Bilateral Globus Pallidus Internus Stimulation Research Articles

Pallidal deep brain stimulation relieves camptocormia in primary dystonia

Camptocormia, characterised by a forward flexion of the thoracolumbar spine may occur in various movement disorders, mainly in Parkinson's disease or in primary dystonia. In severe cases, patients with camptocormia are unable to walk. While treatment options are limited, deep brain stimulation (DBS) with bilateral stimulation of the subthalamic nucleus or globus pallidus internus (GPi) has been proposed as a therapeutic option in refractory cases of Parkinson's disease. Here we present two patients with severe camptocormia as an isolated form of dystonia and as part of generalised dystonia, respectively, which were both treated with bilateral stimulation of the GPi. Symptoms of dystonia were assessed using the Burke-Fahn-Marsden dystonia rating scale (BFM) before and during deep brain stimulation. In both patients there was a significant functional improvement following long-term bilateral GPi stimulation and both patients gained ability to walk. In the first patient with an isolated dystonic camptocormia the BFM motor subscore for the truncal flexion improved by 75 %. The total BFM motor score in the second patient with a camptocormia in generalised dystonia improved by 45 %, while the BFM score for truncal flexion improved by 87 %. In both patients the effect of the bilateral GPi stimulation on camptocormia was substantial, independent of generalisation of dystonia. Therefore, GPi DBS is a possible treatment option for this rare disease.

Deep brain stimulation improves quality of life in pantothenate kinase-associated neurodegeneration

Pantothenate kinase-associated neurodegeneration (PKAN) is an uncommon extrapyramidal movement disorder characterized by the progressive incapacitating dystonia. Medical management is often incapable of reversing the dystonic symptoms. In recent years, stereotactic procedure like deep brain stimulation has been found effective in resolving the disabling dystonia and improving the quality of life. There are few cases in the world literature highlighting the usefulness of this technique. We report a case of 10-year-old girl who underwent bilateral Globus pallidus internus stimulation for PKAN.

Effects of Relative Low-Frequency Bilateral Globus Pallidus Internus Stimulation for Treatment of Cervical Dystonia

Objective: To assess the effect of relative lower amplitude and frequency for globus pallidus internus (GPi) deep brain stimulation (DBS) of cervical dystonia (CD). Materials and Methods: Between February 2005 and October 2008, 14 patients diagnosed with CD underwent bilateral GPi DBS and all the patients received low-frequency stimulation and were followed for more than 2 years. We activated the implantable pulse generator 3–4 days postoperatively and initial amplitude, pulse width, and frequency were set at 1.5 V, 120 µs, and 70 Hz. The Toronto Western Spasmodic Torticolis Rating Scale (TWSTRS) was applied preoperatively and at 1, 6, 12 and 24 months postoperatively. Results: The overall TWSTRS scores improved 71.2% 2 years postoperatively (p = 0.001). The mean improvement was 78.4% in severity subscores, 68.4% in disability, and 66.8% in pain scores for the 2-year follow-up period. The TWSTRS scores were significantly reduced (p < 0.05), suggesting that the most significant improvement of the TWSTRS scores occurred within 1 month. The final amplitude was 2.9/2.7 V with the pulse width of 147.9/147.9 µs and the frequency of 101.1/100 Hz. Conclusion: According to our results, the initial settings of low amplitude and especially relatively low frequency are safe and effective for treatment of CD.

Deep brain stimulation for medically refractory life-threatening status dystonicus in children

Generalized dystonic syndromes may escalate into persistent episodes of generalized dystonia known as status dystonicus that can be life-threatening due to dystonia-induced rhabdomyolysis and/or respiratory compromise. Treatment of these conditions usually entails parenteral infusion of antispasmodic agents and sedatives and occasionally necessitates a medically induced coma for symptom control. The authors report a series of 3 children who presented with medically intractable, life-threatening status dystonicus and were successfully treated with bilateral pallidal deep brain stimulation. Bilateral globus pallidus internus stimulation appears to be effective in the urgent treatment of medically refractory and life-threatening movement disorders.

