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Biomedical subjects

William J Marks

Publications and source records attributed to William J Marks.

At least 19 recordsLinked to original sources
PubMed2007

Effects of unilateral subthalamic and pallidal deep brain stimulation on fine motor functions in Parkinson's disease.

Deep brain stimulation (DBS) is an effective treatment for selected patients with disabling Parkinson's disease (PD). The two main targets are the subthalamic nucleus (STN) and the globus pallidus internus (GPi), although it has not been established whether stimulation at one target is superior to the other. This prospective randomized study assessed the effects of unilateral DBS of the STN versus GPi on fine motor skills in 33 patients with advanced PD. Stimulation of either the STN (18 subjects) or GPi (15 subjects) in the off medication state significantly improved movement time and dexterity, but had little or no effect on reaction time. Overall, the extent of improvement did not differ between the two targets. The degree of improvement in movement time, but not dexterity, was correlated with the extent of preoperative medication responsiveness. Our findings suggest that DBS of the STN or GPi results in a similar improvement in hand movements at short-term follow-up. Preoperative medication responsiveness predicts improvement in some but not other motor tasks.

Adult↗
PubMed2007

Neuropsychological performance following staged bilateral pallidal or subthalamic nucleus deep brain stimulation for Parkinson's disease.

Deep brain stimulation (DBS) has the potential to significantly reduce motor symptoms in advanced Parkinson's disease (PD). Controversy remains about non-motor effects of DBS and the relative advantages of treatment at two brain targets, the globus pallidus internus (GPi) and the subthalamic nucleus (STN). We investigated effects of DBS on neuropsychological functioning in 42 patients with advanced PD randomly assigned to receive staged bilateral DBS surgery of either the GPi or STN. Patients underwent neuropsychological assessment prior to and 6 months after unilateral surgery. Twenty-nine subsequently underwent surgery to the contralateral side and completed a second follow-up neuropsychological evaluation 15 months later. Unilateral treatment resulted in small but statistically significant reductions in performance on several measures, including verbal fluency and working memory. A similar pattern was observed after bilateral treatment. Reductions in verbal associative fluency were significant only after left-sided treatment. There were few significant differences related to treatment at the two surgical targets. Supplementary analyses suggested that decrements in select neuropsychological domains following DBS are unrelated to age or post-surgical reduction in dopaminergic medication dose. Findings are discussed with reference to possible causes of neuropsychological decline and the need for further controlled studies of specific neuropsychological effects of DBS.

Aged↗
PubMed2006

Microelectrode-guided implantation of deep brain stimulators into the globus pallidus internus for dystonia: techniques, electrode locations, and outcomes.

OBJECT: Deep brain stimulation (DBS) of the globus pallidus internus (GPI) is a promising new procedure for the treatment of dystonia. The authors describe their technical approach for placing electrodes into the GPI in awake patients with dystonia, including methodology for electrophysiological mapping of the GPI in the dystonic state, clinical outcomes and complications, and the location of electrodes associated with optimal benefit. METHODS: Twenty-three adult and pediatric patients with various forms of dystonia were included in this study. Baseline neurological status and DBS-related improvement in motor function were measured using the Burke-Fahn-Marsden Dystonia Rating Scale (BFMDRS). The implantation of DBS leads was performed using magnetic resonance (MR) imaging-based stereotaxy, single-cell microelectrode recording, and intraoperative test stimulation to determine thresholds for stimulation-induced adverse effects. Electrode locations were measured on computationally reformatted postoperative MR images according to a prospective protocol. CONCLUSIONS: Physiologically guided implantation of DBS electrodes in patients with dystonia was technically feasible in the awake state in most patients, and the morbidity rate was low. Spontaneous discharge rates of GPI neurons in dystonia were similar to those of globus pallidus externus neurons, such that the two nuclei must be distinguished by neuronal discharge patterns rather than rates. Active electrode locations associated with robust improvement (> 70% decrease in BFMDRS score) were located near the intercommissural plane, at a mean distance from the pallidocapsular border of 3.6 mm.

Adolescent↗
PubMed2005

Spontaneous pallidal neuronal activity in human dystonia: comparison with Parkinson's disease and normal macaque.

