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.

Accelerometric measurement of involuntary movements during pallidal deep brain stimulation of patients with generalized dystonia.

Accelerometric activity during rest and posture was quantified in the upper dominant limb of 14 patients with primary or secondary dystonia and five healthy control subjects. Data were recorded before and after bilateral implantation of the stimulating electrodes in the Globus Pallidus internus. Clinical evaluation was based on the Burke-Marsden-Fahn's Dystonia Rating Scale (BMFDRS). For the patient group, I(t), the integral (i.e. area) of the acceleration power spectrum over the total frequency range (0.6-16 Hz) decreased as the clinical state of the patients improved following deep brain stimulation (p < 0.01) during rest and posture. Ten days after surgery, there were no I(t) differences between control subjects and patients (p > 0.05). A significant correlation was found between the global BMFDRS scores and I(t) for rest (p < 0.01) but not for posture. No significant correlation was found between I(t) and a partial BMFDRS score for the right arm for rest or posture. The integral I(t) provides a valid indicator of the motor activity generated by the arm of the patient but further analyses are needed to monitor patients' progress not only during their hospitalization but also after they are released from the hospital, and to understand why this measure does not correlate with partial BMFDRS scores.

Thallium SPECT-based stereotactic targeting for brain tumor biopsies. A technical note.

MR or CT images acquired under stereotactic conditions are often used to plan and guide brain tumor biopsies. The objective of this study was to design and test a methodology to increase target selection reliability by acquiring stereotactic 201Tl-SPECT data and by integrating them into the surgical planning. The three-headed Philips gamma camera system (Prism 3000) was adapted to stereotactic acquisitions (patient pallet, headholder). A software was developed for the stereotactic target determination based on SPECT images (pixel with the highest metabolic activity inside the tumor). The whole system accuracy was tested with the Elekta phantom adapted to SPECT imaging. The methodology was applied to one brain tumor biopsy. Comparison of the specific phantom coordinates evaluated in SPECT with the theoretical ones did not reveal any significant difference. In this way, our methodology including our homemade software (identification of the stereotactic frame, determination of the pixel with highest metabolic activity within the tumor in the stereotactic coordinate system) was validated. No significant geometric deformations were detected. Clinical feasibility was confirmed in 1 patient with a brain glioma. This study illustrates the feasibility and the accuracy of SPECT acquisitions with the stereotactic Leksell G-frame. The clinical relevance of this methodology is under evaluation. This definition of the target, based on the point with the highest metabolic activity within the tumor, might lead to improved diagnosis in biopsies and patient management. Furthermore, it might prepare the future for therapy aimed at delivering a therapeutic agent within a tumor.

Treatment of dystonic syndromes by chronic electrical stimulation of the internal globus pallidus.

AIM: Dystonia is a medically intractable condition causing twisting or myoclonic movements and abnormal postures. There is an important heterogeneity among etiologies of dystonia. The electrical stimulation of the globus pallidus has been used successfully in primary generalized dystonia. The aim of this study was to examine the long-term efficacy and safety of deep brain stimulation (DBS) in the treatment of primary and secondary generalized dystonia in children and adults. METHODS: Fifty-three patients were included. Electrodes were bilaterally implanted under stereotactic guidance and connected to neurostimulators, subcutaneously inserted. Efficacy was evaluated by comparing scores on the clinical and functional Burke-Marsden-Fahn dystonia rating scales (BMFDRS) before and after implantation. Patients were divided into 3 groups: group 1 comprised 15 patients with DYT1 dystonia; group 2, 17 patients with dystonia of unknown etiology and group 3, 21 patients with secondary dystonia. The mean follow-up was 26.6+/-12.3 months for primary dystonia and 23.1+/-11.8 for secondary dystonia. RESULTS: After 1 year, the improvement of the clinical score is 71% in group 1, 74% in group 2 and 31% in group 3. The functional score was improved by 63% in group 1, 49% in group 2 and 7% in group 3. We did not find any significant difference between children and adults. In secondary dystonia, efficacy of the stimulation is more limited. The efficacy of the stimulation improved with time for the 3 groups. COMCLUSION: Electrical stimulation of the internal globus pallidus proved to be an effective treatment for generalized dystonia and should be considered as first-line therapy.

Magnetic resonance imaging stereotactic target localization for deep brain stimulation in dystonic children.

