Pallidal deep brain stimulation in cervical dystonia: clinical outcome in four cases

OBJECTIVE: Report on the clinical results following bilateral globus pallidus interna deep brain stimulation in four patients (one female and three males) with severe cervical dystonia, mean age 48 years (range 37-67). METHODS: All four patients had failed extensive medical and botulinum toxin treatment. The mean duration of the disease was nine years (range 4-15 years). Patients were assessed pre and postoperatively using the Toronto Western Spasmodic Torticollis Rating Scale (TWSTRS). Pre-operatively, the mean TWSTRS total score was 43.2 (range 28-60.5). Posteroventral pallidal deep brain stimulators were inserted using MRI and microelectrode recording guidance. Last follow-up was 15 months for the four patients. RESULTS: Mean reduction in the TWSTRS total scores at last follow- up was 73% (range 61- 85%). Improvement in pain occurred soon after deep brain stimulation surgery. Motor improvement was delayed and prolonged over several months. Frequent adjustment in the stimulation parameters was necessary in the first three months. CONCLUSION: Bilateral pallidal stimulation is effective in management of selected cases of intractable cervical dystonia.     

Pallidal surgery for the treatment of primary generalized dystonia: long-term follow-up

OBJECTIVE: To describe the results and long-term follow-up after functional surgery of the internal segment of the globus pallidus (GPi) in 10 patients with primary generalized dystonia. PATIENTS AND METHODS: Nine of the 10 patients were positive for the DYT1 gene mutation. Bilateral deep brain stimulation (DBS) of the GPi was performed in three cases, bilateral pallidotomy in two, and combined surgery (unilateral GPi lesion with contralateral stimulation) in the remaining five. All patients were evaluated with the Burke-Fahn-Marsden dystonia scale (BFMDS) before, immediately after surgery, at 3 weeks, 3 and 6 months and then yearly. Follow up time ranged from 15 to 105 months (mean: 66.1 months) with six patients having more than 6 years follow up. RESULTS: All patients improved after surgery. All patients with unilateral or bilateral DBS experienced an immediate improvement before starting stimulation. The magnitude of this initial micro lesion effect did not predict the magnitude of the long-term benefit of DBS. The mean decrease in the in the BFMDS was 34%, 55%, and 65% in the movement scale; and 32%, 48%, and 49% in the disability scale for patients with bilateral pallidal DBS, combined unilateral DBS and contralateral pallidotomy, and bilateral pallidotomy, respectively. Worsening of dystonia after a plateau of sustained benefit was observed in three patients. Two patients required multiple pallidal surgeries. Adverse events included: permanent anarthria (1), misplacement of the electrode requiring further surgery (2), scalp infection (1), and hardware related problems (3). CONCLUSIONS: This long-term follow up study confirms the beneficial effect of pallidal DBS or pallidotomy in primary generalized dystonia. In addition, our results extent previous observations by showing that, in these patients, (1) the microlesion effect of DBS is not predictive of long-term benefit; (2) combined DBS with contralateral pallidotomy appears to be more effective than bilateral pallidal DBS; and (3) dystonia can reappear after an initial good response during long term follow up.     

Cognitive outcome following staged bilateral pallidal stimulation for the treatment of Parkinson's disease.

As neurosurgical treatment of parkinsonian symptoms has become increasingly popular, concern about the cognitive morbidity which may result from such interventions has risen proportionately. Previous reports of cognitive difficulties associated with pallidotomy and thalamotomy, especially in bilateral cases, have provided the impetus for research into chronic electrical deep brain stimulation procedures which are believed to be safer than ablation. Given the lack of neurobehavioral research following bilateral deep brain stimulation procedures, this preliminary study of six Parkinson's disease patients undergoing staged bilateral pallidal stimulation was undertaken. A battery of tests assessing attention, executive function, visuomotor coordination, language, visuoperceptual function, learning memory and mood revealed no significant change in overall level of cognitive functioning after either unilateral or bilateral pallidal deep brain stimulation. No significant declines were observed about three months following bilateral stimulation, and in fact, significant gains in delayed recall and relief of anxiety symptoms were noted. It was concluded from this preliminary data that bilateral pallidal stimulation for the treatment of Parkinson's disease, at least in the absence of operative complications, offers a cognitively safe alternative to ablation.     

