Eggenberger, Eric DO; Cornblath, Wayne MD; Stewart, Donald H. MD
From the Michigan State University Colleges of Osteopathic Medicine and Human Medicine, Department of Neurology and Ophthalmology (EE), East Lansing, Michigan; University of Michigan, Departments of Ophthalmology and Neurology (WC), Ann Arbor, Michigan; and the Charlotte Eye Ear Nose and Throat Associates (DHS), Charlotte, North Carolina.
Manuscript received January 24, 2000; accepted April 24, 2001.
Address correspondence and reprint requests to Eric Eggenberger, DO, Associate Professor, Michigan State University Colleges of Osteopathic Medicine and Human Medicine, Department of Neurology and Ophthalmology, A217 Clinical Center, 138 Service, East Lansing, MI 48824-1313.
Oculopalatal myoclonus, perhaps more accurately described as oculopalatal tremor (OPT), consists of pendular nystagmus with palatal tremor. OPT typically presents in delayed fashion weeks to months after an acute brainstem lesion. Most reports describe continuous palatal tremor in association with vertical pendular nystagmus; however, variations have been noted to include monocular, horizontal or torsional nystagmus, and involvement of other branchial-derived muscles (1). Although patients with OPT often exhibit symptoms related to the acute lesion, the delayed sequelae are typically restricted exclusively to the eyes and palate. Cases of OPT at two institutions were reviewed for the presence of delayed-onset ataxia. We report three cases of OPT with associated delayed occurrence of progressive cerebellar system dysfunction producing disabling ataxia.
A 70-year-old man with hypertension experienced the sudden onset of dysarthria, mild left hemiparesis, dysphagia, and horizontal diplopia in February 1992. A computerized tomography (CT) scan of the brain revealed a 3 × 1-cm pontine hemorrhage. After rehabilitation, he improved neurologically with resolution of the diplopia within 3 months. By July 1992, he no longer required a cane, and by September 1992, he was able to ambulate independently and perform strenuous chores, such as carrying firewood on uneven ground and assisting (without any supportive devise) in the building of his daughter's barn. However, in early 1993, he experienced the insidious onset of primarily gait ataxia, which slowly progressed during 12 months by fall 1993. He required assistance with at least a single-point cane to maintain standing balance and ambulation, and he stopped driving in late 1993 because of new visual symptoms. These symptoms included the inability to read signs when traveling in a car; inability to read scrolling print, such as stock reports on television; and difficulty with visual tracking, such as reading a newspaper. On rare occasion, he noted oscillopsia, only with the OD closed. He was unable to ambulate without his wife's assistance by December 1993, and he began using a wheelchair when a walker became insufficient to maintain balance. Magnetic resonance imaging (MRI) in 1994 revealed bilateral high signal within the inferior olive on T2-weighted images and a 3 × 0.7-cm linear pontine abnormality consistent with residual blood products (primarily hemosiderin) (Fig. 1 and Fig. 2).
Initial neuro-ophthalmologic examination in January 1995 revealed normal afferent visual function. The motility examination documented asymmetric pendular, torsional nystagmus with a slight vertical component, greater in the OS. This nystagmus occurred in synchrony with palatal and respiratory muscle movements (as evidenced by a respiratory pattern punctuated by the superimposition of small amplitude rhythmic inspirations) with an estimated frequency of 2 to 3 Hz. Impaired suppression of the vestibular ocular reflex was observed in the horizontal plane bilaterally via rotary chair testing (patient gain at 50 degrees/s, 0.160 Hz was 0.43; normal < 0.14). A left hypertropia of 1 to 2 prism diopters was present in primary position and left gaze. Marked and disabling appendicular, axial, and gait ataxia was severe enough to confine the patient to a wheelchair. Ambulation required the full assistance of at least one person. Palatal tremor, as evidenced by external neck inspection, persisted in sleep, according to the patient's wife. Treatment trials with low-dose clonazepam (0.125 mg every day or every other day), gabapentin (100 mg every other night), and baclofen (2.5 mg every other night) failed because of sedation or increased ataxia, although the subjective sense of “throat fluttering” was diminished while on these medications.
