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PubMed2005

Effectively desynchronizing deep brain stimulation based on a coordinated delayed feedback stimulation via several sites: a computational study.

In detailed simulations we present a coordinated delayed feedback stimulation as a particularly robust and mild technique for desynchronization. We feed back the measured and band-pass filtered local filed potential via several or multiple sites with different delays, respectively. This yields a resounding desynchronization in a naturally demand-controlled way. Our novel approach is superior to previously developed techniques: It is robust against variations of system parameters, e.g., the mean firing rate. It does not require time-consuming calibration. It also prevents intermittent resynchronization typically caused by all methods employing repetitive administration of shocks. We suggest our novel technique to be used for deep brain stimulation in patients suffering from neurological diseases with pathological synchronization, such as Parkinsonian tremor, essential tremor or epilepsy.

Brain↗
PubMed2002

Thalamic deep brain stimulation for the treatment of tremor due to multiple sclerosis: a prospective study of tremor and quality of life.

OBJECT: In several studies a significant reduction in tremor after thalamic deep brain stimulation (DBS) has been reported among patients with multiple sclerosis (MS). It has not been determined if this results in an improved quality of life. In this study the authors prospectively evaluated the effects of thalamic DBS on tremor and quality of life. METHODS: Videotapes of the patients' tremor were made preoperatively and 2 and 12 months postoperatively, and tremor was scored by a neurologist blinded to the treatment. Patients were tested pre- and postoperatively to measure any changes in their reported ability to perform selected activities of daily living and in their health-related quality of life. Patients were asked to complete a questionnaire about their satisfaction with the surgery. Postoperative changes were examined using paired t-tests. There were significant reductions in postural, action, and overall tremor at 2 and 12 months postoperatively. The patients' reported ability to feed themselves was significantly improved 2 months after surgery (p = 0.01). There were short-term trends toward improvement in reported dressing ability, personal hygiene, and writing. There were no significant changes in the SF-36 subscales or total score. CONCLUSIONS: In this cohort of patients with MS who suffered from tremor, thalamic DBS significantly improved their tremor and ability to feed themselves. Patient satisfaction with the procedure, however, was variable. Preoperative patient education about what functions might (and might not) be improved is crucial to avoid unrealistic expectations. Our results indicate that younger patients with MS tremor who had a shorter disease duration and no superimposed ataxia benefited most from this surgery.

Activities of Daily Living↗
PubMedDate not supplied

[Deep brain stimulation in the treatment of dystonia].

Dystonia refers to movement disorders characterized by sustained muscle contractions that produce abnormal postures and twisting movements. First-line therapy for dystonia includes several classes of pharmacologic agents. Botulinum toxin injections are the treatment of choice for several forms of focal dystonia. Many patients with dystonia do not benefit from these treatments, and for those patients whose symptoms are sufficiently troublesome, surgical treatment can be used to reduce symptoms and to improve function. Formerly the ablative procedures of thalamotomy and pallidotomy were used. More recently, deep brain stimulation (DBS) has emerged not only as the preferred surgical treatment for advanced idiopathic form of Parkinson's disease and severe forms of essential tremor but also for dystonia. For dystonia, stimulation directed at the globus pallidus internus has been the most thoroughly studied to date. Advantages of DBS include its relatively non-destructive nature, its adjustability and reversibility, and its capacity to be used bilaterally in a single surgical session. Use of DBS to treat dystonia is a rapidly evolving area, and preliminary evidence suggests that primary dystonia linked to genetic mutation, especially DYT-1 positive generalized dystonia, and other primary dystonias respond most dramatically to treatment with DBS, whereas secondary dystonia tends to be less responsive.

Deep Brain Stimulation↗
PubMed2004

Accelerometric measurement of involuntary movements during pallidal deep brain stimulation of patients with generalized dystonia.

