Efficacy and Safety of Electroconvulsive Therapy in Patients With Deep Brain Stimulation: Literature Review, Case Report for Patient With Essential Tremor, and Practical Recommendations.

AIM: Deep brain stimulation (DBS) has proven to be an effective therapy of some treatment-resistant psychiatric disorders and movement disorders. Comorbid depressive symptoms are common and difficult to manage. Treatment with electroconvulsive therapy (ECT) may be required. There are few published cases describing the safety and efficacy of ECT for patients with DBS implants, and there are no available guidelines for administration of ECT in patients with DBS and mood disorders. The current study had 3 aims: (i) to conduct a systematic review of case reports on patients with DBS implants who received ECT; (ii) to report the case of a 69-year-old man with a DBS implant for essential tremor, who required ECT; and (iii) to provide practical recommendations for ECT in patients with DBS implants. METHODS: We conducted a systematic review, in accordance with Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines, of existing case reports on patients with DBS implants administered ECT for psychiatric disorders. RESULTS: Our search yielded 25 cases of ECT in patients implanted with DBS systems. In addition, we here describe successful ECT management of major depressive disorder in a patient treated by DBS. We also set forth ECT management guidelines based on points of consensus. The 2 most important practical recommendations are to make sure the DBS system is set to 0 V and turned off before ECT, and to avoid sites near the DBS electrodes. CONCLUSIONS: Electroconvulsive therapy may be an effective and safe treatment for DBS patients with MDD.

Occipital Nerve Stimulation for Refractory Chronic Cluster Headache: A Cost-Effectiveness Study.

INTRODUCTION: Occipital nerve stimulation (ONS) is proposed to treat refractory chronic cluster headache (rCCH), but its cost-effectiveness has not been evaluated, limiting its diffusion and reimbursement. MATERIALS AND METHODS: We performed a before-and-after economic study, from data collected prospectively in a nation-wide registry. We compared the cost-effectiveness of ONS associated with conventional treatment (intervention and postintervention period) to conventional treatment alone (preintervention period) in the same patients. The analysis was conducted on 76 rCCH patients from the French healthcare perspective at three months, then one year by extrapolation. Because of the impact of the disease on patient activity, indirect cost, such as sick leave and disability leave, was assessed second. RESULTS: The average total cost for three months was €7602 higher for the ONS strategy compared to conventional strategy with a gain of 0.07 quality-adjusted life-years (QALY), the incremental cost-effectiveness ratio (ICER) was then €109,676/QALY gained. The average extrapolated total cost for one year was €1344 lower for the ONS strategy (p = 0.5444) with a gain of 0.28 QALY (p < 0.0001), the ICER was then €-4846/QALY gained. The scatter plot of the probabilistic bootstrapping had 80% of the replications in the bottom right-hand quadrant, indicating that the ONS strategy is dominant. The average indirect cost for three months was €377 lower for the ONS strategy (p = 0.1261). DISCUSSION: This ONS cost-effectiveness study highlighted the limitations of a short-time horizon in an economic study that may lead the healthcare authorities to reject an innovative strategy, which is actually cost-effective. One-year extrapolation was the proposed solution to obtain results on which healthcare authorities can base their decisions. CONCLUSION: Considering the burden of rCCH and the efficacy and safety of ONS, the demonstration that ONS is dominant should help its diffusion, validation, and reimbursement by health authorities in this severely disabled population.

How Should we Use Multicolumn Spinal Cord Stimulation to Optimize Back Pain Spatial Neural Targeting? A Prospective, Multicenter, Randomized, Double-Blind, Controlled Trial (ESTIMET Study).

