Volker M. Tronnier

Neuropsychological and psychiatric changes after deep brain stimulation for Parkinson's disease: a randomised, multicentre study.

BACKGROUND Deep brain stimulation (DBS) of the subthalamic nucleus (STN) reduces motor symptoms in patients with Parkinsons disease (PD) and improves their quality of life; however, the effect of DBS on cognitive functions and its psychiatric side-effects are still controversial. To assess the neuropsychiatric consequences of DBS in patients with PD we did an ancillary protocol as part of a randomised study that compared DBS with the best medical treatment. METHODS 156 patients with advanced Parkinsons disease and motor fluctuations were randomly assigned to have DBS of the STN or the best medical treatment for PD according to the German Society of Neurology guidelines. 123 patients had neuropsychological and psychiatric examinations to assess the changes between baseline and after 6 months. The primary outcome was the comparison of the effect of DBS with the best medical treatment on overall cognitive functioning (Mattis dementia rating scale). Secondary outcomes were the effects on executive function, depression, anxiety, psychiatric status, manic symptoms, and quality of life. Analysis was per protocol. The study is registered at ClinicalTrials.gov, number NCT00196911. FINDINGS 60 patients were randomly assigned to receive STN-DBS and 63 patients to have best medical treatment. After 6 months, impairments were seen in executive function (difference of changes [DBS-best medical treatment] in verbal fluency [semantic] -4.50 points, 95% CI -8.07 to -0.93, Cohens d=-;0.4; verbal fluency [phonemic] -3.06 points, -5.50 to -0.62, -0.5; Stroop 2 naming colour error rate -0.37 points, -0.73 to 0.00, -0.4; Stroop 3 word reading time -5.17 s, -8.82 to -1.52, -0.5; Stroop 4 colour naming time -13.00 s, -25.12 to -0.89, -0.4), irrespective of the improvement in quality of life (difference of changes in PDQ-39 10.16 points, 5.45 to 14.87, 0.6; SF-36 physical 16.55 points, 10.89 to 22.21, 0.9; SF-36 psychological 9.74 points, 2.18 to 17.29, 0.5). Anxiety was reduced in the DBS group compared with the medication group (difference of changes in Beck anxiety inventory 10.43 points, 6.08 to 14.78, 0.8). Ten patients in the DBS group and eight patients in the best medical treatment group had severe psychiatric adverse events. INTERPRETATION DBS of the STN does not reduce overall cognition or affectivity, although there is a selective decrease in frontal cognitive functions and an improvement in anxiety in patients after the treatment. These changes do not affect improvements in quality of life. DBS of the STN is safe with respect to neuropsychological and psychiatric effects in carefully selected patients during a 6-month follow-up period. FUNDING German Federal Ministry of Education and Research (01GI0201).

Intraoperative diagnostic and interventional magnetic resonance imaging in neurosurgery

OBJECTIVE The benefits of intraoperative magnetic resonance (MR) imaging for diagnostic and therapeutic measures are as follows: 1) intraoperative update of data sets for navigational systems, 2) intraoperative resection control of brain tumors, and 3) frameless and frame-based on-line MR-guided interventions. The concept of an intraoperative MR scanner in the sterile environment of operating theater is presented, and its advantages, disadvantages, and limitations are discussed. METHODS A 0.2-tesla magnet (Magnetom Open; Siemens AG, Erlangen, Germany) inside a radiofrequency cabin with a radiofrequency-shielded sliding door was installed adjacent to one of the operating theaters. A specially designed patient transport system carried the patient in a fixed position on an air cushion to the scanner and back to the surgeon. RESULTS In a series of 27 patients, intraoperative resection control was performed in 13 cases, with intraoperative reregistration in 4 cases. Biopsies, cyst aspirations, and catheter placements (mainly frameless) were performed under direct MR visualization with fast image sequences. The MR-compatible equipment and the patient transport system are safe and reliable. CONCLUSION Intraoperative MR imaging is a safe and successful tool for surgical resection control and is clearly superior to computed tomography. Intraoperative acquisition of data sets eliminates the problem of brain shift in conventional navigational systems. Finally, on-line MR-guided interventional procedures can be performed easily with this setting. As with all MR systems, individual testing with phantoms, application of correction programs, and determination of the optimal amount of contrast media are absolute prerequisites to guarantee patient safety and surgical success.

Clinical evaluation and follow-up results for intraoperative magnetic resonance imaging in neurosurgery.