Accelerometric activity during rest and posture was quantified in the upper dominant limb of 14 patients with primary or secondary dystonia and five healthy control subjects. Data were recorded before and after bilateral implantation of the stimulating electrodes in the Globus Pallidus internus. Clinical evaluation was based on the Burke-Marsden-Fahn's Dystonia Rating Scale (BMFDRS). For the patient group, I(t), the integral (i.e. area) of the acceleration power spectrum over the total frequency range (0.6-16 Hz) decreased as the clinical state of the patients improved following deep brain stimulation (p < 0.01) during rest and posture. Ten days after surgery, there were no I(t) differences between control subjects and patients (p > 0.05). A significant correlation was found between the global BMFDRS scores and I(t) for rest (p < 0.01) but not for posture. No significant correlation was found between I(t) and a partial BMFDRS score for the right arm for rest or posture. The integral I(t) provides a valid indicator of the motor activity generated by the arm of the patient but further analyses are needed to monitor patients' progress not only during their hospitalization but also after they are released from the hospital, and to understand why this measure does not correlate with partial BMFDRS scores.

Adolescent↗
PubMed2002

A prospective study of thalamic deep brain stimulation for the treatment of movement disorders in multiple sclerosis.

The place for neurosurgical management of movement disorders in multiple sclerosis is unclear. To evaluate the potential benefits of unilateral thalamic deep brain stimulation (DBS) a prospective study was performed. Fifteen patients with confirmed MS and chronic, severe, drug-resistant movement disorders underwent stereotactic surgery to implant a thalamic DBS electrode using CT image guidance and intra-operative neurophysiological testing. The primary outcome measures were reduction in tremor severity and improvement in tests of hand function when the DBS electrode was turned on, 12 months after surgery. Secondary outcome measures included indices of disability, handicap, neuropsychological function and independence. Thirty-seven patients were assessed for treatment, but only 15 underwent surgery. In the 10 patients in whom implantation of the complete DBS system was carried out there was a significant reduction in the severity of tremor (p = 0.02) and improvement in hand function (p = 0.02). There were no benefits in any of the secondary outcome measures. Two patients had thalamocapsular haemorrhages at the site of electrode implantation and two had seizures in the follow-up period. Thalamic stimulation significantly reduced the tremor associated with MS and improved hand function in the targeted upper limb. However, there can be difficulties with identifying an optimal implantation site during operation, significant procedural morbidity and difficulty in predicting immediate outcome. It is also likely that the insignificant benefits of DBS on disability and handicap reflect persisting cerebeller dysmetria, and both the severity and diffuse nature of the disease process in this patient cohort.

Adult↗
PubMed1993

Release of beta-endorphin and methionine-enkephalin into cerebrospinal fluid during deep brain stimulation for chronic pain. Effects of stimulation locus and site of sampling.

The authors systematically studied the release of the endogenous opioid peptides beta-endorphin and methionine (met)-enkephalin into the cerebrospinal fluid (CSF) during deep brain stimulation in patients suffering from otherwise intractable chronic pain. Nine patients were included in the study; six had stimulation electrodes placed in both the periventricular gray matter (PVG) and the thalamic nucleus ventralis posterolateralis (VLP) and three in the PVG only. Immunoreactivity of beta-endorphin and met-enkephalin (beta-EPir and MEir, respectively) was measured by radioimmunoassays in ventricular and lumbar CSF samples obtained before, during, and after stimulation. Prestimulation concentrations of beta-EPir and MEir were lower in ventricular than in lumbar CSF (6.6 +/- 0.5 vs. 13.7 +/- 1.0 pmol/liter, p = 0.0001, for beta-EPir; 33.6 +/- 5.1 vs. 48.3 +/- 3.2 pmol/liter, p < 0.05, for MEir). Ventricular CSF concentrations of both beta-EPir and MEir increased significantly during PVG stimulation, whereas VPL stimulation was without effect. No changes were seen in lumbar CSF levels of the peptides during stimulation in either site. A significant inverse relationship was found between the "during:before stimulation" ratios of visual analog scale ratings and beta-EPir levels during PVG stimulation. The beta-EPir and MEir concentration during:before stimulation ratios were positively correlated, whereas no correlation was present in prestimulation samples from ventricular or lumbar CSF. High-performance liquid chromatography of ventricular CSF pools obtained during PVG stimulation revealed that major portions of beta-EPir and MEir eluted as synthetic beta-endorphin and met-enkephalin, respectively, thus documenting the release of beta-endorphin and met-enkephalin into ventricular CSF during PVG stimulation. The finding of a direct relationship between beta-EPir release and pain alleviation may suggest a role for beta-endorphin in the analgesic mechanism of PVG stimulation.

