A randomized trial of deep-brain stimulation for Parkinson's disease.

BACKGROUND: Neurostimulation of the subthalamic nucleus reduces levodopa-related motor complications in advanced Parkinson's disease. We compared this treatment plus medication with medical management. METHODS: In this randomized-pairs trial, we enrolled 156 patients with advanced Parkinson's disease and severe motor symptoms. The primary end points were the changes from baseline to six months in the quality of life, as assessed by the Parkinson's Disease Questionnaire (PDQ-39), and the severity of symptoms without medication, according to the Unified Parkinson's Disease Rating Scale, part III (UPDRS-III). RESULTS: Pairwise comparisons showed that neurostimulation, as compared with medication alone, caused greater improvements from baseline to six months in the PDQ-39 (50 of 78 pairs, P=0.02) and the UPDRS-III (55 of 78, P<0.001), with mean improvements of 9.5 and 19.6 points, respectively. Neurostimulation resulted in improvements of 24 to 38 percent in the PDQ-39 subscales for mobility, activities of daily living, emotional well-being, stigma, and bodily discomfort. Serious adverse events were more common with neurostimulation than with medication alone (13 percent vs. 4 percent, P<0.04) and included a fatal intracerebral hemorrhage. The overall frequency of adverse events was higher in the medication group (64 percent vs. 50 percent, P=0.08). CONCLUSIONS: In this six-month study of patients under 75 years of age with severe motor complications of Parkinson's disease, neurostimulation of the subthalamic nucleus was more effective than medical management alone. (ClinicalTrials.gov number, NCT00196911 [ClinicalTrials.gov].).

The time course of the return of upper limb bradykinesia after cessation of subthalamic stimulation in Parkinson's disease.

To investigate the time span within which bradykinesia re-occurs, we registered movement parameters immediately after the termination of deep brain stimulation of the subthalamic nucleus (STN) in nine Parkinson patients with chronically implanted bilateral STN electrodes. Two repetitive movements were investigated: finger-tapping and forearm pronation-supination. When stimulation was switched off, the amplitude and velocity of the investigated movements significantly declined, but the frequency did not. The time course of this decline was modeled by an exponential function that yielded time constants between 15 and 30s. The effect of stimulation had completely disappeared within 1 min. These results suggest that it is necessary to wait at least for 1 min after the end of stimulation before performing further assessments.

SUNCT: bilateral hypothalamic activation during headache attacks and resolving of symptoms after trigeminal decompression.

Short-lasting unilateral neuralgiform headache with conjunctival injection and tearing (SUNCT) is a primary head-pain syndrome, which is often refractory to any medical treatment. Concerning the pathophysiology of SUNCT, hypothalamic involvement ipsilaterally to the pain has been suggested based on the clinical features and one functional imaging case report. Here we now report a new case with SUNCT and the concomitant cerebral activation pattern (fMRI) during the pain attacks. In addition to an activation of several brain structures known to be generally involved in pain processing, bilateral hypothalamic activation occurred during the pain attacks, arguing for a central origin of the headache. Interestingly, this patient became completely pain free after surgical decompression of the ipsilateral trigeminal nerve. We hypothesize that in this case with a central predisposition for trigeminal autonomic cephalgias, a peripheral trigger with ectopic excitation might have contributed to the clinical picture of SUNCT.

Computerized tomography-guided kryorhizotomy in 76 patients with lumbar facet joint syndrome.

OBJECT: The authors prospectively evaluated the therapeutic effect of computerized tomography (CT)-guided kryorhizotomy in the treatment of patients with lumbar facet joint syndrome (LFJS) and assessed prognostic factors that predict this effect. METHODS: Between February 2001 and March 2004, CT-guided kryorhizotomy of facet joints was performed in 76 patients with LFJS. A diagnosis was established after three positive CT-guided medial nerve branch blocks. Outcome was determined by evaluating the results of a standardized questionnaire, including visual analog scale (VAS) score, use of medication, ability to work, and physical conditions. Measurement was performed before treatment and repeated postoperatively at 3 days, 3 months, and every 6 months thereafter. On September 2004 all patients underwent clinical reevaluation. The median follow-up period was 22.5 months (range 6-43 months); the median interval to pain reduction was 6 months (range 0.1-31 months) after the first kryorhizotomy. The mean VAS pain score was 6.7 preoperatively and 2.9, 3.2, and 3.4 at 3 days, 3 months, and 6 months postoperatively, respectively. In 40% of patients pain was reduced for 12 months or longer. In patients in whom there was no prior surgical treatment of the relevant spinal segment, the duration of pain relief was significantly longer than in patients who had previously undergone surgery (p < 0.03). Eighteen patients underwent a second, seven a third, and one a fourth kryorhizotomy. No patient reported any side effect. The use of CT guidance guarantees an exact needle-tip position control and documentation for repeated procedures. CONCLUSIONS: Computerized tomography-guided kryorhizotomy is a minimally invasive and repeatable treatment that yields good long-term results in patients with LFJS.

