Neurostimulation for Parkinson's disease with early motor complications.

BACKGROUND: Subthalamic stimulation reduces motor disability and improves quality of life in patients with advanced Parkinson's disease who have severe levodopa-induced motor complications. We hypothesized that neurostimulation would be beneficial at an earlier stage of Parkinson's disease. METHODS: In this 2-year trial, we randomly assigned 251 patients with Parkinson's disease and early motor complications (mean age, 52 years; mean duration of disease, 7.5 years) to undergo neurostimulation plus medical therapy or medical therapy alone. The primary end point was quality of life, as assessed with the use of the Parkinson's Disease Questionnaire (PDQ-39) summary index (with scores ranging from 0 to 100 and higher scores indicating worse function). Major secondary outcomes included parkinsonian motor disability, activities of daily living, levodopa-induced motor complications (as assessed with the use of the Unified Parkinson's Disease Rating Scale, parts III, II, and IV, respectively), and time with good mobility and no dyskinesia. RESULTS: For the primary outcome of quality of life, the mean score for the neurostimulation group improved by 7.8 points, and that for the medical-therapy group worsened by 0.2 points (between-group difference in mean change from baseline to 2 years, 8.0 points; P=0.002). Neurostimulation was superior to medical therapy with respect to motor disability (P<0.001), activities of daily living (P<0.001), levodopa-induced motor complications (P<0.001), and time with good mobility and no dyskinesia (P=0.01). Serious adverse events occurred in 54.8% of the patients in the neurostimulation group and in 44.1% of those in the medical-therapy group. Serious adverse events related to surgical implantation or the neurostimulation device occurred in 17.7% of patients. An expert panel confirmed that medical therapy was consistent with practice guidelines for 96.8% of the patients in the neurostimulation group and for 94.5% of those in the medical-therapy group. CONCLUSIONS: Subthalamic stimulation was superior to medical therapy in patients with Parkinson's disease and early motor complications. (Funded by the German Ministry of Research and others; EARLYSTIM ClinicalTrials.gov number, NCT00354133.).

Deep brain stimulation of the internal globus pallidus in dystonia: target localisation under general anaesthesia.

UNLABELLED: Deep brain stimulation (DBS) of the internal globus pallidus (Gpi) is an effective therapy for various types of dystonia. The authors describe their technical approach for securing appropriate placement of the stimulating electrodes within the Gpi under general anaesthesia, including MRI based individualised anatomical targeting combined with electrophysiological mapping of the Gpi using micro-recording (MER) as well as macrostimulation and report the subsequent clinical outcome and complications using this method. METHOD: We studied 42 patients (male-female ratio 25:17; mean age 43.6 years, range 9 to 74 years) consecutively operated at the Department of Neurosurgery, University Hospital Schleswig-Holstein, Campus Kiel, between 2001 - 2006. One patient underwent unilateral implantation after a right-sided pallidotomy 30 years before and strictly unilateral symptoms; all other implantations were bilateral. Two patients had repeat surgery after temporary removal of uni- or bilateral implants secondary to infection. Overall, 86 DBS electrodes were implanted. In 97% of the implantations, at least three microelectrodes were inserted simultaneously for MER and test stimulation. Initial anatomical targeting was based on stereotactic atlas coordinates and individual adaptation by direct visualisation of the Gpi on the stereotactic T2 or inversion-recovery MR images. The permanent electrode was placed according to the results of MER and test stimulations for adverse effects. FINDINGS: The average improvement from baseline in clinical ratings using either the Burke-Fahn-Marsden-Dystonia (BFMDRS) or Toronto-Western-Spasmodic-Torticollis (TWSTR) rating scale at the last post-operative follow-up (mean 16.4 ; range 3-48 months) was 64.72% (range 20.39 to 98.52%). The post-operative MRI showed asymptomatic infarctions of the corpus caudatus in three patients and asymptomatic small haemorrhages in the lateral basal ganglia in two patients. One patient died due to a recurrent haemorrhage which occurred three months after the operation. The electrodes were implanted as follows: central trajectory in 64%, medial trajectory in 20%, anterior in 9% and lateral dorsal trajectories in 3.5% each. The reduction in BFMDRS or TWSTR motor score did not differ between the group implanted in the anatomically defined (central) trajectory bilateral (-64.15%, SD 23.8) and the physiologically adopted target (uni- or bilateral) (-63.39%, SD 23.1) indicating that in both groups equally effective positions were chosen within Gpi for chronic stimulation (t-test, p > 0.4). CONCLUSIONS: The described technique using stereotactic MRI for planning of the trajectory and direct visualisation of the target, intra-operative MER for delineating the boundaries of the target and macrostimulation for probing the distance to the internal capsule by identifying the threshold for stimulation induced tetanic contractions is effective in DBS electrode implantation in patients with dystonia operated under general anaesthesia. The central trajectory was chosen in only 64%, despite individual adaptation of the target due to direct visualisation of the Gpi in inversion recovery MRI in 43% of the patients, demonstrating the necessity of combining anatomical with neurophysiological information.

