Original ArticleHypertrophic Olivary Degeneration: Neurosurgical Perspective and Literature Review
Introduction
Hypertrophic olivary degeneration (HOD) develops because of insult to the dentato-rubro-olivary (DRO) pathway, also known as the Guillain-Mollaret triangle (GMT). Injury to this pathway can lead to various symptoms of cerebellar dysfunction, commonly palatal tremor or ataxia. Oppenheim first described hypertrophic olivary degeneration in 1887.1 In 1931, Guillain and Mollaret defined the DRO pathway, which includes the inferior olivary nucleus (ION) in the medulla oblongata, the dentate nucleus in the contralateral cerebellum, the red nucleus within the midbrain,2 and the interconnecting fibers (Figure 1). Disruption of the afferent neuronal impulses to the inferior olivary complex results in transsynaptic degeneration, which initially causes hypertrophy of the inferior olivary nucleus, termed HOD, followed by atrophy in the long term.3
Afferent fibers of the dentate nucleus traverse the superior cerebellar peduncle to the contralateral red nucleus. Originating in the red nucleus, fibers of the rubro-olivary tract reach the ION via the central tegmental tract. The ION conveys impulses via climbing fibers within the inferior cerebral peduncle to Purkinje cells in the contralateral cerebellar cortex. The Purkinje cells then convey afferent fibers to the ipsilateral dentate nucleus, completing the GMT. Consequently, the location of insult to the GMT will influence the laterality of HOD.
Although pathologic changes and MRI findings in HOD have been well defined, the relationship between the inciting lesion, onset of clinical symptoms, and disease progression are yet to be explained. In this study, 16 cases of HOD following posterior fossa or brainstem injury were evaluated. Symptomatic HOD can complicate the recovery of patients with posterior fossa or brainstem lesions. In addition, most of the case reports, and a limited number of case series, have been exclusively published in radiology, pathology, or neurology journals with rare case reports in the neurosurgical literature. Therefore, the main objective of this study was to evaluate clinical and imaging findings in patients with HOD, which can complicate patient recovery, and to draw attention of neurosurgeons to this rare but significant degenerative process by performing an extensive literature review.
Section snippets
Materials and Methods
The clinical imaging PACS database at our institution, a tertiary referral center, was searched for head MRI reports generated during the previous 15 years, in which the terms “hypertrophic olivary degeneration” or “HOD” were used. After institutional review board (20150209) approval was obtained, 16 patients (8 male and 8 female) with T2-weighted signal abnormality of the inferior olivary nucleus, consistent with HOD, were identified and included in a retrospective review of clinical symptoms
Results
Of the 16 patients included in this study, 7 (43.7%) patients developed HOD following neurosurgical resection of a posterior fossa tumor, including 3 pilocytic astrocytomas, 2 medulloblastomas, 1 high-grade glial tumor and 1, metastatic neuroendocrine carcinoma. Six (37.5%) patients developed HOD as a sequela of a known cavernous malformation, for which 1 patient underwent resection after subsequent multiple hemorrhages. Of the 3 remaining patients, 2 patients (12.5%) had traumatic brain injury
Etiopathology
Hypertrophic olivary degeneration is a rare disorder caused by brainstem or posterior fossa injury that disrupts the DRO pathway. Disruption of the afferent neuronal impulses to the inferior olivary complex causes transsynaptic degeneration, in which neuronal vacuolation and degeneration, demyelination, and subsequently glial cell hypertrophy occur.4, 5, 6 These cellular changes result in hypertrophy of the olivary nuclei, differentiation of receptor distribution, and abnormal neuronal
Conclusion
In this retrospective review, the most common etiologies of HOD were posterior fossa tumors and cavernomas. Although the majority of the patients included in this study did not have symptoms directly attributable to HOD, the course of recovery from the inciting pathology was complicated in almost one quarter of patients. Thus, it is important that neurosurgeons are able to identify the characteristic clinical and imaging manifestations of HOD, which can complicate the recovery of patients with
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2019, World NeurosurgeryCitation Excerpt :Hypertrophic olivary degeneration (HOD) is a rare neurological condition of trans-synaptic degeneration caused by disruption of the dentatorubro-olivary pathway, otherwise known as the Guillain-Mollaret triangle.1-3 The etiology of the primary lesion includes vascular disease, trauma, multiple sclerosis, and brainstem tumor.3-5 We experienced 2 remarkably similar cases of brainstem lymphoma, which developed HOD, and related oculopalatal or palatal tremor after treatment of the primary lesion.
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2019, World NeurosurgeryCitation Excerpt :Tumors and cavernous malformations were found to be the most frequently reported neurosurgical lesions that culminate in hypertrophic olivary degeneration.10 Furthermore, hypertrophic olivary degeneration was often noticed by 6–12 months following the initiating event.10 The patient reported here followed a similar time frame with radiologic findings initially becoming apparent 1 year after tumor resection.
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Conflict of interest statement: The authors declare that the article content was composed in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.
Mehmet Resid Onen and Kelli Moore contributed equally to this work.