Unilateral extradural motor cortex stimulation is safe and improves Parkinson disease at 1 year.

BACKGROUND: The primary motor cortex, which is part of the corticobasal ganglia loops, may be an alternative option for the surgical treatment of Parkinson disease. OBJECTIVE: To report on the 1-year safety and efficacy of unilateral extradural motor cortex stimulation in Parkinson disease. METHODS: A quadripolar electrode strip was extradurally implanted over the motor cortex. Stimulation was continuously delivered through the electrode paddle contralateral to the most affected clinical side. Subjects were prospectively evaluated by the Unified Parkinson's Disease Rating Scale (UPDRS) and the Parkinson's Disease Quality of Life Questionnaire. In addition, an extensive cognitive and behavioral assessment and electroencephalogram recording were performed. RESULTS: Nine patients were included in this study. No surgical complications or adverse events occurred. Moreover, no cognitive or behavioral changes were observed. Under the off-medication condition, the UPDRS III at baseline was decreased by 14.1%, 23.3%, 19.9%, and 13.2%, at 1, 3, 6, and 12 months, respectively. The motor effects were bilateral, appeared after 3 to 4 weeks of stimulation, and outlasted the stimulation itself for 3 to 4 weeks in 1 case of stimulator accidental switching off. The UPDRS IV was decreased by 40.8%, 42.1%, and 35.5% at 1, 3, and 12 months, respectively. The scores on the Parkinson's Disease Quality of Life Questionnaire were increased at months 3, 6, and 12. CONCLUSION: Extradural motor cortex stimulation is a safe procedure. After 12 months, the patients demonstrated a moderate improvement of motor symptoms (particularly axial symptoms) and quality of life.

Effects of stimulation of the subthalamic nucleus on naming and reading nouns and verbs in Parkinson's disease.

UNLABELLED: An impairment for verbs has been described in patients with Parkinson's disease (PD), suggesting that a disruption of frontal-subcortical circuits may result in dysfunction of the neural systems involved in action-verb processing. A previous study suggested that deep brain stimulation (DBS) of the subthalamic nucleus (STN) during verb generation may affect the ability to select from many competing lexical alternatives. In this study, 12 PD patients who had undergone bilateral STN DBS and completed an 8-year follow-up and 14 matched normal controls were administered action and object naming tasks and verb and noun reading tasks. Their responses were recorded using a microphone, resulting in a signal that marked the onset of the verbal response and allowed to measure response times (RTs). Accuracy was scored manually. RESULTS: Overall performance in naming (independently of stimulation): In naming task controls were faster and more accurate than PD patients. In both groups, performance (accuracy and RTs) was worse on action naming than object naming. PD patients were significantly slower than controls in naming actions. Effect of stimulation: Compared with the OFF stimulation condition, in ON stimulation condition PD patients showed improved performance on object and action naming tasks (increased accuracy, faster RTs), with a decreased number of semantic errors. Some evidence also emerged that action naming in the ON stimulation condition improved more than object naming. On noun and verb reading tasks, although accuracy was at ceiling in both groups and no significant difference was observed in RTs for nouns and verbs, PD patients were slower than controls. CONCLUSIONS: Our findings suggest that STN DBS may improve lexical search in PD patients. We hypothesize that STN stimulation may facilitate the motor components involved in naming and reading tasks (increased speed of speech onset), resulting in shorter RTs in both naming and reading and, to some extent, in increased accuracy in naming due to fewer omissions (no response within the 7500 ms time limit). However, to account for greater accuracy in naming due to decreased number of semantic errors in the ON stimulation condition, we hypothesize that STN stimulation restores the activity of the corticostriatal circuits involved in selection processes of a target word among different alternatives.

Presentation and validation of the multiple sclerosis depression rating scale: a test specifically devised to investigate affective disorders in multiple sclerosis patients.

