Deep brain stimulation for torsion dystonia in children

Introduction Deep brain stimulation (DBS) at the internal globus pallidus (GPi) is an effective treatment for some patients with medically refractory torsion dystonia. In this article, we review the results of pallidal DBS surgery in children with dystonia. Details of the DBS procedure and programming of the DBS devices are discussed. Discussion Pallidal DBS is most effective in patients with primary generalized dystonia. Children and adolescents possessing the DYT1 gene mutation may respond best of all. The presence of static dystonic postures and/or fixed orthopedic contractures may limit the functional response to DBS and may require additional surgery. Conclusion As a group, patients with secondary dystonias respond less well to DBS than patients with primary dystonia. However, patients with dystonia secondary to anoxic brain injury who have grossly intact basal ganglia anatomy may represent a subpopulation for whom pallidal DBS is a viable option.     

Subthalamic and pallidal oscillatory activity in patients with Neurodegeneration with Brain Iron Accumulation type I (NBIA-I)

ObjectivesNeurodegeneration with Brain Iron Accumulation type I (NBIA-I) is a rare hereditary neurodegenerative disorder with pallidal degeneration leading to disabling generalized dystonia and parkinsonism. Pallidal or subthalamic deep brain stimulation can partially alleviate motor symptoms. Disease-specific patterns of abnormally enhanced oscillatory neuronal activity recorded from the basal ganglia have been described in patients with movement disorders undergoing deep brain stimulation (DBS). Here we studied oscillatory activity recorded from the internal globus pallidus (GPi) and the subthalamic nucleus (STN) to characterize neuronal activity patterns in NBIA-I.MethodsWe recorded local field potentials (LFP) from DBS electrodes in 6 juvenile patients with NBIA-I who underwent functional neurosurgery. Four patients were implanted in the STN and two patients in the GPi. Recordings were performed during wakeful rest. An FFT-based approach was used to analyze the power spectrum in the target area.ResultsIn all patients we found distinct peaks in the low frequency (7–12 Hz) and in 5 out 6 also in the beta frequency range (15–30 Hz) with the largest beta peak in the patient that presented with the most prominent bradykinesia. No distinct peaks occurred in the gamma frequency range (35–100 Hz). The oscillatory pattern did not differ between STN and GPi.ConclusionsHere we show for the first time the oscillatory activity pattern in the STN and the GPi in juvenile patients with dystonia plus syndrome due to NBIA-I. The low frequency peak we found is in line with previous studies in patients with isolated idiopathic dystonia. In our cohort, the pallidal beta band activity may be related to more severe motor slowing in dystonia plus syndrome such as NBIA-I.SignificanceOur results further support the link between hyperkinetic motor symptoms such as dystonia and enhanced basal ganglia low frequency activity irrespective of the underlying etiology of dystonia.     

Pallidal neuronal activity: implications for models of dystonia

Dystonia is a neurological syndrome involving sustained contractions of opposing muscles leading to abnormal movements and postures. Recent studies report abnormally low pallidal neuronal activity in patients with generalized dystonia, suggesting hyperkinetic disorders result from underactive basal ganglia output. We examined this hypothesis in 11 patients with segmental and generalized dystonia undergoing microelectrode exploration of the internal globus pallidus (GPi) before pallidotomy or deep brain stimulation (DBS) implantation. The mean firing rates and firing patterns were compared with those in six patients with Parkinson's disease (PD). In seven patients who underwent surgery under local anesthesia, the mean GPi firing rate was 77 Hz, similar to the 74 Hz observed in the PD patients. However, in three dystonic patients under propofol anesthesia, GPi mean firing rate was much reduced (31 Hz), and the firing pattern was distinguished by long pauses in activity, as reported by others. Low-dose propofol in one other dystonia patient also seemed to suppress GPi firing. These results indicate that an abnormally low basal ganglia output is not the sine qua non of dystonia. The widely accepted pathophysiological models of dystonia that propose global decreases in basal ganglia output need to be viewed with caution in light of these findings.     