Effects of deep brain stimulation on prehensile movements in PD patients are less pronounced when external timing cues are provided.

It has been repeatedly demonstrated that the movements of patients with Parkinson's disease (PD) are less impaired when external timing cues are provided. This suggests that the basal ganglia, which are impaired in PD, are less involved in the control of externally timed movements. In the present study, we tested this hypothesis by contrasting the effect of deep brain stimulation (DBS) in the basal ganglia (more precisely, the internal globus pallidum) on internally versus externally timed movements. Our first movement task was a standard prehensile task involving a reach-to-grasp movement. In the externally-timed condition, the target object was moving rapidly away from the subject; in the internally-timed condition, the target object was stationary. We found, that for most aspects of the prehensile movement the effect of DBS was less pronounced in the externally than in the internally timed condition. A similar reduction of the DBS effects in the externally-timed condition was also found for a second movement task, which required an isolated grasping movement. We conclude that the basal ganglia are significantly less involved in the control of externally timed movements.

Analgesia by electrostimulation of the trigeminal ganglion in patients with trigeminopathic pain: a PET activation study.

Electrostimulation of the trigeminal ganglion (TGES) has shown good results in treatment of trigeminopathic pain in selected patients. To map the mechanisms of TGES analgesia, we determined changes in relative regional cerebral blood flow (rCBF) in ten patients with trigeminopathic pain using positron emission tomography. The patients were scanned before stimulation (habitual pain), after short-term stimulation (1 min, stTGES) and after long-term stimulation (ltTGES). Highly significant pain alleviation was reported after ltTGES. Relative rCBF changes after stTGES, which was without significant pain relief, were attributed mainly to intrinsic TGES effects. A statistical comparison of the subtraction images of ltTGES and stTGES disclosed significant rCBF increases after ltTGES in rostral parts of anterior cingulate cortex (ACC) and neighboring orbitofrontal and medial frontal cortices. Regression analysis of rCBF changes and subjective ratings of pain revealed an inverse relationship in the ipsilateral rostral ACC, and only rCBF changes in the caudal part of the contralateral ACC were consistent with the encoding of pain. The present study provides evidence for a pain modulating role of the rostral ACC, critically important in electrostimulation-induced analgesia, and identifies the caudal ACC as a region encoding pain sensation.

Thirty days complication rate following surgery performed for deep-brain-stimulation.

Serious adverse events (SAEs) during the first 30 postoperative days after stereotactic surgery for Deep-Brain-Stimulation performed in 1,183 patients were retrospectively collected from five German stereotactic centers. The mortality rate was 0.4% and causes for death were pneumonia, pulmonary embolism, hepatopathy, and a case of complicated multiple sclerosis. The permanent surgical morbidity rate was 1%. The most frequently observed SAEs were intracranial hemorrhage (2.2%) and pneumonia (0.6%). Skin infection occurred in 5 of 1,183 patients (0.4%). Surgical complications caused secondary AEs (e.g. pneumonia) preferentially in older patients and in patients treated for Parkinson's disease (PD). Complication rates did not differ among the five centers.

Sporadic rapid-onset dystonia-parkinsonism syndrome: failure of bilateral pallidal stimulation.

We report on a woman who had a severe sporadic nonprogressive dystonia-parkinsonism syndrome with rapid onset of symptoms at age 21. Secondary causes for dystonia were ruled out. No response to levodopa/carbidopa was seen. The patient fulfilled all diagnostic criteria of rapid-onset dystonia-parkinsonism, except for autosomal-dominant inheritance. Bilateral deep brain stimulation of the globus pallidus failed to alleviate her symptoms.

Chronic high-frequency globus pallidus internus stimulation in different types of dystonia: a clinical, video, and MRI report of six patients presenting with segmental, cervical, and generalized dystonia.

The results of deep brain stimulation (DBS) of the globus pallidus internus (Gpi) in six patients with generalized, focal, and segmental dystonia are presented. Pre- and postoperative assessments are given for one patient with generalized inherited dystonia and for five patients with idiopathic segmental or cervical dystonia. Clinical symptoms were evaluated before and 3-12 months after surgery using the Burke-Fahn-Marsden (BFM) dystonia rating scale for primary torsion dystonia and the Tsui scale for cervical dystonia. The Short-Form Health Survey (SF-36) was completed by each patient to document preoperative and postoperative health status. Also, neurological status was documented by video before and during chronic stimulation. Magnetic resonance imaging studies were performed to show the anatomical localization of the electrode leads. Five patients showed a progressive improvement within 7 days. One patient with cervical dystonia and Meige's syndrome showed no improvement for 3 months, but beneficial effects were observed after 12 months. On average, the BFM movement scale scores decreased by 72.5% and Tsui scale scores by 63%. SF-36 showed an improvement in health status by an average of 36% according to eight different health categories. We conclude that chronic high-frequency Gpi stimulation in different types of dystonia is a very effective and safe treatment.