Stereotactic localization of the human pedunculopontine nucleus: atlas-based coordinates and validation of a magnetic resonance imaging protocol for direct localization

Abstract

The pedunculopontine nucleus (PPN) is a promising new target for deep brain stimulation (DBS) in parkinsonian patients with gait disturbance and postural instability refractory to other treatment modalities. This region of the brain is unfamiliar territory to most functional neurosurgeons. This paper reviews the anatomy of the human PPN and describes novel, clinically relevant methods for the atlas-based and MRI-based localization of the nucleus. These two methods of PPN localization are evaluated and compared on stereotactic MRI data acquired from a diverse group of 12 patients undergoing implantation of deep brain electrodes at sites other than the PPN. Atlas-based coordinates of the rostral and caudal PPN poles in relation to fourth ventricular landmarks were established by amalgamating information sourced from two published human brain atlases. These landmarks were identified on acquired T1 images and atlas-derived coordinates used to plot the predicted PPN location on all 24 sides. Images acquired using a specifically modified, proton-density MRI protocol were available for each patient and were spatially fused to the T1 images. This widely available and rapid protocol provided excellent definition between gray and white matter within the region of interest. Together with an understanding of the regional anatomy, direct localization of the PPN was possible on all 24 sides. The coordinates for each directly localized nucleus were measured in relation to third and fourth ventricular landmarks. The mean (SD) of the directly localized PPN midpoints was 6.4 mm (0.5) lateral, 3.5 mm (1.0) posterior and 11.4 mm (1.2) caudal to the posterior commissure in the anterior commissure-posterior commissure plane. For the directly localized nucleus, there was similar concordance for the rostral pole of the PPN in relation to third and fourth ventricular landmarks (P>0.05). For the caudal PPN pole, fourth ventricular landmarks provided greater concordance with reference to the anteroposterior coordinate (P<0.001). There was a significant difference between localization of the PPN poles as predicted by atlas-based coordinates and direct MRI localization. This difference affected mainly the rostrocaudal coordinates; the mean lateral and anteroposterior coordinates of the directly localized PPN poles were within 0.5 mm of the atlas-based predicted values. Our findings provide simple, rapid and precise methods that are of clinical relevance to the atlas-based and direct stereotactic localization of the human PPN. Direct MRI localization may allow greater individual accuracy than that afforded by atlas-based coordinates when localizing the human PPN and may be relevant to groups evaluating the clinical role of PPN DBS.

Cholinergic mesencephalic neurons are involved in gait and postural disorders in Parkinson disease

“…Indeed, the direct involvement of PPN neurons in the control of gait and posture is in line with recent clinical data in PD patients showing that low-frequency electrical stimulation of the PPN area improved axial symptoms (10)(11)(12)(13)(14). The contribution of PPN cholinergic neurons could not have been determined previously from studies that used electrical stimulation or pharmacological manipulations.…”

“…In PD, among the different nondopaminergic neuronal systems affected (7), cholinergic cell loss was found in the PPN of patients with the most severe dopaminergic degeneration (8). Based on the assumption that gait failure is induced by PPN lesion or dysfunction (9), recent therapeutic trials tested the efficacy of electrical modulation of the PPN in reducing these symptoms in selected parkinsonian patients (10)(11)(12)(13)(14). However, the variability of the results raised doubts about the initial hypothesis and emphasized the need to determine the role of the PPN, in particular its cholinergic part, in gait and posture.…”

Where and what is the PPN and what is its role in locomotion?

“…The exact location of the PPN is controversial. Moreover, the PPN is not a closed structure with demarcated boundaries, and is thus elusive to clinically available MRI (Zrinzo et al, 2008). Stereotactic atlases generally rely on cytoarchitectural techniques that identify only the rostral component containing the pars compacta.…”

“…Stereotactic atlases generally rely on cytoarchitectural techniques that identify only the rostral component containing the pars compacta. These atlases have guided many surgical centres to implant only the rostral PPN (Zrinzo et al, 2008;Ferraye et al, 2010). However, it is clear from studies using immunohistochemistry that PPN cholinergic neurons of the pars dissipata [revealed by staining with choline-acetyltransferase antibodies (ChAT5)] extend far more caudally (Mesulam et al, 1989).…”

Critical evaluation of the anatomical location of the Barrington nucleus: Relevance for deep brain stimulation surgery of pedunculopontine tegmental nucleus

“…In clinical practice, the location of the PPN on standard clinical imaging can only be inferred from the visualized surrounding structures on MRI (Zrinzo et al, 2008). The PPN lies in the lateral pontine and mesencephalic tegmental reticular zones, straddling the pontomesencephalic junction, with its long axis roughly parallel to that of the fourth ventricle floor.…”