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PubMed2006

[First experiences in deep brain stimulation for cervical dystonia].

BACKGROUND: Cervical dystonia results in severe disability and cannot be effectively treated with medication. Repeat injections of botulinum toxin into the dystonic neck muscles can relieve the symptoms in most patients. When this treatment fails (mostly due to antibody formation), deep brain stimulation can be considered. PATIENTS AND METHODS: We report our experiences with eight patients who were treated with bilateral deep brain stimulation of the globus pallidus interna for cervical dystonia. The mean observation period was 31 months. RESULTS: Six of eight patients experienced relief from symptoms a few days after the implantation. Improvement of symptoms was a mean of 60% during the 1st year. There were no complications. CONCLUSION: In this and in other studies with small numbers of patients, deep brain stimulation has shown a good effect on cervical dystonia. According to our results, the patients who benefit most are those with no dystonic shoulder involvement and who have a tonic rather than clonic symptomatology. It seems probable that deep brain stimulation will become the therapy of choice for otherwise intractable cervical dystonia.

Adult↗

PubMed2002

Deep brain stimulation for tremor [correction of trauma]: patient selection and evaluation.

The selection of patients with movement disorders for deep brain stimulation is becoming a common neurological and neurosurgical task. Deep brain stimulation is suitable for different forms of tremor, which can often not be treated with medication. This suitability applies for essential tremor, monosymptomatic tremor at rest, cerebellar or multiple sclerosis tremor, Holmes' tremor, primary writing tremor or tremor in neuropathies. The appropriate selection of patients is critical for the outcome of surgical relief of tremors. Considering the risks of any stereotactic intervention, the following must apply: (1) motor symptoms lead to a relevant disability in activities of daily living, despite optimal medical treatment; (2) biological age of the patient; (3) neurosurgical contraindications; (4) the patient is neither demented nor severely depressed. If these conditions are fulfilled, the individual chances of improvement of the target symptoms need to be checked, based on the following guidelines: (1) the kind of tremor, (2) the natural course of the tremor, (3) the chances for medical treatment in a particular patient, (4) the outcome of surgery in a specific condition, (5) the individual risks for a patient to suffer from complications. The outcome of surgery for tremor depends on the clinical type and distribution. Distal limb tremors are easier to treat than proximal limb tremors. Intention tremor is more difficult to treat than rest or postural tremor. The indication for surgical treatment depends on the analysis of the individual risk-benefit ratio, which also has to take into account the patients' social, professional, and familial background. The patient needs to be well informed about his individual risk-benefit ratio and of alternative treatments, before undergoing stereotactic surgery.

Brain↗

PubMed2005

Pallidal deep brain stimulation influences both reflexive and voluntary saccades in Huntington's disease.

Deep brain stimulation (DBS) of the globus pallidus internus (GPi) is being evaluated as a potential new therapy for patients with Huntington's disease (HD). In addition to skeletal movement disorders, HD patients have difficulty initiating voluntary saccades and have difficulty in suppressing rapid saccades toward newly appearing stimuli. We measured several saccade parameters in an HD patient who had marked improvement of clinical symptoms with bilateral GPi DBS to determine whether oculomotor performance improved in parallel with clinical scores. Oculomotor performance was assessed using three testing paradigms: pro-saccades, anti-saccades, and memory-guided saccades. The data from the HD patient was also compared to that of two healthy controls. Pallidal DBS decreased pro-saccade latency, total movement time, and the number of correctly executed trials, as well as increasing saccade gain. Memory-saccade performance was negatively affected with stimulation: saccade gain decreased, latency increased, and the patient's ability to suppress unwanted saccades decreased with stimulation. Our data demonstrate a task-specific improvement of oculomotor deficits in this HD patient with pallidal DBS, supporting a role of GPi in oculomotor control.

Adult↗

PubMed2006

Pregnancy in dystonic women with in situ deep brain stimulators.