BACKGROUND: Recent studies have highlighted multicolumn spinal cord stimulation (SCS) efficacy, hypothesizing that optimized spatial neural targeting provided by new-generation SCS lead design or its multicolumn programming abilities could represent an opportunity to better address chronic back pain (BP). OBJECTIVE: To compare multicolumn vs. monocolumn programming on clinical outcomes of refractory postoperative chronic BP patients implanted with SCS using multicolumn surgical lead. MATERIALS AND METHODS: Twelve centers included 115 patients in a multicenter, randomized, double-blind, controlled trial. After randomization, leads were programmed using only one or several columns. The primary outcome was change in BP visual analogic scale (VAS) at six months. All patients were then programmed using the full potential of the lead up until 12-months follow-up. RESULTS: At six months, there was no significant difference in clinical outcomes whether the SCS was programmed using a mono or a multicolumn program. At 12 months, in all patients having been receiving multicolumn SCS for at least six months (n = 97), VAS decreases were significant for global pain (45.1%), leg pain (55.8%), and BP (41.5%) compared with baseline (p < 0.0001). CONCLUSION: The ESTIMET study confirms the significant benefit experienced on chronic BP by patients implanted with multicolumn SCS, independently from multicolumn lead programming. These good clinical outcomes might result from the specific architecture of the multicolumn lead, giving the opportunity to select initially the best column on a multicolumn grid and to optimize neural targeting with low-energy requirements. However, involving more columns than one does not appear necessary, once initial spatial targeting of the "sweet spot" has been achieved. Our findings suggest that this spatial concept could also be transposed to cylindrical leads, which have drastically improved their capability to shape the electrical field, and might be combined with temporal resolution using SCS new modalities.

Efficacy of Occipital Nerve Stimulation to Treat Refractory Occipital Headaches: A Single-Institution Study of 60 Patients.

BACKGROUND: Occipital nerve stimulation (ONS) is shown to be effective in treating various forms of headache. Most studies describe the treatment of occipital neuralgia (ON), but in many patients, the clinical description could also correspond to cervicogenic headache (CGH) or occipital migraine (OM). These different entities (ON, CGH, and OM) may be grouped together under the term occipital headaches. OBJECTIVE: To assess the efficacy of ONS to treat occipital headaches in a large series of patients with a long-term follow-up. MATERIALS AND METHODS: We performed a retrospective review of data on 60 patients with intractable occipital headaches treated with occipital nerve stimulation (ONS), who were referred to our center between October 2008 and October 2014. Details of pain evaluation, location, duration, cause and previous treatment were analyzed. Evaluations included the visual analog scale (VAS), the number of headache days per month (NHD), and the Medication Quantification Scale (MQS). Trials with transcutaneous electrical nerve stimulation (TENS-ONS) were performed and served as a guide for surgery indication (see Patients and Method section). RESULTS: After one year of ONS, mean VAS had decreased from 8.4/10 to 2.8/10 (72.2% reduction [p < 0.001]), and 76% of patients had at least a 50% decrease in mean VAS score. The mean MQS score decreased from 18 to 8.8, corresponding to a reduction of pain medication by an average of 50%. Adverse events concerned 12 patients (20%). Six patients presented with electrode displacement or fracture (10%) and six patients presented with cases of infection (10%) associated with the pulse generator. CONCLUSIONS: The results of this large series confirm that ONS is an effective treatment option for patients with intractable occipital headaches, but the frequency of complications remains quite high and must be taken into account in the surgical decision.

Interest of repetitive transcranial magnetic stimulation of the motor cortex in the management of refractory cancer pain in palliative care: Two case reports.

BACKGROUND: Non-drug treatments should be systematically associated to the medical analgesic treatment during the terminal phase of cancer. CASES PRESENTATION: Patient 1, a 23-year-old woman, presented an adenocarcinoma of the rectum, with liver and lung metastases. Pain was initially treated by oral morphine and a combination of pregabalin and amitriptyline. Ketamine and intrathecal administration of morphine were both ineffective. Patient 2, a 69-year-old woman, presented a cutaneous T-cell lymphoma. She was admitted to the palliative care unit with mixed pain related to cutaneous lymphomatous infiltration. World Health Organization (WHO) step 3 analgesics had not been tolerated. CASES MANAGEMENT: Both patients received five consecutive 20-min sessions of repetitive transcranial magnetic stimulation to the right motor cortex. CASES OUTCOME: Patient 1 experienced a marked improvement of her pain over the days following the first repetitive transcranial magnetic stimulation session. Medical treatment was able to be rapidly decreased by about 50%, which restored an almost normal level of consciousness and lucidity. Patient 2's pain was also markedly decreased over the days following these five consecutive sessions, and repetitive transcranial magnetic stimulation also appeared to have had a beneficial effect on the patient's anxiety and mood. CONCLUSION: In the context of palliative care of cancer patients experiencing refractory pain that is difficult to control by the usual treatments, motor cortex repetitive transcranial magnetic stimulation, due to its noninvasive nature, can be used as an adjuvant therapy to improve various components of pain, including the emotional components. By reducing the doses of analgesics, repetitive transcranial magnetic stimulation decreases the severity of their adverse effects and improves the patient's quality of life.