OBJECTIVE The use of intraoperative magnetic resonance imaging (MRI) in neurosurgery has increased rapidly, and a variety of concepts have recently been presented. Although the feasibility of the procedure has been demonstrated repeatedly, no conclusive analysis of its effects on the surgical procedures, the extent of tumor removal, and outcomes, or its possible problems, has been performed. METHODS Of 242 operations performed with intraoperative MRI, 97 procedures for supratentorial glioma treatment were analyzed with respect to intraoperative imaging results and postoperative outcomes. Analysis of the images included assessment of imaging artifacts, image quality, and extent of tumor removal. Patients were monitored to determine radiological progression, survival times, postoperative complications, and morbidity rates. RESULTS No intraoperative complications related to the imaging procedure were observed. Image quality was good or fair in 85.5% of the cases. Different types of surgically induced imaging changes could be identified. In 56 cases, resection was continued using navigation with intraoperative MRI data sets (rereferencing accuracy, 0.9 mm). For high-grade gliomas, the percentage of cases in which residual tumor was identified by MRI could be significantly reduced from 62% intraoperatively to 33% postoperatively, which was paralleled by a significant increase in survival times for patients without residual tumor. Complication and morbidity rates were within the ranges reported for other studies. CONCLUSION Intraoperative MRI is safe and allows reliable updating of neuronavigational data, with compensation for brain shifting. Surgically induced imaging changes, which have been identified as a possible problem with intraoperative MRI in general, necessitated comparisons with preoperative scans and require future attention. The extent of tumor removal and survival times were increased significantly. Overall, patients seemed to benefit from the method.

Deep brain stimulation for the treatment of Parkinson's disease: subthalamic nucleus versus globus pallidus internus

OBJECTIVES Deep brain stimulation of the basal ganglia has become a promising treatment option for patients with Parkinsons disease who have side effects from drugs. Which is the best target—globus pallidus internus (GPi) or subthalamic nucleus (STN)—is still a matter of discussion. The aim of this prospective study is to compare the long term effects of GPi and STN stimulation in patients with severe Parkinsons disease. PATIENTS AND METHODS Bilateral deep brain stimulators were implanted in the GPi in six patients and in the STN in 12 patients with severe Parkinsons disease. Presurgery and 3, 6, and 12 months postsurgery patients were scored according to the CAPIT protocol. RESULTS Stimulation of the STN increased best Schwab and England scale score significantly from 62 before surgery to 81 at 12 months after surgery; GPi stimulation did not have an effect on the Schwab and England scale. Stimulation of the GPi reduced dyskinesias directly whereas STN stimulation seemed to reduce dyskinesias by a reduction of medication. Whereas STN stimulation increased the unified Parkinsons disease rating scale (UPDRS) motor score, GPi stimulation did not have a significant effect. Fluctuations were reduced only by STN stimulation and STN stimulation suppressed tremor very effectively. CONCLUSION Stimulation of the GPi reduces medication side effects, which leads to a better drug tolerance. There was no direct improvement of bradykinesia or tremor by GPi stimulation. Stimulation of the STN ameliorated all parkinsonian symptoms. Daily drug intake was reduced by STN stimulation. The STN is the target of choice for treating patients with severe Parkinsons disease who have side effects from drugs.

Distinguishing of primary cerebral lymphoma from high-grade glioma with perfusion-weighted magnetic resonance imaging

To assess the usefulness of perfusion-weighted echo-planar magnetic resonance imaging in the differential diagnosis of primary supratentorial lymphoma (PCNSL) and glioblastoma (GBM), 12 patients with a PCNSL and 12 with a GBM were examined using a 1.5 T magnetic resonance (MR) imager. With dynamic-susceptibility contrast MR imaging the intensity-time curves of each tumor were analyzed, and we determined the relative regional cerebral blood volume ratios (rrCBV [tumor/contralateral white matter (WM)]) to find out whether these parameters could be used to separate PCNSL from GBM. The maximum rrCBV ratio in the PCNSL was significantly lower than that of the GBM (P<0.0001). Comparing the intensity-time curves for the two tumor groups, the PCNSL showed a characteristic type of curve with a significant increase in signal intensity above the baseline due to massive leakage of contrast media into the interstitial space. PCNSL tend to have low maximum CBV ratios and typical intensity-time curves. These two parameters may be useful in distinguishing PCNSL from GBM.

Intraoperative Magnetic Resonance Imaging to Update Interactive Navigation in Neurosurgery: Method and Preliminary Experience

We report on the first successful intraoperative update of interactive image guidance based on an intraoperatively acquired magnetic resonance imaging (MRI) date set. To date, intraoperative imaging methods such as ultrasound, computerized tomography (CT), or MRI have not been successfully used to update interactive navigation. We developed a method of imaging patients intraoperatively with the surgical field exposed in an MRI scanner (Magnetom Open; Siemens Corp., Erlangen, Germany). In 12 patients, intraoperatively acquired 3D data sets were used for successful recalibration of neuronavigation, accounting for any anatomical changes caused by surgical manipulations. The MKM Microscope (Zeiss Corp., Oberkochen, Germany) was used as navigational system. With implantable fiducial markers, an accuracy of 0.84 +/- 0.4 mm for intraoperative reregistration was achieved. Residual tumor detected on MRI was consequently resected using navigation with the intraoperative data. No adverse effects were observed from intraoperative imaging or the use of navigation with intraoperative images, demonstrating the feasibility of recalibrating navigation with intraoperative MRI.

