Bilateral subthalamic nucleus stimulation in advanced Parkinson's disease: five year follow-up.

OBJECTIVE: To assess the long-term efficacy and safety of bilateral subthalamic nucleus (STN) stimulation in patients with advanced Parkinson's disease (PD). METHODS: 42 consecutive patients with idiopathic PD treated with bilateral STN stimulation were enrolled. Parkinsonian status, medication intake and neuropsychological evaluation were assessed preoperatively and at 1 and 5 years postoperatively in on and off medication/on and off stimulation conditions. RESULTS: 23 patients could be followed-up 5 years after surgery. In the remaining cases, 5 died, 1 could not be assessed because of device removal for infection, 1 decided not to be stimulated, and 11 were lost of follow-up (one because of a liver carcinoma and the others because they refused the formal four conditions of assessment). STN stimulation reduced the UPDRS motor score by 55 % compared to baseline in the off-medication conditions. Tremor, rigidity, bradykinesia, postural stability, and gait improved by 74 %, 66 %, 59 %, 17 % and 37 %, respectively. UPDRS part II scores were reduced by 38 %. The dopaminergic treatment daily dose was reduced by 54.4 % after surgery. Axial dopa-unresponsive signs worsened in some patients. Among the 42 initial patients we observed the following: 2 brain hemorrhages, 3 infections of the device, 2 phlebitis and 1 pulmonary embolism. In addition, 2 patients needed a repositioning of the electrode. Among the 23 patients followed at 5 years, long lasting side effects consisted in dysarthria (56 %), depression (39 %), eyelid opening apraxia (30.4 %) and apathy (4.3 %). CONCLUSIONS: Our data confirm that bilateral STN stimulation is beneficial in the long-term for PD patients but does not prevent disease progression and the occurence of axial levodopa unresponsive signs in some patients.

Globus pallidus stimulation reduces frontal hyperactivity in tardive dystonia.

Tardive dystonia (TD) is a disabling disorder induced by neuroleptics. Internal globus pallidus (GPi) stimulation can dramatically improve TD. The present positron emission tomography and H(2)(15)O study aimed to characterize the abnormalities of brain activation of TD and the impact of GPi stimulation on these abnormalities in five TD patients treated with GPi stimulation and eight controls. Changes of regional cerebral blood flow (rCBF) were determined: (i) at rest; (ii) when moving a joystick with the right hand in three freely chosen directions in on and off bilateral GPi stimulation. A significant increase of rCBF was found in TD patients in off-stimulation condition compared to controls: (1) during motor execution in the prefrontal, premotor lateral, and anterior cingulate cortex; (2) at rest, in the prefrontal and anterior cingulate cortex and the cerebellum. Internal globus pallidus stimulation led to a reduction of rCBF (1) during motor execution, in the primary motor and prefrontal cortex and the cerebellum; (2) at rest, in the primary motor and anterior cingulate cortex and supplementary motor area. The results are as follows: (1) TD is related to an excess of brain activity notably in the prefrontal and premotor areas; (2) GPi stimulation reduces the activation of motor, premotor, and prefrontal cortex as well as cerebellum.

Epilepsia partialis continua with dystonic hand movement in a patient with a malformation of cortical development.

Malformations of cortical development (MCD) with polymicrogyria and schizencephaly are due to abnormal cortical organization and usually manifest by intractable epilepsy and mental retardation. Epileptical activity is often hard to register and focal dystonia associated with such MCD has previously been described but without any metabolic imaging. We report here a 46-year-old man presenting with late-onset atypical abnormal movements of his left hand associated with right central region MCD. To demonstrate the involvement of an epileptical focus, we performed [(18)F]FDG-PET and fMRI both before and after a single dose of clobazam and diazepam, respectively. Characteristics of the abnormal hand movements, clinical response to the medication, and the result of the [(18)F]FDG-PET and fMRI investigations all favor the diagnosis of epilepsia partialis continua. We conclude that the dystonic movement is part of the partial seizure.

Bilateral subthalamic nucleus stimulation in advanced Parkinson's disease: three years follow-up.

OBJECTIVE: To assess the long-term efficacy and safety of chronic bilateral stimulation of the subthalamic nucleus (STN) in patients with advanced Parkinson's disease (PD). METHODS: 36 consecutive patients with idiopathic Parkinson's disease treated with bilateral stimulation of the STN were studied. Parkinsonian status was assessed preoperatively and at 1 and 3 years postoperatively using the Unified Parkinson's Disease Rating Scale (UPDRS) and neuropsychological evaluation in on and off-medication / on and off stimulation conditions. RESULTS: At 3 years follow-up, STN stimulation reduced the UPDRS motor score by 54.2 % compared to baseline in the off-medication conditions. Tremor, rigidity, bradykinesia, postural stability, and gait improved by 72.2 %, 62.4 %, 56.8 %, 40.5 % and 45.3 %, respectively. UPDRS part II scores were reduced by 41.4 %. The overall dopaminergic drugs dose was reduced by 48.6 % after surgery and four patients were no longer taking antiparkinsonian medication at three years. However, axial dopa-unresponsive signs worsened in some patients. The most frequent transient adverse event consisted in mood disorders in 23 patients. CONCLUSIONS: Our data demonstrate that: 1) bilateral STN stimulation is relatively safe, improves the motor symptoms and drug-related motor complications of PD, and reduces the daily dosage of medication; 2) this benefit is sustained over time despite the occurrence of axial doparesistant signs in some patients.

