myoclonus: This is a condition in which palatal myoclonus is associated with skeletal limb involvement and convergent-divergent nystagmus that can persist during sleep. It can present similarly to OMM although there are several differences that help distinguish the two pathologies. While OMM is caused by Whipple’s disease, oculopalatal myoclonus is usually due to a stroke in the brainstem, specifically, the myoclonic triangle (Guillain-Mollaret triangle [GMT]) that regulates motor activity of the spinal cord. Physical examination reveals pendular nystagmus and rhythmic movement of the soft palate. MRI will clearly show an infarct and will often reveal inferior olive hypertrophy in the medulla, a finding not present in OMM.
Anti-NMDA receptor encephalitis: This is a paraneoplastic condition with neuropsychiatric manifestations with serologic or cerebrospinal fluid antibodies to the NMDA glutamate receptor. It is associated with ovarian teratomas.
Nystagmus not present
Limbo myorhythmia, Holmes tremor, Parkinson’s disease, cerebrovascular infarcts, Listeria encephalitis, multiple sclerosis (MS), tics, Tourette’s syndrome.
It has been shown that the most efficient treatment may be with doxycycline and hydroxychloroquine. Another generally accepted treatment regimen for WD with OMM or OFSM is daily IV ceftriaxone or penicillin G for two weeks, followed by TMP-SMX twice a day for a year. However, chloramphenicol, TMP-SMX, tetracycline, erythromycin, and ceftriaxone are all antibiotics that can cross the blood-brain-barrier and have been found to be effective in WD with CNS manifestation. The minimum length of antibiotic treatment is unclear, but continued therapy for 12+ months can decrease risk of relapse.
Course & Outcome
When diagnosed, Whipple’s disease should be treated with chronic antibiotic therapy. If left untreated, the disease is fatal.
We recommend that all patients diagnosed with WD receive a neuro-ophthalmologic evaluation.
Video: A brief video (2:46) narrated by Shirley Wray, M.D., Ph.D, FRCP showing a patient with OMM (used with permission from NOVEL): http://www.kaltura.com/index.php/extwidget/preview/partner_id/797802/uiconf_id/27472092/entry_id/0_yeuyrjyj/embed/auto
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