Vertical pendular nystagmus and hypertrophic inferior olivary nuclei degeneration: an “odd couple”

Abstract

A 56-year-old man had a hypertensive pontine hemorrhage (Fig. 1a), which resulted in bilateral internuclear ophthalmoplegia, pseudobulbar palsy, and spastic ataxic tetraparesis. Three months after a stroke, while neurological deficits were recovering, the patient manifested progressively blurred vision and oscillopsia, corresponding to a vertical conjugate pendular nystagmus (PN) (video). Electronystagmography showed a 3-Hz frequency and 2–3 amplitude sinusoidal curve, with upand down-phases symmetric for direction and velocity, without null zones and torsional or gaze-evoked components. PN was not modified by eye covering, saccades, head thrust, 20 diopter prisms, optokinetic maneuvers, and sleep. Brain MRI (Fig. 1b, c) showed an hemosiderin-and ferritin-lined cleft confined to the dorsal pontine tegmentum and the central tegmental tract. MR-T2-WI images showed a symmetric enlargement of the inferior olivary nuclei with high signal intensity (Fig. 1c, d), which is the typical appearance of the hypertrophic inferior olivary nuclei degeneration (HIOND). PN did not improve with baclofene (up to 60 mg/day), pregabalin (up to 600 mg/day), memantine (up to 40 mg/ day), clonazepam (up to 3 mg/day), lamotrigine (50 mg/ day) worsened the condition. PN remained unchanged at 1 year of follow-up. The radiological hallmarks of the HIOND are the symmetric olivary enlargement with high T2 signal intensity (Fig. 1d), and the presence of distant lesions in specific locations: contralateral cerebellar dentate nucleus, contralateral superior cerebellar peduncle, ipsilateral dorsomedial red nucleus, and ipsilateral pontine tegmentum [1]. The HIOND, as demonstrated in pathological studies since the beginning of the 20th century [2], is a unique form of neuronal degeneration associated with enlargement, rather than atrophy. Olivary nuclei ‘‘hypertrophy’’ is due to the combination of astrocytosis, gemistocytes, and neuronal vacuolar cytoplasmic enlargement [2], due to abnormal soma-somatic gap junctions, hypertrophic thick neuritis, and demyelination [3]. As the association with specific remote lesions is constant, the HIOND is considered the effect (through transneuronal or transsynaptic degeneration) of the damage of the dentatorubral tract (connecting the dentate nucleus with the controlateral red nucleus) and the central tegmental tract (connecting the red nucleus to the ipsilateral inferior olive). The ensemble of these nuclei and tracts is known as the dentatorubral–olivary pathway or ‘‘Guillain-Mollaret triangle’’ (GMT). A recent study with diffusion tensor imaging (DTI) demonstrated signal changes in all anatomical components of the GMT in patients with HIOND at different stages [3], even when standard MRI is negative. In particular, PN has been related to the damage of the paramedian cerebellar tract projections to the pontine tegmentum and to the consequent denervation of the dorsal cap of the inferior olive. Tegmental pontine lesions, in the case of bilateral PN and Electronic supplementary material The online version of this article (doi:10.1007/s00415-011-6170-2) contains supplementary material, which is available to authorized users.