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Treatment of phenylketonuria-associated tremor with deep brain stimulation: case report.

OBJECTIVE AND IMPORTANCE: Phenylketonuria (PKU) is an inborn error of metabolism that causes severe neurological impairment, despite dietary treatment. We present a case of PKU-induced cerebellar tremor treated with deep brain stimulation. There have been no previously reported cases of a patient with a PKU tremor treated with deep brain stimulation. CLINICAL PRESENTATION: A 36-year-old male patient with PKU presented with signs of cerebellar disease including dysmetria, resting tremor, and intention tremor in the left upper extremity. INTERVENTION: A deep brain stimulation electrode was placed in the ventral intermediate nucleus of the right thalamus. CONCLUSION: Immediately after surgery, the patient had nearly complete resolution of intention tremor in the left arm. His resting tremor in the left hand was also greatly improved. The 30-month follow-up examination revealed maintenance of the immediate postoperative improvement.

Adult↗

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

OBJECTIVE: To evaluate the effects of bilateral deep brain stimulation in the subthalamic nucleus for symptomatic relief of advanced idiopathic Parkinson's disease. DESIGN: Prospective cohort study. SETTING: Patients were assessed and received medical treatment at the Kingston Centre, Southern Health, Melbourne. Surgery took place at Melbourne Neuroscience Centre, The Royal Melbourne Hospital. Both are tertiary public institutions. SUBJECTS: 14 patients with Parkinson's disease with intact cognition and difficult to manage motor symptoms who were referred to Kingston Centre between 1996 and 2000 and were eligible for surgical intervention. INTERVENTIONS: All patients were assessed both after 12 hours' withdrawal from and while taking their levodopa medication on two occasions before surgery. Further assessments were carried out one, three, six and 12 months after surgery. MAIN OUTCOME MEASURES: The Unified Parkinson's Disease Rating Scale motor exam and gait parameters, such as stride length and velocity, were compared at six months after surgery with neither stimulation nor medication, with stimulation only, with medication only, and with stimulation and medication. RESULTS: Stimulators were explanted in one patient after intracranial haemorrhage and relocated to the thalamus in a second. Extraneous factors prevented two patients from attending at six-month follow-up. Motor performance improved significantly with stimulation alone in the 10 remaining patients. Further significant gains were seen with stimulation and medication combined, with an apparent reduction in side-effects such as dyskinesia. CONCLUSIONS: Bilateral deep brain stimulation of the subthalamic nucleus significantly improves motor performance in advanced Parkinson's disease, despite a rather high complication rate.

Adult↗

Primary dystonia is more responsive than secondary dystonia to pallidal interventions: outcome after pallidotomy or pallidal deep brain stimulation.

OBJECTIVE: The response of patients with dystonia to pallidal procedures is not well understood. In this study, we assessed the postoperative outcome of patients with primary and secondary dystonia undergoing pallidotomy or pallidal deep brain stimulation. METHODS: Fifteen patients with dystonia had pallidal surgery (lesions or deep brain stimulation). These included nine patients with primary dystonia (generalized and cervical dystonias) and six with secondary dystonia (generalized, segmental, and hemidystonias). There were nine male patients and six female patients. The mean age at onset was 21 years for primary dystonia and 18 years for secondary dystonia. The primary outcome measure was a Global Outcome Scale score for dystonia at 6 months after surgery. Other outcome measures were the Burke-Fahn-Marsden Dystonia Rating Scale and Toronto Western Spasmodic Torticollis Rating Scale scores. RESULTS: The mean Global Outcome Scale score at 6 months for patients with primary dystonia was 3 (improvement in both movement disorder and function). In contrast, patients with secondary dystonia had a mean score of 0.83 (mild or no improvement in movement disorder with no functional improvement). All patients with primary dystonia had normal brains by magnetic resonance imaging, whereas five of six patients with secondary dystonia had basal ganglia abnormalities on their magnetic resonance imaging scans. CONCLUSION: This study indicates that primary dystonia responds much better than secondary dystonia to pallidal procedures. We could not distinguish a difference in efficacy between pallidotomy and pallidal deep brain stimulation. The presence of basal ganglia abnormalities on the preoperative magnetic resonance imaging scan is an indicator of a lesser response to pallidal interventions for dystonia.