In the past few years, an increasing number of dystonic patients, of both sexes, have undergone insertion of deep brain stimulators (DBS) with consistent improvement of their symptoms and enhancement of their quality of life. We describe 3 women with dystonia who, after insertion of bilateral globus pallidus internus stimulators, succeeded in conceiving and completing pregnancies, 2 of them having married. These histories illustrate the significant positive impact that DBS can have on women's social relationships. Based on this experience, we also provide an overview of some of the issues that might arise in pregnancy and during delivery in dystonic women with an in situ deep brain stimulator.

Adult↗

PubMed2003

Thalamic deep brain stimulation for disabling tremor after excision of a midbrain cavernous angioma. Case report.

Thalamic deep brain stimulation (DBS) has been demonstrated to be effective for the treatment of parkinsonian or essential tremor. To date, however, few data exist to support the application of this method to treat midbrain tremor. A 24-year-old right-handed man underwent radiosurgery and subsequent resection of a recurrently hemorrhaging cavernous angioma located in the left side of the midbrain. The surgery exacerbated severe choreoathetotic resting and action tremors of his right extremities and trunk. The patient underwent placement of a deep brain stimulator into the left ventral intermediate nucleus of the thalamus (Vim). Postoperatively, decreased truncal ataxia and right-sided choreoathetotic tremor were demonstrated, with a 57% increase in dexterity as measured by task testing. The authors demonstrate that DBS can be an effective treatment modality for disabling tremor after resection of a midbrain cavernous angioma.

Adult↗

PubMed2002

Mechanisms of deep brain stimulation: excitation or inhibition.

There is little debate that deep brain stimulation (DBS) has been an effective tool in the treatment of Parkinson's disease as well as other movement disorders. There remains however, considerable debate concerning the mechanism(s) underlying its beneficial effect. The comparable effect of stimulation to ablation in the thalamus on tremor, and in the subthalamic nucleus (STN) and internal segment of the globus pallidus (GPi) on the motor signs associated with PD, have led many investigators to conclude that DBS acts to suppress neuronal activity, decreasing output from the stimulated site. There are, however, data that do not support this argument. Microdialysis studies in GPi showed increased levels of glutamate during STN stimulation, suggesting activation of glutamatergic output from the STN to the GPi. Studies in parkinsonian primates have demonstrated increased mean discharge rates of neurons in GPi during chronic stimulation in STN, and GPi stimulation in humans has been associated with a suppression of neuronal activity in the thalamus. Contrary to what one would expect if stimulation inhibits output from the stimulated structure, stimulation in GPe has been demonstrated to improve bradykinesia. Although arguments for increased output from the stimulated structure seem to conflict with the hypothesis that stimulation acts to inhibit neuronal activity, it is possible to explain these observations through a common mechanism, e.g. activation of fiber pathways. Based on this mechanism, the effect of stimulation on cellular activity in the stimulated site would be increased or decreased dependent on the neurotransmitter of the afferent fibers projecting to that site. However, in addition to activation of afferent fibers, projection axons from neurons in the stimulated structure, also readily excitable by electrical stimulation, would also be tonically activated and discharge independently of the soma, thereby increasing output from the structure during extracellular stimulation. Thus, although high frequency stimulation may inhibit neurons via activation of inhibitory afferents, the output from that structure may be increased as the result of activation of axonal elements leaving the target structure. This hypothesis would explain the present experimental results, is consistent with excitability profiles of neuronal elements based on their biophysical properties, and fits with more recent models emphasizing the role of altered patterns of neuronal activity in the development of hypokinetic and hyperkinetic movement disorders.

Animals↗

PubMed2003

Does the ADL part of the unified Parkinson's disease rating scale measure ADL? An evaluation in patients after pallidotomy and thalamic deep brain stimulation.