Combined pallidal and subthalamic nucleus stimulation in sporadic dystonia-parkinsonism

Multifocal deep brain stimulation (DBS) is a new technique that has been introduced recently. A 39-year-old man with dystonia-parkinsonism underwent the simultaneous implantation of subthalamic nucleus (STN) and globus pallidus internus (GPi) DBS electrodes. While bilateral STN DBS controlled the parkinsonian symptoms well and allowed for a reduction in levodopa, the improvement of dystonia was only temporary. Additional GPi DBS also alleviated dystonic symptoms. Formal assessment at the 1-year follow-up showed that both the parkinsonian symptoms and the dystonia were markedly improved via continuous bilateral combined STN and GPi stimulation. Sustained benefit was achieved at 3 years postoperatively.

Surgically treated movement disorders associated with heterotopia

Heterotopic gray matter has been implicated in epilepsy; however, not much is known regarding heterotopia beyond epilepsy. Here, the authors describe 2 pediatric patients with deep heterotopias contiguous with basal ganglia structures. These heterotopias appear to have manifested as movement disorders. One patient presented with a left-sided myoclonus and choreiform movements associated with a right caudate heterotopia; she experienced vast improvement after resection of periventricular heterotopia. The other patient presented with progressive dystonia and a ballistic movement disorder. Initial bilateral globus pallidus internus stimulation resulted in successful treatment of the dystonia; however, her movement disorder worsened. After an extensive workup, including STATISCOM (statistical ictal SPECT coregistered to MR imaging), the patient underwent cortical stimulation with improvement in her movement disorder. To the best of our knowledge, these cases are the first reported instances of heterotopic gray matter associated with movement disorders. Both patients experienced significant improvements following resection of their heterotopias.

Deep brain stimulation for hyperkinetics disorders: dystonia, tardive dyskinesia, and tics

This review focuses on new insights in deep brain stimulation (DBS) for patients with hyperkinetic movement disorders: dystonia, tardive dyskinesia and Gille de la Tourette's syndrome, during the last 18 months. The recent literature confirms the efficacy of high-frequency stimulation of the globus pallidus internus (GPi) for primary dystonia, generalized or not, with a stable effect over time. The benefit of DBS in other forms of localized dystonia remains to be demonstrated in larger studies. Some clinical and radiological predictive factors have been determined with a predominant influence of the disease duration. Tardive dystonia and myoclonus-dystonia are also improved by GPi stimulation. Encouraging results obtained in cerebral palsy may pave the way for the application of DBS in other secondary dystonia. In Gilles de la Tourette's syndrome, both stimulation of the centre-median/parafascicular nucleus of the thalamus and GPi stimulation (ventromedial) have demonstrated efficacy with stable long-term effect. Thalamic stimulation failed to improve obsessions and compulsions in some patients. Stimulation of the nucleus accumbens has been tested in few cases with contradictory efficacy. In both diseases, complications are rare with no major side effects. The few controlled studies showed that bilateral GPi stimulation is a well tolerated and a long-term effective treatment for hyperkinetic disorders. However, recent published data of DBS applied in different targets or patients (especially secondary dystonia) are mainly uncontrolled case reports, precluding the clear determination of the efficacy of this procedure and the choice of the 'good' target for the 'good' patient.

Deep brain stimulation in the treatment of dyskinesia and dystonia.

Deep brain stimulation (DBS) has become a mainstay of treatment for patients with movement disorders. This modality is directed at modulating pathological activity within basal ganglia output structures by stimulating some of their nuclei, such as the subthalamic nucleus (STN) and the globus pallidus internus (GPi), without making permanent lesions. With the accumulation of experience, indications for the use of DBS have become clearer and the effectiveness and limitations of this form of therapy in different clinical conditions have been better appreciated. In this review the authors discuss the efficacy of DBS in the treatment of dystonia and levodopa-induced dyskinesias. The use of DBS of the STN and GPi is very effective for the treatment of movement disorders induced by levodopa. The relative benefits of using the GPi as opposed to the STN as a target are still being investigated. Bilateral GPi stimulation is gaining importance in the therapeutic armamentarium for the treatment of dystonia. The DYT1 forms of generalized dystonia and cervical dystonias respond to DBS better than secondary dystonia does. Discrimination between the diverse forms of dystonia and a better understanding of the pathophysiological features of this condition will serve as a platform for improved outcomes.

