Laura Cif

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

Long-term follow-up of DYT1 dystonia patients treated by deep brain stimulation: an open-label study.

Long‐term efficacy of internal globus pallidus (GPi) deep‐brain stimulation (DBS) in DYT1 dystonia and disease progression under DBS was studied. Twenty‐six patients of this open‐label study were divided into two groups: (A) with single bilateral GPi lead, (B) with a second bilateral GPi lead implanted owning to subsequent worsening of symptomatology. Dystonia was assessed with the Burke Scale. Appearance of new symptoms and distribution according to body region were recorded. In the whole cohort, significant decreases in motor and disability subscores (P < 0.0001) were observed at 1 year and maintained up to 10 years. Group B showed worsening of the symptoms. At 1 year, there were no significant differences between Groups A (without subsequent worsening) and B; at 5 years, a significant difference was found for motor and disability scores. Within Group B, four patients exhibited additional improvement after the second DBS surgery. In the 26 patients, significant difference (P = 0.001) was found between the number of body regions affected by dystonia preoperatively and over the whole follow‐up. DBS efficacy in DYT1 dystonia can be maintained up to 10 years (two patients). New symptoms appear with long‐term follow‐up and may improve with additional leads in a subgroup of patients.

The diverse phenotype and genotype of pantothenate kinase-associated neurodegeneration

Pantothenate kinase-associated neurodegeneration (PKAN) is a rare autosomal-recessive disorder caused by mutations in the PANK2 gene. The authors report clinical and genetic findings of 16 patients with PKAN. The authors identified 12 mutations in the PANK2 gene, five of which were new. Only nine patients could be classified as classic or atypical PKAN, and intermediate phenotypes are described. Two patients presented with motor tics and obsessive-compulsive behavior suggestive of Tourette syndrome.

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.

Antero-Ventral Internal Pallidum Stimulation Improves Behavioral Disorders in Lesch-Nyhan Disease

The Lesch–Nyhan syndrome is an X‐linked recessive disorder caused by a deficiency in hypoxanthine–guanine phosphoribosyl transferase, a purine salvage enzyme. Affected individuals exhibit a characteristic neurobehavioral disorder with delayed acquisition of motor skills, dystonia, severe self‐mutilations, and aggressive behavior. Deep brain stimulation has been previously proposed for controlling isolated involuntary movements and psychiatric disorders. We applied a double bilateral simultaneous stimulation to limbic and motor internal pallidum in one patient for controlling both behavioral and movement disorders, respectively. The injurious compulsions disappeared; dystonia and dyskinesia were decreased at 28 months follow‐up.

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.

Deep brain stimulation for Huntington's disease: long-term results of a prospective open-label study

UNLABELLED OBJECT.: To date, experience of globus pallidus internus (GPi) deep brain stimulation (DBS) in the treatment of Huntingtons disease (HD) has been limited to a small number of case reports. The aim of this study was to analyze long-term motor outcome of a cohort of HD patients treated with GPi DBS. METHODS Seven patients with pharmacologically resistant chorea and functional impairment were included in a prospective open-label study from 2008 to 2011. The main outcome measure was the motor section of the Unified Huntingtons Disease Rating Scale. The primary end point was reduction of chorea. RESULTS Patients underwent MRI-guided bilateral GPi implantation. The median duration of follow-up was 3 years. A significant reduction of chorea was observed in all patients, with sustained therapeutic effect; the mean improvement on the chorea subscore was 58.34% at the 12-month follow-up visit (p = 0.018) and 59.8% at the 3-year visit (p = 0.040). Bradykinesia and dystonia showed a nonsignificant trend toward progressive worsening related to disease evolution and partly to DBS. The frequency of stimulation was 130 Hz for all patients. DBS-induced bradykinesia was managed by pulse-width reduction or bipolar settings. Levodopa mildly improved bradykinesia in 4 patients. Regular off-stimulation tests confirmed a persistent therapeutic effect of DBS on chorea. CONCLUSIONS GPi DBS may provide sustained chorea improvement in selected HD patients with pharmacologically resistant chorea, with transient benefit in physical aspects of quality of life before progression of behavioral and cognitive disorders. DBS therapy did not improve dystonia or bradykinesia. Further studies including quality of life measures are needed to evaluate the impact of DBS in the long-term outcome of HD.

Factors Predicting Improvement in Primary Generalized Dystonia Treated by Pallidal Deep Brain Stimulation

Despite the beneficial effects of Globus Pallidus internus (GPi) deep brain stimulation (DBS) in patients with primary generalized dystonia (PGD), the degree of improvement varies from one patient to another. The objective of this study was to examine the effects of clinical, anatomical (volume of the GPi), and electrical variables on the postoperative Burke‐Fahn‐Marsden Dystonia rating scale (BFMDRS) motor score to identify which factors may be predictive of the degree of improvement. We reviewed retrospectively the clinical records of 40 steady‐state patients with PGD who had been treated by bilateral GPi lead implantation. The follow‐up period was 2 to 8 years. The correlation between the electrical parameters (voltage, impedance, and current) and the clinical outcome was studied. An analysis of covariance was performed to identify factors predictive of the magnitude of improvement. The most influential factors according to the model are as follows: the preoperative BFMDRS score (P < 0.0001); age at surgery (P < 0.0001); the right GPi volume (P = 0.002); the left stimulated GPi volume (P = 0.005). No significant correlation was found between the electrical parameters used and the mean motor scores in steady state.

Magnetic resonance-based deep brain stimulation technique: a series of 478 consecutive implanted electrodes with no perioperative intracerebral hemorrhage.

OBJECTIVE The aim of this study was to determine the safety of a deep brain stimulation technique consisting of a combination of routine general anesthesia, magnetic resonance imaging direct targeting, and a single penetration technique in a large population of patients undergoing operation for movement disorders. METHODS One hundred ninety-four patients treated with deep brain stimulation between 1996 and 2007 were assessed via a computerized database for intra- and perioperative events. Most patients were young; only 62 of them were older than 40 years (mean age, 31.1 years). General anesthesia was induced in all cases before placement of a magnetic resonance imaging-compatible stereotactic frame. Electrode implantation was done under radioscopic control via a rigid immobile cannula using a single cerebral perforation. No perioperative microelectrode recording or neurostimulation testing was used. Systematic postoperative magnetic resonance imaging was performed before frame removal. RESULTS A total of 478 electrodes were implanted in 220 procedures: 426 for dystonic-dyskinetic syndromes and 52 for Parkinson disease. The mean number of parenchymal penetrations per patient was 2.5 for the dystonic-dyskinetic syndrome group and 2.08 for the Parkinson disease group. Postimplantation magnetic resonance imaging detected no perioperative intraparenchymal hemorrhages. CONCLUSION We consider that the risk of hemorrhagic complication is multifactorial but closely related to the chosen technique.