Dystonia is a movement disorder defined by sustained muscle contractions, causing twisting and repetitive movements and abnormal postures. To understand the abnormalities in pallidal discharge in dystonia, we have analyzed the spontaneous activity of 453 neurons sampled from the internal or external pallidum (GPi or GPe) of 22 patients with dystonia, 140 neurons from 11 patients with Parkinson's disease (PD), and 157 neurons from two normal non-human primates (NHPs; Macacca mulatta). All recordings were performed without systemic sedation. Mean GPi discharge rate in dystonia was 55.3 +/- 1.3 (SE) Hz. This was significantly lower than in the normal NHPs (82.5 +/-2.5 Hz) and lower than in PD patients (95.2 +/- 2.3 Hz). Mean GPe discharge rate in dystonia (54.0 +/- 1.9 Hz) was lower than in the normal NHPs (69.7 +/- 3.3 Hz) and was indistinguishable from that in PD patients (56.6 +/- 3.5 Hz). Mean GPi discharge rate was inversely correlated with dystonia severity. GPi showed increased oscillatory activity in the 2- to 10-Hz range and increased bursting activity in both dystonia and PD as compared with the normal NHPs. Because the abnormalities in discharge patterns were similar in dystonia compared with PD, we suggest that bursting and oscillatory activity superimposed on a high background discharge rate are associated with parkinsonism, whereas similar bursting and oscillations superimposed on a lower discharge rate are associated with dystonia. Our findings are most consistent with a model of dystonia pathophysiology in which the two striatal cell populations contributing to the direct and indirect intrinsic pathways of the basal ganglia both have increased spontaneous activity.

Action Potentials↗
PubMed2005

Deep Brain Stimulation for Dystonia.

Dystonia refers to movement disorders characterized by sustained muscle contractions that produce abnormal postures, twisting movements, and other abnormal involuntary movements. A spectrum of etiologies underlies the various dystonia syndromes, ranging from genetic conditions to brain injury. First-line therapy for dystonia consists of pharmacologic agents of several classes and, particularly for focal dystonia, chemodenervation therapy with botulinum toxin. Many patients with dystonia realize an inadequate response to those treatments, and for such patients whose symptoms are sufficiently troublesome, surgical treatment can be used to reduce symptoms and improve function. Previously, the ablative procedures of thalamotomy and pallidotomy were used, in which a permanent destructive lesion was made in the motor territory of the thalamus or the globus pallidus. More recently, the device-based therapy of deep brain stimulation (DBS) has emerged as the preferred surgical treatment for dystonia and other movement disorders for most patients who require operative intervention. DBS uses a surgically implanted brain lead connected to an implanted neurostimulator to deliver chronic, high- frequency electrical stimulation to one of several deep nuclei. 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 safe manner. Use of DBS to treat dystonia is a rapidly evolving area, and preliminary evidence suggests that primary dystonia linked to genetic mutation, other primary dystonias, and tardive dystonic syndromes respond most dramatically to treatment with DBS, whereas secondary dystonia tends to be less responsive.

Journal Article↗
PubMed2005

Deep brain stimulation for the treatment of Parkinson's disease: overview and impact on gait and mobility.

Abnormality in gait is a cardinal feature of Parkinson's disease. Walking is characterized by relatively preserved sequencing of trunk and limb movements, but diminished velocity, shortened stride length, increased base, and diminished double stance support time. The principle problem producing the gait abnormalities is dopamine deficiency, which is hypothesized to disrupt pallido-thalamic modulation of cortical motor regions that automatically regulate walking. Deep brain stimulation currently is directed at either the globus pallidum internus (GPi) or subthalamic nucleus (STN) and improves many of the abnormal characteristics of parkinsonian gait with efficacy similar to dopamine replacement. The optimal target for stimulation remains uncertain and is currently being addressed in a large VA cooperative study. Our studies show that unilateral stimulation of GPi or STN improves gait to a similar extent. Functional and quantitative gait analyses confirm sustained improvement in gait dynamics with bilateral stimulation for periods for more than several years. Parkinsonian gait is also improved with rehabilitation training, primarily using external visual or auditory cues. The combination of deep brain stimulation, pharmacotherapy, and rehabilitation training may result in more effective comprehensive approaches to the reduced mobility associated with Parkinson's disease.

Deep Brain Stimulation↗
PubMed2004

Microelectrode-guided implantation of deep brain stimulators into the globus pallidus internus for dystonia: techniques, electrode locations, and outcomes.