Pallidal Stimulation for Dystonia

OBJECTIVE:High-frequency deep brain stimulation (DBS) of the globus pallidus internus (GPi) is a new and promising treatment option for severe dystonia. Yet only few studies have been published to date regarding this treatment. We present the results of DBS of the GPi in 17 patients with severe dystonia of different causes. METHODS:In our study, we included 10 patients with primary generalized dystonia, six patients with secondary generalized dystonia, and one patient with a severe dystonic cervical tremor. In all patients, DBS electrodes were implanted bilaterally within the GPi. Mean follow-up time was 36 months (range, 12–66 mo). Preoperative and postoperative evaluations (at least annually) were performed using the Burk-Fahn-Marsden scale. RESULTS:The best improvement was achieved in patients with DYT1-positive dystonia. Patients with DYT1-negative generalized dystonia showed inhomogeneous results. There was no significant change in patients with tardive dystonia. One case of Hallervorden-Spatz disease improved dramatically within the first 2 years. The improvement in the cervical dystonic tremor was disappointing, however. Three years after DBS implantation, we found a secondary worsening of symptoms in one patient with a DYT1-positive dystonia and in the patient with Hallervorden-Spatz disease. CONCLUSION:DBS of the GPi is a new and promising treatment option for dystonia. Secondary worsening may limit this therapy.

Pallidal deep brain stimulation in patients with primary generalised or segmental dystonia: 5-year follow-up of a randomised trial

BACKGROUND Severe forms of primary dystonia are difficult to manage medically. We assessed the safety and efficacy of pallidal neurostimulation in patients with primary generalised or segmental dystonia prospectively followed up for 5 years in a controlled multicentre trial. METHODS In the parent trial, 40 patients were randomly assigned to either sham neurostimulation or neurostimulation of the internal globus pallidus for a period of 3 months and thereafter all patients completed 6 months of active neurostimulation. 38 patients agreed to be followed up annually after the activation of neurostimulation, including assessments of dystonia severity, pain, disability, and quality of life. The primary endpoint of the 5-year follow-up study extension was the change in dystonia severity at 3 years and 5 years as assessed by open-label ratings of the Burke-Fahn-Marsden dystonia rating scale (BFMDRS) motor score compared with the preoperative baseline and the 6-month visit. The primary endpoint was analysed on an intention-to-treat basis. The original trial is registered with ClinicalTrials.gov (NCT00142259). FINDINGS An intention-to-treat analysis including all patients from the parent trial showed significant improvements in dystonia severity at 3 years and 5 years compared with baseline, which corresponded to -20·8 points (SD 17·1; -47·9%; n=40) at 6 months; -26·5 points (19·7; -61·1%; n=31) at 3 years; and -25·1 points (21·3; -57·8%; n=32). The improvement from 6 months to 3 years (-5·7 points [SD 8·4]; -34%) was significant and sustained at the 5-year follow-up (-4·3 [10·4]). 49 new adverse events occurred between 6 months and 5 years. Dysarthria and transient worsening of dystonia were the most common non-serious adverse events. 21 adverse events were rated serious and were almost exclusively device related. One patient attempted suicide shortly after the 6-month visit during a depressive episode. All serious adverse events resolved without permanent sequelae. INTERPRETATION 3 years and 5 years after surgery, pallidal neurostimulation continues to be an effective and relatively safe treatment option for patients with severe idiopathic dystonia. This long-term observation provides further evidence in favour of pallidal neurostimulation as a first-line treatment for patients with medically intractable, segmental, or generalised dystonia. FUNDING Medtronic.

Chronic precentral stimulation in trigeminal neuropathic pain

SummaryThe results of Deep Brain Stimulation in deafferentation pain syndromes, in particular in thalamic pain, indicate that excellent long-term pain relief can hardly ever be achieved. We report 7 cases using Motor-Cortex-Stimulation for treating severe trigeminal neuropathic pain syndromes, i.e., dysaesthesia, anaesthesia dolorosa and postherpetic neuralgia. The first implantation of the stimulation device for precentral cerebral stimulation was performed in June 1993, the last in September 1995. In all but one case the impulse-generator was implanted after a successful period of test stimulation. Successful means a pain reduction of more than 50% as assessed with a Visual Analogue Scale. Excluding one case, in whom a prolonged focal seizure resulting in a postictal speech arrest occurred during test stimulation, there have been no operative complications and the postoperative course was uneventful. In all the other patients the pain inhibition appeared below the threshold for producting motor effects. Initially these patients reported a good to excellent pain relief. In three of 6 patients a good to excellent pain control was maintained for a follow-up period of 5 months to 2 years. In the remaining three patients the positive effect decreased over several months.

Subthalamic nucleus stimulation affects a frontotemporal network: A PET study

Deep brain stimulation (DBS) of the subthalamic nucleus (STN) has become an effective strategy in the treatment of motor symptoms in advanced Parkinsons disease. However, clinical studies have shown that DBS can affect verbal fluency. Seven Parkinsons disease patients with bilateral DBS of the STN were studied with positron emission tomography (PET) to investigate the effects of STN stimulation on regional cerebral blood flow during a verbal fluency task. Activation of the right orbitofrontal cortex and verbal fluency‐associated activation within a left‐sided frontotemporal network were decreased during STN stimulation compared with the OFF state. Our results offer an explanation for the commonest neuropsychological side effect of STN stimulation and show that STN stimulation affects a frontotemporal network during a fluency task. Ann Neurol 2003;54:000–000