Brain metastases are frequently treated with radiation. It is critical to distinguish recurrent or progressive brain metastases (RPBM) from late or delayed radiation injury (LDRI). The purpose of this study was to examine the diagnostic accuracy as well as the prognostic power of 6-18 F-fluoro-L-dopa ( 18 F-FDOPA) PET for differentiating RPBM from LDRI. Methods: Thirty-two patients who had 83 previously irradiated brain metastases and who underwent 18 F-FDOPA PET because of an MR imaging-based suggestion of RPBM were studied retrospectively. PET studies were analyzed semiquantitatively (lesion-to-striatum and lesion-to-normal brain tissue ratios based on both maximum and mean standardized uptake values) and visually (4-point scale). The diagnostic accuracy of PET was verified by histopathologic analysis (n 5 9) or clinical follow-up (n 5 74) on a lesion-by-lesion basis. Receiver operating characteristic curve analysis was used to identify the best diagnostic indices. The power of 18 F-FDOPA PET to predict disease progression was evaluated with the Kaplan-Meier and Cox regression methods. Results: The best overall accuracy was achieved by visual scoring, with which a score of 2 or more (lesion uptake greater than or equal to striatum uptake) resulted in a sensitivity of 81.3% and a specificity of 84.3%. Semiquantitative 18 F-FDOPA PET uptake indices based on lesion-to-normal brain tissue ratios were significantly higher for RPBM than for LDRI. Among the various predictors tested, 18 F-FDOPA PET was the strongest predictor of tumor progression (hazard ratio, 6.26; P , 0.001), and the lesion-to-normal brain tissue ratio or visual score was the best discriminator. The mean time to progression was 4.6 times longer for lesions with negative 18 F-FDOPA PET results than for lesions with positive 18 F-FDOPA PET results (76.5 vs. 16.7 mo; P , 0.001). 18 F-FDOPA PET findings tended to predict overall survival. Conclusion: Metabolic imaging with 18 F-FDOPA PET was useful for differentiating RPBM from LDRI. Semiquantitative indices, particularly lesionto-normal uptake ratios, could be used. A visual score comparing tumor 18 F-FDOPA uptake and striatum 18 F-FDOPA uptake provided the highest sensitivity and specificity and was predictive of disease progression.
Gait dysfunction in Parkinson's disease (PD) does not always respond to bilateral subthalamic nucleus deep brain stimulation (STN-DBS). Since right hemisphere motor networks may be dominant for gait control, identical stimulation of asymmetric circuits could account for gait dysfunction. We compared the effects of bilateral and unilateral STN-DBS on gait kinematics in PD patients who developed gait impairment after STN-DBS. Twenty-two PD patients with >50 % improvement in motor scores, but dopamine-resistant gait dysfunction 6-12 months after bilateral STN-DBS were blindly tested off dopaminergic effects in four randomly assigned DBS conditions: bilateral, right-sided, left-sided and off stimulation. Motor scores (MDS-UPDRS III), gait scores (MDS-UPRDS 2.11-2.13 + 3.9-3.13), turning time (seconds), stride length (meters) and velocity (meters/second) were measured 1 h after DBS changes. Motor and gait scores significantly improved with bilateral versus unilateral STN-DBS. Stride length and velocity (0.95 ± 0.06, 0.84 ± 0.07) significantly improved with bilateral (1.09 ± 0.04, 0.95 ± 0.05), right-sided (1.06 ± 0.04, 0.92 ± 0.05) and left-sided stimulation (1.01 ± 0.05, 0.90 ± 0.05) (p < 0.05). Stride length significantly improved with right-sided versus left-sided (0.05 ± 0.02) and bilateral versus left-sided stimulation (0.07 ± 0.02) (p < 0.05). Turning time (4.89 ± 0.6) tended to improve with bilateral (4.13 ± 0.5) (p = 0.15) and right-sided (4.27 ± 0.6) (p = 0.2) more than with left STN-DBS (4.69 ± 0.5) (p = 0.5). Bilateral STN-DBS yields greater improvement in motor and gait scores in PD patients. Yet, unilateral stimulation has similar effects on gait kinematics. Particularly, right-sided stimulation might produce slightly greater improvements. Although the clinical relevance of differential programming of right versus left-sided STN-DBS is unclear, this approach could be considered in the management of treatment-resistant gait dysfunction in PD.
Phenotype is the set of observable traits of an organism or condition. While advances in genetics, imaging, and molecular biology have improved our understanding of the underlying biology of Parkinson's disease (PD), clinical phenotyping of PD still relies primarily on history and physical examination. These subjective, episodic, categorical assessments are valuable for diagnosis and care but have left gaps in our understanding of the PD phenotype. Sensors can provide objective, continuous, real-world data about the PD clinical phenotype, increase our knowledge of its pathology, enhance evaluation of therapies, and ultimately, improve patient care. In this paper, we explore the concept of deep phenotyping-the comprehensive assessment of a condition using multiple clinical, biological, genetic, imaging, and sensor-based tools-for PD. We discuss the rationale for, outline current approaches to, identify benefits and limitations of, and consider future directions for deep clinical phenotyping.
Background Deep brain stimulation (DBS) effects on postural deformities are still poorly explored. Methods Systematic review in accord with the Preferred Reporting Items for Systematic review and Meta‐Analysis guidelines (PRISMA). Results All 38 studies that met predefined eligibility criteria had high risk of bias attributed to retrospective analysis of heterogeneous populations with variable and incompletely reported demographic and clinical characteristics, definitions, outcomes, DBS indications, targets, and settings. Five patient groups were identified in the 35 studies with individual data available: (1) parkinsonian camptocormia (n = 96): 89 patients underwent subthalamic (STN) and 7 globus pallidus pars interna (GPi) DBS. Camptocormia was the indication in 3 patients. After DBS, camptocormia improved in 57 of 96 patients (4.3–100% improvement) and remained stable or worsened in 39 of 96 patients (2–100% worsening). (2) dystonic camptocormia (n = 16): All underwent GPi‐DBS. They were younger and with shorter disease duration, but longer deformity duration, compared with parkinsonian camptocormia. After GPi‐DBS, camptocormia improved in all patients (50–100% improvement). (3) Parkinsonian Pisa syndrome (n = 14): 11 patients underwent STN‐DBS for motor fluctuations whereas Pisa syndrome was the indication for pedunculopontine and GPi‐DBS in 2 patients. After DBS, Pisa improved in 10 of 14 patients (33.3–66.7% improvement). (4) Dystonic opisthotonus: 2 young patients remarkably responded to GPi‐DBS. (5) Parkinsonian anterocollis: There were variable responses in 3 patients after STN‐DBS for motor fluctuations. Conclusions Low‐quality level of evidence suggests that dystonic camptocormia and opisthotonus improve after GPi‐DBS. Parkinsonian camptocormia, Pisa syndrome, and anterocollis have variable responses, and their dystonic features should be further explored.
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