We evaluated the impact of pallidotomy and thalamic deep brain stimulation (DBS) on disability of patients with advanced Parkinson's disease and investigated whether the activities of daily living (ADL) section of the Unified Parkinson's Disease Rating Scale (UPDRS) measures disability in everyday life. Nineteen patients who had pallidotomy and 14 patients who had thalamic DBS were followed for a mean of 11 months. Evaluation tools included the UPDRS as well as a generic ADL scale, called ADL taxonomy. The 13 items belonging to the ADL part of the UPDRS were classified into two categories according to whether the items described a disability or impairment. The total scores of the UPDRS Part II (ADL) were ameliorated in both the pallidotomy and the thalamic DBS groups. When analysing separately the scores from the two categories of the ADL part of the UPDRS, i.e., disability and impairment, only patients who underwent pallidotomy showed improvement in disability-related items. These findings were confirmed when evaluating the patients with the ADL taxonomy. The ADL part of the UPDRS contains a mixture of impairment- and disability-related items. This mixture may confound results when evaluating the impact of surgery on ADL.

Activities of Daily Living↗

PubMed1980

Deep brain stimulation in mesencephalic lemniscus medialis for chronic pain.

Stereotactic deep brain stimulation (DBS) with chronically implanted special devices intermittently activated by the patient himself has led to a new concept in the treatment of chronic central pain, such as the thalamic pain syndrome, herpes-zoster neuralgia, anaesthesia dolorosa, radicular and plexus lacerations, stump pain with and without causalgia and cancer pain. Our results in 32 cases (March 31, 1979) with lemniscus medialis stimulation, including the specific and nonspecific somatosensory nuclei or periaqueductal gray matter show in 53% of our cases, a reduction of pain of over 50%. The follow-up period was 47 months. These results are better than those obtained from stimulating only one of the systems. Mesencephalic lemniscus medialis DBS, introduced by one of the authors (Mundinger), leads to a functional blockade of spinothalamic, lemniscus medialis and spino-reticular systems. In cases where a positive morphine test had been done previously, endorphin secretion also plays a role. It is assumed that the effect of endorphin production lasts longer than the stimulation itself, especially in periaqueductal mesencephalic gray matter and medial pulvinar stimulation.

Adult↗

PubMed2003

Brain flow changes before and after deep brain stimulation of the subthalamic nucleus in Parkinson's disease.

Deep brain stimulation (DBS) of the subthalamic nucleus (STN) markedly improves motor symptoms and reduces medication needs in Parkinson's disease (PD) patients. However, its effect on brain function has remained unclear. We used SPECT and the tracer ECD to measure regional cerebral blood flow before and 6 months after DBS of the STN in 22 PD patients and 13 healthy controls. PD patients were divided into good and poor responders to DBS, if changes in "off" UPDRS motor scores after surgery were >60% or <40%, respectively. Statistical analysis was performed using the SPM99 software. At baseline, all PD patients showed significant perfusion reductions in cortical areas (premotor frontal, parietal, and occipital). After DBS, changes were normalized only in the good responders, while cortical defects in the poor responders were unchanged. No flow decrements were detected in basal ganglia and thalamus in both groups, suggesting that DBS does not have a "lesion-like" effect. We conclude that good surgery outcome is associated with normalization of cortical flow abnormalities in PD.

Case-Control Studies↗

PubMed2002

Technical complication in deep brain stimulation.

With a growing number of patients treated with deep brain stimulation (DBS) operations for both hardware-related complications and routine replacements of impulse generators will be performed more frequently. Failure of DBS systems have to be analyzed thoroughly as this thwarts the enormous efforts required for proper electrode implantation and operative revisions increase the morbidity associated with DBS. A female patient implanted with DBS electrodes for advanced Parkinson's disease presented with straining of the right extension lead and deteriorating gait because of electrode migration. This was due to a malpositioned set screw connector adapting the electrode lead to the extension wire which had been placed below the mastoid process. Following surgical revision with implantation of a new electrode into the STN, electrode dislocation recurred requiring another surgical revision. This was due to renewed connector migration from its parietal position into the cervical region. Straining of extension leads should be recognized as a warning sign for (imminent) electrode dislocation or lead fracture. This may just be the case with connectors located below the mastoid process or in the cervical region, a risk which appears to be increased further with reduced-length extensions. Renewed dislocation of revised extensions may be prevented by securing the position of the connector (e.g. with manipulates).