Hypothalamic deep brain stimulation for cluster headache: experience from a new multicase series.

Deep brain stimulation (DBS) of the posterior hypothalamus was found to be effective in the treatment of drug-resistant chronic cluster headache. We report the results of a multicentre case series of six patients with chronic cluster headache in whom a DBS in the posterior hypothalamus was performed. Electrodes were implanted stereotactically in the ipsilateral posterior hypothalamus according to published coordinates 2 mm lateral, 3 mm posterior and 5 mm inferior referenced to the mid-AC-PC line. Microelectrode recordings at the target revealed single unit activity with a mean discharge rate of 17 Hz (range 13-35 Hz, n = 4). Out of six patients, four showed a profound decrease of their attack frequency and pain intensity on the visual analogue scale during the first 6 months. Of these, one patient was attack free for 6 months under neurostimulation before returning to the baseline which led to abortion of the DBS. Two patients had experienced only a marginal, non-significant decrease within the first weeks under neurostimulation before returning to their former attack frequency. After a mean follow-up of 17 months, three patients are almost completely attack free, whereas three patients can be considered as treatment failures. The stimulation was well tolerated and stimulation-related side-effects were not observed on long term. DBS of the posterior inferior hypothalamus is an effective therapeutic option in a subset of patients. Future controlled multicentre trials will need to confirm this open-label experience and should help to better define predictive factors for non-responders.

Deep brain stimulation for movement disorders and its neuropsychological implications.

Deep brain stimulation (DBS) has gained increasing attention as a therapy for movement disorders. Neuropsychological alterations can accompany the disease evolution and medical therapy of PD. Also, interfering abruptly with the biological balance by means of a surgical intervention into complex circuits with motor but also cognitive and limbic functions, could potentially cause severe problems. Because cognitive or emotional impairments may have an even stronger impact on quality of life, than motor symptoms, care must be taken to perform surgery in the safest possible way to exclude adverse effects in these domains. Detailed neuropsychological evaluations may become helpful to further understand the mechanisms underlying some aspects of the clinical pictures both pre- and postoperatively and to define risk populations, that should be excluded from this intervention.

Effect of propofol anesthesia on pallidal neuronal discharges in generalized dystonia.

We present the results of continuous microelectrode recordings from individual pallidal neurons in patients with idiopathic torsion dystonia under different levels of propofol anesthesia. Neither the estimated plasma concentration of propofol nor the level of consciousness had a consistent effect on abnormally low neuronal firing rates. Our data support the pathophysiological model of a decreased basal ganglia output in dystonia and argue against a possible pharmacological artifact.

Deep brain stimulation for idiopathic or secondary movement disorders.

Deep brain stimulation has gained increasing interest in the treatment of movement disorders. Presenting our clinical series of 179 patients operated upon since 1999, the indications, risks and benefits for the patients are discussed in order to further improve the techniques and their applications.

Surgery and outcome for aneurysmal subarachnoid hemorrhage in elderly patients.

OBJECTIVE: The goal was to report treatment results of elderly patients (over 70 years) who underwent clipping of aneurysms after subarachnoid hemorrhage (SAH). MATERIAL AND METHODS: From 1994 to 2000 41/284 (14%) patients older than 70 years were operated on aneurysmal SAH in our department. Localization of ruptured aneurysm was anterior communicating artery (n = 14), middle cerebral artery (n = 14), internal carotid artery (n = 6), anterior cerebral artery (n = 2), pericallosal artery (n = 1) and multiple in 4 patients. We used the Hunt and Hess classification for initial grading and the Glasgow Outcome Score at day 30 after surgery. RESULTS: Patients with HH 1-3 had a low mortality (1/18, 6%), whereas 9 of 23 patients (39%) with HH 4-5 decreased within 30 days after surgery. Overall mortality was 24.5% (10/41) at 30 days after surgery. Most patients (n = 32) underwent early surgery (within 72 hours). Shunt dependent hydrocephalus developed in 15 patients (37%). The outcome was better in patients graded HH 1-3, in those without serious atherosclerotic changes in angiography, and in AcoA and ICA localization compared to MCA. CONCLUSION: Advanced age does not preclude successful surgery for ruptured aneurysm. Most important factor for outcome was a good initial clinical status, though the majority of our patients presented with poor grades. Early surgical clipping and postoperative intensive care can attain a favorable outcome in a significant percentage of elderly patients.

