Jean-Marc Gurruchaga

Transplantation in Parkinson's disease: PET changes correlate with the amount of grafted tissue.

An erratum for this article appears in the January, 2004 issue of Movement Disorders (Mov Disord 2004;12:119).

Outcome of Bilateral Subthalamic Nucleus Stimulation in the Treatment of Parkinson’s Disease: Correlation with Intra-Operative Multi-Unit Recordings but Not with the Type of Anaesthesia

Background: Deep brain stimulation (DBS) of the subthalamic nucleus (STN) gained general acceptance in the treatment of Parkinson’s disease (PD). Objective: To study the clinical outcome and the predicting factors of efficacy of chronic STN stimulation, while DBS electrodes were implanted under local or general anaesthesia with intra-operative electrophysiological guidance based on multi-unit recordings. Methods: We included a large single-centre cohort of 54 patients with advanced PD (mean age: 59 years; disease duration: 14 years). Clinical evaluation was performed by the Unified Parkinson’s Disease Rating Scale (UPDRS) before and 1 year after surgical placement of DBS electrodes. Results: In the on-stimulation and off-medication condition, the UPDRS part III score was reduced by 56% compared to the off-stimulation condition or pre-operative off-drug score. In the on-stimulation and on-medication condition, this score was reduced by 73%. The severity of motor fluctuations and dyskinesia (UPDRS part IV) and the activities of daily living (UPDRS part II) were reduced by 65 and 80%, respectively, in the on-stimulation/on-medication condition compared to the pre-operative baseline. The daily dose of antiparkinsonian treatment was diminished by 72%. Among the various pre- and intra-operative data, the most important predictive factor for clinical efficacy of STN stimulation was the length of hyperactivity along the best track observed in intra-operative multi-unit recordings. Other predictive factors included age, disease duration and pre-operative levodopa responsiveness or baseline off-drug values of the Hoehn and Yahr and UPDRS part III scores. In contrast, the type of anaesthesia (local vs. general) did not significantly influence the clinical outcome. Conclusion: The present results are in the average of previously published results, but they have been obtained from a large single-centre cohort of patients with important reductions in the daily dose of antiparkinsonian drugs. This study confirmed the efficacy of the STN-DBS technique and emphasized the value of an original intra-operative electrophysiological approach based on multi-unit and not single-unit quantified recordings. This method allows DBS electrode implantation to be safely performed under general anaesthesia without lessening the rate of efficacy of the procedure.

Spinal cord stimulation for chronic pain improved motor function in a patient with Parkinson's disease.

Spinal cord stimulation (SCS) is a validated therapy for various chronic pain syndromes [1] that was recently shown to improve locomotor behaviour in rodent model of Parkinson’s disease (PD) [2]. We report herein the antiparkinsonian effect of SCS in a patient implanted for lower limb neuropathic painwho later developed PD. A 74-year oldmanwas successfully treated since the age of 61 by SCS implanted at T9-T10 level for a failed back surgery syndrome. Parameters of stimulation were as follows: 70–100 Hz frequency, 410 ms pulse width, 3.5 V (Symmix quadripolar electrode and Itrel-3 pulse generator, Medtronic, Inc., Minneapolis, USA). At the age of 69, the patient developed a tremor-dominant type of PD predominating on right side. A [123-I]FP-CIT dopamine transporter SPECT imaging showed asymmetric striatal loss of binding consistent with PD. Tremor was partially controlled by levodopa (1200 mg/day). We assessed the effect of SCS on motor PD symptoms in four sessions (two to five weeks apart) after overnight dopaminergic medication withdrawal. In sessions 1, 2, and 4, the patient was successively evaluated in offand on-stimulation conditions, while he remained off-drug. In session 3, offand onstimulation conditions were tested before and after (off-/on-drug) the administration of a single suprathreshold dose of levodopa/carbidopa (350/35 mg). SCS frequency was set at 130 Hz (the highest frequency allowed by the generator) during the sessions, but was left at 100 Hz between the sessions, except between sessions 3 and 4 where SCS frequency was maintained at 130 Hz for five weeks. All examinations were performed while SCS was switched on or off for 30–60 min. Outcome measures were the motor score of the Unified Parkinson’s Disease Rating Scale (UPDRS-III), time to walk 7 m, turn, and walk back, and pain level in the lower limbs scored on a 0–10 visual analogue scale. In session 3, tremor was assessed using surface EMG recordings. All motor features, with the exception of rigidity, were videotaped and independently rated by two blinded neurologists who had to agree on the final score. Rigidity was rated by consensus between the two neurologists who performed the tests. Double-blind evaluationwas not feasible, since the patient felt paresthesiae and pain relief in the lower limbs when the stimulator was on. The study was approved by the local ethics committee.