Adult↗
PubMed2006

Effect of deep brain stimulation and L-Dopa on electrocortical rhythms related to movement in Parkinson's disease.

In the early stages of Parkinson's disease (PD), impaired motor preparation has been related to a decrease in the latency of mu rhythm event-related desynchronisation (ERD) compared with control subjects, suggesting hypo activation of the contralateral, primary sensorimotor (PSM) cortex. Following movement, a decrease in amplitude of beta rhythm ERS was observed over the same region and thought to be related to impairment in cortical deactivation. By monitoring ERD/ERS, we aimed (i) to extend to advanced PD the observations made in less-advanced parkinsonism and (ii) to test the effect of acute L-Dopa, internal pallidal or subthalamic stimulation on these abnormalities. For the clinical evaluation the motor score of UPDRS decreased by about 60% under subthalamic stimulation and following acute L-Dopa administration and by 40% under internal pallidal stimulation. The following concurrent ERD/ERS changes under subthalamic stimulation and L-Dopa were observed: a marked increase in mu ERD latency during movement preparation over contralateral central region; an increase in mu ERD during movement execution over bilateral central regions; a decrease in mu ERD latency over bilateral frontocentral region and an increase in beta ERS over contralateral central region after movement. On the contrary, mu ERD latency was not improved under internal pallidal stimulation. Changes of mu and beta rhythm parameters seemed to be inversely correlated with bradykinesia. Mu rhythm ERD latency and the beta ERS amplitude further decreased in advanced PD compared with early stages, suggesting greater impairment of cortical activation/deactivation as the disease progresses and a partial restoration in relation to clinical improvement under treatments. Consequently, it appears that L-Dopa and deep brain stimulation partially restored the normal patterns of cortical oscillatory activity in PD, possibly by decreasing the low frequency hyper synchronisation at rest. This mechanism could be involved at the basal ganglia level in the sensorimotor integration implicated in the movement control.

Antiparkinson Agents↗
PubMedDate not supplied

Deep brain stimulation therapy for the vegetative state.

Twenty-one cases of a vegetative state (VS) caused by various kinds of brain damage were evaluated neurologically and electrophysiologically three months after brain injury. These cases were treated by deep brain stimulation (DBS) therapy, and followed up for over 10 years. The mesencephalic reticular formation was selected as a target in two cases, and the thalamic centre median-parafascicular (CM-pf) complex was selected as a target in the other 19 cases. Eight of the 21 patients emerged from the VS, and became able to obey verbal commands. However, they remained in a bedridden state except for one case. DBS therapy may be useful for allowing patients to emerge from a VS, if the candidates are selected according to appropriate neurophysiological criteria. A special neurorehabilitation system may be necessary for emergence from the bedridden state in the treatment of VS patients. Further, DBS therapy is expected to provide a useful method in minimally conscious state (MCS) patients to achieve consistent discernible behavioural evidence of consciousness, and emergence from the bedridden state.

Adult↗
PubMed2002

Deep brain stimulation of the globus pallidus internus (GPI) for torsion dystonia--a report of two cases.

