PATHOPHYSIOLOGY OF HOD
Axons from the dentate nucleus travelling through the superior cerebellar peduncle cross the midline at the level of the midbrain to reach the contralateral red nucleus (dentatorubral tract); the second connection is between the red nucleus and the ipsilateral inferior olivary nucleus (central tegmental tract).
The triangle is completed by ION efferents fibers crossing the midline,
entering the inferior cerebellar peduncle,
and terminating into the contralateral dentate nucleus.
Fig. 8: Schematic representation of Guillain-Mollaret triangle.
References: Department of Radiological Sciences, Catholic University of Sacred Heart, Policlinico Agostino Gemelli - Roma (RM)/IT
Although it is an anatomic triangle,
HOD can result from lesions of the first two limbs of the triangle,
and not from lesions involving olivo-dentate fibers,
since ION deafferentation is thought to be the source of the ensuing hypertrophic degenerative changes.
In fact fibers projecting from the dentate nucleus,
into the ION are mainly inhibitory (GABAergic).
A disruption in this pathway leads to excessive excitation of the ION and contributes to its hypertrophy.
This uncontrolled excitation in the ION is responsible for neuronal death with subsequent atrophy in time.
PATTERN OF PRESENTATION
Three possible patterns of presentation can occur from the disruption of this triangle:
1) Ipsilateral HOD: if the lesion involves the central tegmental tract,
degeneration occurs in the ipsilateral ION.
Fig. 9: 1) Ipsilateral HOD: occurs when primary lesion is limited to brainstem (central tegmental tract).
References: Department of Radiological Sciences, Catholic University of Sacred Heart, Policlinico Agostino Gemelli - Roma (RM)/IT
Fig. 10: A small hemorrhage in central tegmental tract causing ipsilateral HOD.
HOD is evident in axial and coronal T2-w images (A and C).
A puntate hemosiderin deposit is documented by axial GRE image (B).
References: Department of Radiological Sciences, Catholic University of Sacred Heart, Policlinico Agostino Gemelli - Roma (RM)/IT
2) Contralateral HOD: when the primary lesion affects the dentatorubral tract,
the contralateral ION is involved.
Fig. 11: 2) Contralateral HOD: occurs when primary lesion is in the cerebellum (dentate nucleus or superior cerebellar peduncle).
References: Department of Radiological Sciences, Catholic University of Sacred Heart, Policlinico Agostino Gemelli - Roma (RM)/IT
Fig. 12: Contralateral HOD.
Hyperintensity and hypertrophy of left ION is evident in axial FLAIR (A), and in axial and coronal T2-w images. A small hemorrhage is demonstrated by GRE image in right dentate nucleus.
References: Department of Radiological Sciences, Catholic University of Sacred Heart, Policlinico Agostino Gemelli - Roma (RM)/IT
3) Bilateral HOD: a lesion affecting both the central tegmental tract and the superior cerebellar peduncle results in bilateral degeneration.
Fig. 13: 3) Bilateral HOD: occurs when primary lesion involves both central tegmental tract and superior cerebellar peduncle.
References: Department of Radiological Sciences, Catholic University of Sacred Heart, Policlinico Agostino Gemelli - Roma (RM)/IT
Fig. 14: Bilateral HOD. An hemorrhagic lesion involves both central tegmental tract and superior cerebellar peduncle.
References: Department of Radiological Sciences, Catholic University of Sacred Heart, Policlinico Agostino Gemelli - Roma (RM)/IT
CAUSES OF HOD
A variety of lesions involving the dentato-rubro-olivary pathway have been implicated in development of HOD.
They include primary haemorrhage,
cavernous haemangioma,
vascular malformation,
infarction,
trauma,
posterior fossa surgery,
and idiopathic.
HAEMORRHAGE: AVM
Fig. 15: Bilateral HOD following an hemorrhage coming from a ruptured AVM.
A: CT without contrast demonstrating the hemorrhage involving both central tegmental tract and superior cerebellar peduncle.
B: PA angiogram of vertebral artery demonstrating vessels coming from left posterior cerebral artery to the AVM (red arrow).
C: lateral angiogram of left internal carotid artery demonstrating another small vessel coming from ophthalmic ICA to join the AVM (red arrow).
D-E: T2-w and FLAIR axial images, three months after the hemorrhage, demonstrating hypertrophy and hyperintensity of both IONs -bilateral HOD- (arrows).
F: T2-w coronal fat sat image demonstrating bilateral HOD and the primary lesion.
References: Department of Radiological Sciences, Catholic University of Sacred Heart, Policlinico Agostino Gemelli - Roma (RM)/IT
POST-TRAUMATIC
Fig. 24: Post-traumatic bilateral HOD, due to massive brain destruction following head trauma with involvement of Guillain-Mollaret triangle (bilateral red nuclei). In this case there is a coexistence of bilateral Wallerian degeneration making anterior medulla hyperintensity much more evident.
References: Department of Radiological Sciences, Catholic University of Sacred Heart, Policlinico Agostino Gemelli - Roma (RM)/IT
POST-SURGICAL
Fig. 16: 1 month MR scan shows bilateral HOD in a patient surgically treated for a posterior fossa medulloblastoma. Bilateral mild hypertrophic and hyperintense ION is demonstrated by T2-w images (red arrows in A and B). A bilateral lesion of dentate nuclei is evident in GRE images (single red arrow in C and D).
References: Department of Radiological Sciences, Catholic University of Sacred Heart, Policlinico Agostino Gemelli - Roma (RM)/IT
IDIOPATHIC HOD
Fig. 17: Bilateral HOD is showed in T2-w axial image (A), without an evident lesion involving the Guillain-Mollaret triangle. FLAIR (C) and DWI ((B) images depicted a left occipital stroke in the vascular territory of posterior cerebral artery. In this case HOD could probably be explained by an insufficient vertebro-basilar system.