Depression and Coping as Predictors of Change After Deep Brain Stimulation in Parkinson's Disease

BACKGROUND This study examined changes in motor function and quality of life (QoL) after subthalamic nuclei deep brain stimulation (STN-DBS) in patients with Parkinson disease (PD) and the role of psychosocial predictors on individual changes. METHODS Forty-one patients with advanced PD (29 men and 12 women; mean age: 62.0 ± 8.0; disease duration: 14.5 ± 5.7) completed self-report questionnaires before surgery and at 6 and 12 months after surgery. Psychosocial measures assessed coping strategies (Ways of Coping Checklist-Revised), symptoms of depression (Beck Depression Inventory version II), anxiety (State-Trait Anxiety Inventory), and QoL (Parkinson Disease Questionnaire 39 Items, Medical Outcomes Study 36-Item Short-Form Health Survey). RESULTS After surgery, motor function (Unified Parkinson Disease Rating Scale III and IV), global QoL (Parkinson Disease Questionnaire 39 Items) and Physical Component Summary of the Medical Outcome Study Short Form 36-items Health Survey improved, whereas the Mental Component Summary tended to deteriorate. Depression and anxiety were stable. Improvements in motor function and QoL were associated with younger age, shorter duration of illness, higher baseline distress (depression and anxiety), and changes in problem-focused coping. Improvements in mental QoL were associated with a less frequent use of coping focused on seeking social support. CONCLUSIONS STN-DBS is associated with major positive changes in PD affecting motor function and QoL. These changes are related to psychological variables, including emotional distress and coping. A better focus on these individual characteristics is necessary to improve care of patients with PD who undertake STN-DBS.

Spinal Stimulation for Movement Disorders

Epidural spinal cord stimulation (SCS) is currently proposed to treat intractable neuropathic pain. Since the 1970s, isolated cases and small cohorts of patients suffering from dystonia, tremor, painful leg and moving toes (PLMT), or Parkinson’s disease were also treated with SCS in the context of exploratory clinical studies. Despite the safety profile of SCS observed in these various types of movement disorders, the degree of improvement of abnormal movements following SCS has been heterogeneous among patients and across centers in open-label trials, stressing the need for larger, randomized, double-blind studies. This article provides a comprehensive review of both experimental and clinical studies of SCS application in movement disorders.

Improvement in developmental stuttering following deep brain stimulation for Parkinson's disease

1353-8020/

Three-dimensional SPACE fluid-attenuated inversion recovery at 3 T to improve subthalamic nucleus lead placement for deep brain stimulation in Parkinson's disease: from preclinical to clinical studies

– see front matter 2012 Elsevier Ltd. http://dx.doi.org/10.1016/j.parkreldis.2012.07.011 While bilateral subthalamic nucleus deep brain stimulation (STN-DBS) can dramatically improve the cardinal motor symptoms of Parkinson’s disease (PD), it may also worsen speech, verbal fluency or gait impairment. Developmental stuttering, defined as a disturbance of speech fluency usually appearing before the age of ten, with syllable repetitions, prolongations and blocks, differs from PD dysarthria, although a stuttering-like phenomenon may occasionally occur in PD [1]. The possible impact of STN-DBS for PD on coincident stuttering is unclear, although a worsening of stuttering following STN-DBS has been described in two patients [2,3]. Here we report the case of a PD patient whose developmental stuttering improved after STN-DBS. A right-handedmanwith a family history of stuttering had stuttered since childhood. Akineto-rigid PD, predominating on the right side, was diagnosed at the age of 46. Fluctuations and dyskinesia occurred following initiation of dopatherapy and persisted despite treatment optimization. Pre-operative evaluation showed a good response to acute levodopa challenge, normal cognition, and no specific abnormalities on brain MRI. The risk-benefit ratio of STN-DBS was discussed with the patient, notably with regard to a potential aggravation of his stuttering. The surgical procedure was finally performed 7 years after PD onset. Under general anesthesia, 2 electrodes (Medtronic, model 3389) were implanted in the STNs with MRI-guided target definition (Siemens, Germany) and micro-electrophysiological recordings. The electrodes were connected to a subcutaneous impulse generator (Medtronic, model Kinetra). Postoperative brain imaging confirmed the location of the electrodes in the right and left STNs (data not shown). Twelve months after surgery the levodopa-equivalent daily dose had been reduced from 2860 mg pre-operatively to 1270 mg (66% reduction). Themotor score of the Unified Parkinson’s Disease Scale (UPDRS-III, maximum: 108), assessed while off medication, was respectively 24 and 14 with DBS switched off and on (42% improvement). Parameters includedmonopolar stimulationwith contacts 2 and 6; amplitude 2.1 V on the right side and 2.3 V on the left side; 90 ms pulse width; and frequency 130 Hz.