Electric Stimulation Therapy↗

PubMed2003

Cellular effects of deep brain stimulation: model-based analysis of activation and inhibition.

Deep brain stimulation (DBS) is an effective therapy for medically refractory movement disorders. However, fundamental questions remain about the effects of DBS on neurons surrounding the electrode. Experimental studies have produced apparently contradictory results showing suppression of activity in the stimulated nucleus, but increased inputs to projection nuclei. We hypothesized that cell body firing does not accurately reflect the efferent output of neurons stimulated with high-frequency extracellular pulses, and that this decoupling of somatic and axonal activity explains the paradoxical experimental results. We studied stimulation using the combination of a finite-element model of the clinical DBS electrode and a multicompartment cable model of a thalamocortical (TC) relay neuron. Both the electric potentials generated by the electrode and a distribution of excitatory and inhibitory trans-synaptic inputs induced by stimulation of presynaptic terminals were applied to the TC relay neuron. The response of the neuron to DBS was primarily dependent on the position and orientation of the axon with respect to the electrode and the stimulation parameters. Stimulation subthreshold for direct activation of TC relay neurons caused suppression of intrinsic firing (tonic or burst) activity during the stimulus train mediated by activation of presynaptic terminals. Suprathreshold stimulation caused suppression of intrinsic firing in the soma, but generated efferent output at the stimulus frequency in the axon. This independence of firing in the cell body and axon resolves the apparently contradictory experimental results on the effects of DBS. In turn, the results of this study support the hypothesis of stimulation-induced modulation of pathological network activity as a therapeutic mechanism of DBS.

Action Potentials↗

PubMed2000

Mechanism of action of deep brain stimulation.

Initial observations in patients with tremor treated with deep brain stimulation (DBS) of the thalamus suggested that application of high-frequency stimulation (HFS) had a lesion-like effect. New clinical information from patients treated with DBS of the subthalamic nucleus (STN) and globus pallidus internus (GPi) suggested a more complex mechanism of action. Recent experiments in the rat have shown that HFS of the STN was accompanied by increased release of glutamate and dopamine in the substantia nigra and striatum, respectively. Observations made in the GPi of parkinsonian patients during surgery suggest that stimulation may excite GABA release in axons from afferent connections. Therefore, although depolarization block may remain a major mechanism of action, generation of action potentials and release of neurotransmitters may also be involved in the therapeutic effects of DBS in Parkinson's disease.

Animals↗

PubMed2000

Bilateral deep brain stimulation of the subthalamic nucleus in Parkinson's disease.

Deep brain stimulation (DBS) of the subthalamic nucleus (STN) is rapidly becoming the preferred surgical choice for the treatment of advanced Parkinson's disease (PD). We report initial results in 15 patients after 12 months and in nine patients evaluated between 30 and 36 months postoperatively. Our experience confirms the robust antiparkinsonian effect of DBS of the STN in advanced PD. The severity of "off" episodes, as assessed by the Unified Parkinson Disease Rating Scale (UPDRS), was drastically reduced by 74% at 12 months, and dyskinesia scores (Dyskinesia Rating Scale) decreased. The levodopa daily dose was reduced by 55% at 12 months. A double-blind assessment to determine the effect of stimulation performed in nine patients at 3 months in the "off" medication condition was very significant (p<0.05). Nine patients have been followed for 3 years with maintained efficacy in the UPDRS "off" score and the dyskinesia score. The experience of other groups using a similar technique is reviewed. The overall assessment indicates a high antiparkinsonian effect of DBS of the STN even in advanced patients. The existence of a learning curve for this procedure should be taken into account when initial results are evaluated.

