CASE REPORTS
Year : 2021 | Volume
: 4 | Issue : 1 | Page : 34--38
Oculopalatal tremor: Illustrative cases with a review of literature
Meenakshisundaram Umaiorubahan, Sreenivas Meenakshisundaram
Arunai Neuro Centre, Chennai, Tamil Nadu, India
Correspondence Address:
Dr. Sreenivas Meenakshisundaram
Arunai Neuro Centre, Majestic Apartments, Arcot Road, Saligramam, Chennai 600093, Tamil Nadu.
India
Abstract
Oculopalatal tremor (OPT) is a unique clinical sign characterized by involuntary movements of the soft palate in synchrony with ocular nystagmus, usually the pendular type. It is highly suggestive of and is a delayed complication of a brainstem lesion, often a stroke. The mechanism and clinical implications of OPT are still not fully elucidated and present a treatable complication of brainstem disease. We searched PubMed and Google Scholar for articles with keywords “Oculopalatal tremor.” Most relevant articles were reviewed, based on the number of citations and information was collated by both the authors. We present two cases of OPT which illustrate the clinical spectrum of OPT.
How to cite this article:
Umaiorubahan M, Meenakshisundaram S. Oculopalatal tremor: Illustrative cases with a review of literature.Ann Mov Disord 2021;4:34-38
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How to cite this URL:
Umaiorubahan M, Meenakshisundaram S. Oculopalatal tremor: Illustrative cases with a review of literature. Ann Mov Disord [serial online] 2021 [cited 2023 Jun 1 ];4:34-38
Available from: https://www.aomd.in/text.asp?2021/4/1/34/313934 |
Full Text
Key Messages:
The mechanism and clinical implications of oculopalatal tremor are still not fully elucidated
Oculopalatal tremor is a treatable complication of brainstem disease.
Oculopalatal tremor is of 2 types: midline and lateral. This usually, but not always, correlates to the location of the lesion.
Introduction
Oculopalatal tremor (OPT) is a unique clinical sign characterized by involuntary movements of the soft palate in synchrony with ocular nystagmus, usually the pendular type. It is highly suggestive of and is a delayed complication of a brainstem lesion, often a stroke. The mechanism and clinical implications of OPT are still not fully elucidated and present a treatable complication of brainstem disease.
Methodology
We searched PubMed and Google Scholar for articles with keywords “Oculopalatal tremor.” PubMed revealed 46 articles, whereas Google Scholar search returned 388 articles. Most relevant articles were reviewed, based on the number of citations and information was collated by both the authors.
Case 1
An 18-year-old male presented to the emergency with a history of neck trauma, following an accidental fall into a well. He was ataxic and dysarthria at presentation. Investigations revealed a dissection of the left vertebral artery and ischemia of the medulla. He was conservatively managed and discharged. On review, 18 months later, he was found to have palatal tremor, which was symmetrical. On further follow-up, 5 years later, he was found to have OPT, which was symmetric, with concurrent rhythmical movements of the perioral and frontal muscles. The vertical nystagmus was found to be exacerbated on closing his eyes. Imaging at this time revealed atrophy of the brainstem and cerebellum, with no signs of inferior olivary hypertrophy Figure 1]. His OPT did not respond well to drugs [Supplementary Video 1 [SUPPORTING:1]].{Figure 1}
Case 2
A 48-year-old man presented with unsteadiness, which increased on closing his eyes. He had a history of cerebellar infarct 8 months back. On examination, he was found to have asymmetrical palatal tremor with asymmetrical horizontal and torsional nystagmus which was more on the left. On closing his eyes, he was found to have an asymmetrical vertical nystagmus. Initial magnetic resonance imaging (MRI) had shown a left cerebellar infarct [Figure 2]. Repeat MRI could not be taken at the current visit due to claustrophobia. His OPT responded well to clonazepam [Supplementary Video 2 [SUPPORTING:2]].{Figure 2}
History
The first clinical description was made in 1886 by Spencer as “pharyngeal and laryngeal nystagmus” in a patient with a brain tumor.[1] The inferior olivary nucleus (ION) was found to be conspicuously enlarged in these patients. Such “hypertrophy” of the olive was reported by Oppenheim,[2] later Thomas,[3] and subsequently Marie and Guillain.[4] The Guillain Mollaret triangle was implicated as the site of lesion in 1931 in a landmark paper.[5] This triangle is formed by the contralateral dentate nucleus, the ipsilateral red nucleus, and the ipsilateral ION [Figure 3].{Figure 3}
Clinical Features
The synchronous eye movements are usually nystagmoid but can also be saccadic in nature. The nystagmus is typically vertical and pendular but can be horizontal and torsional. The abnormal eye movements can also be dissociative in the two eyes. The nystagmus can be unilateral or bilateral, symmetrical, or asymmetrical. Convergent-divergent nystagmus has been reported by Galvez-Ruiz et al.[6] The nystagmus in OPT was reported by Tilikete and Desestret[7] to be of lower (1–3 Hz) frequency, larger in amplitude, of higher velocity and more irregular than in patients with acquired pendular nystagmus.
