Oculomasticatory Myorhythmia

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Identifier 042-1
Title Oculomasticatory Myorhythmia
Creator Shirley H. Wray, MD, PhD, FRCP
Contributors John Selhorst, MD, Saint Louis University, St. Louis, Missouri
Affiliation (SHW) Professor of Neurology, Harvard Medical School; Director, Unit for Neurovisual Disorders, Massachusetts General Hospital, Boston, Massachusetts
Subject Somnolence; Supranuclear Paralysis of Up and Downgaze; Pendular Vergence Oscillations; Oculomasticatory Myorhythmia; Tropheryma Whippelii - Infection; CNS Whipple's Disease; Supranuclear Paralysis of Up and Downgaze Infection - Whipple's Disease; Oculomasticatory Myorhythmia (Whipple's)
History This case, previously reported in 1986, is published courtesy of John Selhorst, M.D., Saint Louis University School of Medicine, St. Louis, MO. (4) The patient is a 46 year old man who, over a period of six months, lost the ability to read and complained of excessive somnolence, occasional urinary incontinence, and recent 6-kg weight loss. A disabling, seronegative, non-deforming migratory arthritis had developed three years earlier. Gastrointestinal symptoms and fever had not occurred. Family History: Negative for neurological or arthritic disease. Neuro-ophthalmological examination: Visual acuity 20/50 right eye, 20/100 left eye Mild exposure keratitis, No uveitis by biomicroscopy Normal pupil reflexes Normal fundus exam Eye movements: 1. Mild bilateral ptosis 2. 1 Hz smooth rhythmic convergence and divergence oscillations in primary gaze 3. Slow hypometric horizontal volitional saccades slightly restricted. 4. Rotation-induced horizontal eye movements full, compensatory saccades absent. 5. Supranuclear paralysis of vertical gaze 6. Voluntary vergence movements were disrupted by the continuous oscillations. Additional signs: Rhythmic elevation and depression movements of the mandible due to concurrent contractions of the masticatory muscles. The rhythmic jaw movements were synchronous with the ocular oscillations. Both the eye and jaw movements were continuous during the day, persistent in sleep, and unaltered by environmental stimuli. Palatal myoclonus was never observed. Hematological Studies: Sedimentation rate 87 mm/per hour Circulating immune complexes Raji cell, C1-Q binding markedly elevated. Serum immunoelectrophoresis mildly increased IgA and IgG, no monoclonal peaks Lumbar Puncture: Cerebrospinal fluid 1 WBC, Protein 41mg/dl, Glucose 49 mg/dl, IgG/albumin ratio 0.40 (normal <0.25) EEG: Normal. Visual, auditory and somatosensory evoked potentials: normal. Brain CT: Normal MRI and Angiograpy: normal. Diagnosis: Dr. Selhorst made a diagnosis of oculomasticatory myorhythmia (OMM) and suspected Whipple's disease. Intestinal Biopsy: showed normal duodenum, a site often not involved in Whipple's disease. A search of the literature, however, brought to Dr. Selhorst's attention DeJonghe's report in 1979 of a man with Whipple's disease and cerebral symptoms. DeJonghe gave little attention to the movement disorder, but close review of the original report of DeJonghe's patient by Van Bogaert some 16 years earlier revealed an eye movement disorder consistent with OMM. Pathology Slides: Dr. Selhorst prevailed upon the GI attending to obtain a fluoroscopically guided biopsy of the duodenal-jejunal junction that proved positive for Tropheryma whippelii (T. whippelii) Whipple's disease. Figures 1 and 2 are sections from a biopsy of the duodenal jejunal junction stained with periodic acid Schiff (PAS) that show well-preserved intestinal villi with dilated lymphatics (large empty areas) and PAS positive staining of fat globules in the mucosa and more importantly bacterium digested within submucosal macrophages and the Tropheryma whippelii bacterium digested within the macrophage. Figure 3A shows a PAS-stained multinucleated giant cell (open arrow) and macrophages (dark arrow). Figure 3B is an electron microscopic image of intracellular bacilli in longitudinal section (closed arrows) and in cross-section (open arrows)). Treatment: The patient was treated intravenous penicillin (2 million units every 4 hours) for 14 days and simultaneously with oral trimetho- prim/sulfamethoxazole (TMP/SMX) (160 mg/800 mg., 3 x daily) for seven weeks. Trials of oral trihexyphenidyl (ranging to 16 mg daily), oral clonazepam (4 mg daily), and oral prednisone (60 mg daily) were ineffective in reducing the constant movements and deteriorating status. Prednisone had no effect on the persistent arthralgias. TMP/SMX was discontinued after two months, and oral tetracycline was begun at a dose of 250 mg. 4x daily. The patient's mentation began to improve several days after beginning tetracycline but the movement disorder persisted. He was discharged after 125 days of hospitalization on tetracycline and followed up over the next six months. Over this time there was a decrease in the amplitude of the eye and jaw movements and recovery of 10 degrees of vertical gaze. His previous lethargy and insomnia left him and mental function improved further. The arthralgias remitted completely. Follow-up ten years later found the man enjoying good health with a minimal amount of OMM.