Improved Outcomes and Therapy Longevity after Salvage Using a Novel Spinal Cord Stimulation System for Chronic Pain: Multicenter, Observational, European Case Series.

Spinal cord stimulation (SCS) is proven to effectively relieve chronic neuropathic pain. However, some implanted patients may face loss of efficacy (LoE) over time, and conversion to more recent devices may rescue SCS therapy. Recent SCS systems offer novel stimulation capabilities, such as temporal modulation and spatial neural targeting, and can be used to replace previous neurostimulators without changing existing leads. Our multicenter, observational, consecutive case series investigated real-world clinical outcomes in previously implanted SCS patients who were converted to a new implantable pulse generator. Data from 58 patients in seven European centers were analyzed (total follow-up 7.0 years, including 1.4 years after conversion). In the Rescue (LoE) subgroup (n = 51), the responder rate was 58.5% at the last follow-up, and overall pain scores (numerical rating scale) had decreased from 7.3 ± 1.7 with the previous SCS system to 3.5 ± 2.5 (p < 0.0001). Patients who converted for improved battery longevity (n = 7) had their pain scores sustained below 3/10 with their new neurostimulator. Waveform preferences were diverse and patient dependent (34.4% standard rate; 44.8% sub-perception modalities; 20.7% combination therapy). Our results suggest that patients who experience LoE over time may benefit from upgrading to a more versatile SCS system.

Subthalamic nucleus stimulation reverses spinal motoneuron activity in parkinsonian patients.

Although a cardinal symptom of Parkinsonian disease, up to now, rigidity has been investigated much less than spasticity in hemiplegic patients. Many pathophysiological mechanisms may at least theoretically contribute to Parkinsonian rigidity, from altered viscoelastic muscle properties to inability of parkinsonian patients to relax. However, as demonstrated many years ago, motoneuron responses to muscle afferent volleys are involved in rigidity since afferent volleys are suppressed after dorsal root section. To our knowledge, homosynaptic depression (i.e. the fact that motoneuron responses to Ia afferent volleys exhibit a frequency-related depression) has not been studied in parkinsonian disease, despite the fact that in spastic patients, changes in homosynaptic depression are significantly correlated at wrist and ankle levels with the severity of spasticity. Thus, in the present series of experiments, we investigated in parkinsonian patients with chronic implantation of both subthalamic motor nuclei, the amount of homosynaptic depression at wrist and ankle levels on and off deep brain stimulation. Off deep brain stimulation, the frequency-related depression disappeared, the patients became rigid and the amount of homosynaptic depression was significantly correlated with the severity of rigidity. On deep brain stimulation, the frequency-related depression was restored and the rigidity suppressed, suggesting that homosynaptic depression is one of the mechanisms underlying rigidity in Parkinson's disease. Moreover, the unexpected finding that changes in the rigidity score and the amount of homosynaptic depression are time-locked to the onset of deep brain stimulation leads us to reconsider the mechanisms underlying changes in homosynaptic depression.

Efficient intracerebral delivery of AAV5 vector encoding human ARSA in non-human primate.

Metachromatic leukodystrophy (MLD) is a lethal neurodegenerative disease caused by a deficiency in the lysosomal arylsulfatase A (ARSA) enzyme leading to the accumulation of sulfatides in glial and neuronal cells. We previously demonstrated in ARSA-deficient mice that intracerebral injection of a serotype 5 adeno-associated vector (AAV) encoding human ARSA corrects the biochemical, neuropathological and behavioral abnormalities. However, before considering a potential clinical application, scaling-up issues should be addressed in large animals. Therefore, we performed intracerebral injection of the same AAV vector (total dose of 3.8 x 10(11) or 1.9 x 10(12) vector genome, three sites of injection in the right hemisphere, two deposits per site of injection) into three selected areas of the centrum semiovale white matter, or in the deep gray matter nuclei (caudate nucleus, putamen, thalamus) of six non-human primates to evaluate vector distribution, as well as expression and activity of human ARSA. The procedure was perfectly tolerated, without any adverse effect or change in neurobehavioral examination. AAV vector was detected in a brain volume of 12-15 cm(3) that corresponded to 37-46% of the injected hemisphere. ARSA enzyme was expressed in multiple interconnected brain areas over a distance of 22-33 mm. ARSA activity was increased by 12-38% in a brain volume that corresponded to 50-65% of injected hemisphere. These data provide substantial evidence for potential benefits of brain gene therapy in patients with MLD.