Adolescent↗

Placement of deep brain stimulator electrodes using real-time high-field interventional magnetic resonance imaging.

A methodology is presented for placing deep brain stimulator electrodes under direct MR image guidance. The technique utilized a small, skull-mounted trajectory guide that is optimized for accurate alignment under MR fluoroscopy. Iterative confirmation scans are used to monitor device alignment and brain penetration. The methodology was initially tested in a human skull phantom and proved capable of achieving submillimeter accuracy over a set of 16 separate targets that were accessed. The maximum error that was obtained in this preliminary test was 2 mm, motivating use of the technique in a clinical study. Subsequently, a total of eight deep brain stimulation electrodes were placed in five patients. Satisfactory placement was achieved on the first pass in seven of eight electrodes, while two passes were required with one electrode. Mean error from the intended target on the first pass was 1.0 +/- 0.8 mm (range = 0.1-1.9 mm). All procedures were considered technical successes and there were no intraoperative complications; however, one patient did develop a postoperative infection.

Brain↗

One for two? Exchanging implanted pulse generators for deep brain stimulation.

The use of a dual channel implantable pulse generator (IPG) for deep brain stimulation during de novo implantation is now routine in many centers. When the generator batteries of bilateral single channel generators expire, the issue of whether to exchange two single channel generators for one dual channel generator arises. This presents many debatable clinical, practical and fiscal issues. We discuss these issues and describe the "one for two" technique we have adopted for exchanging IPGs.

Brain↗

Central nystagmus induced by deep-brain stimulation for epilepsy.

PURPOSE: The goal of the present study was to describe the localization of central nystagmus induced as a side effect of electrical deep-brain stimulation for epilepsy. METHODS: Bilateral deep-brain stimulating electrodes were inserted in the centromedian nucleus of the thalamus to control seizures in a patient with intractable epilepsy. RESULTS: Cathodal high-frequency stimulation through the deepest contact of each electrode elicited cycles of slow ipsiversive conjugate eye deviations, each followed by rapid contralateral jerks. The involved electrode contacts were situated at the mesodiencephalic junction just inferior to the centromedian nucleus of the thalamus and rostral to the superior colliculus. Right-sided stimulation evoked left beating nystagmus and left-sided stimulation evoked right beating nystagmus. Stimulation through other electrode contacts did not induce nystagmus. Electronystagmography showed the nystagmus to have constant velocity slow phases. CONCLUSIONS: A central nystagmogenic area exists in humans that appears to be homologous to the nucleus of the optic tract, a region described in nonhuman primates to play a role in the generation of optokinetic nystagmus.

Adult↗

Difference in surgical strategies between thalamotomy and thalamic deep brain stimulation for tremor control.

Stereotactic targeting strategies differ between thalamotomy and thalamic deep brain stimulation (DBS) for tremor control. In thalamotomy, a minimal radiofrequency lesion created within the lateral portion of the nucleus ventralis intermedius (Vim) often affords the best control of parkinsonian tremor, supporting the assumption that there is a concentrated cluster of cells within this area which is responsible for tremor. However, this assumption may not always be true; such neural elements sometimes appear to spread out across wide areas. Cells with tremor-frequency activity are widely distributed over the areas extending from the Vim to the nuclei ventralis oralis posterior and anterior (Vop and Voa). All of these cells appear to be more or less involved in tremor generation, especially in patients with essential tremor and post-stroke tremor. In contrast to radiofrequency lesions for thalamotomy, electrodes for DBS can be arranged in such a way that wide areas can be stimulated, if necessary. For this purpose, it is critically important to determine optimal placement and orientation of DBS leads for arranging the electrodes to yield maximal benefits in patients with tremor.

Deep Brain Stimulation↗

Mohs micrographic surgery in a patient with a deep brain stimulator: a review of the literature on implantable electrical devices.

