Professional Documents
Culture Documents
Hypertrophic Olivary Degeneration in A Child Following - 2014 PDF
Hypertrophic Olivary Degeneration in A Child Following - 2014 PDF
©AANS, 2014
Radiology and Radiological Science; and 2Division of Pediatric Neurosurgery, The Johns Hopkins School of
Medicine, Baltimore, Maryland
Hypertrophic olivary degeneration (HOD) is a dynamic process caused by disruptive lesions affecting compo-
nents of the Guillain-Mollaret triangle (GMT). The authors applied diffusion tensor imaging (DTI) to investigate
longitudinal changes of the GMT components in a child with HOD after neurosurgery for a midbrain tumor. Diffu-
sion tensor imaging data were acquired on a 1.5-T MRI scanner using a balanced pair of diffusion gradients along
20 noncollinear directions 1 day and 3, 6, and 9 months after surgery. Measurements from regions of interest (ROIs)
were sampled in the affected inferior olivary nucleus, ipsilateral red nucleus, and contralateral superior and inferior
cerebellar peduncles and dentate nucleus. For each ROI, fractional anisotropy and the mean, axial, and radial dif-
fusivities were calculated. In the affected inferior olivary nucleus, the authors found a decrease in fractional anisot-
ropy and an increase in mean, axial, and radial diffusivities 3 months after surgery, while 3 months later fractional
anisotropy increased and diffusivities decreased. For all other GMT components, changes in DTI scalars were less
pronounced, and fractional anisotropy mildly decreased over time. A detailed analysis of longitudinal DTI scalars in
the various GMT components may shed light on a better understanding of the dynamic complex histopathological
processes occurring in pediatric HOD over time.
(http://thejns.org/doi/abs/10.3171/2014.1.PEDS13490)
H
ypertrophic olivary degeneration (HOD) is a sec- red nucleus, and 3) the ipsilateral central tegmental tract, or
ondary transsynaptic deafferentation of the inferior rubro-olivary tract, descending from the red nucleus to the
olivary nucleus that occurs after disruption of the original inferior olivary nucleus.8
dentato-rubro-olivary pathway, or Guillain-Mollaret trian- Diffusion tensor imaging (DTI) is an advanced MRI
gle (GMT).7 The GMT is defined by 3 gray matter nuclei: technique that allows investigation of the organization,
the dentate nucleus, the red nucleus, and the inferior oli- microstructure, and integrity of gray and white matter
vary nucleus.8 These anatomical structures are connected structures in vivo.5,13,15 Recent cross-sectional studies in
by 3 pathways: 1) olivary-dentate fibers, or olivocerebellar children and adults with HOD showed that DTI can dem-
fibers, arising from the hilum of the inferior olivary nucle- onstrate and quantify the disruption of the GMT’s com-
us and crossing the midline through the inferior cerebel- ponents.4,12,17 However, HOD is a dynamic process, and
lar peduncle to reach the contralateral dentate nucleus, 2) progressive changes have been shown by neuropathologi-
dentatorubral fibers arising from the contralateral dentate cal examination and conventional MRI.6,7 The purpose of
nucleus, entering their own superior cerebellar peduncle this study is to investigate longitudinal DTI changes of
and decussating within the midbrain to reach the opposite the GMT’s components in a child with HOD after neuro-
surgery for a midbrain tumor.
Abbreviations used in this paper: DTI = diffusion tensor imaging; This article contains some figures that are displayed in color
GMT = Guillain-Mollaret triangle; HOD = hypertrophic olivary de online but in black-and-white in the print edition.
generation; ROI = region of interest.