Object. Deep brain stimulation (DBS) of the globus pallidus internus (GPi) is a promising new procedure for the treatment of dystonia. The authors present their technical approach for placement of electrodes into the GPi in awake patients with dystonia, including the methodology used for electrophysiological mapping of the GPi in the dystonic state, clinical outcomes and complications, and the location of electrodes associated with optimal benefit. Methods. Twenty-three adult and pediatric patients who had various forms of dystonia were included in this study. Baseline neurological status and improvement in motor function resulting from DBS were measured using the Burke-Fahn-Marsden Dystonia Rating Scale (BFMDRS). Implantation of the DBS lead was performed using magnetic resonance (MR) imaging-based stereotaxy, single-cell microelectrode recording, and intraoperative test stimulation to determine thresholds for stimulation-induced adverse effects. Electrode locations were measured on computationally reformatted postoperative MR images according to a prospective protocol. Conclusions. Physiologically guided implantation of DBS electrodes in patients with dystonia is technically feasible in the awake state in most cases, with low morbidity rates. Spontaneous discharge rates of GPi neurons in dystonia are similar to those of globus pallidus externus neurons, such that the two nuclei must be distinguished by neuronal discharge patterns rather than by rates. Active electrode locations associated with robust improvement (> 50% decrease in BFMDRS score) were located near the intercommissural plane, at a mean distance of 3.7 mm from the pallidocapsular border. Patients with juvenile-onset primary dystonia and those with the tardive form benefited greatly from this procedure, whereas benefits for most secondary dystonias and the adult-onset craniocervical form of this disorder were more modest.

Adolescent↗
PubMed2004

Efficacy and tolerability of the new antiepileptic drugs, I: Treatment of new-onset epilepsy: report of the TTA and QSS Subcommittees of the American Academy of Neurology and the American Epilepsy Society.

PURPOSE: To assess the evidence demonstrating efficacy, tolerability, and safety of seven new antiepileptic drugs [AEDs; gabapentin (GBP), lamotrigine (LTG), topiramate (TPM), tiagabine (TGB), oxcarbazepine (OXC), levetiracetam (LEV), and zonisamide (ZNS), reviewed in the order in which these agents received approval by the U.S. Food and Drug Administration] in the treatment of children and adults with newly diagnosed partial and generalized epilepsies. METHODS: A 23-member committee, including general neurologists, pediatric neurologists, epileptologists, and doctors in pharmacy, evaluated the available evidence based on a structured literature review including MEDLINE, Current Contents, and Cochrane Library for relevant articles from 1987 until September 2002, with selected manual searches up to 2003. RESULTS: Evidence exists, either from comparative or dose-controlled trials, that GBP, LTG, TPM, and OXC have efficacy as monotherapy in newly diagnosed adolescents and adults with either partial or mixed seizure disorders. Evidence also shows that LTG is effective for newly diagnosed absence seizures in children. Evidence for effectiveness of the new AEDs in newly diagnosed patients with other generalized epilepsy syndromes is lacking. CONCLUSIONS: The results of this evidence-based assessment provide guidelines for the prescription of AEDs for patients with newly diagnosed epilepsy and identify those seizure types and syndromes for which more evidence is necessary.

Acetates↗
PubMed2004

Efficacy and tolerability of the new antiepileptic drugs, II: Treatment of refractory epilepsy: report of the TTA and QSS Subcommittees of the American Academy of Neurology and the American Epilepsy Society.

PURPOSE: To assess the evidence demonstrating efficacy, tolerability, and safety of seven new antiepileptic drugs (AEDs) [gabapentin (GBP), lamotrigine (LTG), topiramate (TPM), tiagabine (TGB), oxcarbazepine (OXC), levetiracetam (LEV), and zonisamide (ZNS)] in the treatment of children and adults with refractory partial and generalized epilepsies. METHODS: A 23-member committee, including general neurologists, pediatric neurologists, epileptologists, and doctors in pharmacy, evaluated the available evidence based on a structured literature review including MEDLINE, Current Contents, and Cochrane Library for relevant articles from 1987 to March 2003. RESULTS: All of the new AEDs were found to be appropriate for adjunctive treatment of refractory partial seizures in adults. GBP can be effective for the treatment of mixed seizure disorders, and GBP, LTG, OXC, and TPM for the treatment of refractory partial seizures in children. Limited evidence suggests that LTG and TPM also are effective for adjunctive treatment of idiopathic generalized epilepsy in adults and children, as well as treatment of the Lennox-Gastaut syndrome. CONCLUSIONS: The choice of AED depends on seizure and/or syndrome type, patient age, concomitant medications, and AED tolerability, safety, and efficacy. The results of this evidence-based assessment provide guidelines for the prescription of AEDs for patients with refractory epilepsy and identify those seizure types and syndromes for which more evidence is necessary.