Bevacizumab as salvage therapy for progressive brain stem gliomas.

OBJECTIVE: There is no standard of care for patients with progredient brain stem gliomas. Therefore, we report about clinical, radiological and metabolic response to anti-angiogenic treatment with bevacizumab in a series of 3 patients with gliomas involving the brain stem. PATIENTS AND METHODS: Three patients with histologically confirmed gliomas involving the brain stem were treated with bevacizumab for tumor progression. The clinical data, histopathological findings as well as MRI and PET follow up examinations during bevacizumab therapy were retrospectively analyzed. RESULTS: The histopathological diagnosis revealed an anaplastic astrocytoma WHO grade III in two patients and an astrocytoma WHO grade II in 1 patients with clinical and neuroradiological signs of malignization. One patient is still progression-free 97 weeks after initiation of bevacizumab therapy. Mean progression-free survival and overall survival for the other two patients after initiation of bevacizumab therapy was 34.5 weeks and 43.5 weeks. During bevacizumab therapy mean KPS improved from 60 to 80 and mean dosage of daily dexamathasone was reduced from 7.3 mg to 1.3 mg. MRI showed a decrease of T2 weighted hyperintense lesions in all patients and a decrease of contrast enhancement in two patients. (18)F-FET-PET showed a decrease of tracer uptake in all cases (mean maximum decrease: 25%). CONCLUSION: In this series treatment of progressive gliomas involving the brain stem with bevacizumab resulted in an improved clinical condition of the patients as well as a reduction of the T2 weighted lesions and reduced amino acid uptake in the tumor area. It therefore may represent a therapeutic salvage option for this type of tumor.

Intraindividual comparison of histopathological diagnosis obtained by stereotactic serial biopsy to open surgical resection specimen in patients with intracranial tumours.

BACKGROUND: There are concerns in the literature about the accuracy of histopathological diagnosis obtained by stereotactic biopsy in patients with brain tumours. The aim of this study was to analyse intraindividually the histopathological accuracy of stereotactic biopsies of intracerebral lesions in comparison to open surgical resection. MATERIALS AND METHODS: Between 2007 and 2011 a total of 635 patients underwent stereotactic serial biopsy in our department. Among these patients we identified 51 patients, who underwent magnetic resonance (MR) based stereotactic biopsy and subsequent open resection within 30 days. Mortality and morbidity data as well as final histopathological diagnoses of both procedures were compared with regard to tumour grade and tumour cell type. Patients with discrepancies between the histological diagnosis obtained by biopsy and open resection were classified into three subgroups (same cell type but different grading; same grading but different cell type and different grading as well as different cell type). RESULTS: The mean number of tissue samples taken by stereotactic serial biopsy from each patient was 12 (range 7-21). Minor morbidity was 6% and major morbidity was 14% after open surgery compared to no morbidity after stereotactic biopsy. Mortality was 2% after stereotactic biopsy (one patient died after stereotactic biopsy as a result of a fatal bleeding) compared to 0% in the resection group. Silent bleeding rate without any clinical symptoms was 8% in the biopsy group. A complete correlation of histopathological findings between the biopsy group and the resection group was achieved in 76% and was increased to 90% by analyzing clinical and neuroradiological information. In patients with recurrence the correlation was higher (94%) than for patients with primary brain lesions (67%). The discrepancies between the open resection group and biopsy group were analysed. CONCLUSION: Stereotactic MR guided serial biopsy is a minimal invasive procedure with low morbidity and high diagnostic accuracy for diagnosis and grading of brain tumours. Diagnostic accuracy of stereotactic biopsy can be enhanced further by careful interpretation of neuroradiological and clinical information.

Electrode implantation for deep brain stimulation in dystonia: a fast spin-echo inversion-recovery sequence technique for direct stereotactic targeting of the GPI.