A 50-year-old man developed sneeze-induced cephalgia in February 1985. A CT scan revealed a fourth ventricular mass, and subtotal resection via a suboccipital approach yielded a pathologic diagnosis of choroid plexus papilloma versus low-grade ependymoma. He received 40 Gy radiation to the brain with a 25 Gy boost to the posterior fossa and 21 Gy to the spinal axis. He did well until 1992, when he developed the insidious onset of dysarthria and ataxia involving the trunk and extremities. MRI revealed the unchanged appearance of a 7-mm fourth ventricular nodule. His dysarthria and ataxia progressed and blurred vision developed in 1993. Neuro-ophthalmologic evaluation in September 1994 revealed vision of 20/20 OU with normal contrast sensitivity, color vision, pupils, confrontational visual fields, biomicroscopy, and funduscopic examination. The motility examination was notable for vertical pendular nystagmus synchronous with palatal tremor, orthophoria, and full ductions OU. Review of a 1992 MRI revealed T2 hyperintensity within the inferior olive and the dentate nucleus. There were no white matter lesions elsewhere in the brain to suggest MRI-demonstrable radiation sequelae.
A 43-year-old woman with a past medical history of attention deficit disorder and obsessive–compulsive disorder developed a large subarachnoid hemorrhage related to the rupture of an aneurysm at the junction of the basilar and superior cerebellar arteries on April 26, 1993. Initial level of consciousness was depressed, consistent with Hunt and Hess grade III and Glasgow coma score in the 7 to 8 range. She required mechanical ventilation and intracranial pressure monitoring, and underwent ventriculostomy on April 28, 1993, for hydrocephalus. After clinical improvement, craniotomy was performed on May 19, 1993, and the aneurysm was successfully clipped as documented by a subsequent angiogram. Postoperatively, the patient noted diplopia secondary to a partial left oculomotor nerve palsy and an incongruous right superior quadrantanopia. In late summer 1993, the patient developed vertical oscillopsia.
Neuro-ophthalmologic examination in September 1993 revealed oculopalatal tremor, with pendular vertical eye movements OU. Palatal region tremor persisted in sleep, according to the patient's husband. MRI in October 1993 revealed an incidental posterior fossa arachnoid cyst, left inferior olive hyperintensity (Fig. 3), and multiple high-signal abnormalities in the white matter on T2-weighted images. Treatment with clonazepam and baclofen were successful in decreasing the oscillopsia. The patient noted the insidious onset of imbalance in the fall 1994, which progressively increased until she required a wheelchair for distance by spring 1995. MRI in November 1994 revealed unchanged high signal within the left inferior olive and bilateral high-signal lesions in the centrum semiovale. Examination revealed a wide-based ataxic gait with mild heel-to-shin and finger-to-nose difficulty. The ataxia stabilized by late 1995 and has not significantly changed with subsequent examinations to date.
Oculopalatal myoclonus was originally described by Spencer (2) more than 100 years ago. The term myoclonus is a misnomer when applied to these patients (1), and the palatal component has been more correctly labeled palatal tremor (3). The term symptomatic palatal tremor has been suggested in place of oculopalatal myoclonus in order to distinguish this entity from essential palatal tremor (4–7). Our report concerns symptomatic palatal tremor; however, this term fails to identify the source of greatest distress, namely pendular nystagmus. The term oculopalatal tremor more accurately describes the clinical phenomenology in these patients.
Oculopalatal tremor occurs as a late consequence following an acute brainstem lesion after a median range of 10 to 11 months (range from 0–49 months) (8,9). Case 2 in our series represents the longest reported interval (7 years) between the initial lesion and the development of OPT.
