ABSTRACT ID NO: 1159 HYPERTROPHIC INFERIOR OLIVARY NUCLEUS DEGENERATION- AN ENIGMA

BACKGROUND Hypertrophic inferior olivary nucleus degeneration is a rare entity that occurs due to a unique type of transneuronal degeneration resulting from a primary lesion in the Guillain-Mollaret triangle. This condition is unique owing to the fact that the degeneration results in hypertrophy rather than atrophy of the nucleus. MRI appearances vary according to the duration from the initial insult as well as the pathological stages. We hereby report two cases diagnosed at our institution, one following pontine hemorrhage and another following posterior fossa epidermoid cyst excision.

LEARNING OBJECTIVES Hypertrophic inferior olivary nucleus degeneration is an entity that occurs when there is a focal pathology involving the the dentato-rubral-olivary pathway which is known as the Guillain- Mollaret triangle. The Guillain-Mollaret triangle connects the ipsilateral red nucleus and the inferior olivary nucleus with the contralateral dentate nucleus. Figure 1- shows the pathway of the Guillain Mollaret triangle. Efferent fibers from the dentate nucleus in the cerebellum (orange dot) traverse in the superior cerebellar peduncle to the contralateral red nucleus in the midbrain (red dot). From here, efferent fibres traverse via the central tegmental tract to the ipsilateral inferior olivary nucleus in the brainstem (yellow dot). The pathway ends with efferent fibers from the inferior olivary nucleus traversing via the inferior cerebellar peduncle to the contralateral dentate nucleus.

Hypertrophic olivary nucleus degeneration can occur secondary to lesions affecting the first two limbs of the triangle and not from lesions involving the olivo-dentate fibres. ETIOLOGY: -Common pathologies that can cause this condition are: a)Hemorrhage b)Cavernous hemangioma c)Vascular malformations d)Infarction e)Trauma f)Surgery for posterior fossa lesions g)Idiopathic.

` CLINICAL FEATURES: Typically the onset of pathology is typically three weeks after the initial insult. However, the time of onset of symptoms varies. Patients usually present with Holmes’ tremor, palatal myoclonus and ocular myoclonus. Palatal myoclonus may not always be seen in patients with hypertrophic olivary degeneration. PATHOLOGY: According to Goto et al, six phases of pathological changes are seen from the time of onset. a)No change within 24 hours. b)Degeneration of olivary anniculum after 7 days. c)Mild olivary hypertrophy until 3 weeks. d)Olivary enlargement until 8.5 months. e)Olivary pseudohypertrophy until 9.5 months. f)Olivary atrophy after years.

MRI FEATURES: Hypertrophic olivary degeneration cannot be evaluated with MRI till the pathology reaches the third phase of mild olivary hypertrophy. On MRI, the classic finding is T2W/FLAIR hyperintensity and enlargement of the inferior olivary nucleus located in the brainstem which shows no diffusion restriction or abnormal enhancement. Patterns of presentation: Three patterns of presentation can occur depending on the site of the primary lesion in the dentato-rubral-olivary pathway. Unilateral and ipsilateral - lesion in the brainstem. Unilateral and contralateral - lesion in cerebellum/cerebellar peduncles. Bilateral - Midline lesion at the point of decussation/lesion in ipsilateral brainstem and cerebellum.

According to Goyal and Birbamer, hypertrophic olivary degeneration changes in MRI occurs in three stages: a)T2 FLAIR signal hyperintensity without hypertrophy of the inferior olivary nucleus (occurs 4-6 months after primary insult). b)T2W/FLAIR signal hyperintensity with hypertrophy of the inferior olivary nucleus (occurs from 6-16 months after primary insult). c)Resolution of hypertrophy with/without atrophy and persistent signal hyperintensity in T2W/FLAIR images (occurs 16 months after primary insult) d)3-4 years after the lesion, hypertrophy resolves and a faint linear or punctate hyperintensity can persist.

DIFFERENTIAL DIAGNOSIS: Focal T2 signal hyperintensity involving the antero-lateral part of the medulla alone is not diagnostic of Hypertrophic inferior olivary nucleus degeneration since similar changes can be seen in: a)Infarction b)Demyelination c)Infections-AIDS, TB. d)Sarcoidosis e)Tumors like lymphoma, astrocytomas, metastases.

CASE 1 A 42 year old male patient who was a known case of fourth ventricle epidermoid cyst and underwent tumor excision 6 months prior, presented with complaints of progressive diplopia, gait disturbance,weakness of the right hand with difficulty in writing, slurring of speech which began about one month following surgery. On examination, there was right sixth cranial nerve palsy with gaze evoked nystagmus, right cerebellar signs and visible palatal myoclonus. Patient was referred to our department for a contrast MRI Brain.

Axial MRI images showing residual post operative changes seen as altered signal intensity around the fourth ventricle and right inferior cerebral peduncle which appear hypointense on T1W image (Figure 2) and hyperintense on T2 FLAIR (Figure 3) and T2W image (Figure 4). FIGURE : 2FIGURE : 3FIGURE : 4

Figure 5: Axial T2W image shows post- operative changes around the fourth ventricle (blue arrow) and right middle cerebellar peduncle (red arrow). Figure 6: DWI shows a small residual lesion in the fourth ventricle (yellow arrow) with restriction of diffusion.

Mild oblong hypertrophy and hyperintensity of bilateral inferior olivary nucleus (yellow arrow) seen in Axial T2W (Figure 7), Axial FLAIR (Figure 8) and Coronal T2W (Figure 9) images. FIGURE : 7FIGURE : 8FIGURE : 9

Figure 10: Post-contrast T1W axial image shows no enhancement of the hypertrophied inferior olivary nuclei (yellow arrow). Figure 11: DWI shows no restricted diffusion in the region of inferior olivary nuclei.

CASE 2 A 50 year old hypertensive male patient, presented with weakness in left upper and lower limbs since three months and progressive slurring of speech since one month. He had a past history of acute onset of left hemiparesis, slurring of speech and right third cranial nerve palsy three months back. A CT brain taken at the time showed acute brain stem hemorrhage and chronic infarcts in the basal ganglia region. On examination, hypotonia was present in the left upper and lower limbs, left plantar reflex was extensor and right third cranial nerve palsy was present. Palatal myoclonus was absent. Patient was referred to the Department of Radiology for a contrast MRI Brain.

Axial MRI images show chronic hemorrhage in the right side of midbrain (Figure 11) and central and posterior aspect of the Pons and the cerebral peduncle (Figure 12) which shows susceptibility artifact on T2 FFE image (Figure 13). FIGURE : 11 FIGURE :12FIGURE : 13

Oblong hypertrophy and hyperintensity of right inferior olivary nucleus (red arrow) seen in Axial T2W (Figure 14), Coronal T2W (Figure 15) and Axial T2W FLAIR (Figure 16) images. FIGURE : 14FIGURE : 15FIGURE : 16

Figure 18: Post-contrast T1W axial image shows no enhancement of the hypertrophied right inferior olivary nucleus. Figure 19: DWI shows no restricted diffusion in the region of the right inferior olivary nucleus.

CONCLUSION Hypertrophic inferior olivary nucleus degeneration is a rare entity that can be missed or erroneously diagnosed. The presence of an inciting lesion in the brainstem or cerebellum, signal changes confined to the olivary nucleus with or without enlargement and absence of contrast enhancement together help to cinch the diagnosis.

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