Case Report
Fig. 2. Axial T2-weighted images (A–D) and color-coded fractional anisotropy maps (E–H) at the level of the medulla 1 day
and 3, 6, and 9 months after surgery. Three months after surgery, the left inferior olivary nucleus appeared mildly enlarged and
exhibited T2 hyperintensity (arrow in B). Enlargement and T2 hyperintensity of the left inferior olivary nucleus became more
prominent 6 and 9 months after surgery (arrows in C and D). Retrocerebellar artifacts after midline suboccipital craniotomy are
seen in panel A. Axial color-coded fractional anisotropy maps show a mild attenuation in signal of the left inferior olivary nucleus
(arrows in E–H) at 3, 6, and 9 months after surgery compared with the right inferior olivary nucleus.
phenomenon affecting the inferior olivary nucleus. It is this causes the removal of inhibition of the electrotonic
caused by disruptive lesions of the afferent GMT com- gap junctions in the inferior olivary nucleus.3,18 On his-
ponents (dentatorubral tract and central tegmental tract) topathology, disinhibition and deafferentation of the in-
resulting in a transsynaptic deafferentation of the infe- ferior olivary nucleus result in vacuolar degeneration
rior olivary nucleus.7 In children, disruptive lesions of and enlargement of neurons and an increase in glial cells
the GMT may include low- and high-grade tumors and and hypertrophy of astrocytes.6 Hypertrophic olivary
vascular malformations.10,12,14,16,21 Neurophysiologically, degeneration is not static, but it is a reactive, dynamic,
TABLE 1: Diffusion tensor imaging scalars derived from the left GMT components on 4 postsurgical follow-up studies*
* AD = axial diffusivity; DN = dentate nucleus; FA = fractional anisotropy; ICP = inferior cerebellar peduncle; ION = inferior olivary
nucleus; MD = mean diffusivity; RD = radial diffusivity; RN = red nucleus; SCP = superior cerebellar peduncle.
† Values are × 10−3 mm2/sec.
Fig. 3. Longitudinal evolution of DTI scalars for the different components of the left GMT. AD = axial diffusivity; DN = dentate
nucleus; FA = fractional anisotropy; ICP = inferior cerebellar peduncle; ION = inferior olivary nucleus; MD = mean diffusivity; RD
= radial diffusivity; RN = red nucleus; SCP = superior cerebellar peduncle.
and evolving process that may take months to years to phy within the first 6 months after the disruptive event,
progress.1,7 Goto et al.6 classified the pathological changes 2) T2 hyperintense signal and hypertrophy of the infe-
in HOD into 6 phases: 1) no olivary changes, observed rior olivary nucleus up to 3–4 years after HOD onset, and
within 24 hours after onset; 2) degeneration of the oli- 3) T2 hyperintense signal with progressive resolution of
vary amiculum (the capsule of white matter composing inferior olivary nucleus hypertrophy.7 These stages take
the periphery of the oliva) at 2 to 7 days or more; 3) oli- into account the dynamic course of HOD and match mac-
vary hypertrophy (the stage of mild olivary enlargement roscopic changes of the inferior olivary nucleus in HOD,
with neuronal hypertrophy and no glial reaction) at about such as increased content of water as part of vacuolar de-
3 weeks; 4) culminant olivary enlargement (the stage of generation and gliosis (both are depicted by a hyperin-
hypertrophy of both neurons and astrocytes) at about 8.5 tense signal on T2-weighted images). Conventional MRI,
months; 5) olivary pseudohypertrophy (the stage of neu- however, does not provide detailed information about
ronal dissolution with gemistocytic astrocytes) at about the microscopic structural change in the inferior olivary
9.5 months and later; and 6) olivary atrophy (the stage of nucleus and involvement of the other GMT components.