Accurate diagnosis of depression in patients affected by MS is important, as it may be a cause of reduced quality of life and increased suicide risk. We present a new scale, the Multiple Sclerosis Depression Rating Scale (MSDRS), and assess its diagnostic accuracy in comparison to the Beck Depression Inventory (BDI). A total of 94 MS participants were classified as non-depressed (N = 44) or affected by mood disorder associated to MS with depressive manifestations (MSD-MDDM; N = 37) or with a major depression-like episode (MSD-MDL; N = 13). Each participant underwent a psychiatric interview, MSDRS, and BDI; diagnostic accuracy was evaluated using area under the ROC curve (AROC). The diagnostic accuracy of MSDRS and BDI was comparable when diagnosing both MSD-MDDM and MSD-MDL (AROC respectively 0.8998 and 0.8659); the MSDRS showed higher accuracy for the diagnosis of MSD-MDL (AROC respectively 0.9278 and 0.8314; p = .038). The MSDRS may be a reliable tool for the diagnosis of depression in MS.

Motor and cognitive outcome in patients with Parkinson's disease 8 years after subthalamic implants.

Deep brain stimulation of the subthalamic nucleus represents the most important innovation for treatment of advanced Parkinson's disease. Prospective studies have shown that although the beneficial effects of this procedure are maintained at 5 years, axial motor features and cognitive decline may occur in the long term after the implants. In order to address some unsolved questions raised by previous studies, we evaluated a series of 20 consecutive patients who received continuous stimulation for 8 years. The overall motor improvement reported at 5 years (55.5% at Unified Parkinson's Disease Rating Scale-motor part, P < 0.001 compared with baseline) was only partly retained 3 years later (39%, P < 0.001, compared with baseline; -16.5%, P < 0.01, compared with 5 years), with differential effects on motor features: speech did not improve and postural stability worsened (P < 0.05). The preoperative levodopa equivalent daily dose was reduced by 58.2% at 5 years and by 60.3% at 8 years. In spite of subtle worsening of motor features, a dramatic impairment in functional state (-56.6% at Unified Parkinson's Disease Rating Scale-Activities of Daily Living, P < 0.01) emerged after the fifth year of stimulation. The present study did not reveal a predictive value of preoperative levodopa response, whereas few single features at baseline (such as gait and postural stability motor scores and the preoperative levodopa equivalent daily dose) could predict long-term motor outcome. A decline in verbal fluency (slightly more pronounced than after 5 years) was detected after 8 years. A significant but slight decline in tasks of abstract reasoning, episodic memory and executive function was also found. One patient had developed dementia at 5 years with further progression at 8 years. Executive dysfunction correlated significantly with postural stability, suggesting interplay between axial motor deterioration and cognition. Eight years after surgery, no significant change was observed on scales assessing depression or anxiety when compared with baseline. At 8 years, there was no significant increase of side-effects when compared with 5-year follow-up. In conclusion, deep brain stimulation of the subthalamic nucleus is a safe procedure with regard to cognitive and behavioural morbidity over long-term follow-up. However, the global benefit partly decreases later in the course of the disease, due to progression of Parkinson's disease and the appearance of medication- and stimulation-resistant symptoms.

High frequency extradural motor cortex stimulation transiently improves axial symptoms in a patient with Parkinson's disease.

In a primate model of Parkinson's disease (PD), the benefit of extradural motor cortex stimulation (EMCS) was associated with high-frequency stimulation (130 Hz), whereas no significant motor improvement was achieved at 10 Hz or intermediate frequencies of stimulation. We report the case of a 72-year-old female patient affected by severe PD who underwent bilateral EMCS. In baseline med-off condition the patient was unable to arise from a chair and to stand without assistance. Stimulation at 3 and 60 Hz failed to provide any improvement of symptoms, whereas, when stimulating at 130 Hz, axial akinesia and walking improved consistently: the patient, in med-off condition, was able to arise from chair and to walk without assistance. The patient underwent two brain 99mTc- Ethylcysteinate Dimer-SPECT studies: semiquantitative and Statistical Parametric Mapping revealed that the regional cerebral perfusion was significantly increased in the supplementary motor area during stimulation at 130 Hz. After five months, the benefit of EMCS gradually disappeared.