Electric Stimulation Therapy↗

PubMed2005

Psychiatric symptoms in patients with Parkinson disease presenting for deep brain stimulation surgery.

OBJECT: Postoperative psychiatric symptoms have been associated with subthalamic deep brain stimulation (DBS) for Parkinson disease (PD), and preoperative psychiatric vulnerability, the effects of surgery, stimulation, medication changes, and psychosocial adjustment have been proposed as causative factors. The variables involved in whether preoperative psychiatric symptoms improve or worsen following surgery are not yet known. In the present study, preoperative psychiatric symptoms were systematically assessed in patients with PD presenting for routine preoperative psychiatric assessment. METHODS: Forty consecutive patients with PD presenting for DBS were interviewed using the Mini International Neuropsychiatric Inventory. Current depressive symptoms were quantified using clinician- and patient-rated depression scales. Seventy-eight percent of patients had at least one lifetime or current Axis I psychiatric diagnosis. The prevalence of depression was 60% (95% confidence interval [CI] 45-85), psychosis 35% (95% CI 25-50), and anxiety 40% (95% CI 25-55). These prevalence rates were comparable to or greater than those in the general population of patients with PD. Twenty-three percent of patients required psychiatric treatment for current symptoms prior to being considered eligible for DBS. CONCLUSIONS: As part of the selection process for surgery, members of the study population were chosen for their lack of overt dementia or other active disabling psychiatric symptomatology. The incidence rates of psychiatric disorders, including those diseases occurring in the general population affected with PD, were greater than expected. Data in the present study lead one to question the reliability of patient-rated depression scales as the sole instrument for assessing depression. The authors highlight the need for evidence-based guidelines in the management of these preoperative symptoms as well as the involvement of psychiatric personnel in the assessment and management of these symptoms.

Aged↗

PubMed2005

Permanent neurological deficit related to magnetic resonance imaging in a patient with implanted deep brain stimulation electrodes for Parkinson's disease: case report.

OBJECTIVE AND IMPORTANCE: Deep brain stimulation (DBS) is an accepted treatment for patients with Parkinson's disease refractory to medication. The efficacy of this therapy has led to increasing numbers of patients receiving DBS implants. Importantly, physicians caring for patients with implantable neurostimulators must be aware of treatment guidelines for these patients, including the use of therapeutic ultrasound, diathermy, and imaging studies such as magnetic resonance imaging (MRI). CLINICAL PRESENTATION: We describe a case of serious, permanent neurological injury secondary to a radiofrequency lesion produced by heating of a DBS electrode associated with MRI of the lumbar spine in a patient with Parkinson's disease. INTERVENTION: MRI may be performed safely in patients with DBS devices only by following the specific guidelines of the manufacturer. The generalization of these conditions to other neurostimulation system positioning schemes, other scanners, and other imaging scenarios can lead to significant patient injuries. CONCLUSION: To prevent catastrophic incidents, the manufacturer's guidelines should be followed carefully because they are known to result in the safe performance of MRI examinations of patients with neurostimulation systems used for DBS.

Brain Injuries↗

PubMed2006

Subthalamic nucleus deep brain stimulation: summary and meta-analysis of outcomes.