The palatal tremor is usually of a low frequency (2–3 Hz) but can be faster too. The muscles affected can include those derived from branchial arches including the muscles of the palate, pharynx, larynx, eye, head, neck, and diaphragm.
Oscillopsia is almost universally reported by patients with OPT and is the subjective clinical manifestation of the abnormal eye movements. However, the palatal component is almost always a sign than a symptom. Some patients have been reported to develop ataxia and dysarthria later in the disease.
The causes of OPT are numerous but the commonest acquired cause is a brainstem stroke (60%–70%).[7] Among tumors, cavernous hemangiomas are the most frequent. Other causes include infection and inflammation, trauma, and demyelination. It is important to remember at this juncture that ION hypertrophy (without OPT) has been reported due to toxins (such as metronidazole, lithium, carbamazepine, and ciprofloxacin), and mitochondriopathies (Leigh syndrome). A rare degenerative cause is progressive ataxia with palatal tremor (PAPT).[6],[8] This can be both sporadic and familial.
Sporadic PAPT can present with gait, trunk, and limb ataxia along with dysarthria and non-specific cerebellar ocular motor dysfunction. MRI changes of olivary hypertrophy are commonly seen.
Familial PAPT is more complex and may present without olivary MRI changes. This has been associated with three main etiologies: Alexander’s disease, POLG mutation, and SCA 20.
Types of Oculopalatal Tremor
There are 2 distinct types of OPT described in the literature:
Midline OPT, with symmetrical bilateral palatal movements and symmetrical vertical nystagmus, which is suggestive of a degenerative etiology or a metabolic or toxic cause. In Case 1, as described above, a midline OPT was seen. This was probably due to secondary brainstem degeneration [Supplementary Video 1].
Lateral OPT, with asymmetrical or unilateral involvement of the palatal muscles with unequal vertical nystagmus and conjugate torsional movements, which is suggestive of a lateralized lesion which is probably acquired. In Case 2, as described above, a lateral OPT was seen, secondary to a brainstem stroke [Supplementary Video 2].
However recent studies have not shown a definite correlation between laterality of signs and site of lesion.[9] A study on a series of 22 patients found that unilateral OPT was almost always associated with unilateral lesions, whereas symmetric, bilateral OPT could be seen with either unilateral or bilateral lesions.
Pathophysiology
The pathophysiology of OPT has been a point of debate for a very long time. The key structure that is often implicated in the inferior olive and historically, there have been studies both favoring and opposing its role, at least primarily.
Does the Inferior Olive Play Any Role?
The muscles involved in OPT (as discussed before) are of branchial arch origin. But, the cerebellum and inferior olive, although somatotopically mapped, do not favor branchimeric musculature. Hence, Kane and Thach[10] postulated that palatal myoclonus was more likely to arise from the central tegmental tract lesions leading to denervation of the nucleus ambiguous. Moreover, ION shrinkage has been reported at autopsy even in those who had persistent clinical symptoms. Kim et al.[9] proposed the involvement of other nearby structures such as the neural integrators in the pontomedullary tegmentum or caudal inferior olive which could lead to vertical-torsional or horizontal pendular nystagmus. These experiments argue against ION as the sole source of OPT. But PET studies[11] after amelioration of OPT with clonazepam showed no decrease in ION activity (although cerebellar activity decreased).
To understand the pathophysiology of OPT, we need to understand the physiologic behavior of the ION neurons. Specific calcium ion channels (CaV 3.1 T-type) are expressed highly in ION neurons. Abnormal modulation of these calcium ion channels might contribute to abnormal oscillations in ION neurons. Moreover, in vitro the ION neurons have the capacity to oscillate spontaneously at 0.5–12 Hz, but respond best to current with frequencies of 3–6 or 9–12 Hz.[12] The interneuronal connection between the ION neurons is via dendrodendritic gap junctions which allows electrotonic coupling. This electrotonic coupling favors ION neuronal synchronicity and leads in vitro to spontaneous organization of synchronously oscillating clusters of neurons.