Pallidal neuron activity determines responsiveness to deep brain stimulation in cervical dystonia

ObjectiveIn patients with cervical dystonia we sought for the differences in neuronal behavior of pallidal regions where deep brain stimulation resulted in favorable therapeutic response compared to those where the response was absent.MethodsWe compared single-unit activity of 564 neurons recorded from deep brain stimulation sensitive and non-sensitive regions in 17 cervical dystonia patients.ResultsGlobus pallidus internus regions responsive to the deep brain stimulation had lower firing rates and bursting compared to non-responsive areas. The differences were robust in locations where neuronal responses correlated with neck movements. Per the effects of deep brain stimulation, the pallidal regions were classified in weak, intermediate, and excellent responsive. Pallidal regions with weak response to deep brain stimulation had fewer burst neurons and higher firing rate compared to neurons in areas with excellent response. The burst index was significantly decreased in excellent response regions. There was a significant decrease in the alpha band oscillation score but a substantial increase in the gamma band in excellent response neurons.ConclusionThe pallidal region that would be responsive to deep brain stimulation has distinct physiology compared to the non-responsive region.SignificanceThese results provide novel insights into globus pallidus interna neurons' physiology in cervical dystonia.     

Neuronal activity in the globus pallidus in primary dystonia and off-period dystonia

Decreased neuronal activity and altered firing patterns in the globus pallidus have been commonly observed in primary dystonia. Intraoperative neuronal recording in a patient with off-period dystonia revealed that the mean firing rates were considerably low in both the internal and external segments of the globus pallidus and that firing was irregular in the internal segment of the globus pallidus when dystonia developed, as compared with firing patterns in off-state parkinsonian patients without dystonia. These altered firing patterns were immediately reversed to those of off-state parkinsonism after relief of dystonia. These results suggest that primary dystonia and off-period dystonia result from the same physiological change in the basal ganglia. Ablation and stimulation of the internal segment of the globus pallidus can abolish both types of dystonia by blocking the abnormal activity of pallidal neurons.

     

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.     

Cognitive outcome after unilateral pallidal stimulation in Parkinson's disease

OBJECTIVES: Chronic high frequency electrostimulation of the globus pallidus internus mimics pallidotomy and improves clinical symptoms in Parkinson's disease. The aim of this study was to investigate the cognitive consequences of unilateral deep brain stimulation. METHODS: Twenty non-demented patients with Parkinson's disease (age range 38-70 years) were neuropsychologically assessed 2 months before and 3 months after unilateral pallidal stimulation. The cognitive assessment included measures of memory, spatial behaviour, and executive and psychomotor function. In addition to group analysis of cognitive change, a cognitive impairment index (CII) was calculated for each individual patient representing the percentage of cognitive measures that fell more than 1 SD below the mean of a corresponding normative sample. RESULTS: Neurological assessment with the Hoehn and Yahr scale and the unified Parkinson's disease rating scale disclosed a significant postoperative reduction in average clinical Parkinson's disease symptomatology (p<0.001). Repeated measures multivariate analysis of variance (using right/left side of stimulation as a between subjects factor) showed no significant postoperative change in cognitive performance for the total patient group (main effect of operation). The side of stimulation did not show a significant differential effect on cognitive performance (main effect of lateralisation). There was no significant operation by lateralisation interaction effect. Although the patients experienced significant motor symptom relief after pallidal stimulation, they remained mildly depressed after surgery. Analysis of the individual CII changes showed a postoperative cognitive decline in 30% of the patients. These patients were significantly older and took higher preoperative doses of levodopa than patients showing no change or a postoperative cognitive improvement. CONCLUSIONS: Left or right pallidal stimulation for the relief of motor symptoms in Parkinson's disease seems relatively safe, although older patients and patients needing high preoperative doses of levodopa seem to be more vulnerable for cognitive decline after deep brain stimulation.     