Chronic stimulation of subthalamic nucleus improves levodopa-induced dyskinesias in Parkinson's disease

Ventroposterior pallidotomy, and pallidal and subthalamic nucleus (STN) stimulation, are proposed to treat severe Parkinson’s disease (PD) with levodopa-induced motor complications. Pallidal surgery decreases levodopa-induced dyskinesias (LID). Parkinsonism evaluated by the motor part of the Unified Parkinson’s Disease Rating Scale (UPDRS) improves by about 30% after unilateral pallidotomy. STN stimulation can greatly improve parkinsonian disability, but its effects on LID are unknown because the first patients treated with STN stimulation were selected with mild or absent LID since spontaneous STN lesions can induce hemiballism. However, our initial experience with STN stimulation showed that stimulation-induced abnormal movements could be controlled by setting the stimulation voltage below the dyskinesia threshold. Moreover, the substantial decrease in levodopa dosage, which was made possible by the antiparkinsonian benefit, allowed a decrease in LID in the long-term. Thus, STN stimulation was also proposed for patients with severe LID. We selected all consecutive patients with young-onset PD, since this population is generally levodopa-sensitive and prone to develop severe LID. Eight patients with a mean age of 51 (SD 10) years and a mean disease duration of 16 (5) years were operated on bilaterally in the STN because of severe motor fluctuations (motor score on the UPDRS 57·5 [14·5] off-drug and 18·2 [10·6] on-drug). The study was approved by the Grenoble University ethical committee and all patients gave their written, informed consent. The surgical procedure has been described previously. 6 months after surgery, the motor score of the UPDRS improved from 58 (16) to 17 (8) (–71%) in the off-drug condition when stimulation was switched on. This improvement was seen in all the major parkinsonian symptoms. The dyskinesia score (six body parts, each scored 0–4, maximum score 24), assessed during the maximum motor response of a levodopa test with the same dose as preoperatively (early morning +50–100 mg), decreased from 11·4 (6·6) preoperatively to 6·8 (4·3) postoperatively onstimulation. Dyskinesia duration and disability (UPDRS items 32+33), which assess LID during activities of daily living under chronic stimulation, decreased from 4·0 (1·9) to 1·4 (0·9) (–65%). The antiparkinsonian drug dosage calculated as levodopa equivalent decreased from 1560 (930) to 680 (420) mg daily (–56%). With chronic STN stimulation, LID were greatly improved, in a similar percentage as with bilateral globus-pallidusinternus stimulation. With unilateral pallidotomy, contralateral LID are substantially improved although a big reduction of levodopa is not possible. Targeting the STN instead of the globus pallidus internus has the advantage of inducing a more pronounced antiakinetic effect. The decrease in LID induced by STN stimulation can be explained mainly by the decrease in levodopa dosage. This is why the improvement in dyskinesias is more obvious in activities of daily living than during the levodopa test with a dose identical to that given before surgery. Moreover, as highfrequency stimulation is supposed to act through neuroinhibition, the chronic inhibition of STN neurons can change the dyskinesia threshold with time, in the same way as the progressive abatement of hemiballism after a vascular lesion of the STN. Replacing the pulsatile levodopa-induced decrease of STN activity by a chronic stable decrease seems to improve dyskinesias. After 4 years of experience of STN stimulation, this surgical treatment improves LID with time, contrary to our initial fears. As the improvement in all the main parkinsonian motor symptoms is substantial in patients with a good levodopa response, the STN is suggested as the target of choice for the neurosurgical treatment of PD, even in patients with severe LID. However, randomised studies comparing different surgical procedures are required to better understand their respective value.