Abbas F Sadikot — Page 2

PubMed2002

Optimal location of thalamotomy lesions for tremor associated with Parkinson disease: a probabilistic analysis based on postoperative magnetic resonance imaging and an integrated digital atlas.

OBJECT: Renewed interest in stereotactic neurosurgery for movement disorders has led to numerous reports of clinical outcomes associated with different treatment strategies. Nevertheless, there is a paucity of autopsy and imaging data that can be used to describe the optimal size and location of lesions or the location of implantable stimulators. In this study the authors correlated the clinical efficacy of stereotactic thalamotomy for tremor with precise anatomical localization by using postoperative magnetic resonance (MR) imaging and an integrated deformable digital atlas of subcortical structures. METHODS: Thirty-one lesions were created by stereotactic thalamotomy in 25 patients with tremor-dominant Parkinson disease. Lesion volume and configuration were evaluated by reviewing early postoperative MR images and were correlated with excellent, good, or fair tremor outcome categories. To allow valid comparisons of configurations of lesions with respect to cytoarchitectonic thalamic boundaries, the MR image obtained in each patient was nonlinearly deformed into a standardized MR imaging space, which included an integrated atlas of the basal ganglia and thalamus. The volume and precise location of lesions associated with different clinical outcomes were compared using nonparametric statistical methods. Probabilistic maps of lesions in each tremor outcome category were generated and compared. Statistically significant differences in lesion location between excellent and good. and excellent and fair outcome categories were demonstrated. On average, lesions associated with excellent outcomes involved thalamic areas located more posteriorly than sites affected by lesions in the other two outcome groups. Subtraction analysis revealed that lesions correlated with excellent outcomes necessarily involved the interface of the nucleus ventralis intermedius (Vim; also known as the ventral lateral posterior nucleus [VLp]) and the nucleus ventrocaudalis (Vc; also known as the ventral posterior [VP] nucleus). Differences in lesion volume among outcome groups did not achieve statistical significance. CONCLUSIONS: Anatomical evaluation of lesions within a standardized MR image-atlas integrated reference space is a useful method for determining optimal lesion localization. The results of an analysis of probabilistic maps indicates that optimal relief of tremor is associated with lesions involving the Vim (VLp) and the anterior Vc (VP).

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PubMedDate not supplied

Glutamate and regulation of proliferation in the developing mammalian telencephalon.

Increasing evidence suggests that classical neurotransmitters play an important morphogenetic role during development of the mammalian central nervous system. Using in vitro and in vivo models, we have previously identified a role for the N-methyl-D-aspartate (NMDA) subclass of glutamate receptors in the proliferation of striatal progenitors. Here, we compare the roles of ionotropic glutamate receptors in the proliferation of either striatal or cortical progenitors. In culture, glutamate receptor activation promoted proliferation of both striatal and cortical neuroblasts. However, cortical and striatal neuroblasts responded to distinct ionotropic receptors. Cortical cultures were sensitive to AMPA/KA receptor blockade, whereas striatal neuroblast proliferation was altered by NMDA antagonists. In vivo, BrdU uptake in the proliferative ventricular zone was reduced in embryos following acute administration of ionotropic glutamate receptor antagonists. In keeping with in vitro observations, proliferation in cortical and striatal ventricular regions was reduced, respectively, by either AMPA/KA or NMDA receptor blockade. We also determined whether forebrain-derived progenitors expanded as neurospheres in the presence of growth factors show similar ionotropic glutamatergic responses. Cells in neither dorsal nor ventral telencephalon-derived neurospheres showed altered proliferation following exposure to either class of ionotropic glutamate receptor antagonist. Together, these findings suggest that glutamate influences the proliferation of forebrain neuronal progenitors, but not more primitive populations represented in multipotential progenitors expanded in vitro. The effects on neuroblast proliferation in different forebrain domains are heterogeneous and are mediated by distinct subclasses of ionotropic glutamate receptors.

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