Deep brain stimulation of the internal globus pallidus for refractory tardive dystonia

We report a rapid, dramatic and sustained improvement following bilateral pallidal stimulation in two patients affected by intractable generalized tardive dystonia. Both patients had a chronic psychiatric disorder and developed chronic disabling generalized dystonic symptoms persisting despite prolonged withdrawal of neuroleptics and all available symptomatic treatment. The clinical benefit in both patients persisted throughout all the follow up period of 13 and 7 months. The favorable and prolonged response in our two patients suggests that deep brain stimulation may be an effective treatment for medically refractory tardive dystonia.     

Patients' perceptions of life shift after deep brain stimulation for primary dystonia—A qualitative study

Studies of deep brain stimulation for dystonia have shown significant motor improvement. However, patients' perceptions of surgery and its effects have been less studied. We aimed to explore perceptions of changes in life in patients with primary dystonia after deep brain stimulation. Thirteen patients underwent thematic interviews 8–60 months after pallidal deep brain stimulation. Interviews were transcribed verbatim and analyzed with grounded theory. Patients described a profound impact of dystonia on daily life. After surgery, physical changes with a more upright posture and fewer spasms translated into an easier, more satisfying life with greater confidence. Notwithstanding this positive outcome, the transition from a limited life before surgery to opportunities for a better life exhibited obstacles: The “new life” after deep brain stimulation was stressful, including concern about being dependent on the stimulator as well as having to deal with interfering side effects from deep brain stimulation. The whole coping process meant that patients had to quickly shift focus from struggling to adapt to a slowly progressive disorder to adjustment to a life with possibilities, but also with new challenges. In this demanding transition process, patients wished to be offered better professional guidance and support. Even though deep brain stimulation provides people with primary dystonia with a potential for better mobility and more confidence, patients experienced new challenges and expressed the need for support and counseling after surgery. Grounded theory is a useful method to highlight patients' own experience and contributes to a deeper understanding of the impact of deep brain stimulation on patients with dystonia. © 2011 Movement Disorder Society     

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.     

High-frequency pallidal stimulation eliminates tic-related neuronal activity in a nonhuman primate model of Tourette syndrome

High-frequency deep brain stimulation targeting the output nucleus of the basal ganglia, the globus pallidus internus, has been suggested as a treatment modality for intractable Tourette syndrome and basal-ganglia-mediated motor tics. Recent studies on the modeling of motor tics induced by focal injections of bicuculline to the striatum, a putative model of Tourette syndrome, have shown that tics induce a widespread modulation within both segments of the globus pallidus. The purpose of this study was to investigate, using the bicuculline-induced Tourette syndrome model, whether and how high-frequency deep brain stimulation targeted to the globus pallidus internus could modulate tic-related activity in the pallidum. The perievent rate changes coinciding with tic expression under the on-stimulation and off-stimulation conditions were examined to determine the effect of high-frequency stimulation on pallidal activity. The results showed that the stimulation blocked tic-related phasic changes in the firing pattern of pallidal cells in parallel with a reduction of the peak amplitude of tic events in the electromyography record. This finding supports the premise that deep brain stimulation targeted to the globus pallidus internus could be a viable treatment option for Tourette syndrome, and the use of pallidal stimulation for motor tics warrants further study.     

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     

Failure of long-term pallidal stimulation corrected by subthalamic stimulation in PD

Bilateral high-frequency continuous stimulation of the internal globus pallidus or subthalamic nucleus constitutes a new therapeutic approach for the treatment of patients with severe PD. The authors report two patients in whom stimulation of the globus pallidus failed to give long-term relief and was successfully replaced by bilateral subthalamic stimulation. The results emphasize the reversibility of deep brain stimulation therapy and suggest that the subthalamic target is preferable to the pallidal target.     