The pathophysiologic link of OPT to the triangle connecting the dentate nucleus, the contralateral red nucleus, and the inferior olive was proposed in 1931 (10). Several theories have been advanced to explain the tardive occurrence of OPT, with more recent focus on the inferior olive as a oscillatory rhythmic generator (4,11,12). Disruption of the gamma-aminobutyric acid (GABA)–ergic system that serves to inhibit electronic coupling of inferior olive neurons may result in hypersynchronous firing, thus producing OPT (13). Positron-emission tomography scanning in patients with palatal myoclonus has demonstrated increased glucose metabolism in the inferior olive, providing a functional imaging correlate for this theory (14). Histopathologic examination of the inferior olivary nucleus in patients with OPT demonstrates enlarged vacuolated neurons and enlarged astrocytes (pseudohypertrophy, or hypertrophic degeneration) with increased acetylcholinesterase products (15,16). MRI provides a radiographic correlate for this change, typically demonstrating hyperintensity within the inferior olive, which we have referred to as the “pimento sign” (Fig. 1 and Fig. 3) (Johnstone, Personal communication) (17).
Management of OPT with anticholinergics, benzodiazepine derivatives such as clonazepam, gabapentin, scopolamine, carbamazepine, 5-hydroxytryptophan, and baclofen, have produced variable success (18–20). The patient in case 1 in our series failed to benefit from trials with several of these agents, primarily because of drug intolerance, whereas the patient in case 3 obtained visual relief from combination therapy including clonazepam and baclofen.
Sperling and Herrmann (21) described two patients in 1985 with the spontaneous onset of progressive ataxia associated with palatal myoclonus that developed in the absence of an identifiable acute brainstem lesion. One of these patients had OPT with MRI-demonstrable inferior olive hyperintensity. These patients were distinguished by the absence of an identifiable acute lesion and one patient's lack of ocular involvement. Reports by Deuschl et al. (4–6) documented delayed ataxia in association with oculopalatal tremor. These authors focused on the contrast between four patients with essential palatal tremor and six patients with symptomatic palatal tremor plus nystagmus (4). Among the six patients with symptomatic palatal tremor, two patients experienced worsening of their symptoms during the months after the acute insult (patient 9 poststroke and patient 10 after brainstem cavernoma hemorrhage). Progression was characterized as “slight” in these two patients (although at least one of the patients became wheelchair-bound). The investigators felt that this delayed progression “. . . suggests cerebellar dysfunction may have progressed even with a monophasic central nervous system insult” (4). Our patients confirm this late-onset ataxia as a real and potentially disabling event after the development of OPT.
The delayed onset of ataxia or movement disorders without OPT has rarely been reported weeks to years after acute lesions, including generalized hypoxic–ischemic insult, stroke, or trauma (22–26). Traumatic brain-injured patients who developed subsequent movement disorders have generally suffered more serious injuries, as evidenced by their significantly lower Glasgow coma scores on admission. The presence of generalized cerebral edema on initial CT scanning was significantly associated with the later development of movement disorders in one report (27). The association between larger initial lesion size and delayed development of neurologic sequelae in these patients parallels our experience with OPT and tardive ataxia.
Oculopalatal tremor appears to occur on a spectrum as a delayed sequela in a minority of patients after acute brainstem lesions. The emergence of tardive ataxia may represent an extreme on this clinical expression. The delayed ataxia proved to be the most disabling feature in two of our patients (from cases 1 and 2). All three of our cases, clinically and radiographically, showed large bilateral acute brainstem lesions, suggesting that such characteristics, in addition to inferior olive sparing, are prerequisites for the development of delayed ataxia with OPT. The apparent rarity of OPT with tardive ataxia may be related to these unique lesion requirements. Often patients with such large bilateral brainstem lesions die acutely or the lesion destroys the inferior olive and accordingly fail to develop OPT. Among the subset of patients that develop OPT, tardive ataxia may be incomplete in expression, masked by a lesion acutely involving coordination, or attributed to a new lesion such as recurrent infarction. Clinicians should be cognizant of the possibility of worsening deficits, including gait ataxia in this patient population, especially among those patients with large bilateral acute lesions.
Our three cases of OPT are distinguished by the late onset of progressive extremity and gait ataxia consistent with cerebellar system dysfunction. Case 2 is also unique because it represents the longest reported delay between the acute lesion and subsequent development of OPT (7 years). It appears that larger, bilateral, yet nonfatal acute brainstem lesions that spare the inferior olive are a prerequisite for the development of OPT with tardive ataxia.
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