Influence of subthalamic deep brain stimulation versus levodopa on motor perseverations in Parkinson's disease.

Patients with Parkinson's disease (PD) show impairment in generating random motor sequences reflecting a higher order motor deficit in set-shifting and suppression of perseverative behavior. The impact of deep brain stimulation (DBS) of the subthalamic nucleus (STN) on motor perseverations has not yet been elucidated. In 35 patients with PD, we evaluated the effect of STN-DBS and levodopa on motor perseverations using the Vienna perseveration task. The task was performed 6 months after implantation of stimulation electrodes in the following three conditions: Stimulation off/medication off (Stim OFF/Med OFF), Stim ON/Med OFF, and Stim OFF/Med ON. Perseverations were measured by redundancy of second order (R(2)) with higher values indicating more severe perseverations. ANCOVA analysis revealed that influence of STN-DBS on R(2) significantly depended on R(2) severity during Stim OFF/Med OFF (F = 4.69, P = 0.035). Accordingly, we classified patients with PD into two groups based on the R(2) value during off treatment. In patients with mild perseveration (R(2) < 35) neither STN-DBS nor levodopa changed perseverations. By contrast, in patients with severe perseveration (R(2) > 35), STN-DBS significantly reduced R(2) by 9.7 +/- 2.6 (P < 0.001) whereas levodopa had no impact (R(2) reduction 3.7 +/- 1.6, P = 0.081). This demonstrates that STN-DBS, by reducing motor perseveration, influences higher order aspects of motor behavior of patients with PD.

Herzog J ，Möller B ，Witt K ，Pinsker MO ，Deuschl G ，Volkmann J ... -  《-》

Differential effects of levodopa and subthalamic nucleus deep brain stimulation on bradykinesia in Parkinson's disease.

Cardinal symptoms of Parkinson's disease (PD) respond well to treatment with levodopa and deep brain stimulation (DBS) of the subthalamic nucleus (STN). However, it has remained unclear whether levodopa and STN-DBS have differential effects on bradykinesia. We investigated 8 PD-patients with STN-electrodes in four conditions: STN-DBS and levodopa (ON(MED)/ON(STIM)), STN-DBS only (OFF(MED)/ON(STIM)), levodopa only (ON(MED)/OFF(STIM)), without STN-DBS/levodopa (OFF(MED)/OFF(STIM)). Fourteen volunteers served as controls. Subjects performed fastest possible (1) pronation/supination of the forearm (diadochokinesia) and (2) flexion and extension of the index finger (finger movements). Movements were recorded using a 3D-ultrasound-system. Maximum frequency, amplitude, and smoothness of movements were determined. During OFF(MED)/OFF(STIM), all parameters were worser than in all other conditions. In proximal diadochokinesia, OFF(MED)/ON(STIM) significantly improved the amplitude and frequency, whereas ON(MED)/OFF(STIM) had no significant effect. In contrast, we found a stronger effect of levodopa (ON(MED)/OFF(STIM)) on amplitudes of distal finger movement than on amplitudes of diadochokinesia. Combination of treatments during ON(MED)/ON(STIM) further improved both movements. However, maximum frequency remained lower in PD-patients during ON(MED)/ON(STIM) compared with controls. This study demonstrates a better effect of levodopa on distal finger movements and STN-DBS on proximal diadochokinesia. Furthermore, a complementary effect of both therapies on brain areas involved in bradykinesia can be assumed.

Timmermann L ，Braun M ，Groiss S ，Wojtecki L ，Ostrowski S ，Krause H ，Pollok B ，Südmeyer M ，Ploner M ，Gross J ，Maarouf M ，Voges J ，Sturm V ，Schnitzler A ... -  《-》

Acute psychotropic effects of bilateral subthalamic nucleus stimulation and levodopa in Parkinson's disease.

High-frequency deep brain stimulation (DBS) of the subthalamic nucleus (STN) improves the motor symptoms of Parkinson's disease (PD). Opposite changes in mood, such as mania or depression, have been reported after surgery, but it is not known whether these side effects are specifically related to STN DBS. To learn whether STN DBS also influences the limbic loop, we investigated acute subjective psychotropic effects related to levodopa or bilateral STN DBS. After a median postoperative follow-up of 12 months, 50 PD patients completed the Addiction Research Center Inventory (ARCI), assessing subjective psychotropic effects in four conditions: off-drug/on-stimulation; off-drug/off-stimulation; on-drug/off-stimulation; and on-drug/on-stimulation. Both levodopa and STN DBS improved all the ARCI subscales, indicating subjective feelings of well being, euphoria, increase in motivation, and decrease in fatigue, anxiety, and tension. A suprathreshold dose of levodopa was significantly more effective than STN DBS, using the same electrical parameters as for chronic stimulation, on four of the five ARCI subscales. We concluded that 1) both STN DBS and levodopa have synergistic acute beneficial psychotropic effects in PD, 2) the psychotropic effects of both treatments need to be considered in the long-term management of chronic STN DBS, and 3) the results indicate an involvement of the limbic STN in mood disorders of PD.

Funkiewiez A ，Ardouin C ，Krack P ，Fraix V ，Van Blercom N ，Xie J ，Moro E ，Benabid AL ，Pollak P ... -  《MOVEMENT DISORDERS》

Effects of DBS, premotor rTMS, and levodopa on motor function and silent period in advanced Parkinson's disease.

Bäumer T ，Hidding U ，Hamel W ，Buhmann C ，Moll CK ，Gerloff C ，Orth M ，Siebner HR ，Münchau A ... -  《-》

Bilateral deep brain stimulation in Parkinson's disease: a multicentre study with 4 years follow-up.

Rodriguez-Oroz MC ，Obeso JA ，Lang AE ，Houeto JL ，Pollak P ，Rehncrona S ，Kulisevsky J ，Albanese A ，Volkmann J ，Hariz MI ，Quinn NP ，Speelman JD ，Guridi J ，Zamarbide I ，Gironell A ，Molet J ，Pascual-Sedano B ，Pidoux B ，Bonnet AM ，Agid Y ，Xie J ，Benabid AL ，Lozano AM ，Saint-Cyr J ，Romito L ，Contarino MF ，Scerrati M ，Fraix V ，Van Blercom N ... -  《-》