Anatomy Massive infiltration of infected tissue by macrophages typifies Whipple's disease. The bacillus T whippelii multiplies in both monocytes and macrophages in Whipple's disease. The supranuclear paralysis of up and downward gaze suggests that infective process infiltrated the rostral nucleus of the medial longitudinal fasciculus and posterior commissure. The isolation of PVOs from all extraneous stimuli suggests that the pathological changes in the rostral midbrain probably surrounded, but did not destroy, a nearby component for convergence-divergence movements. The authors speculated that these unique movements can be produced only by an illness that microscopically interrupts ill-defined pathways interconnecting with brainstem oculomotor and trigeminal motor nuclei. The infinitesimal, multifocal nature of the Whipple's infection satisfies this structural requirement. The precise pathologic mechanism responsible for the PVOs and rhythmic masticatory myorhythmia is unknown.
Pathology The inflammatory reaction in the brain has a predilection for the periaqueductal gray matter, the hypothalamus and the hippocampus, and also the cerebral cortex, basal ganglia and cerebellum. The classic tool for diagnosing Whipple's disease is PAS staining of small-bowel biopsy specimens, which on light microscopical examination show magenta-stained inclusions within the macrophages of the lamina propria. (Figure 1 and 2). Several biopsy samples should be studied, because the lesions are often focal and sparse. Immunohistochemical staining with polyclonal rabbit anti-T Ripley antibody has been used to detect the organism in various tissues, and bodily fluids such as the aqueous humor and on blood monocytes, providing direct visualization of the bacilli. Polymerase chain-reaction (PCR) assays can be used to detect T-whippelii. The bacterial 16S ribosomal RNA sequence can be amplified directly from a variety of tissue(s) and body fluids including CSF, first with broad-range primers and then with specific primers. Now, on the basis of genome analysis, a new quantitative real-time PCR assay has been developed that targets repeated sequences of T-whippelii with substantially greater sensitivity than the earlier PCR assays and the same specificity. As with all PCR assays, it is critical to avoid contamination of the DNA sample and to include positive and negative controls to validate the test. It is important to pay attention to a positive PCR assay even when a duodenal biopsy specimen is negative on PAS staining. Autopsy case: A second patient with OMM reported by Schwartz et al died of pneumonia and came to autopsy. Her brain showed diffuse histological and electron microscopical evidence of Whipple's disease confined to the CNS, particularly involving the diencephalon and mesencephalon. Lesions in these areas were too extensive to allow for clinicopathological correlation with the eye movement disorder. The inferior olivary nuclei were normal.