OBJECT: The actual distortion present in a given series of magnetic resonance (MR) images is difficult to establish. The purpose of this study was to validate an MR imaging-based methodology for stereotactic targeting of the internal globus pallidus during electrode implantation in children in whom general anesthesia had been induced. METHODS: Twelve children (mean follow up 1 year) suffering from generalized dystonia were treated with deep brain stimulation by using a head frame and MR imaging. To analyze the influence of distortions at every step of the procedure, the geometrical characteristics of the frame were first controlled using the localizer as a phantom. Then pre- and postoperative coordinates of fixed anatomical landmarks and electrode positions, both determined with the head frame in place, were statistically compared. No significant difference was observed between theoretical and measured dimensions of the localizer (Student's t-test, ¿t¿ > 2.2 for 12 patients) in the x, y, and z directions. No significant differences were observed (Wilcoxon paired-sample test) between the following: 1) pre- and postoperative coordinates of the anterior commissure (AC) (deltax = 0.3+/-0.29 mm and deltay = 0.34+/-0.32 mm) and posterior commissure (PC) (deltax = 0.15+/-0.18 mm and deltay = 0.34+/-0.25 mm); 2) pre- and postoperative AC-PC distance (deltaL = 0.33+/-0.22 mm); and 3) preoperative target and final electrode position coordinates (deltax = 0.24+/-0.22 mm; deltay = 0.19+/-0.16 mm). CONCLUSIONS: In the authors' center, MR imaging distortions did not induce detectable errors during stereotactic surgery in dystonic children. Target localization and electrode implantation could be achieved using MR imaging alone after induction of general anesthesia. The remarkable postoperative improvement in these patients confirmed the accuracy of the procedure (Burke-Marsden-Fahn Dystonia Rating Scale score delta = -83.8%).

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

Dystonia is a rare disease of childhood, often leading to devastating 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.

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.

Protective role of the virus-specific immune response for development of severe neurologic signs in simian immunodeficiency virus-infected macaques.

The pathogenesis of human immunodeficiency virus-associated motor and cognitive disorders is poorly understood. In this context both a protective and a harmful role of the immune system has been discussed. This question was addressed in the present study by correlating the occurrence of neurologic disease in simian immunodeficiency virus (SIV)-infected macaques with disease progression and the humoral and cellular intrathecal antiviral immune response. Overt neurologic signs consisting of ataxia and apathy were observed at a much higher frequency in rapid progressor animals (6 of 12) than in slow progressors (1 of 7). Whereas slow progressors mounted a strong antiviral antibody (Ab) response as evidenced by enzyme-linked immunosorbent and immunospot assays, neither virus-specific Ab titers nor Ab-secreting cells could be found in the cerebrospinal fluid (CSF) or brain parenchyma of rapid progressors. Similarly, increased infiltration of CD8(+) T cells and cytotoxic T lymphocytes specific for viral antigens were detected only in the CSF of slow progressors. The finding that neurologic signs develop frequently in SIV-infected macaques in the absence of an antiviral immune response demonstrates that the immune system does not contribute to the development of motor disorders in these animals. Moreover, the lower incidence of neurologic symptoms in slow progressors with a strong intrathecal immune response suggests a protective role of the virus-specific immunity in immunodeficiency virus-induced central nervous system disease.

Dynamics of the immune system response in cerebrospinal fluid and blood of SIVmac-infected rhesus monkeys.

Paired sera and CSF samples were collected from SIVmac-infected macaques. Animals infected with SIVmac251 maintained low gag and high env-specific antibody levels in plasma. Increasing env-specific antibody titers in CSF were associated in one animal with strong intrathecal synthesis. SIVmac239-infected monkeys revealed high antibody titers of gag and env-specificity, in one animal accompanied by weak intrathecal synthesis of virus-specific antibodies. In all animals, the CD4/CD8 ratio in CSF decreased faster compared to blood.

Cell-specific immuno-probes for the brain of normal and mutant Drosophila melanogaster. I. Wildtype visual system.

We have screened antibodies for immunocytochemical staining in the optic lobes of the brain of Drosophila melanogaster. Seven polyclonal antisera and five monoclonal antibodies are described that selectively and reproducibly stain individual cells and/or produce characteristic staining patterns in the neuropile. Such antisera are useful for the cellular characterization of molecular and structural brain defects in visual mutants. In the wildtype visual system we can at present separately stain the following: the entire complement of columnar "T1" neurons; a small set of presumptive serotonergic neurons; some 3000 cells that contain and synthesize gamma-amino butyric acid (GABA); and three groups of cells that bind antibodies to Ca2+-binding proteins. In addition, small groups of hitherto unknown tangential cells that send fine arborizations into specific strata of the medulla, and two patterns of characteristic layers in the visual neuropile have been identified by use of monoclonal antibodies generated following immunization of mice with homogenates of the brain of Drosophila melanogaster.