Hypertrophic olivary degeneration (HOD) is a trans-neuronal degeneration secondary to focal lesions involving the dentato-rubral-olivary pathway,
also know as Guillain-Mollaret triangle.
This is a functional pathway composed by neural connections between the red nucleus,
the ipsilateral inferior olivary nucleus (ION),
and the contralateral dentate nucleus of the cerebellum.
Fig. 1: Guillain-Mollaret triangle: red nucleus (in red), ipsilateral inferior olivary nucleus (in yellow) and contralateral dentate nucleus of cerebellum (in orange)
References: Department of Radiological Sciences, Catholic University of Sacred Heart, Policlinico Agostino Gemelli - Roma (RM)/IT
Histologically the affected ION demonstrates cell body enlargement,
vacuolation of the cytoplasm,
astrocytic hyperplasia and proliferation,
demyelination,
and fibrillary gliosis.
Goto et al described six phases of pathological changes over a time frame ranging from immediate onset to several years: 1) first hours: no olivary change; 2) until seven days: degeneration of olivary amiculum; 3) until the third week: mild olivary hypertrophy (neuronal hypertrophy without glial reaction); 4) until eight months and a half: olivary enlargement (neuronal and astrocytes hypertrophy); 5) after nine months and a half: olivary pseudohypertrophy (neuronal loss and presence of gemistocytic astrocytes); 6) after some years: olivary atrophy.
Consequently HOD cannot be identified with MR until the third phase,
in which MR images show prolongation of T2 relaxation,
as demonstrated by Kitajima et al.
Fig. 2: Histological demonstration of ION enlargement (HOD) in two different patients.
Modified by Gautier JC, Blackwood W. Enlargement of inferior olivary nucleus in association with lesions of the central tegmental tract or dentate nucleus. Brain Vol 84, part 3. 1961.
References: brain.oxfordjournals.org
MR IMAGING
The best diagnostic clue for HOD diagnosis is a nonenhancing,
T2w hyperintensity of an enlarged ION.
Fig. 3: Different morphology between normal ION and hypertrophic ION.
References: Department of Radiological Sciences, Catholic University of Sacred Heart, Policlinico Agostino Gemelli - Roma (RM)/IT
According to Goyal and Birbamer HOD changes in MR can be divided in 3 stages:
1) T2w/FLAIR signal hyperintensity without hypertrophy of ION (0 to 4-6 months from primary lesion).
2) T2w/FLAIR signal hyperintensity with hypertrophy of ION (4-6 to 10-16 months).
3) Resolution of hypertrophy with or without atrophy and persistent signal hyperintensity in T2w/FLAIR images (after 16 months).
Fig. 4: A typical evolution of inferior olivary nucleus morphology and signal intensity in a Patient with post-operative HOD (bilateral lesion of dentate nucleus).
The slight T2 hyperintensity after 1 week, followed by an increase of signal and mild hypertrophy after 1 month, that persisted for 9 month and decreased after one year.
References: Department of Radiological Sciences, Catholic University of Sacred Heart, Policlinico Agostino Gemelli - Roma (RM)/IT
With time,
generally 3-4 years after the lesion,
hypertrophy resolves and a faint linear or punctate hyperintensity of ION can persist indefinitely.
Fig. 5: Two exemples of linear and punctate changes after 12 months in two different Patients.
References: Department of Radiological Sciences, Catholic University of Sacred Heart, Policlinico Agostino Gemelli - Roma (RM)/IT
Fig. 6: MR findings in HOD
References: Department of Radiological Sciences, Catholic University of Sacred Heart, Policlinico Agostino Gemelli - Roma (RM)/IT
In this context gradient echo images (GRE),
or even better,
susceptibility weighted images (SWI),
can help in determining signs of previous hemorrhages of the structures of Guillain-Mollaret triangle: red nucleus,
dentate nucleus,
or superior cerebellar peduncles.
Fig. 7: Gradient echo images (GRE) and susceptivity weighted images (SWI) are very useful in demonstrating deposits of hemosiderin along Guillain-Mollaret triangle.
References: Department of Radiological Sciences, Catholic University of Sacred Heart, Policlinico Agostino Gemelli - Roma (RM)/IT
Clinical presentation of HOD includes palatal myoclonus,
dentatorubral (or Holmes’) tremor and ocular myoclonus.
Palatal myoclonus has been described as a rhythmic involuntary movement of the oropharynx,
including the soft palate and uvula.
Severe myoclonus of cervical muscles and diaphragm has been reported and can precede palatal myoclonus.
Clinical presentation reflects involvement of both the central tegmental tract and the dentato-rubral pathway.