Chronic deep brain stimulation in patients with tardive dystonia without a history of major psychosis

Tardive dystonia usually occurs with a delay after neuroleptic exposure in patients with major psychosis. A subgroup of patients, however, is given such medication for “mild depression” or “neurasthenia.” Tardive dystonia, in general, may respond favorably to pallidal deep brain stimulation (DBS). Nevertheless, it remains unclear thus far whether or not similar beneficial outcome is achieved with pallidal DBS in different subgroups of patients with tardive dystonia. Four women (mean age 59 years at surgery) underwent stereotactic pallidal DBS in the frame of an observational study. Tardive dystonia occurred secondary to medication with fluspirilene and haloperidol, and injection of long‐acting depot neuroleptics prescribed for mild depression or “nervousness.” Assessment included the Burke‐Fahn‐Marsden (BFM) scale preoperatively and at 12 months follow‐up. Extended follow‐up was available at a mean of 27.3 months postoperatively (range 16–36 months). There were no surgically related complications. All 4 patients experienced sustained statistically significant benefit from pallidal DBS. Mean improvement at 12 months was 77% for the BFM motor score (range, 45–91%; P = 0.043), and 84% at the last available follow‐up (range, 70–91%; P = 0.03). This was paralleled by improvement of the BFM disability score. Chronic pallidal DBS in patients with tardive dystonia without a history of major psychosis provides sustained improvement which is similar to that in other subgroups of patients with tardive dystonia. This effect is stable on extended follow‐up for up to 3 years. © 2010 Movement Disorder Society     

Gait disturbance and deep brain stimulation

Gait disturbance, one of the axial symptoms, is caused by various disorders, including basal ganglia disease. Deep brain stimulation (DBS) has widened the spectrum of therapeutic options for patients with gait disturbance due to Parkinson disease and dystonia. In gait disturbance caused by basal ganglia disease, the main targets of DBS are the subthalamic nucleus (STN) and globus pallidus internus (GPi). STN DBS is more than GPi DBS effective for treating levodopa-responsive parkinsonian symptoms, including gait disturbance. GPi DBS is effective for the treatment of primary segmental or generalized dystonia. The pedunculopontine tegmental nucleus (PPN), which is involved in locomotion, is one of the new targets for treating gait disturbance in Parkinson disease. We review DBS in the treatment of gait disturbance due to Parkinson disease and dystonia.     

Postanoxic generalized dystonia improved by bilateral Voa thalamic deep brain stimulation.

A patient with severe postanoxic dystonia and bilateral necrosis of the basal ganglia, who was confined to a wheelchair, underwent bilateral ventralis oralis anterior deep brain stimulation (Voa-DBS) after 6 weeks of unsuccessful bilateral pallidal DBS (GPi-DBS). After 4 months of high intensity Voa-DBS, cognitively unimpaired, he showed major improvement in dystonia, became ambulant, but committed suicide. Brain examination confirmed the correct location of the electrodes in GPi and Voa on both sides.     

A family with a hereditary form of torsion dystonia from Northern Sweden treated with bilateral pallidal deep brain stimulation

To evaluate pallidal DBS in a non‐DYT1 form of hereditary dystonia. We present the results of pallidal DBS in a family with non‐DYT1 dystonia where DYT5 to 17 was excluded. The dystonia is following an autosomal dominant pattern. Ten members had definite dystonia and five had dystonia with minor symptoms. Four patients received bilateral pallidal DBS. Mean age was 47 years. The patients were evaluated before surgery, and “on” stimulation after a mean of 2.5 years (range 1–3) using the Burke‐Fahn‐Marsden scale (BFM). Mean BFM score decreased by 79 % on stimulation, from 42.5 ± 24 to 9 ± 6.5 at the last evaluation. Cervical involvement improved by 89%. The 2 patients with oromandibular dystonia and blepharospasm demonstrated a reduction of 95% regarding these symptoms. The present study confirms the effectiveness of pallidal DBS in a new family with hereditary primary segmental and generalized dystonia. © 2009 Movement Disorder Society     

Deep brain stimulation for dystonia: outcome at long-term follow-up

OBJECTIVE: Deep brain stimulation (DBS) has emerged as a useful therapeutic option for patients with insufficient benefit from conservative treatment. METHODS: Nine patients with chronic DBS who suffered from cervical dystonia (4), generalized dystonia (2), hemidystonia (1), paroxysmal dystonia (1) and Meige syndrome (1) were available for formal follow-up at three years postoperatively, and beyond up to 10 years. All patients had undergone pallidal stimulation except one patient with paroxysmal dystonia who underwent thalamic stimulation. RESULTS: Maintained improvement was seen in all patients with pallidal stimulation up to 10 years after surgery except in one patient who had a relative loss of benefit in dystonia ratings but continued to have improved disability scores. After nine years of chronic thalamic stimulation there was a mild loss of efficacy which was regained when the target was changed to the pallidum in the patient with paroxysmal dystonia. There were no major complications related to surgery or to chronic stimulation. Pacemakers had to be replaced within 1.5 to 2 years, in general. CONCLUSION: DBS maintains marked long-term symptomatic and functional improvement in the majority of patients with dystonia.     