Safe, efficient, and reproducible gene therapy of the brain in the dog models of Sanfilippo and Hurler syndromes.

Recent trials in patients with neurodegenerative diseases documented the safety of gene therapy based on adeno-associated virus (AAV) vectors deposited into the brain. Inborn errors of the metabolism are the most frequent causes of neurodegeneration in pre-adulthood. In Sanfilippo syndrome, a lysosomal storage disease in which heparan sulfate oligosaccharides accumulate, the onset of clinical manifestation is before 5 years. Studies in the mouse model showed that gene therapy providing the missing enzyme α-N-acetyl-glucosaminidase to brain cells prevents neurodegeneration and improves behavior. We now document safety and efficacy in affected dogs. Animals received eight deposits of a serotype 5 AAV vector, including vector prepared in insect Sf9 cells. As shown previously in dogs with the closely related Hurler syndrome, immunosuppression was necessary to prevent neuroinflammation and elimination of transduced cells. In immunosuppressed dogs, vector was efficiently delivered throughout the brain, induced α-N-acetyl-glucosaminidase production, cleared stored compounds and storage lesions. The suitability of the procedure for clinical application was further assessed in Hurler dogs, providing information on reproducibility, tolerance, appropriate vector type and dosage, and optimal age for treatment in a total number of 25 treated dogs. Results strongly support projects of human trials aimed at assessing this treatment in Sanfilippo syndrome.

Additional Benefit of Intraoperative Electroacupuncture in Improving Tolerance of Deep Brain Stimulation Surgical Procedure in Parkinsonian Patients.

BACKGROUND: Deep brain stimulation (DBS) is an effective technique to treat patients with advanced Parkinson's disease. The surgical procedure of DBS implantation is generally performed under local anesthesia due to the need for intraoperative clinical testing. However, this procedure is long (5-7 h on average) and, therefore, the objective that the patient remains co-operative and tolerates the intervention well is a real challenge. OBJECTIVE: To evaluate the additional benefit of electroacupuncture (EA) performed intraoperatively to improve the comfort of parkinsonian patients during surgical DBS implantation. METHODS: This single-center randomized study compared two groups of patients. In the first group, DBS implantation was performed under local anesthesia alone, while the second group received EA in addition. The patients were evaluated preoperatively, during the different stages of the surgery, and 2 days after surgery, using the 9-item Edmonton Symptom Assessment System (ESAS), including a total sum score and physical and emotional subscores. RESULTS: The data of nine patients were analyzed in each group. Although pain and tiredness increased in both groups after placement of the stereotactic frame, the ESAS item "lack of appetite", as well as the ESAS total score and physical subscore increased after completion of the first burr hole until the end of the surgical procedure in the control group only. ESAS total score and physical subscore were significantly higher at the end of the intervention in the control group compared to the EA group. After the surgical intervention (D2), anxiety and ESAS emotional subscore were improved in both groups, but the feeling of wellbeing improved in the EA group only. Finally, one patient developed delirium during the intervention and none in the EA group. DISCUSSION: This study shows that intraoperative electroacupuncture significantly improves the tolerance of DBS surgery in parkinsonian patients. This easy-to-perform procedure could be fruitfully added in clinical practice.

Combining Awake Anesthesia with Minimal Invasive Surgery Optimizes Intraoperative Surgical Spinal Cord Stimulation Lead Placement.