Generalized dystonia is known as a type of movement disorder in which pharmacotherapeutic options are very limited. Deep Brain Stimulation (DBS) is well established for Parkinson's disease (PD) and tremor dominant movement disorders. We report on two cases of generalized dystonia which were successfully treated by chronic high frequency stimulation in the Globus pallidus internus (GPI). Two 26 and 27 years old males suffered from severe torsion dystonia and multisegmental dystonia of the lower limbs. Case 1 is a familiar type of dystonia (DYT1 positive). The onset of symptoms in both cases was at age 7. The complaints were initially treated with orally administered benzodiazepines, anticholinergic drugs, later by baclofen and L-DOPA. However there was no response. Case 2 was a patient with a history of left side dominated dystonia since the age of 8. It was first diagnosed as a psychogenic movement disorder. Prior to surgery he was treated with L-DOPA, anticholinergics, Baclofen without any effect. There was only a limited effect on high doses of diazepam. The patient is DYT1 negative. The target point was on both sides the GPI. Intraoperative computerized tomography (CT) and ventriculography (VG) were used for target setting. Furthermore microrecordings were helpful to ensure the exact electrode position. Surgery was performed under analgosedation. Two weeks after surgery we first observed a relief of symptoms in both cases. A significant reduction in the Burke-Fahn-Marsden-Dystonia Movement Rating Scale was observed at the 6 month follow-up (case 1: 95%, case 2: 80%). In case 1 a slight dystonic movement of the left ankle was the only remaining symptom under stimulation. The medication was continuously reduced. At the 24 month follow-up the effect of stimulation remained unchanged. However high stimulation parameters are required to maintain an optimal effect (mean 3.5 V, 400 microseconds, 145 Hz).

Adult↗
PubMed2006

Bilateral subthalamic nucleus deep brain stimulation improves certain aspects of postural control in Parkinson's disease, whereas medication does not.

Postural control requires precise integration of sensory inputs and motor output, but clinical assessments of postural control do not differentiate between these. Previously, we found that this differentiation is important in Parkinson's disease (PD) as there was a dissociated effect of medication versus pallidotomy on sensory aspects of postural instability. In this study, we address several questions that emerged from that work in 28 different patients with PD off and on medication, before and after bilateral subthalamic nucleus deep brain stimulation (B-STN DBS): (1) In a different cohort is there still an unusually large percentage of patients with postural instability in sensory-deprived conditions? (2) Are more specific measures of motor aspects of postural control using dynamic posturography (postural movement velocity [MV] and reaction time [RT]) abnormal in PD as seen clinically using the Postural Instability and Gait Disorder score of the Unified Parkinson's Disease Rating Scale? (3) What is the effect of B-STN DBS versus medication on sensory versus motor aspects of postural instability in PD? The results included (1) substantially more patients (39%) versus controls (5%) exhibited postural instability in conditions of limited sensory feedback; (2) postural MV and postural RT were abnormal off medication preoperatively (N(subset) = 23; P < 0.001 for both); (3) B-STN DBS improved abnormal sensory aspects of postural instability (P < 0.05) and postural MV (P = 0.005), whereas medication did not. Neither B-STN DBS nor medication improved postural RT. For the group as a whole, STN DBS plus medication was better therapy than medication preoperatively for sensory aspects of postural control (P = 0.003).

Brain↗
PubMed2006

Deep brain stimulation in Tourette's syndrome: two targets?

In this report, we describe the effects of bilateral thalamic stimulation in one patient and of bilateral pallidal stimulation in another patient. Both patients suffered from intractable Tourette's syndrome (TS). Any conservative treatment had failed or had been stopped because of unbearable side effects in the 2 patients. In both cases, there was no comorbidity except for associated behavioral symptoms (compulsions). Electrodes were implanted at the level of the medial part of the thalamus (centromedian nucleus, the substantia periventricularis, and the nucleus ventro-oralis internus) in one patient and in the posteroventral part of the globus pallidus internus (GPi) in the other patient. In both cases, deep brain stimulation (DBS) resulted in a substantial reduction of tics and compulsions. These data show that bilateral DBS of the thalamus as well as of the GPi can have a good effect on tics and behavioral symptoms in patients suffering from intractable TS.

Adult↗
PubMed2004

Deep brain stimulation in myoclonus-dystonia syndrome.