Pallidal DBS for dystonia in the age of personalized medicine

In response to the correspondence by Albanese and co-workers, we discuss etiology as a factor predicting outcome of pallidal DBS in dystonia, reanalysing our dataset on causes of non-response to pallidal DBS in isolated dystonia by looking only at patients with a diagnosis of idiopathic dystonia at time of surgery.     

A case series and systematic review of rapid eye movement sleep behavior disorder outcome after deep brain stimulation in Parkinson's disease

REM-sleep behavior disorder (RBD) is a parasomnia and a common sleep disorder in Parkinson's disease (PD). While deep brain stimulation (DBS) is an established treatment for advanced PD with beneficial effects on cardinal PD motor symptoms, the data on the impact of DBS on RBD are limited and often controversial.We reviewed published articles that reported on RBD in the context of DBS surgery via systematic PubMed search. We identified 75 studies and included 12 studies, involving a total of 320 subjects, in our review. Results in respect to EMG activity outcome after subthalamic stimulation are inconsistent. We found no study that reported on RBD outcome after pallidal DBS and no DBS study quantified complex behavior during REM sleep.We also added data on RBD outcome after subthalamic (N = 4 patients) or pallidal (N = 3 patients) DBS from patients with PD with RBD, obtained as part of a prospective DBS study in our centre. Our case series showed an increase of complex behavior during REM (CB-REM) after surgery, independent of DBS target. Conversely, we found a trend towards increasing REM sleep without atonia (RSWA) in subthalamic-stimulated patients and a trend towards decreased RSWA in pallidal stimulated patients.We conclude that CB-REM and RSWA might represent two distinct elements in RBD and should be assessed separately, especially in studies that report on RBD outcome after treatment interventions. Further, larger, prospective, controlled studies in different DBS targets, reporting separately on the different RBD modalities, are needed.     

Deep brain stimulation in the treatment of severe dystonia

A retrospective study of a consecutive series of 19 patients with medically intractable dystonia treated with uni- or bilateral deep brain stimulation (DBS) is reported. A minimal follow-up of 6 months was available, up to eleven years in one patient. The first twelve consecutive patients (4 with primary and 8 with secondary dystonia) were treated with chronic stimulation of the posterior part of the ventrolateral thalamic nucleus (VLp). In this group global functional outcome was improved in 8 patients, although dystonia movement and disability scale scores did not show significant improvement. Of the 12 patients treated first by VLp DBS, three (1 primary and 2 secondary dystonia) underwent pallidal (GPi) DBS after the VLp DBS failed to improve their symptoms. The last seven consecutive patients (5 primary and 2 secondary dystonia) were treated directly with GPi DBS. Extracranial infection prevented chronic GPi DBS in one patient. In another GPi patient, preliminary negative tests with the electrodes discouraged implantation of the stimulators, and the patient was not treated with chronic DBS. In the remaining group of eight patients including those previously treated with VLp DBS, chronic GPi DBS resulted in a significant improvement in the dystonia movement scale and disability scores. Although this is a retrospective study dealing with dystonia of heterogeneous etiology, the results strongly suggest that GPi DBS has a better outcome than VLp DBS Received: 22 January 2001 / Received in revised form: 28 February 2001 / Accepted: 1 March 2001     

Long‐Term Follow‐Up Study of Chronic Deep Brain Stimulation of the Subthalamic Nucleus for Cervical Dystonia

Objectives. Medically refractory cervical dystonia has recently been treated using deep brain stimulation (DBS), targeting the subthalamic nucleus (STN). There has been limited literature regarding short‐term outcomes and no literature regarding long‐term outcomes for refractory cervical dystonia following DBS of the STN. Materials and Methods. Two patients with medically refractory cervical dystonia underwent STN DBS. Patients were rated using the Toronto Western Spasmodic Torticollis Rating Scale (TWSTRS) preoperatively and immediately postoperatively as well as just prior to turning on the stimulators and subsequently at 24–48 hours, six months, one, two, and three years after stimulation. Microrecordings were used to identify the STN and substantia nigra reticulata (SNr). Results. Significant immediate and sustained long‐term improvements were seen in motor, disability, pain, and total TWSTRS scores. In one patient, only unilateral stimulation was required. The STN and SNr were easily identified as having activity similar to off‐state Parkinson's patients. Conclusions. DBS therapy for cervical dystonia utilizing the STN as the surgical target may be novel and may be an alternative target to the globus pallidus internus as supported by this first long‐term outcome report. Further studies need to be performed to confirm these conclusions.     