Spinal cord stimulation (SCS) is an effective and validated treatment to address chronic refractory neuropathic pain in persistent spinal pain syndrome-type 2 (PSPS-T2) patients. Surgical SCS lead placement is traditionally performed under general anesthesia due to its invasiveness. In parallel, recent works have suggested that awake anesthesia (AA), consisting of target controlled intra-venous anesthesia (TCIVA), could be an interesting tool to optimize lead anatomical placement using patient intra-operative feedback. We hypothesized that combining AA with minimal invasive surgery (MIS) could improve SCS outcomes. The goal of this study was to evaluate SCS lead performance (defined by the area of pain adequately covered by paraesthesia generated via SCS), using an intraoperative objective quantitative mapping tool, and secondarily, to assess pain relief, functional improvement and change in quality of life with a composite score. We analyzed data from a prospective multicenter study (ESTIMET) to compare the outcomes of 115 patients implanted with MIS under AA (MISAA group) or general anesthesia (MISGA group), or by laminectomy under general anesthesia (LGA group). All in all, awake surgery appears to show significantly better performance than general anesthesia in terms of patient pain coverage (65% vs. 34-62%), pain surface (50-76% vs. 50-61%) and pain intensity (65% vs. 35-40%), as well as improved secondary outcomes (quality of life, functional disability and depression). One step further, our results suggest that MISAA combined with intra-operative hypnosis could potentialize patient intraoperative cooperation and could be proposed as a personalized package offered to PSPS-T2 patients eligible for SCS implantation in highly dedicated neuromodulation centers.

Subthalamic nucleus stimulation in severe obsessive-compulsive disorder.

BACKGROUND: Severe, refractory obsessive-compulsive disorder (OCD) is a disabling condition. Stimulation of the subthalamic nucleus, a procedure that is already validated for the treatment of movement disorders, has been proposed as a therapeutic option. METHODS: In this 10-month, crossover, double-blind, multicenter study assessing the efficacy and safety of stimulation of the subthalamic nucleus, we randomly assigned eight patients with highly refractory OCD to undergo active stimulation of the subthalamic nucleus followed by sham stimulation and eight to undergo sham stimulation followed by active stimulation. The primary outcome measure was the severity of OCD, as assessed by the Yale-Brown Obsessive Compulsive Scale (Y-BOCS), at the end of two 3-month periods. General psychopathologic findings, functioning, and tolerance were assessed with the use of standardized psychiatric scales, the Global Assessment of Functioning (GAF) scale, and neuropsychological tests. RESULTS: After active stimulation of the subthalamic nucleus, the Y-BOCS score (on a scale from 0 to 40, with lower scores indicating less severe symptoms) was significantly lower than the score after sham stimulation (mean [+/-SD], 19+/-8 vs. 28+/-7; P=0.01), and the GAF score (on a scale from 1 to 90, with higher scores indicating higher levels of functioning) was significantly higher (56+/-14 vs. 43+/-8, P=0.005). The ratings of neuropsychological measures, depression, and anxiety were not modified by stimulation. There were 15 serious adverse events overall, including 1 intracerebral hemorrhage and 2 infections; there were also 23 nonserious adverse events. CONCLUSIONS: These preliminary findings suggest that stimulation of the subthalamic nucleus may reduce the symptoms of severe forms of OCD but is associated with a substantial risk of serious adverse events. (ClinicalTrials.gov number, NCT00169377.)

Treatment of refractory chronic cluster headache by chronic occipital nerve stimulation.

BACKGROUND: Greater occipital nerve stimulation (ONS) has been recently proposed to treat severe chronic cluster headache patients (CCH) refractory to medical treatment. We report the results of a French multidisciplinary cohort study. METHODS: Thirteen CCH patients were operated and data were collected prospectively. All of them suffered from CCH according to the International Headache Society classification, lasting for more than 2 years, refractory to pharmacological prophylactic treatment with adequate trials, with at least one daily attack. Chronic ONS was delivered through a subcutaneous occipital electrode connected to an implanted generator, in order to induce paraesthesias perceived locally in the lower occipital region. RESULTS: After surgery (mean follow-up 14,6 months), the mean attack frequency and intensity decreased by 68% and 49%, respectively. At last follow-up, 10/13 patients were considered as responders (improvement >50%). Prophylactic treatment could be stopped or reduced in 8/13 cases. Local infection occurred in one patient, leading to hardware removal. CONCLUSIONS: Our data confirmed the results of the 36 similar cases reported in the literature, suggesting that ONS may act as a prophylactic treatment in chronic CH. Considering their respective risks, ONS should be proposed before deep brain stimulation in severe refractory CCH patients.

Long-Term Efficacy of Occipital Nerve Stimulation for Medically Intractable Cluster Headache.

