Post-traumatic Hypertrophic Olivary Degeneration with Palatal Myoclonus–A Case Report

Introduction

Hypertrophic olivary degeneration (HOD), caused by injury to the dentato-rubro-olivary pathway, also known as the Guillain-Mollaret triangle (GMT), is a rare form of transsynaptic degeneration. The GMT is composed of 3 main neuroanatomic structures, namely, the ipsilateral red nucleus, inferior olivary nucleus (ION), and the contralateral dentate nucleus (Figure 1). ¹ Previous studies have shown that injury to the GMT and its associated pathways have led to hypertrophy of the ION and is characterized by hyperintensities of the ION on T2-weighted and fluid-attenuated inversion recovery (FLAIR) magnetic resonance imaging (MRI) sequences.^1,2 Contradictory to traditional neural physiology, when the afferent pathway leading to the ION is damaged, there is an increase in the volume because of an increase in astrocytes within the olivary body, and thus, this loss of neuronal input leads to hypertrophy rather than atrophy. ¹

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Figure 1.

Guillain-Mollaret Triangle This illustration depicts the anatomic relationship of the Guillain-Mollaret Triangle, which comprises the red nucleus, the dentate nucleus, and the inferior olivary nucleus. It also highlights the connecting pathways, including the central tegmental tract, dentatorubral tract, and the inferior cerebellar peduncle.

HOD often presents with palatal myoclonus, although the exact pathophysiology is not fully appreciated. Palatal myoclonus, often called palatal tremor, is an involuntary, rhythmic, and oscillatory movement of the soft palate that can be subcategorized into essential and symptomatic subtypes. 3 Essential palatal myoclonus has no known structural etiology, and patients often have a chief complaint of audible ear clicking, whereas the symptomatic form can be attributed to a structural lesion, usually involving the GMT.^4,5 Additionally, palatal myoclonus is renowned as one of the few movement disorders to persist during sleep. ⁴

Unfortunately, there are no current standardized treatment recommendations for either form of palatal myoclonus. However, there have been isolated case reports showing efficacy with different treatment modalities. Scott et al ⁶ described a patient with palatal myoclonus who responded well to sumatriptan, with cessation of involuntary palatal movement and audible clicking. Other research has shown that botulinum toxin ⁷ and carbamazepine ⁸ have also resulted in decreased symptomology of palatal myoclonus. Of note, each of these cases has touched on treatment options among adult patients. Thus, in this report, we present a pediatric case of HOD to better elucidate both a unique etiology (eg, posttraumatic) and effective management options for the palatal myoclonus present in this patient.

Case

A 7-year-old boy with a medical history of a motor vehicle accident with resultant epilepsy with electrographic-only seizures and right-sided spastic hemiplegia with developmental delays presented to the outpatient neurology clinic. Two years after the motor vehicle accident, the patient started experiencing quivering and twitching of the right side of his lip, palate, and neck, which persisted during sleep.

The initial MRI after symptom onset noted only moderate diffuse cerebellar atrophy. However, 9 months later, a repeat MRI noted a mild T2-weighted hyperintense signal within the inferior olivary nuclei suggestive of HOD (Figure 2). Additionally, the patient had a long-term video electroencephalogram (EEG) that captured the abnormal facial twitching with audible palatal clicking that was not associated with any corresponding electrographic changes.

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Figure 2.

An Axial T2-weighted MRI of the Brain This image demonstrates significant atrophy of cerebellar hemispheres and subtle T2 hyperintensity signal noted in the inferior olivary nucleus suggestive of hypertrophic olivary degeneration in a 7-year-old boy with palatal myoclonus

In light of his history of epilepsy, multiple antiseizure medications were attempted, including clobazam, lacosamide, and levetiracetam, but none of these showed long-term efficacy. Subsequently, the patient was started on carbamazepine with marked improvement of the palatal myoclonus. Initially, multiple dose adjustments were needed to maintain a therapeutic effect; however, the patient has now been stable on carbamazepine oral suspension 120 mg twice daily (9.2 mg/kg/d) for more than 6 months, which the patient reported to be tolerating well with no adverse effects.

This case demonstrates the anatomic importance of the Guillain-Mollaret triangle (GMT). Specifically, efferent fibers from the dentate nucleus ascend via the dentatorubral tract of the superior cerebellar peduncle, decussating just inferior to the red nucleus without synapsing, before continuing to the ION. The efferent fibers of the ION then cross over to the contralateral dentate nucleus, completing the triangle. Therefore, the red nucleus represents a landmark, rather than acting as an active participant in the GMT. 1

Traumatic disruption of this pathway, due to the motor vehicle accident this particular patient experienced 2 years prior, resulted in subsequent palatal myoclonus. Zhang et al (2023) ⁹ described HOD as a dynamic and evolving process that can take months to years to progress. Even after MRI findings suggestive of HOD are apparent, the development of palatal myoclonus can also be variable in onset and can range from weeks to months, ¹⁰ with the median onset being 10-11 months following the primary lesion. ³ The pathogenesis of palatal myoclonus in relation to HOD is not completely understood. However, research has shown that the dentate nucleus is modulated via γ-aminobutyric acid (GABA) inhibition.¹⁰ When a lesion disrupts this inhibition, the ION neurons enlarge because of an increase in astrocytes. ¹ The delay in development of palatal myoclonus after insult can be attributed to the histologic crescendo of vacuolar degeneration, followed by neuronal and astrocytic hypertrophy, and culminating in the process of gliosis (Zhang et al, 2023). ⁹

Originally, the working differential diagnosis of the abnormal movements in this patient included epilepsia partialis continua given the patient's history of epilepsy. Epilepsia partialis continua is a rare epileptic condition characterized by intractable focal-onset seizures, often with preserved awareness. ¹¹ However, the EEG in this patient captured the abnormal facial movements with no electrographic correlates. Furthermore, multiple antiseizure medications (ASMs), including clobazam, lacosamide and levetiracetam, were attempted with minimal relief or change in frequency of the palatal myoclonus.

Nevertheless, carbamazepine, an anticonvulsant that modulates voltage-gated sodium channels, proved effective in the treatment of palatal myoclonus in this patient. However, during a literature review on the efficacy of carbamazepine in treating palatal myoclonus, conflicting case reports were identified. A case report by Sakai et al ⁸ documented clinical improvement with carbamazepine, whereas another report by Ferro and Castro-Caldas (1981) ¹² observed worsening of the tremor after initiating use of the medication. The reasoning behind this disparity is unclear, but may be attributed to the interindividual variability of pharmacodynamics and pharmacogenetics.

Some of the most common etiologies of HOD have been studied through case reports involving both adult and pediatric populations. However, pediatric cases are rare and are predominantly associated with posterior cranial fossa tumors.^13,14 In adults, causes include hemorrhage, infarct, vascular malformations (eg, cavernoma), and neoplasm. ¹ HOD occurring due to trauma is an incredibly rare etiology with only one other case reported in the literature, which occurred in a 27-year-old man. ¹⁵ To our knowledge, there have been no previous reports of posttraumatic HOD occurring in an individual younger than 18 years discovered during our literature review. Consequently, this case aims to contribute clinical insights to the literature that might encourage the advancement of the treatment of palatal myoclonus in the pediatric population.