BACKGROUND: Implantable electrical devices are becoming increasingly common in the patient population presenting for Mohs micrographic surgery. In addition to understanding the potential intraoperative complications with implantable cardioverter-defibrillators and pacemakers, the Mohs surgeon needs to be aware of the relatively new treatment of movement disorders using implanted deep brain stimulators. OBJECTIVE: We present only the second reported case of Mohs surgery in a patient with a deep brain stimulator. In an attempt to help minimize adverse events during a procedure, we review the more commonly encountered electrical devices as well as the newer deep brain stimulators. We provide guidelines for the avoidance of electromagnetic interference during an electrosurgical procedure. METHODS: This 76-year-old patient with Parkinson's disease and an implanted deep brain stimulator underwent Mohs surgery for excision of a squamous cell carcinoma on the ear. In an attempt to minimize electromagnetic interference with his implanted device, hemostasis was obtained with the aid of a battery-operated heat-generating handheld electrocautery device. RESULTS: The patient tolerated the procedure well without complications or reports of discomfort. CONCLUSION: Patients with implanted electrical devices are subject to electromagnetic interference during an electrosurgical procedure. Care must be taken in this expanding patient population during a Mohs surgical procedure.

Aged↗

Problems with deep brain stimulation devices referred to private practice for follow up.

Increasingly, more centers perform deep brain stimulation (DBS) for the treatment of movement disorders; however, the majority of publications focus on treatment outcomes at tertiary care centers. We retrospectively evaluated nine consecutive patients who were implanted with DBS, initially programmed at other centers, and eventually referred to a community practice for follow up.

Aged↗

Thalamic deep brain stimulation activates the cerebellothalamocortical pathway.

To investigate the mechanism of action of deep brain stimulation (DBS), the authors studied the effects of thalamic DBS on the cerebellothalamocortical (CTC) pathway. With DBS turned off, excitability of the CTC pathway was reduced. Turning DBS on resulted in facilitation of the CTC pathway. Therefore, thalamic DBS appears to activate rather than inhibit the target area.

Adult↗

Deep brain stimulation for generalised dystonia and spasmodic torticollis.

Dystonia appears distinct from the other tremulous disorders in that improvement following deep brain stimulation frequently appears in a delayed and progressive manner. The rate of this improvement and the point at which no further progress can be expected are presently unknown. The establishment of these parameters is important in the provision of accurate and relevant prognostic information to these patients, their carers, and their treating physicians. We studied 12 consecutive patients with generalised dystonia (n=6) and spasmodic torticollis (n=6) who underwent bilateral globus pallidus internus (GPi) deep brain stimulation (DBS) and were followed up for a minimum of 2 years postoperatively. Standard rating scales were used to quantify their neurological improvement. Both groups experienced a statistically significant improvement in their rating scores at both one and two years following surgery. At 2 years follow-up, the spasmodic torticollis group exhibited a 59% improvement in their total Toronto Western Spasmodic Torticoilis Rating Scale (TWSTRS) rating score and the generalised dystonia group attained a 46% improvement in their overall Burke, Fahn and Marsden Dystonia Rating Scale (BFMDRS) evaluation. Ninety-five percent of the final improvement was attained by 6.4 months in the generalised dystonia group and by 6.6 months in those with spasmodic torticollis. There was no significant improvement after one year postoperatively. These findings add further support to GPi DBS as an effective treatment for generalised dystonia and spasmodic torticollis, and furnish important information as to the expected rate of improvement and the point at which no further gains can be reasonably anticipated.

Adolescent↗

Basal ganglia neural responses during behaviorally effective deep brain stimulation of the subthalamic nucleus in rats performing a treadmill locomotion test.