BACKGROUND: Occipital nerve stimulation (ONS) has been proposed to treat refractory chronic cluster headache (rCCH) but its efficacy has only been showed in small short-term series. OBJECTIVE: To evaluate ONS long-term efficacy in rCCH. METHODS: We studied 105 patients with rCCH, treated by ONS within a multicenter ONS prospective registry. Efficacy was evaluated by frequency, intensity of pain attacks, quality of life (QoL) EuroQol 5 dimensions (EQ5D), functional (Headache Impact Test-6, Migraine Disability Assessment) and emotional (Hospital Anxiety Depression Scale [HAD]) impacts, and medication consumption. RESULTS: At last follow-up (mean 43.8 mo), attack frequency was reduced >50% in 69% of the patients. Mean weekly attack frequency decreased from 22.5 at baseline to 9.9 (P < .001) after ONS. Preventive and abortive medications were significantly decreased. Functional impact, anxiety, and QoL significantly improved after ONS. In excellent responders (59% of the patients), attack frequency decreased by 80% and QoL (EQ5D visual analog scale) dramatically improved from 37.8/100 to 73.2/100. When comparing baseline and 1-yr and last follow-up outcomes, efficacy was sustained over time. In multivariable analysis, low preoperative HAD-depression score was correlated to a higher risk of ONS failure. During the follow-up, 67 patients experienced at least one complication, 29 requiring an additional surgery: infection (6%), lead migration (12%) or fracture (4.5%), hardware dysfunction (8.2%), and local pain (20%). CONCLUSION: Our results showed that long-term efficacy of ONS in CCH was maintained over time. In responders, ONS induced a major reduction of functional and emotional headache-related impacts and a dramatic improvement of QoL. These results obtained in real-life conditions support its use and dissemination in rCCH patients.

Pallidal stimulation in advanced Parkinson's patients with contraindications for subthalamic stimulation.

The aim of this study was to evaluate the efficacy and safety of bilateral pallidal (GPi) deep brain stimulation (DBS) 6 months after surgery in advanced parkinsonian patients whose dopa-resistant axial motor signs or cognitive decline constituted contraindications for subthalamic nucleus (STN) DBS. Seventeen patients with a mean age of 59.3 ± 7.1 years (range, 45-70), mean disease duration of 12.5 ± 4.3 years (range, 7-20), and contraindications for STN DBS, underwent bilateral GPi DBS. They were evaluated before surgery and 6 months afterward, in accordance with Core Assessment Program for Intracerebral Transplantation recommendations. There were mean improvements of 41.1% in the UPDRS III motor score in the off-dopa condition and 20.3% in the activities of daily living score. Motor fluctuations were reduced by 22.9% and dyskinesias by 68.6%. Axial motor signs improved in the off-dopa condition by 34.2%. Neuropsychological performances remained unchanged at the 6-month assessment. Bilateral GPi DBS is both safe and effective in advanced parkinsonian patients with untreatable motor fluctuations, for whom STN DBS is contraindicated due to dopa-resistant axial motor signs or cognitive decline. As such, it should be regarded as a viable option for these patients.

Globus pallidus stimulation reduces frontal hyperactivity in tardive dystonia.

Tardive dystonia (TD) is a disabling disorder induced by neuroleptics. Internal globus pallidus (GPi) stimulation can dramatically improve TD. The present positron emission tomography and H(2)(15)O study aimed to characterize the abnormalities of brain activation of TD and the impact of GPi stimulation on these abnormalities in five TD patients treated with GPi stimulation and eight controls. Changes of regional cerebral blood flow (rCBF) were determined: (i) at rest; (ii) when moving a joystick with the right hand in three freely chosen directions in on and off bilateral GPi stimulation. A significant increase of rCBF was found in TD patients in off-stimulation condition compared to controls: (1) during motor execution in the prefrontal, premotor lateral, and anterior cingulate cortex; (2) at rest, in the prefrontal and anterior cingulate cortex and the cerebellum. Internal globus pallidus stimulation led to a reduction of rCBF (1) during motor execution, in the primary motor and prefrontal cortex and the cerebellum; (2) at rest, in the primary motor and anterior cingulate cortex and supplementary motor area. The results are as follows: (1) TD is related to an excess of brain activity notably in the prefrontal and premotor areas; (2) GPi stimulation reduces the activation of motor, premotor, and prefrontal cortex as well as cerebellum.

