Neuronal Laterality & Postoperative Changes of GABA+Glu. Activity by In Vivo 1H MRS

Son, Byung Chul; Kim, Moon Chan; Cho, Sung Hwan; Jun, Sin Soo; Kang, Joon Ki; Choe, Bo Young; Choi, Kyu Ho

Abstract

Object of this study was to to evaluate the laterality of local cerebral cellular metabolism in various locations of the brain related to the symptomatic side of patients with clinically diagnosed idiopathic Parkinson's disease (IPD) and to verify GABA-related pathophysiology in IPD by comparing postoperative changes in (GABA+Glutamate)/Cr ratio from patients with IPD after stereotactic pallidotomy and thalamotomy. Fourteen patients with IPD(10 males and 4 females: age range 39-67 years) participated in the study. The patients were classified into two disease subgroups, one for tremor dominant group(n=7, T group), and the other bradykinesia and rigidity dominant one(n=7, B&R group). For T group, stereotactic VL(Vop, Vim) thalamotomy and subthalamotomy was performed and for the B&R group, stereotactic posteroventrolateral pallidotomy was selected. In Vivo 1H MRS study was performed on a 1.5 T MRI/MRS system(GE Sigma Advantage, version 4.8) using STEAM sequence after water suppression with CHESS RF pulse and dephasing gradients. After peak areas of creatine/phosphocreatine(Cr), choline-containning compound(Cho), N-Acetyl Aspartate(NAA), r-aminobutyric acid, (GABA) and glutamate(Glu) were calculated and processed, the metabolic ratios of NAA/Cr, Cho/Cr, and (GABA+Glu)/Cr in three different locations were calculated and compared with clinical symptoms and its changes after surgery. For the neuronal laterality in patients with IPD, there was significant differences of NAA/Cr ratio between the right and left sides of substantia nigra, thalamus and pallidum(p=0.00170). The magnitude of difference in NAA/Cr ratios between right and left side were significantly larger in substantia nigra(p=0.0141). Compared to the normal control values(1.82+/-0.52 in ages 27-50, 1.71+/-0.54 in ages 51-70 years), the neuronal loss was generally observed in at least one of three locationsin all patients. Moreover, NAA/Cr ratio was substantially lower in ipsilateral than contralateral substantia nigra of the parkinsonian symptomatic side. For preoperative(GABA+Glu)/Cr ratios of thalamus contralateral to the symptomatic side compared to that of ipsilateral, it was significant larger in thalamus of B&R group and significant smaller in T group. In the pallidotomy group, there was significant increase in the operated pallidum, whereas significant decrease in (GABA+Glu)/Cr ratios were noted in the operated side thalamus. And in the thalamotomy group, there were significant increase in the operated thalamus, whereas in the operated side pallidum, significant decrease in (GABA+Glu)/Cr ratios were noted. Neuronal laterality, pallidal neuronal loss and postoperative changes in GABA activity in patients with IPD were demonstrated on the basis of NAA/Cr and (GABA+Glu)/Cr ratio by In Vivo 1H MRS. The neuronal laterality was detected in the substantia nigra of all the parkinsonian patient, and NAA/Cr ratios in unilateral and bilateral disease were consistently lower in ipsilateral than in contralateral substantia nigra of the Parkinsonian disease side. Our result suggests that there may be another ongoing pathological process of ipsilateral neuronal degeneration with contralateral dopaminergic neuronal loss. The result of neuronal loss in pallidum supports with the previous reports concerning striatal degeneration in IPD. Our results concerning postoperative changes of (GABA+Glu)/Cr ratio suggests that separate pathophysiologic mechanisms may be involved in the development of two dominant symptom groups of IPD. That is, for the B&R group, pallidal overinhibition to the thalamus by the GABA-ergic system as previously noted, but for T group, a process other than GABA inhibitory mechanism with or without it may be involved.