Current-dependent Ocular Tilt Reaction in STN-DBS: evidence for a putative incerto-interstitial pathway?

Objective: To report a patient with Parkinson’s disease presenting with a combined vestibular, oculomotor and postural syndrome dependent of deep brain stimulation (DBS) of the subthalamic nucleus. Methods: In a systematic monopolar review, eye, head and trunk position in roll and pitch plane were documented as a function of stimulation amplitude and field direction. Repeat ocular coherence tomography was used to estimate ocular torsion. The interstitial nucleus of Cajal (INC), zona incerta (ZI) and ascending vestibular fiber tracts were segmented on MRI using both individual and normative structural and connectomic data. Thresholded symptom-associated volumes of tissue activated (VTA) were calculated based on documented stimulation parameters. Results: Ipsilateral ocular tilt reaction and body lateropulsion as well as contralateral torsional nystagmus were elicited by the right electrode in a current-dependent manner and subsided after DBS deactivation. With increasing currents, binocular tonic upgaze and subsequently body retropulsion could be elicited, consistent with an irritative effect on the Interstitial Nucleus of Cajal (INC). Symptom-associated VTA was found to overlap with the dorsal zona incerta (dZI) and the lateral ipsilateral vestibulothalamic tract (IVTT), while lying in close proximity to the medial IVTT and rather distant to the INC proper. As described in non-human primates, a ZI-to-INC, “incerto-interstitial” tract (IIT) with contact to the medial-uppermost portion of the VTA could be traced. By ways of directional current steering laterally to both tracts, therapeutic response could be preserved while vestibular side effects were minimized. Conclusion: Unilateral stimulation of mesencephalic vestibular-related circuitry induces an ipsilateral vestibular, oculomotor and postural roll-plane syndrome, which converts into a combined pitch-plane syndrome, when functional activation expands to the bilateral INC. The phenomenology of the roll-plane syndrome in this patient points to an activation of INC neurons by DBS, hypothetically via a potentially aberrant incerto-interstitial pathway. Directional current steering proved useful in managing this rare side effect.

The ipsilateral vestibulothalamic tract in the human brain

Although there are a few studies of portions of the vestibular system such as the vestibulocerebellar tract and the neural connectivity of the vestibular nuclei (VN), no study of the ipsilateral vestibulothalamic tract (VTT) (originating from the VN and mainly connecting to the lateral thalami nuclei) has been reported. In the current study, using diffusion tensor tractography (DTT), we investigate the reconstruction method and characteristics of the ipsilateral VTT in normal subjects. Thirty-three subjects were recruited for this study. For the ipsilateral VTT, the seed region of interest (ROI) was placed on the VN, which was isolated on the FA map using adjacent structures as follows: the reticular formation (anterior boundary), posterior margin of medulla and pons (posterior boundary), medial lemniscus (medial boundary) and restiform body (lateral boundary). The target ROI was placed at the lateral thalamic nuclei using known anatomical locations. The DTT parameters of the ipsilateral VTT were measured. The ipsilateral VTTs that originated from the vestibular nuclei ascended postero-laterally to the upper pons and antero-medially to the upper midbrain via the medial longitudinal fasciculus, and terminated the lateral thalamic nuclei. No significant differences were observed in DTT parameters of the ipsilateral VTT between the right and left hemispheres (p > 0.05). Using DTT, we reconstructed the ipsilateral VTT and observed the anatomical characteristics of the ipsilateral VTT in normal subjects. We believe that the methodology and results in this study could be helpful to researchers and clinicians in this field.