Pallidal deep brain stimulation in patients with cervical dystonia and severe cervical dyskinesias with cervical myelopathy

OBJECTIVES: Surgical treatment of complex cervical dystonia and of cervical dyskinesias associated with cervical myelopathy is challenging. In this prospective study, the long term effect of chronic pallidal stimulation in cervical dystonia and on combining the technique with spinal surgery in patients with severe cervical dyskinesias and secondary cervical myelopathy is described. METHODS: Eight patients with a history of chronic dystonia who did not achieve adequate benefit from medical treatment or botulinum toxin injection participated in the study. Five patients had complex cervical dystonia with tonic postures and phasic movements. Three patients had rapidly progressive cervical myelopathy secondary to severe cervical dyskinesias and dystonia in the context of a generalised movement disorder. Quadripolar electrodes were implanted in the posteroventral lateral globus pallidus internus with stereotactic CT and microelectrode guidance. In the three patients with secondary cervical myelopathy, spinal surgery was performed within a few weeks and included multilevel laminectomies and a four level cervical corporectomy with spinal stabilisation. RESULTS: Improvement of the movement disorder was noted early after pallidal surgery, but the full benefit could be appreciated only with a delay of several months during chronic stimulation. Three months after surgery, patients with cervical dystonia had improved by 38% in the severity score, by 54% in the disability score, and by 38% in the pain score of a modified version of the Toronto western spasmodic torticollis rating scale. At a mean follow up of 20 months, the severity score had improved by 63%, the disability score by 69%, and the pain score by 50% compared with preoperatively. There was also sustained amelioration of cervical dyskinesias in the three patients who underwent spinal surgery. Lead fractures occurred in two patients. The mean amplitude needed for chronic deep brain stimulation was 3.8 V at a mean pulse width of 210 micros, which is higher than that used for pallidal stimulation in Parkinson's disease. CONCLUSIONS: Chronic pallidal stimulation is effective for complex cervical dystonia and it is a useful adjunct in patients with cervical dyskinesias and secondary cervical myelopathy who undergo spinal surgery.     

Posttraumatic Hemidystonia Treated with Unilateral Globus Pallidus Interna Stimulation: Long‐Term Follow‐up and Radiologic Features

Objective: Hemidystonia is a unilateral clinical presentation of dystonia, and it is usually refractory to current methods of medical treatment. Recently, deep brain stimulation has given some hope of recovery to dystonic patients. Materials and Methods: A 30‐year‐old right‐handed man with no abnormal perinatal history or family history of movement disorders was admitted to our institution. The patient had suffered right‐sided dystonia for more than three years after severe head trauma sustained four years prior. Results: We performed a stereotactic implantation of an electrode into the left globus pallidus internus (GPi) and he showed excellent response to pallidal stimulation during long‐term follow‐up. Conclusions: We present a unique case of secondary posttraumatic hemidystonia treated with contralateral GPi stimulation with an excellent outcome. Pallidal stimulation can be a good treatment option for posttraumatic hemidystonia in selected cases.     

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.     

Bilateral pallidal stimulation for sargoglycan epsilon negative myoclonus

We report on the clinical efficacy of bilateral globus pallidus internus deep brain stimulation in two patients with myoclonus dystonia/essential myoclonus who lack mutations in the epsilon sarcoglycan gene.The primary outcome measures were the Burke–Fahn–Marsden Dystonia Scale motor severity and the Unified Myoclonus Rating Scale scores, and the secondary outcome measure was the 36-item Short Form Health Survey score at the last postoperative follow up. Neuronal firing rates were also calculated from microelectrode recordings.At the last postoperative follow-up (16 weeks for Patient 1 and 18 weeks for Patient 2), there was 57.1% (Patient 1) improvement in the Burke–Fahn–Marsden Dystonia Scale motor severity score and 31.3% (Patient 1) and 69% (Patient 2) in the Unified Myoclonus Rating Scale score while individual SF-36 scores showed improvement in most subdomains.Bilateral globus pallidus internus deep brain stimulation can be effective in ameliorating epsilon sarcoglycan negative myoclonus with or without concurrent dystonia. Whether an epsilon sarcoglycan negative status represents a less favorable prognostic factor for pallidal deep brain stimulation remains to be elucidated.     

