Elsevier

World Neurosurgery

Volume 112, April 2018, Pages e763-e771
World Neurosurgery

Original Article
Hypertrophic Olivary Degeneration: Neurosurgical Perspective and Literature Review

https://doi.org/10.1016/j.wneu.2018.01.150Get rights and content

Highlights

  • HOD may complicate the recovery of patients with posterior fossa or brainstem lesions.

  • Posterior fossa tumors and cavernomas are the most common etiology of HOD in this series.

  • Neurosurgeons who are treating lesions involving dentate-rubro-olivary tract should be aware of clinical and imaging signs of HOD.

Background

Hypertrophic olivary degeneration (HOD) occurs because of posterior fossa or brainstem lesions that disrupt the dentato-rubro-olivary tract, well known as the Guillain-Mollaret triangle. Clinical and radiologic hallmarks of this condition are palatal myoclonus and T2 hyperintensity of the inferior olivary complex on magnetic resonance imaging (MRI), respectively. Because symptomatic HOD can complicate the recovery of patients with posterior fossa or brainstem lesions, the purpose of this study is to evaluate clinical and imaging findings of patients with HOD.

Methods

Sixteen patients (8 female and 8 male) with a mean age of 40.7 years, (range, 5–83 years) years were included in this study based on clinical symptoms and MRI findings.

Results

We reviewed the clinical and imaging findings in 16 cases of HOD at our institution. Seven patients (43.7%) had posterior fossa tumors, 6 patients (37.5%) had cavernoma, 2 patients (12.5%) sustained traumatic brain injury, and only 1 patient (6.2%) had cerebellar infarction. Posterior fossa surgery was performed in 13 (81.2%) of these patients. HOD was detected a mean of 7.2 months (range, 0.5–18 months) after surgery or primary neurologic insult. Unilateral HOD was observed in 10 patients (62.5%), while bilateral HOD was observed in only 6 patients (37.5%). Seven patients (43.7%) were asymptomatic for HOD, whereas 5 patients (31.2%) had symptoms attributable to HOD. Two patients died because of primary tumors, although mean follow-up after detection of HOD on MRI was 52.2 months (range, 1–120 months) in the remaining 14 patients. In these cases, no change in clinical symptoms or imaging findings was detected during follow-up.

Conclusions

In this series, posterior fossa tumors and cavernomas were the most common causes of HOD. Although most of the patients with HOD remained asymptomatic, HOD complicated the course of recovery in almost one quarter of the patients included in this study. Neurosurgeons should be aware of HOD, which has characteristic clinical and imaging findings. In addition, HOD can complicate the recovery of patients with disruption to the dentato-rubro-olivary tract.

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

References (32)

  • H.U. Oppenheim

    Olivendegeneration bei Atheromatese der basalen Himarterien

    Berl Klin Wschr

    (1887)
  • G.M.P. Guillain

    Deux cas de myoclonies synchrones et rhythmes velo-pharyngo-layrngo-oculo-diaphragmatiques

    Rev Neurol

    (1931)
  • M. Goyal et al.

    Hypertrophic olivary degeneration: metaanalysis of the temporal evolution of MR findings

    Am J Neuroradiol

    (2000)
  • J.R. Anderson et al.

    Hypertrophic olivary degeneration and Purkinje cell degeneration in a case of long-standing head injury

    J Neurol Neurosurg Psychiatry

    (1973)
  • G. Giaccone et al.

    Progressive supranuelearpalsy withhypertrophyof the olives: an immunocytochemical study of the cytoskeleton of argyrophilic neurons

    Acta Neuropathol

    (1988)
  • N. Goto et al.

    Olivary enlargement: chronological and morphometric analyses

    Acta Neuropathol

    (1981)
  • M. Hornyak et al.

    Hypertrophic olivary degeneration after surgical removal of cavernous malformations of the brain stem: report of four cases and review of the literature

    Acta Neurochir (Wien)

    (2008)
  • K. Ogawa et al.

    Pathological study of pseudohypertrophy of the inferior olivary nucleus

    Neuropathology

    (2010)
  • C.C. Phatouros et al.

    Hypertrophic olivary degeneration: case report in a child

    Pediatr Radiol

    (1998)
  • D.C. Aberfeld

    The hypertrophic degeneration of the olives

    Acta Neurol Scand

    (1966)
  • D. Cachia et al.

    A rare presentation of hypertrophic olivary degeneration secondary to primary central nervous system lymphoma

    JAMA Neurol

    (2013)
  • C.M. Carr et al.

    Frequency of bilateral hypertrophic olivary degeneration in a large retrospective cohort

    J Neuroimaging

    (2014)
  • I. Crosbie et al.

    Teaching NeuroImages: hemorrhagic cavernoma with secondary development of hypertrophic olivary degeneration

    Neurology

    (2013)
  • A. Dinçer et al.

    Diffusion tensor imaging of guillain-mollaret triangle in patients with hypertrophic olivary degeneration

    J Neuroimaging

    (2011)
  • D.H. Harter et al.

    Hypertrophic olivary degeneration after resection of a pontine cavernoma: case illustration

    J Neurosurg

    (2004)
  • T. Hayashi et al.

    Hypertrophic olivary degeneration after traumatic subarachnoid hemorrhage

    Int Med

    (2014)
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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.

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