Simone Hemm

Treatment of DYT1-generalised dystonia by stimulation of the internal globus pallidus.

In seven selected patients with dystonia musculorum deformans-1 generalised dystonia (DYT1), continuous bilateral stimulation of the globus pallidus internus was associated with substantial improvement of dystonia and functional disability.

Pallidal stimulation improves pantothenate kinase–associated neurodegeneration

Pantothenate kinase–associated neurodegeneration (PKAN) causes a progressive generalized dystonia which remains pharmacologically intractable. We performed bilateral internal globus pallidus stimulation in six patients with genetically confirmed PKAN who obtained a major and long‐lasting improvement of their painful spasms, dystonia, and functional autonomy. This study shows the benefits of pallidal DBS for the dystonia of PKAN patients. Ann Neurol 2005;57:738–741

Deep brain stimulation in myoclonus-dystonia syndrome.

Myoclonus–dystonia syndrome (MDS) is an autosomal dominant disorder characterized by bilateral myoclonic jerks. An 8‐year‐old boy presenting with early onset, medically intractable, MDS due to a mutation in the ϵ‐sarcoglycan gene (SGCE) underwent chronic bilateral stimulation of the globus pallidus internus, which eliminates both myoclonus and dystonia. We conclude that deep brain stimulation can be an effective and safe treatment for MDS.

Deep Brain Stimulation for Dystonia

Stimulation electrodes are implanted under general anesthesia, without intra-operative electrophysiology or clinical testing, based only on stereotactic MRI and direct anatomical localization of the postero-ventro-basal GPi. We retrospectively analyzed the surgical procedure that has been designed and implemented in our center, using the Leksell G frame, for initiating deep brain stimulation in 65 dystonic patients. We report the surgical technique and the hardware and software complications. We recommend immediate postoperative stereotactic MRI under general anesthesia as a prerequisite to check the reliability of MR acquisition (magnet stability) and the exact localization of each electrode. This technique allowed us to reduce the duration of the operation to 4 h, including general anesthesia, frame fixation, MRI acquisition, implantation of two electrodes under radioscopic control, immediate postoperative stereotactic MRI and frame removal. Surgery-related morbidity was very low with a 0% hemorrhage rate and three delayed unilateral infections re-operated 6 months later. Hardware and software complications were rare. The advances in 3D-MR imaging permit the electrode implantation for deep brain stimulation without resorting to intraoperative localization techniques, which is especially helpful in children and for treating dystonia. The maximum follow-up period is 58 months (first case: November 1996). GPi stimulation has proven to be an effective treatment for most dystonic syndromes with particular efficacy in the disease due to the DYT1 mutation.

Evolution of Brain Impedance in Dystonic Patients Treated by GPi Electrical Stimulation

Deep Brain Stimulation is an effective treatment of generalized dystonia. Optimal stimulation parameters vary between patients. This article investigates the influence of electrical brain impedance and delivered current on the brain response to stimulation. Twenty‐four patients were bilaterally stimulated in the globus pallidus internus through two implanted four‐contact electrodes. The variation of brain impedance and current measurements was correlated with stimulation parameters, time course, and clinical outcome. When a contact was activated, a statistically significant and reversible decrease of brain impedance was found. Impedance and current values and their variations with time significantly differed between patients. The absolute impedance did not significantly correlate with the final outcome. We conclude that the reversible decrease of impedance reflects an adaptive long‐term mechanism, which could be due to a plasticity phenomenon, but has no prognostic value. Impedance and current measurements give new complementary information for parameter adjustment and trouble shooting and should therefore be included in all patients’ follow‐up.

Stereotactic implantation of deep brain stimulation electrodes: a review of technical systems, methods and emerging tools

Deep brain stimulation (DBS) has become increasingly important for the treatment and relief of neurological disorders such as Parkinson’s disease, tremor, dystonia and psychiatric illness. As DBS implantations and any other stereotactic and functional surgical procedure require accurate, precise and safe targeting of the brain structure, the technical aids for preoperative planning, intervention and postoperative follow-up have become increasingly important. The aim of this paper was to give an overview, from a biomedical engineering perspective, of a typical implantation procedure and current supporting techniques. Furthermore, emerging technical aids not yet clinically established are presented. This includes the state-of-the-art of neuroimaging and navigation, patient-specific simulation of DBS electric field, optical methods for intracerebral guidance, movement pattern analysis, intraoperative data visualisation and trends related to new stimulation devices. As DBS surgery already today is an information technology intensive domain, an “intuitive visualisation” interface for improving management of these data in relation to surgery is suggested.