neuronal disappearance with olivary atrophy and prom- As in the studied patient, the other components of the
inent degeneration of the amiculum olivae) after a few GMT appear unremarkable on conventional MRI except
years. for the component directly affected by the primary lesion
Neuroimaging is necessary for diagnosis and con- or neurosurgical procedure. However, the involvement of
firmation of HOD and allows for study of the pathobi- the other GMT components plays an important role in
ology of HOD in vivo. Conventional neuroimaging is the manifestation of HOD symptoms. Secondary damage
mandatory for the diagnosis of HOD.2,7,11,16 Hypertrophic of the olivary-dentate tract may cause over-excitation of
olivary degeneration is characterized by enlargement and the dentate nucleus and result in functional impairment of
increased T2 hyperintense signal of the inferior olivary the patient’s ability to estimate the direction of gravity as
nucleus.7,11,16 On postcontrast T1-weighted images, hyper- recently demonstrated in a patient with HOD.20
trophic inferior olivary nuclei are typically not enhanc- Diffusion tensor imaging was shown to shed light on
ing.19 Familiarity with HOD and its neuroimaging ap- the pathobiology of HOD and microstructural changes
pearance in pediatric patients will help to avoid potential occurring in the GMT components. At the mean post-
misdiagnosis of HOD as tumor recurrence, or, in high- surgical time of 20 months, Dinçer et al. demonstrated
grade primary tumors, for example, medulloblastomas, as an increase in radial diffusivity, mean diffusivity, and
metastatic lesions. axial diffusivity and a decrease in fractional anisotropy
Conventional neuroimaging allows only a limited in all anatomical components of the GMT in 10 adults
understanding of the pathobiology of HOD. In our pa- with HOD.4 A decrease in fractional anisotropy and an
tient, a mild enlargement and T2 hyperintensity of the left increase in radial diffusivity most likely represent demy-
inferior olivary nucleus was visible 3 months after sur- elination in the late phase of HOD. Eight months after
gery, which subsequently increased 6 months after sur- surgery, Meoded et al. found higher fractional anisotropy
gery. On conventional MRI, 3 distinct stages with specific and axial diffusivity values of the inferior olivary nuclei
time intervals have been described: 1) T2 hyperintense and lower fractional anisotropy but higher radial diffusiv-
signal of the inferior olivary nucleus without hypertro- ity values of all other GMT components in a child with
bilateral HOD compared with age-matched controls.12 An of more causative treatments. Additionally, longitudinal,
increase in fractional anisotropy in the inferior olivary quantitative DTI studies may monitor therapeutic results
nuclei may reflect rearrangement of regenerating axons in patients with HOD.
and shrunken neurons. Decreased fractional anisotropy Preoperative DTI and fiber tractography allow the
and increased radial diffusivity in the other GMT com- study of the integrity and course of the GMT as well as
ponents most likely reflect the demyelination process the study of the GMT’s anatomical relationship to the
associated with axonal degeneration in accordance with mass lesion, and these modalities determine children at
histopathological studies. In this article, we applied DTI risk for HOD. In a similar approach, DTI and fiber trac-
to investigate dynamic changes of the different GMT tography are used to assess the risk of superior quadrantic
components in a child with HOD. In the left inferior oli- visual field deficits by injury of the Meyer’s loop in tem-
vary nucleus, fractional anisotropy had a variable course poral lobe resection.22,23 Integration of GMT fiber trac-
and decreased at 3 months after surgery. A decrease in tography into stereo-navigational systems together with
fractional anisotropy, an increase in radial diffusivity T1-weighted anatomical images may reduce the risk of
and mean diffusivity, and an almost unchanged axial dif- HOD due to GMT injury by neurosurgery. The feasibil-
fusivity may reflect transsynaptic deafferentation at an ity of integration of GMT fiber tractography into stereo-
early stage of HOD with only mild olivary enlargement, navigational systems for patients with brainstem lesions
which was depicted on conventional MRI. Six months as well as its capability to prevent occurrence of HOD has
after surgery, fractional anisotropy mildly increased and to be addressed by future prospective studies.
mean diffusivity, axial diffusivity, and radial diffusivity We are aware of some limitations in our report, in-
decreased. At this time, culminant olivary enlargement cluding the study of only 1 child with HOD, the retro-
secondary to hypertrophy of both neurons and astrocytes spective nature of the study and the ROI-based analysis,
was achieved.6 Olivary hypertrophy is expected to in- which is investigator dependent.