Disease/Diagnosis CNS Whipple's Disease; Oculomasticatory Myorhythmia
Clinical This patient with CNS Whipple's disease appears cachectic and somnolent. He has: • Complete supranuclear paralysis of up and downgaze. • Slow pendular vergence oscillations (PVOs) synchronized with • Concurrent contractions of the masticatory muscles which led to the diagnosis of oculomasticatory myorhythmia. The eye movements, recorded with binocular electrooculograms over a band width 0-40 Hz, showed • Vergence oscillations to approximately 20 degrees amplitude with a frequency variation between 0.8 and 1.2 Hz and duration of 400 to 600 mseconds. • An analysis of peak velocities (15 to 200 degrees/second) with respect to peak amplitude (5 to 25 degrees) revealed dynamics characteristic of normal vergence movements. Electromyogram recordings of the masseter and genioglossus muscles were made and superimposed on the eye movement recording to show that discharges of muscle potentials are synchronous with the convergence phase of the oscillation. (See Figure 4, which illustrates Figure 3 from Schwartz MA et al. Ann Neurol 1986;20:677-683.) Conclusions from the analysis of eye movement recordings 1. PVOs are smooth rather than saccadic and have the velocity characteristics of normal convergence and divergence eye movements. Despite the absence of other components of the near triad (miosis and accommodation), the disorder retains certain features characteristic of normal vergence movements. 2. The eye movements are disjunctive, and furthermore the peak velocities achieved for various amplitudes are typical of normal vergence movements. 3. The pathological alterations resulting in PVO implicate a separately functioning, physiologically normal vergence system within the brainstem. 4. The continuous nature of PVOs distinguishes them from the nystagmus that occurs with Parinaud's syndrome, which is episodic and provoked by voluntary saccadic eye movements, especially attempted upgaze. 5. In cerebral Whipple's disease the abnormal eye movements have been ascribed to oscillations of the vergence system; hence the term pendular vergence oscillations. PVOs may represent a definitive neuro-ophthalmic sign of Whipple's disease. Oculomasticatory myorhythmia (OMM) is pathognomonic of Whipple's disease and thought to be a form of segmental rhythmic myoclonus of the brainstem involving ocular and masticatory segments of the midbrain and upper pons and, less apparently, segments of the lower pons and medulla. Selhorst et al concluded that patients with OMM should be treated presumptively for Whipple's disease of the central nervous system, even if a jejunal biopsy is normal.
Presenting Symptom Excessive sleepiness
Ocular Movements Supranuclear Paralysis of Up and Downgaze; Pendular Vergence Oscillations; Oculomasticatory Myorhythmia
Neuroimaging See ID932-1
Treatment See above
Etiology Infection with Tropheryma whippelii
Supplementary Materials Oculomasticatory Myorhythmia: https://collections.lib.utah.edu/details?id=2174220
Date 1986
References 1. Buttner-Ennerver JA, Buttner U, Cohen B. Baumgartner. Vertical gaze paralysis and the rostral interstitial nucleus of the medial longitudinal fasciculus. Brain 1982;105:125-149. http://www.ncbi.nlm.nih.gov/pubmed/7066670 2. DeJonghe P, Martin JJ, Budka H, Ceuterick C. Cerebral manifestations of Whipple's disease. Acta Neurol Belg 1979;79:305-313. http://www.ncbi.nlm.nih.gov/pubmed/94229 3. Leigh RJ, Zee DS. Diagnosis of Nystagmus and Saccadic Intrusions. Ch 10:475-558. In: The Neurology of Eye Movements. 4th Ed. Oxford University Press, New York 2006. 4. Schwartz MA, Selhorst JB, Ochs AL, Beck RW, Campbell WW, Kim Harris J, Waters B, Velasco ME. Oculomasticatory myorhythmia: A unique movement disorder occurring in Whipple's Disease. Ann Neurol 1986;20:677-683. http://www.ncbi.nlm.nih.gov/pubmed/2434019 5. VanBogaert L, Lafon R, Pages P, Lahauge R. Sur une encéphalite subaiguë non classable, principalement charactérisée par des myoythmies oculo-facio-cervicales. Rev. Neurol (Paris) 1963;109:443-453. 6. Whipple GH. A hitherto undescribed disease characterized anatomically by deposits of fat and fatty acids in the intestinal mesenteric lymphatic tissues. Bull. Johns Hopkins Hospital 1907;128:382-391.
Language eng
Format video/mp4
Type Image/MovingImage
Source Video Dr. Selhorst
Relation is Part of 932-1
Collection Neuro-Ophthalmology Virtual Education Library - Shirley H. Wray Neuro-Ophthalmology Collection: https://novel.utah.edu/Wray/
Publisher North American Neuro-Ophthalmology Society
Holding Institution Spencer S. Eccles Health Sciences Library, University of Utah
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ARK ark:/87278/s6tq8z4m
Setname ehsl_novel_shw
ID 188601
Reference URL https://collections.lib.utah.edu/ark:/87278/s6tq8z4m