Pallidal deep brain stimulation is effective, and improves quality of life in primary segmental and generalized dystonia

Background –  Dystonia is one of the most prevalent movement disorders, and may lead to abnormal postures, pain, significant disability and social isolation if not well treated. In widespread segmental or generalized dystonia efficient treatment options were lacking until the recent introduction of deep brain stimulation of the internal globus pallidus (pallidal DBS).
Methods –  The first case series and single-blinded controlled study showed promising results regarding the effect of pallidal DBS on dystonic movements, pain and disability, but the impact of this treatment on health-related quality of life (HRQoL) remained uncertain. Then, as part of the first randomized, and sham stimulation-controlled trial performed by the DBS for Dystonia Study Group, HRQoL was evaluated using the Short Form-36 Health Survey (SF-36) at baseline, after the 3 months sham-controlled phase, and after 6 months of continuous pallidal DBS, in 40 patients with severe primary segmental or generalized dystonia.
Results –  The 3-month sham-stimulation controlled phase resulted in significant improvement of dystonic movements, pain and disability in the active stimulation group, and four of the eight SF-36 domain scores also improved significantly compared with the sham-stimulated group. After 6 months of active stimulation in all patients, significant improvement in all eight SF-36 domains was observed, with comparable improvement in the segmental and generalized dystonia groups.
Conclusion –  Convincing evidence has been obtained that pallidal DBS effectively reduces dystonia-related symptoms, and markedly improves HRQoL in patients suffering from otherwise intractable, primary segmental or generalized dystonia, thus providing new opportunities for this patient group.     

Pallidotomy versus pallidal stimulation

Both posteroventral pallidotomy and pallidal deep brain stimulation (DBS) have a documented effect on Parkinsonian symptoms. DBS is more costly and more laborious than pallidotomy. The aim of this study was to analyse the respective long-term effect of each surgical procedure on contralateral symptoms in the same patients. Five consecutive patients, two women and three men, who at first surgery had a mean age of 64 years and a mean duration of disease of 18 years, received a pallidotomy contralateral to the more symptomatic side of the body. At a mean of 14 months later, the same patients received a pallidal DBS on the side contralateral to the pallidotomy. All patients had on-off phenomena and dyskinesias. There were three left-sided and two right-sided pallidotomies, and, subsequently, two left-sided and three right-sided pallidal DBS. The latest evaluation was performed 37 months (range 22-60) after the pallidotomy and 22 months (range 12-33) after the pallidal DBS. Mean UPDRS motor score pre-operatively was 49 and at last follow-up 33 (32.7% improvement, p<0.05). Appendicular items 20-26 contralateral to pallidotomy remained improved more significantly than contralateral to DBS. Dyskinesia scores were also improved more markedly contralateral to the pallidotomy. Two patients exhibited moderate dysarthria and one patient severe dysphonia following DBS. Symptoms contralateral to the chronologically older pallidotomy, especially dyskinesias, rigidity and tremor, were still more improved than symptoms contralateral to the more recent pallidal DBS, despite numerous post-operative patient visits to optimise stimulation parameters.     

Globus pallidus stimulation in advanced Parkinson's disease.

Deep brain stimulation (DBS) of the globus pallidus internus (GPi) has become an accepted therapeutic modality in selected Parkinson's disease (PD) patients with severe levodopa-induced dyskinesias (LID) and on-off motor fluctuations. In comparison to subthalamic nucleus DBS there is a paucity of data on GPi DBS outcomes. We present our experience with a group of 20 PD patients (9 unilateral, 11 bilateral) who underwent GPi stimulation. PD motor symptoms were assessed using the Unified Parkinson's Disease Rating Scale (UPDRS) part III scores and subscores, and dyskinesia using the Abnormal Involuntary Movement Scale (AIMS), UPDRS part IVa, and clinical global impression (CGI). At mean follow-up time of 7 months, bilateral stimulation reduced off-period motor scores by a mean of 46% and on-period motor scores by 18%. Unilateral stimulation reduced off-period motor scores by 18%. Dyskinesia severity was reduced by 76%, which was maintained after a mean follow-up time of 35 months. Antiparkinsonian medication dosage was unchanged. No major adverse effects were seen. Unilateral and bilateral GPi DBS provides lasting benefit in PD patients with severe LID. Beneficial effects on off-period motor symptoms are greater with bilateral stimulation; however, with maintenance of dopaminergic medication, unilateral procedures can also provide important and sustained benefits.