Action potentials from ION neurons travel up the climbing fibers to cause complex spikes in the Purkinje cells and the deep cerebellar nuclei.
When hypertrophy of the ION occurs, abnormal somatic gap junctions will also develop, thus increasing the strength of the electrotonic coupling and the development of synchronization. But the synchronized ION output is too small to induce noticeable ocular oscillations in physiologic studies. Hence these oscillations would need an amplification. This amplification is probably provided by the cerebellar cortex.
The critical cause is thought to be the removal of inhibition of the electrotonic gap junctions.[13],[14],[15],[16] Over a period of few weeks or months following the causative lesion, hypertrophy of ION nuclei occurs and the ION neurons enlarge due to the abnormal gap junctions established as stated above.[17],[18],[19],[20],[21] It is also of interest that the eye movement waveforms are different in each patient (in contrast to vestibular nystagmus).
The points that favor the involvement of the ION are as follows:
(a) Most OPT patients show ION hypertrophy
(b) The cerebellar signs occur opposite to the side of the abnormal ION
(c) OPT patients have abnormal motor learning (which requires an intact olivocerebellar connection)
(d) OPT frequency is within the range of the discharge from synchronous ION neurons
(e) ION hypertrophy occurs before OPT appears, and
(f) ION neurons can shrink and die over time, as does the OPT which can diminish or cease
The Dual Mechanism Model
Shaikh et al.[22] have postulated an oscillator-modulator model. This dual mechanism model could reproduce the basic features of OPT. With the use of simulations, it has been shown that reducing the influence of the cerebellar cortex on the oculomotor pathway leads to a reduction in the amplitude of the ocular tremor and makes it more periodic, but does not change the frequency. Reducing the coupling in the ION neurons also reduced the amplitude but again did not change their frequency. Hence, the dual-mechanism is plausible and consists of an oscillator––the tremor oscillations originate in the hypertrophic ION, and a modulator––the oscillations are amplified by learning in the cerebellum.
Neuroimaging
The changes are primarily seen in the ION. Initially, a hyperintensity is noticed on T2 or proton-density images (which can be seen as early as 1 week or up to several years later following the causative lesion). ION hypertrophy occurs over weeks or months. Hypertrophy may last only a few years, but the hyperintense signal is a permanent marker. The hyperintensity is due to neuronal hypertrophy, gliosis, increased water content, and attendant demyelination/ vacuolization. ION hypertrophy on MRI is caused by further astrocytic and neuronal changes. Ultimately, ION atrophy will occur due to neuronal and astrocytic death.[23],[24],[25] Other modalities of imaging such as PET-scan, fMRI.[26],[27] Diffusion tensor imaging and susceptibility weighted imaging have all been studied in small numbers and have all, in general, supported the role of dentate-olivary pathway dysfunction in the genesis of OPT. In Case 1, MRI did not show olivary hypertrophy and atrophy of the inferior olive was noted. As discussed above, atrophy of the ION may occur over time.
Treatment
Attempts to treat OPT are often frustrating. The response to many drugs is minimal if at all. But, some medicines have shown a reduction in the amplitude of the eye movements but do not affect the frequency.
Based on the dual mechanism hypothesis, treatment could be aimed at reducing ION output or decreasing the cerebellar output. The drugs that have been studied include:
a. Gabapentin––at doses of 300mg q.i.d––reduced the median eye speed and improved visual acuity[28],[29]
b. Mematine at doses of 10mg q.i.d––similar to gabapentin in a crossover trial[28],[29]
The other drugs that have been tried with limited or anecdotal success include baclofen, divalproex sodium, meclizine, primidone, and levetiracetam.
DBS of the red nucleus was attempted unsuccessfully in a single patient.[30]
Conclusion
OPT is a distinct clinical entity with diverse characteristics. Patient 1 could be followed up for a significant period of time and the evolution of the OPT to involve many other muscles was noticed. Patient 2 had a lateralized palatal tremor with a different eye movement. An interesting finding in both the patients was the exacerbation of the eyelid and facial muscles on voluntary closure of the eyes. This is a feature not described in the literature. Even the movement of the eyes could be well made out through the closed eyelids. It would be important for the examining clinician to look for this to make out the full extent of the abnormal movements.
The dual mechanism hypothesis appears to be plausible, more so due to the response to gabapentin shown by patients. More specific therapies are bound to be found as we understand the mechanisms better and pharmacotherapy becomes more targeted.
Financial support and sponsorship
Nil.
Conflicts of interest
There are no conflicts of interest.
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