Myoclonus-dystonia syndrome (MDS) is an autosomal dominant disorder characterized by bilateral myoclonic jerks. An 8-year-old boy presenting with early onset, medically intractable, MDS due to a mutation in the epsilon-sarcoglycan gene (SGCE) underwent chronic bilateral stimulation of the globus pallidus internus, which eliminates both myoclonus and dystonia. We conclude that deep brain stimulation can be an effective and safe treatment for MDS.

Anticonvulsants↗
PubMed2006

State of the art: deep brain stimulation in Parkinson's disease.

Surgical therapy for Parkinson's disease has a long history beginning in the 1930s with empirical exploration of different brain targets, such as resection of the primary motor cortex or extirpation of the caudate. Recently, there has been a renaissance of functional neurosurgery for the treatment of advanced Parkinson's disease, particularly deep brain stimulation (DBS). To date, DBS of the globus pallidus interna and subthalamic nucleus has been reported to relieve motor symptoms and levodopa-induced dyskinesia in patients with advanced Parkinson's disease. DBS also has different advantages over pallidotomy and subthalamotomy, including reversibility, decreased risk of reoperation and decreased morbidity. In addition to well-experienced neurologists and neurosurgeons, a multidisciplinary team approach is fundamental and critical to ensure success in the DBS procedure in individual patients. With the advances in neuroimaging, neurophysiology and localization techniques, it is increasingly likely that there will be more surgical targets in the future that can also improve cardinal features of Parkinson's disease, or even nonmotor manifestations of this condition.

Deep Brain Stimulation↗
PubMed1991

Characterization and modification of brain activity with deep brain stimulation in patients in a persistent vegetative state: pain-related late positive component of cerebral evoked potential.

A series of eight patients in a persistent vegetative state (PVS) were subjected to chronic deep brain stimulation (DBS) for the purpose of promoting recovery from the PVS. The characteristics of the brain activity in these patients were evaluated from the late positive component of the cerebral evoked potential in response to painful stimuli (pain-related P250). While any neurological scoring system for the comatose state includes evaluations of motor reactions to painful stimuli, the pain-related P250 is unique in terms of its ability to assess the cortical responsiveness to painful stimuli directly and quantitatively without involving functions of the motor system. It was found that the pain-related P250 was more or less depressed in patients in a PVS. It was repeatedly demonstrated in four patients, however, that the pain-related P250 could be transiently increased by preceding stimulation of the mesencephalic reticular formation. Furthermore, a persistent increase in the pain-related P250 was produced in these four patients following chronic DBS of the mesencephalic reticular formation or nonspecific thalamic nuclei for more than 6 months, and this was correlated with the clinical improvements. These results imply that responsiveness at the cortical level to pain is depressed in the PVS. It also appears that some fraction of the depression may, however, be functionally produced and potentially reversible.

Brain↗
PubMed2002

Deep brain stimulation of the centre median-parafascicular complex in patients with movement disorders.

The centre median-parafascicular (CM-Pf) complex of the thalamus is considered to be a possible target for deep brain stimulation (DBS) in patients with movement disorders. In a prospective study on the effect of CM-Pf DBS versus somatosensory thalamic DBS on chronic neuropathic pain, three of 12 patients had additional movement disorders. Bifocal quadripolar electrodes were implanted by computed tomography guided stereotactic surgery under local anaesthesia contralaterally to the side of the pain for test stimulation. Two of the three patients with movement disorders had permanent implantation of CM-Pf electrodes. During test stimulation of the left CM-Pf complex for several days, a 67 year old woman received no benefit with respect to the neuropathic pain, but the choreoathetotic movements of her right foot ceased. As the pain syndrome was not improved, she decided not to have permanent implantation. A 74 year old man with postzoster neuralgia and allodynia enjoyed excellent relief from his pain with chronic CM-Pf DBS. In addition, improvement in the tremor at rest was noted. A 72 year old man had sustained reduction in his stump dyskinesias. Further evaluation of the possible role of the "forgotten" central and medial thalamic nuclei in the treatment of movement disorders may be warranted.

Aged↗