Subthalamic nucleus (STN) deep brain stimulation (DBS) is currently the most common therapeutic surgical procedure for patients with Parkinson's disease (PD) who have failed medical management. However, a recent summary of clinical evidence on the effectiveness of STN DBS is lacking. We report the results of such a systematic review and meta-analysis. A comprehensive review of the literature using Medline and Ovid databases from 1993 until 2004 was conducted. Estimates of change in absolute Unified Parkinson's Disease Rating Scale (UPDRS) scores after surgery were generated using random-effects models. Sources of heterogeneity were explored with meta-regression models, and the possibility of publication bias was evaluated. Patient demographics, reduction in medication requirements, change in dyskinesia, daily offs, quality of life, and a ratio of postoperative improvement from stimulation compared to preoperative improvement by medication from each study were tabulated and average scores were calculated. Adverse effects from each study were summarized. Thirty-seven cohorts were included in the review. Twenty-two studies with estimates of standard errors were included in the meta-analysis. The estimated decreases in absolute UPDRS II (activities of daily living) and III (motor) scores after surgery in the stimulation ON/medication off state compared to preoperative medication off state were 13.35 (95% CI: 10.85-15.85; 50%) and 27.55 (95% CI: 24.23-30.87; 52%), respectively. Average reduction in L-dopa equivalents following surgery was 55.9% (95% CI: 50%-61.8%). Average reduction in dyskinesia following surgery was 69.1% (95% CI: 62.0%-76.2%). Average reduction in daily off periods was 68.2% (95% CI: 57.6%-78.9%). Average improvement in quality of life using PDQ-39 was 34.5% +/- 15.3%. Univariable regression showed improvements in UPDRS III scores were significantly greater in studies with higher baseline UPDRS III off scores, increasing disease duration prior to surgery, earlier year of publication, and higher baseline L-dopa responsiveness. Average baseline UPDRS III off scores were significantly lower (i.e., suggesting milder disease) in later than in earlier studies. In multivariable regression, L-dopa responsiveness, higher baseline motor scores, and disease duration were independent predictors of greater change in motor score. No evidence of publication bias in the available literature was found. The most common serious adverse event related to surgery was intracranial hemorrhage in 3.9% of patients. Psychiatric sequelae were common. Synthesis of the available literature indicates that STN DBS improves motor activity and activities of daily living in advanced PD. Differences between available studies likely reflect differences in patient populations and follow-up periods. These data provide an estimate of the magnitude of the treatment effects and emphasize the need for controlled and randomized studies.

Deep Brain Stimulation↗

PubMed2005

Fracture of subthalamic nucleus deep brain stimulation hardware as a result of compulsive manipulation: case report.

OBJECTIVE AND IMPORTANCE: Trichotillomania (TTM) is an impulse control disorder characterized by the recurrent pulling of one's hair resulting in noticeable hair loss. There has been no definite association drawn between Parkinson's disease (PD) and TTM, although there is a suggestion that obsessive-compulsive symptomatology may be more prevalent in left-side predominant PD. We believe that it is important to be aware of psychiatric comorbidities in the surgical treatment of PD, as they may significantly impact the postoperative course. CLINICAL PRESENTATION: We describe the case of a 58-year-old woman with an eleven-year history of left-side predominant PD who also suffered from TTM. She underwent subthalamic nucleus deep brain stimulation (STN-DBS) and subsequently developed significant wound complications of her left-sided deep brain stimulation leads. It was noted during the postoperative period that the patient was picking her left-sided, but not right-sided, incision-a behavior that was felt to be a part of this patient's impulse control disorder. INTERVENTION: Multiple wound revisions and eventual replacement of her left-sided deep brain stimulation lead was performed as a result of hardware malfunction secondary to wound manipulation by the patient. CONCLUSION: Before surgery, this patient's TTM was right-sided, but after subthalamic nucleus deep brain stimulation, her wound picking was only left-sided. This case suggests that subthalamic nucleus deep brain stimulation may have a role in unleashing the symptomatology of TTM through an as yet poorly understood mechanism. Furthermore, there is also an implication that the pathophysiology of PD and TTM may be intertwined.

Deep Brain Stimulation↗

PubMed2006

Deep brain stimulation to treat hyperkinetic symptoms of Cockayne syndrome.

Cockayne syndrome manifests a spectrum of neurological dysfunction that includes medically intractable movement disorders. Deep brain stimulation has not been well studied in such rare neurodegenerative conditions. In this case, stimulation of the ventral intermediate nucleus of the thalamus was used to manage severe motor symptoms in a young man with Cockayne syndrome. There was a marked and progressive response to thalamic stimulation within weeks of surgery. These results suggest that patients with Cockayne syndrome should be considered for deep brain stimulation to treat refractory movement disorders.

Adolescent↗