First case of X-linked dystonia-parkinsonism ("Lubag") to demonstrate a response to bilateral pallidal stimulation.

"Lubag" or X-linked dystonia-parkinsonism (XDP) is a genetic syndrome afflicting Filipino men. Intracranial surgical procedures for Lubag have been unsuccessful. We report a 45-year-old Filipino male with genetically confirmed XDP who underwent bilateral pallidal deep brain stimulation (DBS) surgery. The patient started to exhibit improvement on initial programming, most notably of his severe jaw-opening dystonia. At 1-year follow-up, his Burke-Fahn-Marsden dystonia score and motor Unified Parkinson's Disease Rating Scale score were improved by 71% and 62%, respectively, with the stimulators on compared to stimulators off state. Bilateral pallidal DBS may be a viable option for Lubag patients with medically refractory symptoms.     

Review of the functional surgical treatment of dystonia

A review of functional surgery for dystonia is presented. Recently renewed interest in stereotaxy for dystonia has followed the resurgence of pallidotomy and the introduction of deep brain stimulation (DBS) in Parkinson's disease (PD) in the early 1990s. However, even since the 1950s, small series of patients treated with ablative surgery have been carefully studied, providing useful information, notably regarding the tolerability of surgery. In the setting of dystonia, thalamotomy was first performed with substantial benefits, but some authors outlined the great variability in outcome, and the high incidence of operative side-effects. In the 'modern' era of functional surgery for movement disorders, the globus pallidus internus (GPi) has emerged to be currently the best target for dystonia, based on small series of patients published in the last few years. Both bilateral posteroventral pallidotomy (PVP) and bilateral pallidal stimulation, performed by several teams, have benefited a variety of patients with severe dystonia, the most dramatic improvements being seen in primary dystonia with a mutation in the DYT1 gene. Whereas patients with secondary dystonia have often shown a lesser degree of improvement, some publications have nevertheless reported major benefit. There is today a strong need for carefully controlled studies comparing secondary and primary dystonia, DYT1 and non-DYT1 dystonia, ablative surgery and DBS, with additional assessment of neuropsychological changes, especially in children treated with bilateral pallidal procedures.     

Surgical Treatment of Parkinson’s Disease: Patients, Targets, Devices, and Approaches

Surgical treatment for Parkinson’s disease (PD) has evolved from ablative procedures, within a variety of brain regions, to implantation of electrodes into specific targets of the basal ganglia. Electrode implantation surgery, referred to as deep brain stimulation (DBS), is preferred to ablative procedures by many experts owing to its reversibility, programmability, and the ability to be safely performed bilaterally. Several randomized clinical studies have demonstrated the effectiveness of DBS surgery for control of PD symptoms. Many brain targets, including the subthalamic nucleus and the globus pallidus internus, have emerged as potentially effective, with each target being closely associated with important pros and cons. Selection of appropriate PD candidates through a methodical interdisciplinary screening is considered a prerequisite for a successful surgical outcome. Despite recent growth in DBS knowledge, there is currently no consensus on the ideal surgical technique, the best surgical approach, and the most appropriate surgical target. DBS is now targeted towards treating specific PD-related symptoms in a given individual, and not simply addressing the disease with one pre-defined approach. In this review we will discuss the historical aspects of surgical treatments, the selection of an appropriate DBS candidate, the current surgical techniques, and recently introduced DBS-related technologies. We will address important pre- and postoperative issues related to DBS. We will also discuss the lessons learned from the randomized clinical studies for DBS and the shifting paradigm to tailor to a more patient-centered and symptom-specific approach.     

Changes in forearm reciprocal inhibition following pallidal stimulation for dystonia

The authors recorded forearm H reflex reciprocal inhibition and clinical outcome in eight patients with primary torsion dystonia before and 1, 3, and 6 months after pallidal deep brain stimulation (DBS). There was progressive increase in reciprocal inhibition after surgery, which correlated with clinical improvement. The authors conclude that pallidal DBS for dystonia results in functional reorganization of the nervous system, which includes a long-term increase in spinal inhibition.     