OBJECTIVE: Deep brain stimulation (DBS) of the globus pallidus internus (GPi) is an effective treatment for medically refractory primary dystonia. We present our technique for direct preoperative visualization of the target using a fast spin-echo inversion-recovery (FSE-IR) sequence. METHODS: Twenty-three consecutive patients (mean age 41 years, range 9-68 years, male to female ratio 11:12) with severe dystonia were operated using a combination of FSE-IR imaging for direct visualization of the globus pallidus internus with stereotactic, gadolinium-enhanced T1-MPRage images. The complete procedure, including stereotactic MRI, was performed under general anesthesia with propofol and remifentanyl. We used multichannel microdrive systems (Medtronic; Alpha-Omega) to introduce up to five parallel microelectrodes for microelectrode recordings (MER) and test stimulation with the central trajectory directed at the anatomically predefined target. The initial standard coordinates in relation to the mid-commissural point (mid-AC-PC) were as follows: lateral 21 mm, anterior 3 mm, and inferior 2 mm, which were then adapted to the individual case based on direct visualization of the target area and further refined by the intraoperative neurophysiology. RESULTS: In ten patients (43%) atlas-based standard coordinates were modified based on the direct visualization of the GPi in the FSE-IR images (bilaterally in seven patients, unilaterally in three). The modified targets ranged from 18.5 to 23.5 mm (mean 20.76 mm) laterally, 1-7 mm (mean 2.75 mm) anteriorly and 1-2 mm (mean 1.95 mm) inferiorly to the mid-AC-PC. We implanted the permanent electrode based on the results of MER and intraoperative stimulation performed to determine the threshold for pyramidal tract responses on the central trajectory in 67%, medially in 16%, anteriorly in 11%, laterally in 4%, dorsally in 2%. The procedure resulted in excellent clinical benefits (average reduction of the Burke-Fahn-Marsden Dystonia Rating Score (BFMDRS) or the Toronto Western Spasmodic Torticollis Rating Scale (TWSTRS) were respectively 65.9%, range 20.9-91.4%) within the first year after surgery. Safety was demonstrated by the absence of intracranial bleeding or other surgical complications causing neurological morbidity. CONCLUSION: Inversion recovery sequences are an excellent tool for direct visualization of the GPi. These images can be fused to stereotactic MRI or CCT and may help to improve anatomical targeting of the GPi for the implantation of DBS electrodes.

Accuracy and distortion of deep brain stimulation electrodes on postoperative MRI and CT.

OBJECTIVE: Postoperative monitoring of the electrode position is important to evaluate the best stimulation site in deep brain stimulation. MR imaging is excellent for ruling out postoperative complications e.g. haemorrhage, but its accuracy in electrode localisation is still controversial. The reasons for this are the size of the artefact around the electrode and its unclear relation to the electrode position (concentric or eccentric). The goal of this study was to determine the relation and size of these artefacts to the electrodes by comparing the position of the electrodes in postoperative MR and CT imaging. MATERIAL AND METHODS: Five patients underwent deep brain stimulation of the subthalamic nucleus due to levodopa-induced motor complications in Parkinson's disease. A stereotactic CT and a non-stereotactic MR were performed for postoperative localisation of the electrode position. The stereotactic MR for planning of the trajectories and targets was done under general anaesthesia. The latter two were fused to the stereotactic MR and the position of the DBS electrode contacts was determined on CT and MRI. The size of the artefact was measured at the level of each contact in two directions, anterior to posterior (AP) and lateral. Altogether 40 contacts were evaluated. RESULTS: Mean size of the CT-artefact was 2.6 mm AP (range, 2.0-3.2 mm) and 2.6 mm laterally (range, 2.0-3.8 mm). In comparison, mean size on the MRI was 3.5 mm AP (range, 2.9-5.3 mm) and 3.8 mm laterally (range, 2.9-4.8 mm). A trajectory with a 1.2 mm diameter (size of the DBS electrode) was centred on the electrodes' artefact of the CT and the MRI. The difference between the contact coordinates was calculated as deviation of the artefact around the electrode on the MR. Mean deviation was 0.2 mm on the x-axis (range, 0-0.5 mm), 0.5 mm on the y-axis (range, 0-1.1 mm) and 0.3 mm on the z-axis (range, 0-0.7 mm). There were no significant differences (t-test, p > 0.4). CONCLUSION: The size of the electrodes' artefact was smaller on CT compared to MR. Furthermore, the position was not precisely concentric around the electrode. Nevertheless, the mean deviation after measuring the contact position in both CT and MR was less than 1 mm in all three planes. Both techniques are eligible for postoperative localisation of DBS electrodes, with a small imprecision of the non-stereotactic MR compared to the stereotactic CT. This might be compensated by the fact that postoperative MR can rule out asymptomatic postoperative complications e.g. haemorrhages or infarctions, without radiation exposure of the patient.

Failure of deep brain stimulation of the posterior inferior hypothalamus in chronic cluster headache - report of two cases and review of the literature.

