F143 Systemic assessment of motor pathophysiology of corticobasal syndrome

Abstract

Introduction Corticobasal syndrome (CBS) is a kind of tauopathy with parkinsonism presenting chronic onset of progressive unilateral motor impairment, including subjective weakness, dystonia and parkinsonism, and cognition change, such as apraxia, sensory-motor dysfunction or memory impairment. Although several types of pathophysiology have been reported on CBS, a systemic physiological study on CBS has been lacking. Seeing the symptoms of CBS is a mixture of parkinsonism and other movement disorders, e.g. dystonia, we designed this study to investigate a wide range of motor physiology, including different forms of plasticity, the connection between the premotor cortex (PMd) and M1, and inhibitory circuits in the cortex, brainstem and spinal cord, in patients with CBS. Methods We rolled in 21 patients with CBS diagnosed by Cambridge criteria and age-matched health subjects. All subjects signed informed consent under supervision of approval of the Ethics Board of Chang Gung Memorial Hospital at Linkou. Studied protocols included (1) Motor LTP-like plasticity by cTBSc0: cTBS followed by 1-min slightly voluntary contraction of the contralateral FDI muscle, (2) SICI recruitment curve before and after cTBSc0, (3) depotentiation assessed by cTBSc0 and subsequent 10 s of cTBS (cTBS150), (4) brainstem blink reflex recovery cycle (BR), (5) spinal reciprocal inhibition (RI), and (6) PMd-M1 connectivity by assessing M1 excitability change in response to cTBS given to PMd. Results Although cTBSc0 successfully induced LTP, depotentiation was abnormal in patients with CBS. The SICI recruitment curve shifted to the left as compared to the controls in the baseline, and was moved toward to normal after cTBSc0. The blink reflex recovery curve was identical between CBS patients and healthy controls. RI showed reduced 3rd phase and normal 1st and 2nd phases, and the PMd-M1 connectivity was abnormal in patients with CBS. Conclusion Different from a previous study showing reduced LTP using iTBS, the current study revealed normal motor plasticity in CBS. Similar results were also found in PD patient at the medication ON state, in which cTBSc0, but not iTBS, was able to induce motor plasticity. The abnormal depotentiation in CBS who has not dyskinesia is different from that in PD patients and could be closer to the pathophysiology of dystonia. Abnormal SICI, which was normalized by cTBSc0, abnormal the third, but not other, phase(s) of RI and normal blink reflex recovery curve suggest the pathophysiology is mainly located in the cerebrum, while the brainstem and spinal cord are preserved. The abnormal PMd-M1 connectivity may be unspecific and has been also seen in both PD and dystonia. In summary, patients with CBS show unique presentation in a combination of different physiological assessments, suggesting the possibility of development of physiological biomarker for CBS. Moreover, rTMS over M1 may improve CBS according to the results in SICI.