Brain mapping in stereotactic surgery: A brief overview from the probabilistic targeting to the patient-based anatomic mapping

In this article, we briefly review the concept of brain mapping in stereotactic surgery taking into account recent advances in stereotactic imaging. The gold standard continues to rely on probabilistic and indirect targeting, relative to a stereotactic reference, i.e., mostly the anterior (AC) and the posterior (PC) commissures. The theoretical position of a target defined on an atlas is transposed into the stereotactic space of a patients brain; final positioning depends on electrophysiological analysis. The method is also used to analyze final electrode or lesion position for a patient or group of patients, by projection on an atlas. Limitations are precision of definition of the AC-PC line, probabilistic location and reliability of the electrophysiological guidance. Advances in MR imaging, as from 1.5-T machines, make stereotactic references no longer mandatory and allow an anatomic mapping based on an individual patients brain. Direct targeting is enabled by high-quality images, an advanced anatomic knowledge and dedicated surgical software. Labeling associated with manual segmentation can help for the position analysis along non-conventional, interpolated planes. Analysis of final electrode or lesion position, for a patient or group of patients, could benefit from the concept of membership, the attribution of a weighted membership degree to a contact or a structure according to its level of involvement. In the future, more powerful MRI machines, diffusion tensor imaging, tractography and computational modeling will further the understanding of anatomy and deep brain stimulation effects.

Treatment of early-onset dystonia: update and a new perspective

Abstract Dystonia is a rare disease of childhood, often leading to dev-astating functional impairment. Medical treatment is reviewed, although its efficacy is often limited. Recent advances in functional neurosurgery have opened up a new field in the management of dystonic patients, and the results of deep brain stimulation are given particular emphasis.

Co-registration of Stereotactic MRI and Isofieldlines During Deep Brain Stimulation

OBJECT The parameter adjustment process during deep brain stimulation (DBS) for dystonia remains time consuming and based on clinical observation alone. The aim was to correlate the electric field with the GPi anatomy to be able to study the stimulated volume. METHODS We developed a computer-assisted method (model) for visualizing electric field in reference to the stereotactic space. Electric field values were correlated with the GPi anatomy (stereotactic Magnetic Resonance Imaging) in one reference patient. RESULTS Using this methodology it becomes possible to correlate the electric field distributions for patient specific parameters with the anatomical information. The application to one patient showed that the 0.1V/mm isofieldline fits best with the lateral GPi borders at the level of the stimulated contacts. CONCLUSIONS The electric field is a crucial parameter as it is assumed to be responsible for triggering action potentials. Electric field visualisation allows the calculation of the stimulated volume for a given isoline. Its application to our whole patient population might help in determining a threshold for obtaining a therapeutic effect, to date unknown, and consequently in optimizing the parameter setting in each patient.

New electrophysiological mapping combined with MRI in parkinsonian's subthalamic region.

The subthalamic nucleus (STN) is the main target for deep brain stimulation in Parkinson’s disease. We analysed the relationships between magnetic resonance imaging (MRI) anatomy and spontaneous neuronal activity to confirm the potential of microelectrode recordings to assist in determining the optimal surgical target. Ten bilateral surgeries were performed after 1.5‐T (T2‐weighted) anatomical MRI identification of the STN, zona incerta (ZI), Forel’s field H2 (H2) and substantia nigra (SN). Spontaneous neuronal activity was recorded simultaneously along the distal 10 mm on a central track (optimally covering the STN) and a 2‐mm anterior track. We calculated off‐line mean firing rate and burst frequency on 248 neurons clustered according to anatomical structure. Subjective visual analysis of signal was also realized on‐line, during surgery, to classify patterns of activity. Mean firing rate and burst frequency increased from H2–ZI to SN. The mean firing rate was higher in SN only using paired comparison (SN vs. its neighbours). The burst frequency was lower in H2 than in SN; using comparison with neighbours, it was lower in H2 and ZI. An irregular high activity (type 2C) was more often detected in STN and SN than in H2 and ZI. Anatomical boundaries and unitary recordings appear to be linked, supporting the ability of MRI to provide a detailed anatomy. Electrophysiological mapping combined with MRI is a useful tool for precise targeting in the subthalamic region.