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Show Journal of Neuro- Ophthalmology 19( 4): 229- 231, 1999. © 1999 Lippincott Williams & Wilkins, Inc., Philadelphia Opsoclonus in a Patient With Cerebellar Dysfunction Maurizio Versino, M. D., Andrea Mascolo, M. D., Giovanni Piccolo, M. D., Roberto Alloni, and Vittorio Cosi, M. D. After two days of malaise, headache, nausea, and vomiting, a 26- year- old man suddenly developed opsoclonus and stance and gait ataxia, without myoclonus. Having excluded a paraneoplastic etiology, we assumed that the disorder was probably related to a viral infection. Spontaneous resolution occurred in about two months. Opsoclonus became flutter dysmetria and then resolved. Saccadic eye movement recording disclosed the occurrence of hypermetria, increased velocity, and delayed latency, which also resolved. In this patient, the correspondence between clinical and ocular motor abnormality courses suggests a transient cerebellar dysfunction as the possible pathophysiologic mechanism for opsoclonus. Key Words: Cerebellum- Opsoclonus. Opsoclonus consists of involuntary conjugate saccadic oscillations in all directions, without intersaccadic interval. Onset can be gradual or abrupt, and oscillations can be as large as 30- 40° ( mean: 10- 20°); they may be continuous, or may present as series of 2- 13- Hz bursts lasting 5- 7 seconds ( 1). They may persist in sleep, and may be associated with other symptoms and signs, including myoclonus, cerebellar signs, and decreased mental status ( 2). About 50% of cases are idiopathic, and probably include some undiagnosed viral encephalitis. About 20% of cases are paraneoplastic ( 3), and other causes include infectious, metabolic, and toxic diseases ( 2). The pathophysiology of opsoclonus, however, is still unclear ( 4). We describe a patient who developed an opsoclonus; the course of clinical and ocular motor signs suggested a cerebellar impairment. CASE REPORT A 26- year- old man suddenly complained of " shaking vision" and of stance and gait difficulties after two days of malaise, severe headache, nausea, and vomiting. Initially, he was admitted to a local hospital with a diagnosis of possible meningoencephalitis. Shortly after admission, he developed a psychomotor agitation that remitted Manuscript received March 29, 1999; accepted August 24, 1999. From the Dipartimento Scienze Neurologiche, Universita di Pavia ( M. V., R. A., V. C.); and Fondazione Istituto Neurologico C. Mondino, Pavia ( M. V., A. M., G. P., V. C.), Italy. Address correspondence to Maurizio Versino, Dipartimento Scienze Neurologiche, Universita di Pavia, Fondazione Istituto Neurologico C. Mondino, Via Palestro 3- 27100, Pavia, Italy. with neuroleptic and benzodiazepine administration. He was treated with ceftriaxone and acyclovir without significant improvement of neurologic symptoms. On admission to our center, about 10 days after symptom onset, he had a mild degree of agitation but he was alert and well oriented. Neurologic examination revealed: opsoclonus, which was mainly horizontal not enhanced by fixation and reduced in lateral gaze; generalized hypotonia; truncal ataxia and an inability to walk or to stand without human support. There was no myoclonus. Routine laboratory studies disclosed normal values, with the exception of creative phosphokinase level ( 4,150 U/ L) with normal motor strength, probably related to the psychomotor agitation mentioned above, which normalized before discharge. The serum antibody levels for herpes simplex virus, cytomegalovirus, Epstein Barr virus, hepatitis B virus, and human immunodeficiency virus were normal. The level of urinary catecholamines was normal. Cerebrospinal fluid examination only showed a mild lymphocytic pleocytosis ( 25 cells/ mm3) with normal albumin and IgG content, normal IgG index, and polyclonal distribution of both CSF and serum IgG. Neither serum nor CSF showed any immunohisto-chemical reactivity against rat cerebellar tissue. Results of computed tomography and MRI of the head, chest radiograph, and thyroid and testicle echography were normal. Electroencephalography showed bilateral frontal beta activity, sporadic bilateral anterior theta waves, and periods of drowsiness. The patient was treated with steroids ( 6- methylpred-nisolone 250 mg i. v., for 10 days) and with clonazepam ( 4 mg/ day), and slowly improved. Before discharge, about 40 days from symptom onset, he still showed mild truncal, stance, and gait ataxia; opsoclonus had become flutter dysmetria ( Fig. 1), i. e., a transient burst of horizontal back- to- back saccades at the end of each voluntary or reflexive saccade. One month later, he was symptom free, and neurological examination showed nothing abnormal, with the exception of some saccadic oscillations still present at the end of sac-cades, which disappeared only 4 months later. After 1 year, the only remaining detectable signs were some saccadic