crease fractional anisotropy, while astrocytic prolifera-
tion or gliosis is expected to reduce it. Because fractional Conclusions
anisotropy increased in our patient 6 months after surgery,
it is arguable that neuronal hypertrophy may play a pre- Our study shows that longitudinal detailed DTI anal-
ponderant role in comparison with gliosis. Nine months ysis of the various components of GMT may shed light
after surgery, fractional anisotropy remained stable, but on the dynamic complex histopathological processes oc-
mean diffusivity, axial diffusivity, and radial diffusivity curring in pediatric HOD over time. Future studies with
increased. The lack of further increase in fractional an- a larger number of subjects and dedicated high angular
isotropy may represent a modified balance between neu- DTI study of the brainstem may better address this issue.
ronal hypertrophy and astrocytic proliferation. At about 9
months and later after surgery, neuronal dissolution and Disclosure
gemistocytic astrocytes represent the prominent histolog- The authors report no conflict of interest concerning the mate-
ical findings.6 In the other GMT components, changes in rials or methods used in this study or the findings specified in this
DTI scalars are present but are less pronounced than in paper.
the inferior olivary nucleus. A decrease in fractional an- Author contributions to the study and manuscript preparation
isotropy and an increase in radial diffusivity (particularly include the following. Conception and design: Poretti, Huisman.
in the inferior cerebellar peduncle and superior cerebel- Acquisition of data: all authors. Analysis and interpretation of data:
lar peduncle) most likely reflect secondary demyelination Poretti, Orman, Bosemani. Drafting the article: Orman. Critically
associated with axonal degeneration, which occurs in revising the article: all authors. Reviewed submitted version of man-
uscript: all authors. Approved the final version of the manuscript on
transneuronal degeneration. This finding is in accordance behalf of all authors: Poretti. Study supervision: Poretti.
with histopathological studies and previous DTI stud-
ies.4,12 In the red nucleus, however, changes in DTI scalars
over time are more prominent, particularly the increase in References
mean diffusivity, axial diffusivity, and radial diffusivity. 1. Birbamer G, Buchberger W, Felber S, Aichner F: MR appear-
The marked, global increase of the diffusivity in the red ance of hypertrophic olivary degeneration: temporal relation-
nucleus is likely due to the primary lesion and postsurgi- ships. AJNR Am J Neuroradiol 13:1501–1503, 1992
cal changes with resolution of necrotic tissue and forma- 2. Birbamer G, Gerstenbrand F, Aichner F, Buchberger W, Che-
tion of cystic spaces. melli A, Langmayr J, et al: MR-imaging of post-traumatic oli-
vary hypertrophy. Funct Neurol 9:183–187, 1994
Neurological symptoms in patients with HOD in- 3. De Zeeuw CI, Simpson JI, Hoogenraad CC, Galjart N, Koek-
clude palatal myoclonus, truncal and limb ataxia, and koek SK, Ruigrok TJ: Microcircuitry and function of the infe-
ocular movement disorders. These symptoms may be rior olive. Trends Neurosci 21:391–400, 1998
severe, have a major impact on activities of daily living, 4. Dinçer A, Özyurt O, Kaya D, Koşak E, Öztürk C, Erzen C, et
and consequently decrease the patient’s quality of life sig- al: Diffusion tensor imaging of Guillain-Mollaret triangle in
nificantly. In adults with HOD, symptomatic therapeutic patients with hypertrophic olivary degeneration. J Neuroim-
approaches using, for example, benzodiazepines or anti- aging 21:145–151, 2011
5. Feldman HM, Yeatman JD, Lee ES, Barde LH, Gaman-Bean
epileptic drugs have been attempted with varying results.9 S: Diffusion tensor imaging: a review for pediatric research-
A more detailed understanding of the pathobiology of ers and clinicians. J Dev Behav Pediatr 31:346–356, 2010