Deep brain stimulation of globus pallidus internus for dystonia

Neuromodulation is the functional modification of neural structures through the use of electrical stimulation. Its most clinically applicable use is deep brain stimulation (DBS) of basal ganglia structures in Parkinson's disease (PD) and essential tremor (ET). More recently, it has been used as a means of treating dystonic movement disorders. The main target of DBS for dystonia is the posteroventral globus pallidus internus (GPi), although the thalamus has been used as an alternate target in a minority of cases. In comparison to the effects seen in PD, the improvement in dystonic postures appear to differ in several ways--delay of clinical benefit, higher voltage requirements, and varied stimulator settings. In this review, the authors discuss the clinical characteristics, pathophysiology, microelectrode recording (MER) signatures, optimal surgical targets, programming parameters and outcomes in dystonia.     

It's not just the basal ganglia: Cerebellum as a target for dystonia therapeutics

Dystonia is a common movement disorder that devastates the lives of many patients, but the etiology of this disorder remains poorly understood. Dystonia has traditionally been considered a disorder of the basal ganglia. However, growing evidence suggests that the cerebellum may be involved in certain types of dystonia, raising several questions. Can different types of dystonia be classified as either a basal ganglia disorder or a cerebellar disorder? Is dystonia a network disorder that involves the cerebellum and basal ganglia? If dystonia is a network disorder, how can we target treatments to alleviate symptoms in patients? A recent study by Chen et al, using the pharmacological mouse model of rapid‐onset dystonia parkinsonism, has provided some insight into these important questions. They showed that the cerebellum can directly modulate basal ganglia activity through a short latency cerebello‐thalamo‐basal ganglia pathway. Further, this article and others have provided evidence that in some cases, aberrant cerebello‐basal ganglia communication can be involved in dystonia. In this review we examine the evidence for the involvement of the cerebellum and cerebello‐basal ganglia interactions in dystonia. We conclude that there is ample evidence to suggest that the cerebellum plays a role in some dystonias, including the early‐onset primary torsion dystonia DYT1 and that further studies examining the role of this brain region and its interaction with the basal ganglia in dystonia are warranted. © 2017 International Parkinson and Movement Disorder Society     

Deep brain stimulation for movement disorders before DBS for movement disorders

Deep brain stimulation (DBS) is an established surgical treatment for Parkinson’s disease (PD), essential tremor and dystonia. It is generally acknowledged that the development of DBS as we know it today started with the publication of Benabid, Pollak et al in 1987 on thalamic DBS for tremor. This technique gained momentum in the mid-Nineties after that Pollak and Benabid introduced the subthalamic nucleus as a target in advanced PD.This paper reviews the gestational pre-natal era of deep brain stimulation, before 1987. The origin of DBS can be traced back to the practice of intra-operative electrical stimulation, used for target exploration prior to lesioning, during the early years of stereotactic functional neurosurgery. During the 60s, Sem-Jacobsen and others implanted externalised electrodes which were used for intermittent stimulation and evaluation during weeks or months, prior to subsequent ablation of thalamic and other basal ganglia targets. In the early 70s Bechtereva treated PD patients using “therapeutic electrical stimulation” through electrodes implanted for up to 1.5 years. In the late 70s and early 80s the term Deep Brain Stimulation was coined and few groups attempted treatment of Parkinson’s disease, non-Parkinsonian tremor and dystonia with high-frequency stimulation using chronically implanted DBS systems. Cumbersome, un-sophisticated DBS hardware, together with the general decline of all surgery for PD following the introduction of levodopa, may have contributed to the lack of popularity of old-times DBS. It is to the credit of the Grenoble Group to have reinvented, modernised and expanded modern DBS in surgical treatment of movement disorders.     

Chronic bilateral pallidal stimulation in a patient with DYT-1 positive primary generalized dystonia. A long-term follow-up study

Primary generalized dystonia is a medically refractory progressive disease of the brain causing near total functional handicap of affected patients. The authors present the effectiveness of bilateral globus pallidus internus (GPi) stimulation in one patient with primary DYT-1 positive dystonia. Pharmacotherapy completely failed to control generalized dystonic movements. The patient was referred for surgical treatment and underwent bilateral implantation of DBS leads in the GPi. The formal objective assessment included the Burke-Fahn-Marsden dystonia rating scale (BFMDRS). Clinical and functional BFMDRS assessments were performed before and after surgery till 5 years postoperatively. All stimulation-induced side effects were reversible. Chronic bilateral pallidal stimulation is an effective and safe treatment in patients with primary generalized DYT-1 positive dystonia. The effectiveness of pallidal stimulation was proved by the objective validated BFMDRS assessment at 5 years follow-up examination.