oscillations at the end of divergence eye movements. We were able to study reflexive saccades only shortly before discharge and at the subsequent outpatient check- 229 230 M. VERSINO ETAL. 5 degrees 400 ms FIG. 1. The left ( continuous line) and right ( dotted line) eye tracings of a 10° leftward saccade recorded monocularly with the infrared reflection technique ( Skalar IROG system) at 40 ( A), 100 ( B), 220 ( C), and 580 ( D) days from symptom onset. Saccades proved to be hypermetric, and ended with flutter dysmetria in ( A); this pattern was clearly attenuated in ( B), and disappeared in both ( C) and ( D). ups. Figure 1 shows the evolution of flutter dysmetria, and Table 1 reports the saccade parameters. Saccade parameters were obtained by binocular electrooculographic recordings with a reflexive saccade paradigm ( see ref. 10 for more details). In each recording session, the patient made about 56 saccades from primary position and target displacement ranged from 5 to 35°. In the first recording session, made shortly before discharge, we were able to collect only 20 saccades, mainly for 5 and 10° target displacements. When measured shortly before his discharge, saccades were mainly hypermetric in all directions, and showed a delayed latency, whereas peak velocity and duration were " supernormal." After 2 months, saccades were only slightly hypermetric, and were normal 4 months and 1 year later. DISCUSSION Our patient presented an opsoclonus associated with other neurologic signs that were probably viral in origin, which spontaneously resolved themselves. It is not yet established whether the cerebellum or the brainstem, or both, are involved in the pathophysiology of opsoclonus ( 4). In our patient, the disappearance of flutter dysmetria, which followed opsoclonus, matched the saccade shift from hyper- to normometria. This suggests a reversible dysfunction involving the cerebellar fastigial nuclei ( FN), which tailor saccade accuracy and control saccade acceleration and deceleration through connections to brainstem ocular motor structures ( 5). The latter include the inhibitory projections from caudal FN to omnipause neurons, which in turn tonically inhibit the saccade burst generator to prevent saccadic intrusions ( 6), and gate the burst generator activity during saccades. Accordingly, a miscontrol on omnipause neurons by FN may explain saccade oscillations ( 7), saccade dysmetria, ( 8) and, possibly, the increased saccade velocity detectable at the first saccade recording session ( 9). The latter finding implies a cerebellar involvement in saccade dynamic, but it must be considered cautiously because, at the first recording session, the patient was still bothered by the oscillopsia he complained of at the end of each saccade, and we were able to collect 20 saccades, most of which for small target displacement. However, a recent article showed that saccade velocity was reduced by a lesion affecting the oculomotor vermis but not the FN TABLE 1. Saccade parameters at different times from symptom onset Time from onset ( days) 40 ( discharge) 100 220 580 Normal range ( 95% confidence interval) Duration ( mos) 61.05 83.11 93.96 91.72 63.4- 93.1 Peak velocity ( degrees) 1,010 584 450 469 397- 915 Gain 2.68 1.03 0.88 0.89 0.87- 1.03 Latency ( mos) 322.7 259.5 230.8 221.9 176- 321 Duration is the theoretical saccade duration for 20° saccade amplitude derived from the amplitude- duration relationship computed from the patient's duration and amplitude raw data by means of linear regression. Peak velocity corresponds to the maximum ( saturation) peak velocity value, for a theoretical saccade of infinite amplitude, derived from the amplitude- peak velocity relationship computed from the patient's peak velocity and amplitude raw data by means of linear regression. Gain is the mean value of the ratios of real to desired saccade amplitude ( i. e., target displacement). Latency is the mean value of the delays from target displacement and saccade onset. ./ Neiiro- Ophlhalmol, Vol. 19, No. 4, 1999 CEREBELLAR OPSOCLONUS 231 ( 11). This datum is in keeping with our finding because the oculomotor vermis outflow consists of inhibitory projections to the FN; accordingly, a lesion involving the FN should increase saccade velocity. In our patient, the occurrence of hypermetric saccades suggests a FN impairment ( 8). Moreover, FN impairment may explain the truncal, stance, and gait ataxia, because the rostral FN projects to the vestibular nuclei. Finally, the initial saccade latency delay and the subsequent latency reduction can be explained by the titration of clonazepam. We conclude that this case of opsoclonus, which was not associated with a cancer and recovered, can be considered a cerebellar dysfunction on the basis of the evolution of other concomitant ocular motor and clinical signs. REFERENCES 1. Buttner U, Straube A, Handke V. 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