HOD and its dynamic changes over time using noninva- 6. Goto N, Kaneko M: Olivary enlargement: chronological and
sive techniques such as DTI may allow the development morphometric analyses. Acta Neuropathol 54:275–282, 1981
7. Goyal M, Versnick E, Tuite P, Cyr JS, Kucharczyk W, Mon- 18. Shaikh AG, Hong S, Liao K, Tian J, Solomon D, Zee DS, et al:
tanera W, et al: Hypertrophic olivary degeneration: metaanal- Oculopalatal tremor explained by a model of inferior olivary
ysis of the temporal evolution of MR findings. AJNR Am J hypertrophy and cerebellar plasticity. Brain 133:923–940,
Neuroradiol 21:1073–1077, 2000 2010
8. Habas C, Guillevin R, Abanou A: In vivo structural and func- 19. Shinohara Y, Kinoshita T, Kinoshita F, Kaminou T, Watanabe
tional imaging of the human rubral and inferior olivary nu- T, Ogawa T: Hypertrophic olivary degeneration after surgical
clei: a mini-review. Cerebellum 9:167–173, 2010 resection of brain tumors. Acta Radiol [epub ahead of print],
9. Hornyak M, Osborn AG, Couldwell WT: Hypertrophic oli- 2013
vary degeneration after surgical removal of cavernous mal- 20. Tarnutzer AA, Palla A, Marti S, Schuknecht B, Straumann D:
formations of the brain stem: report of four cases and review Hypertrophy of the inferior olivary nucleus impacts percep-
of the literature. Acta Neurochir (Wien) 150:149–156, 2008 tion of gravity. Front Neurol 3:79, 2012
10. Jellinger K: Hypertrophy of the inferior olives. Report on 29 21. Vossough A, Ziai P, Chatzkel JA: Red nucleus degeneration
cases. Z Neurol 205:153–174, 1973 in hypertrophic olivary degeneration after pediatric posterior
11. Kitajima M, Korogi Y, Shimomura O, Sakamoto Y, Hirai T, Mi- fossa tumor resection: use of susceptibility-weighted imaging
yayama H, et al: Hypertrophic olivary degeneration: MR imag- (SWI). Pediatr Radiol 42:481–485, 2012
ing and pathologic findings. Radiology 192:539–543, 1994 22. Winston GP, Daga P, Stretton J, Modat M, Symms MR, Mc
12. Meoded A, Poretti A, Ilica AT, Perez R, Jallo G, Burger PC, Evoy AW, et al: Optic radiation tractography and vision in an-
et al: Diffusion tensor imaging in a child with hypertrophic terior temporal lobe resection. Ann Neurol 71:334–341, 2012
olivary degeneration. Cerebellum 12:469–474, 2013 23. Yogarajah M, Focke NK, Bonelli S, Cercignani M, Acheson J,
13. Pajevic S, Pierpaoli C: Color schemes to represent the orienta- Parker GJ, et al: Defining Meyer’s loop-temporal lobe resec-
tion of anisotropic tissues from diffusion tensor data: applica- tions, visual field deficits and diffusion tensor tractography.
tion to white matter fiber tract mapping in the human brain. Brain 132:1656–1668, 2009
Magn Reson Med 42:526–540, 1999
14. Phatouros CC, McConachie NS: Hypertrophic olivary degener-
ation: case report in a child. Pediatr Radiol 28:830–831, 1998
15. Poretti A, Meoded A, Rossi A, Raybaud C, Huisman TA: Dif- Manuscript submitted September 23, 2013.
fusion tensor imaging and fiber tractography in brain malfor- Accepted January 14, 2014.
mations. Pediatr Radiol 43:28–54, 2013 Please include this information when citing this paper: published
16. Sanverdi SE, Oguz KK, Haliloglu G: Hypertrophic olivary online February 14, 2014; DOI: 10.3171/2014.1.PEDS13490.
degeneration in children: four new cases and a review of the Address correspondence to: Andrea Poretti, M.D., Section of
literature with an emphasis on the MRI findings. Br J Radiol Pediatric Neuroradiology, Division of Pediatric Radiology, Russell
85:511–516, 2012 H. Morgan Department of Radiology and Radiological Science,
17. Shah R, Markert J, Bag AK, Curé JK: Diffusion tensor imag- Charlotte R. Bloomberg Children’s Center, Sheikh Zayed Tower,
ing in hypertrophic olivary degeneration. AJNR Am J Neu- Rm. 4174, 1800 Orleans St., Baltimore, MD 21287. email: aporett1
roradiol 31:1729–1731, 2010 @jhmi.edu.