Bilateral deep brain stimulation of the globus pallidus to treat tardive dyskinesia.

CONTEXT: Tardive dyskinesia (TD) is a common and potentially disabling disorder induced by use of antipsychotic drugs for which medical treatment often gives disappointing results. OBJECTIVE: To assess the efficacy of bilateral deep brain stimulation of the internal part of the globus pallidus to treat severe TD. DESIGN: Prospective phase 2 multicenter study. SETTING: Six French university hospitals. Patients Patients with severe TD refractory to medical treatment were studied to evaluate the severity of abnormal involuntary movements before and after 6 months of bilateral globus pallidus deep brain stimulation. A 2-step open Fleming procedure was used to avoid unnecessary accrual of patients. A successful outcome was defined as a decrease of more than 40% in the main outcome measure at 6 months. The early stopping rule was invoked if the number of successful outcomes in 10 patients was fewer than 2, or 5 or more. A double-blind evaluation in the presence and absence of stimulation was performed at 6 months after surgery. Main Outcome Measure Change in score on the Extrapyramidal Symptoms Rating Scale. RESULTS: At 6 months after surgery, the Extrapyramidal Symptoms Rating Scale score had decreased compared with baseline by more than 40% (mean improvement, 61%; range, 44%-75%) in the first 10 patients included. In accord with the 2-step open Fleming procedure, we ended the trial at the first step and concluded that pallidal stimulation is an effective treatment for TD. The efficacy of the treatment was confirmed by a double-blind evaluation, with a mean decrease of 50% (range, 30%-66%) (P = .002) in the Extrapyramidal Symptoms Rating Scale score when stimulation was applied compared with the absence of stimulation. There were no marked changes in the patients' psychiatric status. CONCLUSION: Although these results need to be confirmed in a larger group of patients with a longer follow-up, bilateral globus pallidus deep brain stimulation seems to offer a much-needed new treatment option for disabling TD.

Long-Term Follow-Up Comparative Study of Hydroxyapatite and Autologous Cranioplasties: Complications, Cosmetic Results, Osseointegration.

OBJECTIVE: A three-dimensional reconstruction technique using the CustomBone (CB) prosthesis allows custom-made cranioplasty (CP) possessing osseointegration properties owing to its porous hydroxyapatite (HA) composition. This reconstruction technique has replaced less expensive techniques such as subcutaneously preserved autologous bone (SP). Our primary objective was to evaluate complications between CB and SP CP techniques. A secondary objective was to assess cosmetic results and osseointegration of CPs. METHODS: This single-center study comprised patients undergoing delayed CB or SP CP after craniectomy between 2007 and 2014. A prospective interview was conducted to collect all data, including 2-year follow-up clinical and radiologic data. Cosmetic results were assessed by a qualitative score, and osseointegration was assessed by measuring relative fusion at the CP margins. RESULTS: Of 100 patients undergoing CB or SP CP between 2007 and 2014, 92 (CB, n = 44; SP, n = 48) participated in the prospective interview. No significant difference in complication rates was observed between the 2 groups. The main complication specific to the CB group was fracture of the prosthesis observed in 20.8% patients. A higher rate of good cosmetic results was observed in the CB group (92.5% vs. 74.3%, P = 0.031). In the CB group, 51% of patients demonstrated no signs of bone fusion of the CP. CONCLUSIONS: Although the CB prosthesis is associated with cosmetic advantages, the porous hydroxyapatite composition makes it fragile in the short-term and long-term, and effective osseointegration remains uncertain.

Treatment of refractory headache secondary to intracranial endovascular procedure by transcutaneous electrical nerve stimulation of the occipital nerve.

This pilot study aimed at assessing the effect of transcutaneous electrical nerve stimulation (TENS) of the occipital nerve (ON) to treat chronic refractory headache secondary to intracranial endovascular procedures (iEVP) in 4 patients. The duration of ON-TENS therapy was only 1 month (n=2) or longer than 4 months (n=2). Overall, pain intensity decreased from 7.8 (on a 0-10 scale) at baseline to 0.8 at 6 months after ON-TENS therapy initiation (-90%), while drug treatment was reduced from 34.3 to 0.8 (-98%) on the medication quantification scale. ON-TENS is a simple technique that may benefit patients with post-iEVP refractory headache.