OBJECTIVE: Deep brain stimulation (DBS) has become a standard procedure for movement disorders such as Parkinson's disease, essential tremor or dystonia. Recently, deep brain stimulation of the posterior hypothalamus has been shown to be effective in the treatment of drug-resistant chronic cluster headache. METHODS: DBS of the posterior inferior hypothalamus was performed on two patients with chronic cluster headaches, one 55-year-old man with medically intractable chronic cluster headache since 1996, and one 31-year-old woman with a chronic form since 2002. Both patients showed continuous worsening headaches in the last years despite high dose medical treatment. The patients fulfilled the published criteria for DBS in chronic cluster headaches. Electrodes were implanted stereotactically in the ipsilateral posterior hypothalamus according to the published coordinates (2 mm lateral, 3 mm posterior, 5 mm inferior) referenced to the mid-AC-PC line. RESULTS: The intra- and postoperative course was uneventful and postoperative MRI control documented regular position of the DBS electrodes. The current stimulation parameters were at 12 months postoperatively 0 neg., G pos.; 5.5 V; 60 micros; 180 Hz (Case 1) and 0 neg., G pos.; 3.0 V; 60 micros; 185 Hz, at 3 months postoperatively (Case 2). Surgery- or stimulation-related side effects were not observed. Both patients showed initial pain reduction in the first days whereas 12 respectively 3 month follow-up did not show a significant reduction in attack frequency or intensity. CONCLUSION: Deep brain stimulation of the posterior inferior hypothalamus is an experimental procedure and should be restricted to selected therapy-refractory patients and should be performed in centers experienced in patient selection and performance of DBS as well as postoperative pain treatment. A prospective multi-centre study is necessary to evaluate its effectiveness.

Bilateral subthalamic stimulation in Parkin and PINK1 parkinsonism.

OBJECTIVES: To study the frequency of different gene mutations in patients with early-onset parkinsonism and bilateral subthalamic nucleus deep brain stimulation (STN-DBS) and the short- and long-term surgical outcome in mutation-positive (MUT+) and -negative (MUT-) patients. METHODS: Eighty patients with disease onset at age

Neuronavigation and resection of lesions located in eloquent brain areas under local anesthesia and neuropsychological-neurophysiological monitoring.

BACKGROUND: The aim of this study was to determine the safety and maximal extension of tumor resection achievable with a combination of awake craniotomy under local anesthesia, neuronavigation, and continuous neuropsychological and neurophysiological monitoring in patients with lesions within the eloquent brain. METHODS: We have performed 55 resections of different pathologies with neuronavigation on 52 patients from January 1998 to December 2002. Mean age was 49 years, the male to female ratio was 37 to 15. All patients underwent a continuous examination by a neuropsychologist and repetitive cortical stimulations during the resection, and a 3-month postoperative neurological examination to determine functional outcome. Neurological outcome and results of resection of patients with gliomas were compared to a control group of 27 patients with lesions in the central region who were operated under general anesthesia during the same time period. RESULTS: Tumor resection was stopped when a macroscopic total cytoreduction was achieved, or at the onset of neurological dysfunction. There was a higher rate of complete tumor resection (77% vs. 33%) and a lower rate of neurological deterioration (33% vs. 12%) in the study group compared to the control group. Overall, a complete resection in the study group was achieved in 40 patients (72%), a partial resection in 28%. Five patients developed a new deficit during surgery which resolved completely after a change of surgical strategy, 14 patients had a new deficit after surgery which improved within 3 months in 6 patients. There was no operative mortality. CONCLUSION: The combination of neuronavigation with cortical stimulation and repetitive neurological and language examinations allows a more radical resection of tumors in eloquent brain areas, otherwise considered as inoperable.

Metastatic meningioma WHO grade II of the cervical spine: case report and review of the literature.

The authors report a rare case of metastatic atypical meningioma WHO grade II involving the dorso-lateral region of the cervical spine and causing spinal cord compression in a 76-year-old man. The patient was treated surgically in June 1998 for an atypical parasagittal meningioma in the right frontal lobe. Local recurrence with extension to the left hemisphere required surgical treatment in January 2000, and in December 2000 recurrence caused paraplegia of the lower extremities and paresis of the left arm. A 3 (rd) operation was carried out in January 2001, followed by radiotherapy with a total dose of 45 Gy. The patient presented again in March 2003 because of pain in the neck and a progredient new paresis and paresthesia of the right arm. Computed tomogram of the cervical spine showed a large tumor with compression of the spinal cord. MRI was not possible due to a pacemaker which had been implanted in the meantime. Surgical subtotal removal of the tumor via hemilaminectomy of the 3 (rd) and 4 (th) cervical vertebrae was performed. After decompression of the cervical spine the paresis of the right arm improved, the paraplegia of the legs and the left arm, existing since December 2000, remained unchanged. Histological findings of the cranial lesions and the metastatic lesion had a similar appearance and were compatible with atypical meningioma (WHO grade II).