Deep brain stimulation (DBS) of the subthalamic nucleus (STN) is an effective treatment for Parkinson's disease (PD). In spite of proven therapeutic success, the mechanism underlying the benefits of DBS has not been resolved. A multiple-channel single-unit recording technique was used in the present study to investigate basal ganglia (BG) neural responses during behaviorally effective DBS of the STN in a rat model of PD. Rats underwent unilateral dopamine (DA) depletion by injection of 6-hydroxyDA (6-OHDA) into one side of the medial forebrain bundle and subsequently developed a partial akinesia, which was assessed during the treadmill locomotion task. High frequency stimulation (HFS) of the STN restored normal treadmill locomotion behavior. Simultaneous recording of single unit activity in the striatum (STR), globus pallidus (GP), substantia nigra pars reticulata (SNr), and STN revealed a variety of neural responses during behaviorally effective HFS of the STN. Predominant inhibitory responses appeared in the STN stimulation site. Nearly equal numbers of excitatory and inhibitory responses were found in the GP and SNr, whereas more rebound excitatory responses were found in the STR. Mean firing rate did not change significantly in the STR, GP, and SNr, but significantly decreased in both sides of STN during DBS. A decrease in firing rate in the contralateral side of STN provides neural substrate for the clinical observation that unilateral DBS produces bilateral benefits in patients with PD. In addition to the firing rate changes, a decrease in burst firing was observed in the GP and STN. The present study indicates that DBS induces complex modulations of the BG circuit and further suggests that BG network reorganization, rather than a simple excitation or inhibition, may underlie the therapeutic effects of DBS in patients with PD.

Adrenergic Agents↗

Progression of Parkinson's disease following thalamic deep brain stimulation for tremor.

We assessed the long-term effect of thalamic deep brain stimulation (DBS) on motor symptoms and progression of Parkinson's disease (PD) in PD patients treated for resting and postural/action tremor. Thalamic DBS was performed in 17 patients with treatment-resistant resting and postural/action tremor. Nine patients were available for follow-up examination a mean of 5.5 years after surgery. Three had tremor-dominant PD. DBS produced marked improvement in resting and postural/action tremor in target upper extremity in all 9 patients, which persisted unchanged at the time of the last follow-up visit 5.5 years after surgery. PD severity with DBS 'on' and 'off' 1 year after surgery was compared to PD severity at the last follow-up visit using UPDRS (Unified Parkinson's Disease Rating Scale) III motor scores and individual motor item subscores. Patients were tested while on medication. There was no significant worsening of tremor, rigidity, speech, postural stability, gait, or axial bradykinesia with DBS either on or off at the last follow-up visit compared to the 12-month visit. UPDRS III motor scores were unchanged. However, global assessment of PD progression and increased mean L-dopa dose and L-dopa equivalent daily dose at the time of last follow-up visit indicated that a progression of PD had occurred.

Aged↗

Uncovering the hidden placebo effect in deep-brain stimulation for Parkinson's disease.

OBJECTIVE: To determine the magnitude of the placebo effect in deep-brain stimulation (DBS) for Parkinson's disease (PD). BACKGROUND: The placebo effect in PD is related to the expectation of clinical benefit. Changes in expectation occurring in DBS crossover studies can be used to estimate the associated placebo effect. For example, the response to active-DBS is predicted to be greater in patients who have previously experienced the effect of placebo-DBS than in those without such an experience. METHODS: Data were obtained by searches of Medline and PubMed using three keywords: Parkinson's disease, deep-brain stimulation, and crossover study. Between-group comparisons of the effect of active-DBS were performed by t-test and analysis of covariance. RESULTS: Data on 126 PD patients were available for analysis. These patients participated in a multicenter, two-period, placebo-controlled crossover study on the efficacy of DBS for PD. As predicted, active-DBS was found to be more effective when preceded by placebo-DBS (i.e. in the high expectation group) than when not (i.e. in the lower expectation group). The estimated magnitude of the placebo effect in DBS was equivalent to 39% of the magnitude of the effect of active-DBS. CONCLUSIONS: There is a prominent placebo effect associated with DBS in PD. Crossover studies may be useful for estimating the placebo effect in other medical conditions.

Analysis of Variance↗

Deep brain stimulation: postoperative issues.