Acetates↗
PubMed2003

Locations of movement-related cells in the human subthalamic nucleus in Parkinson's disease.

The subthalamic nucleus (STN) is an emerging target for deep brain stimulator (DBS) implantation for the treatment of advanced Parkinson's disease (PD). Understanding the somatotopic organization of the STN is important for surgical navigation within the nucleus. We analyzed intraoperative data obtained during 54 procedures for the implantation of STN stimulators to assess the locations of movement-related cells. Cells were considered movement-related if they exhibited modulation of the cell discharge during passive movement of the contralateral upper or lower extremity. Microelectrode track reconstructions were plotted on a human brain atlas, using the location of the DBS electrode from postoperative magnetic resonance images as a registration mark in reconstructing microelectrode track locations. Movement-related cells were predominantly located in the dorsal part of the nucleus. The majority of the cells were related to proximal joint manipulation. Arm-related cells were located laterally and at the rostral and caudal poles, whereas leg-related cells were located medially and centrally. The finding of three or more leg-related cells on a given microelectrode track was predictive of a medial localization within the motor area. Our findings are consistent with the small number of published studies on STN somatopy in the human and the nonhuman primate.

Action Potentials↗
PubMed2002

Quantitative 1H magnetic resonance spectroscopy and MRI of Parkinson's disease.

Magnetic resonance imaging (MRI) and (1)H magnetic resonance spectroscopy (MRS) of the substantia nigra, basal ganglia, and cerebral cortex were performed on 10 patients with Parkinson's disease (PD) and 13 age-matched, healthy control subjects. Compared to controls, PD patients had approximately 24% lower creatine in the region of the substantia nigra and smaller volumes of the putamen (11%), globus pallidus (16%), and prefrontal cortex (6%; all P < 0.05). No other significant between-group differences were found in nine regions examined. Thus, quantitative MRI may show regional neurodegenerative changes outside the substantia nigra in PD but PD-linked extranigral metabolic abnormalities, if they exist, may be difficult to detect with current (1)H MRS methods. In additional, exploratory tests, volumes of the caudate (r = -0.56), putamen (r = -0.66), and globus pallidus (r = -0.60; all P < 0.05) were negatively correlated with the volume of the substantia nigra pars compacta in controls. In PD these correlations did not hold. Instead, pallidal volume in PD was positively correlated with compacta volume (r = 0.64; P < 0.05). This relationship suggests that basal ganglia volumes may be influenced by dopaminergic innervation from the substantia nigra in normal and PD subjects.

Aged↗
PubMed2002

Implantation of deep brain stimulators into the subthalamic nucleus: technical approach and magnetic resonance imaging-verified lead locations.

OBJECT: Chronic deep brain stimulation (DBS) of the subthalamic nucleus (STN) is a procedure that is rapidly gaining acceptance for the treatment of symptoms in patients with Parkinson disease (PD), but there are few detailed descriptions of the surgical procedure itself. The authors present the technical approach used to implant 76 stimulators into the STNs of patients with PD and the lead locations, which were verified on postoperative magnetic resonance (MR) images. METHODS: Implantation procedures were performed with the aid of stereotactic MR imaging, microelectrode recording (MER) in the region of the stereotactic target to define the motor area of the STN, and intraoperative test stimulation to assess the thresholds for stimulation-induced adverse effects. All patients underwent postoperative MR imaging, which was performed using volumetric gradient-echo and T2-weighted fast-spin echo techniques, computational reformatting of the MR image into standard anatomical planes, and quantitative measurements of lead location with respect to the midcommissural point and the red nucleus. Lead locations were statistically correlated with physiological data obtained during MER and intraoperative test stimulation. CONCLUSIONS: The authors' approach to implantation of DBS leads into the STN was associated with consistent lead placement in the dorsolateral STN, a low rate of morbidity, efficient use of operating room time, and robust improvement in motor function. The mean coordinates of the middle of the electrode array, measured on postoperative MR images, were 11.6 mm lateral, 2.9 mm posterior, and 4.7 mm inferior to the midcommissural point, and 6.5 mm lateral and 3.5 mm anterior to the center of the red nucleus. Voltage thresholds for several types of stimulation-induced adverse effects were predictive of lead location. Technical nuances of the surgery are described in detail.

Aged↗