Assessing health-related quality of life with the SCOPA-PS in French individuals with Parkinson's disease having undergone DBS-STN: A validation study

OBJECTIVE Deep brain stimulation (DBS) of the subthalamic nucleus (STN) is a well-established therapy for motor symptoms in patients with pharmacoresistant Parkinsons disease (PD). However, the procedure, which requires multimodal perioperative exploration such as imaging, electrophysiology, or clinical examination during macrostimulation to secure lead positioning, remains challenging because the STN cannot be reliably visualized using the gold standard, T2-weighted imaging (T2WI) at 1.5 T. Thus, there is a need to improve imaging tools to better visualize the STN, optimize DBS lead implantation, and enlarge DBS diffusion. METHODS Gradient-echo sequences such as those used in T2WI suffer from higher distortions at higher magnetic fields than spin-echo sequences. First, a spin-echo 3D SPACE (sampling perfection with application-optimized contrasts using different flip angle evolutions) FLAIR sequence at 3 T was designed, validated histologically in 2 nonhuman primates, and applied to 10 patients with PD; their data were clinically compared in a double-blind manner with those of a control group of 10 other patients with PD in whom STN targeting was performed using T2WI. RESULTS Overlap between the nonhuman primate STNs segmented on 3D-histological and on 3D-SPACE-FLAIR volumes was high for the 3 most anterior quarters (mean [± SD] Dice scores 0.73 ± 0.11, 0.74 ± 0.06, and 0.60 ± 0.09). STN limits determined by the 3D-SPACE-FLAIR sequence were more consistent with electrophysiological edges than those determined by T2WI (0.9 vs 1.4 mm, respectively). The imaging contrast of the STN on the 3D-SPACE-FLAIR sequence was 4 times higher (p < 0.05). Improvement in the Unified Parkinsons Disease Rating Scale Part III score (off medication, on stimulation) 12 months after the operation was higher for patients who underwent 3D-SPACE-FLAIR-guided implantation than for those in whom T2WI was used (62.2% vs 43.6%, respectively; p < 0.05). The total electrical energy delivered decreased by 36.3% with the 3D-SPACE-FLAIR sequence (p < 0.05). CONCLUSIONS 3D-SPACE-FLAIR sequences at 3 T improved STN lead placement under stereotactic conditions, improved the clinical outcome of patients with PD, and increased the benefit/risk ratio of STN-DBS surgery.

Unilateral thalamic stimulation safely improved fragile X–associated tremor ataxia: A case report†‡

INTRODUCTION The aims of this study were to validate the French version of the SCales for Outcomes in Parkinsons Disease-PsychoSocial (SCOPA-PS) in individuals with Parkinsons disease (PD) who underwent deep brain stimulation of the subthalamic nucleus (DBS-STN), to confirm the unifactorial structure of this questionnaire, and to establish its psychometric properties. METHODS Routinely used psychological questionnaires (BDI-II, STAI-Y, PDQ-39, UPDRS III) and the SCOPA-PS were used for a cross-sectional observational study of 154 PD patients. SCOPA-PS acceptability, scaling assumption, reliability, ordinal confirmatory factor analysis and validity were assessed. RESULTS The ICC for two-week test-retest reliability was 0.88. SEM was 8.42. In confirmatory factor analysis, the one-factor model showed an acceptable fit to the data (Chi(2)/df=2.130; CFI=0.976; RMSEA=0.086). No floor or ceiling effects were observed. Skewness was 0.33. Item-total correlation coefficients ranged from 0.47 to 0.71. Cronbachs alpha was 0.86. SCOPA-PS SI correlated with PDQ-39 SI (rs=0.83) and with state-anxiety and depression (rs=0.56 and 0.69 respectively). The SCOPA-PS SI was higher in more depressed patients and in those with the most severe PD motor symptoms. CONCLUSION AND DISCUSSION SCOPA-PS French version is a one-factor scale with satisfactory psychometric properties consistent with other language versions. This short scale can be used to evaluate the psychosocial component of QoL in PD patients treated with DBS-STN.