Numerous factors need to be taken into account when managing a patient with Parkinson's disease (PD) after deep brain stimulation (DBS). Questions such as when to begin programming, how to conduct a programming screen, how to assess the effects of programming, and how to titrate stimulation and medication for each of the targeted sites need to be addressed. Follow-up care should be determined, including patient adjustments of stimulation, timing of follow-up visits and telephone contact with the patient, and stimulation and medication conditions during the follow-up assessments. A management plan for problems that can arise after DBS such as weight gain, dyskinesia, axial symptoms, speech dysfunction, muscle contractions, paresthesia, eyelid, ocular and visual disturbances, and behavioral and cognitive problems should be developed. Long-term complications such as infection or erosion, loss of effect, intermittent stimulation, tolerance, and pain or discomfort can develop and need to be managed. Other factors that need consideration are social and job-related factors, development of dementia, general medical issues, and lifestyle changes. This report from the Consensus on Deep Brain Stimulation for Parkinson's Disease, a project commissioned by the Congress of Neurological Surgeons and the Movement Disorder Society, outlines answers to a series of questions developed to address all aspects of DBS postoperative management and decision-making with a systematic overview of the literature (until mid-2004) and by the expert opinion of the authors. The report has been endorsed by the Scientific Issues Committee of the Movement Disorder Society and the American Society of Stereotactic and Functional Neurosurgery.

Bacterial Infections↗

Effect of deep brain stimulation on different speech subsystems in patients with multiple sclerosis.

The effect of deep brain stimulation on articulation and phonation subsystems in seven patients with multiple sclerosis (MS) was examined. Production parameters in fast syllable-repetitions were defined and measured, and the phonation quality during vowel productions was analyzed. Speech material was recorded for patients (with and without stimulation) and for a group of healthy control speakers. With stimulation, the precision of glottal and supraglottal articulatory gestures is reduced, whereas phonation has a greater tendency to be hyperfunctional in comparison with the healthy control data. Different effects on the two speech subsystems are induced by electrical stimulation of the thalamus in patients with MS.

Adult↗

Thalamic deep brain stimulation: comparison between unilateral and bilateral placement.

BACKGROUND: Unilateral thalamic deep brain stimulation (DBS) is accepted as an effective treatment for essential tremor (ET) and the tremor of Parkinson disease (PD). There are, however, relatively little data concerning bilateral thalamic DBS and no thorough comparisons between the 2 methods. METHODS: To assess the relative benefit of a staged second contralateral DBS placement in patients with PD and ET, we compared preoperative baseline assessments with those at 3 months after the initial implantation, and again at 3 months after the second contralateral implantation. The assessments included the Unified Parkinson's Disease Rating Scale for patients with PD (n = 8) and a modified Unified Tremor Rating Assessment for patients with ET (n = 13). The design included open and blinded (unknown activation status) assessments. RESULTS: Overall, after the second implantation, all specific measures assessing tremor contralateral to that side improved in patients with PD and ET, generally without sacrificing those contralateral to the first side implantation. Midline tremors (face and head) improved only after the second side implantation. In patients with ET, functional and subjective scores tended to further improve after the second placement; however, patients with PD had less subjective improvement. Hand tremor scores in patients with ET randomized to "on" stimulation improved from 6.7 +/- 0.9 to 1.3 +/- 1.2 (P<.005). The scores of patients with PD randomized to on stimulation improved from 9.3 +/- 1.0 to 1.0 +/- 0.5. (Data are given as mean +/- SD.) Tremor scores did not change from baseline in those patients randomized to "off" stimulation in either group. Adverse events related to stimulation increased after the second implantation in both groups. CONCLUSIONS: Bilateral thalamic DBS is more effective than unilateral DBS at controlling bilateral appendicular and midline tremors of ET and PD. Despite this, overall functional disability only improved in patients with ET, possibly secondary to more problematic adverse events in patients with PD, especially balance problems. Bilateral DBS should be considered when unilateral DBS does not offer satisfactory benefit, especially in patients with ET.

Aged↗