Contribution of Jules Froment to the study of parkinsonian rigidity.

Rigidity is commonly defined as a resistance to passive movement. In Parkinson's disease (PD), two types of rigidity are classically recognized which may coexist, "leadpipe " and "cogwheel". Charcot was the first to investigate parkinsonian rigidity during the second half of the nineteenth century, whereas Negro and Moyer described cogwheel rigidity at the beginning of the twentieth century. Jules Froment, a French neurologist from Lyon, contributed to the study of parkinsonian rigidity during the 1920s. He investigated rigidity of the wrist at rest in a sitting position as well as in stable and unstable standing postures, both clinically and with physiological recordings using a myograph. With Gardère, Froment described enhanced resistance to passive movements of a limb about a joint that can be detected specifically when there is a voluntary action of another contralateral body part. This has been designated in the literature as the "Froment's maneuver " and the activation or facilitation test. In addition, Froment showed that parkinsonian rigidity diminishes, vanishes, or enhances depending on the static posture of the body. He proposed that in PD "maintenance stabilization " of the body is impaired and that "reactive stabilization " becomes the operative mode of muscular tone control. He considered "rigidification " as compensatory against the forces of gravity. Froment also demonstrated that parkinsonian rigidity increases during the Romberg test, gaze deviation, and oriented attention. In their number, breadth, and originality, Froment's contributions to the study of parkinsonian rigidity remain currently relevant to clinical and neurophysiological issues of PD.

Chorea induced by globus pallidus externus stimulation in a dystonic patient.

Bilateral high-frequency stimulation of the internal part of the pallidum has proven its efficacy in improving motor symptoms of dystonia. In Parkinson's disease, the stimulation of the external pallidum (GPe) can induce dyskinesias. This has never been described in dystonia. We report here a case of abnormal movements induced by the stimulation of GPe in a dystonic patient and discuss the pathophysiological mechanisms.

Can chronic subthalamic nucleus stimulation induce de novo tremor in Parkinson's disease?

Subthalamic nucleus stimulation dramatically improves parkinsonian symptoms, notably the tremor. The occurrence of a tremor in the first 6 months after the surgical procedure in patients without tremor preoperatively is much less common. We report on the cases of 3 patients who developed such modification of their parkinsonian symptomatology. Physiopathological hypotheses are discussed.

Role of dopaminergic treatment in dopamine receptor down-regulation in advanced Parkinson disease: a positron emission tomographic study.

BACKGROUND: In patients with advanced Parkinson disease (PD) who are undergoing long-term treatment with a dopaminergic medication, a down-regulation of striatal dopamine D2 receptor expression has been demonstrated and interpreted as a consequence of either the disease itself or dopaminergic drug administration. OBJECTIVE: To compare, using positron emission tomography, the striatal binding of raclopride carbon C 11, a dopamine D2 receptor ligand, in PD patients who completely discontinued dopaminergic therapy (off drug) with that in PD patients who continued receiving dopaminergic therapy (on drug) after undergoing subthalamic nucleus stimulation. MAIN OUTCOME MEASURES: The positron emission tomographic data were acquired in off-stimulation and, for 12 hours, off-medication conditions. Five off-drug PD patients, 7 on-drug PD patients, and 8 healthy subjects participated. RESULTS: In off-drug PD patients, the putaminal raclopride C 11 binding was 24% higher than in on-drug PD patients. The same tendency was noted for the caudate nucleus, but was not significant (P=.07). Compared with control subjects, the putaminal raclopride C 11 binding was increased by 21% in off-drug and was normal in on-drug PD patients. Compared with controls, the caudate raclopride C 11 binding was reduced by 23% in on-drug and was normal in off-drug PD patients. Further analysis using statistical parametric mapping showed a significant increase of binding bilaterally in the caudate nucleus and putamen in off-drug compared with on-drug PD patients (P=.002 at cluster level). CONCLUSIONS: The down-regulation of dopamine D2 receptors probably relates to the long-term and intermittent administration of dopaminergic treatments rather than to disease progression. This phenomenon is reversed by the complete withdrawal of dopaminergic drugs. Furthermore, an up-regulation of putaminal dopamine D2 receptors is demonstrated in late-stage PD after dopaminergic drug withdrawal.