References: Department of Radiological Sciences, Catholic University of Sacred Heart, Policlinico Agostino Gemelli - Roma (RM)/IT
DIFFERENTIAL DIAGNOSIS
MRI differential diagnosis of HOD includes every T2w hyperintensity located in the anterolateral medulla:
- infarction
- demyelination
- tumor (astrocytoma,
metastases,
and lymphoma)
- infection (tuberculosis,
AIDS,
rhombencephalitis)
- lesion involving corticospinal tract:(Wallerian degeneration,
adrenoleukodystrophy,
amyoptrophic lateral sclerosis)
- other inflammatory process (e.g.
sarcoidosis)
Some examples of these pathologies are shown below,
with the best diagnostic clues for differential diagnosis.
INFARCTION
Clinical presentation is acute,
with alternating brainstem syndrome.
DWI shows restricted diffusion.
GRE could indicate hemorrhagic transformation.
MRA demonstrates stenosis/dissection/occlusion of ipsilateral vertebral artery or posterior inferior cerebellar artery.
T1-w post-gad displays enhancement due to BBB disruption in subacute phase.
Fig. 18: Ischemic lesion involving the left hemimedulla due to V4 segment dissection of left vertebral artery (Babinski-Nageotte syndrome).
Hyperintensity and mild hypertrophy of left hemimedulla is evident in axial T2-w (A), in axial FLAIR (B), and in coronal T2-w images.
Faint hyperintensity is documented in DWI images, b1000 (D).
Left vertebral artery dissection is demonstrated - red arrows- in MIP post-constrast MR-angiography (E), and even in angio-CT (F).
Strong enhancement of the lesion, due to blood–brain barrier damage, is evident in coronal and axial post-constrast T1-w images.
References: Department of Radiological Sciences, Catholic University of Sacred Heart, Policlinico Agostino Gemelli - Roma (RM)/IT
DEMYELINATION: multiple sclerosis
Only in 10 % of cases is infratentorial,
and almost always associated with supratentorial lesions.
Can be bilateral or monolateral.
DWI and T1-w post-gad findings vary depending on disease activity.
Fig. 19: Multiple hyperintense lesions in T2-w images: involvement of antero-lateral part of medulla is evident (single red arrow in first image), as well as multiple lesions in pons, both middle cerebellar peduncles, and supratentorial periventricolar white matter. Multiple supratentorial lesions are also demonstrated in coronal images.
References: Department of Radiological Sciences, Catholic University of Sacred Heart, Policlinico Agostino Gemelli - Roma (RM)/IT
TUMOR: pilocytic astrocytoma
Pilocytic astrocytoma is tipically located in medulla in children,
and it appears as an expansive/exophytic lesion with well defined margins.
T1-w post-gad can show variable and fluctuant enhancement.
Non morphological MR can help in differential diagnosis: high r-CBV values in perfusion,
with curve overshooting; high level of Cho in MRS.
Fig. 20: Brain tumor - pilocytic astrocytoma:
- A: Axial T2-w and FLAIR images demonstrating hyperintensity and swelling of antero-lateral left medulla.
- Coronal and sagittal T2-w images confirming hyperintensity and swelling of antero-lateral left medulla.
- Sagittal, coronal and axial post contrast T1-w images showing faint enhancement of the lesion.
References: Department of Radiological Sciences, Catholic University of Sacred Heart, Policlinico Agostino Gemelli - Roma (RM)/IT
LESION INVOLVING CORTICOSPINAL TRACT: Wallerian degeneration
Contiguous T2-hyperintensity along topographic distrubution of corticospinal tract and primary lesion is cortical or subcortical.
DWI allows early detection (stage I).
Chronic evolution is corticospinal tract atrophy.
Fig. 21: Post-surgical Wallerian degeneration.
A: coronal T2-w fat sat images.
B: axial T2-w fat sat images.
C: post-constrast T1-w images.
References: Department of Radiological Sciences, Catholic University of Sacred Heart, Policlinico Agostino Gemelli - Roma (RM)/IT
INFECTION: rhombencephalitis
Clinical presentation suggests an infection.
Whole brainstem can be affected with a variable blurred T2-w hyperintensity.
T1-w post-gad may show variable enhancement.
Abscesses and leptomeningeal spread can be the evolution.
Laboratories findings (liquor and haematological) confirm the diagnosis.
Fig. 22: EBV rhombencephalitis.
Involvement of anterior part of medulla is mostly evident in T2-w (B,E,F) and FLAIR images (C,G), but even in T1-w IR images (A) (red arrows). Faint diffusion restriction in DWI (D), with no contrast enhancement (H).
References: Department of Radiological Sciences, Catholic University of Sacred Heart, Policlinico Agostino Gemelli - Roma (RM)/IT
Fig. 23: Faint T2 (A-B) and FLAIR (C) hyperintensity within medulla, even involving inferior olivar nuclei. No contrast enhancement after gad-administration (D).
References: Department of Radiological Sciences, Catholic University of Sacred Heart, Policlinico Agostino Gemelli - Roma (RM)/IT
In summary the clinical context represents the best diagnosis clue.
The lack of contrast enhancement,
moreover,
is against many tumors or an infection.
No restricted diffusion excludes acute ischemic lesion.
ION hypertrophy,
an associated lesion of the Guillain-Mollaret triangle and typical symptoms,
such as palatal myoclonus,
can define the diagnosis.