Parkinson Disease: Kumar R

Kern DS, Kumar R. · College of Medicine, University of Vermont, Burlington, Vermont, USA. · Neurologist. · Pubmed #17848864 No free full text.

Abstract: BACKGROUND: Deep brain stimulation (DBS) for the treatment of neurologic diseases has markedly increased in popularity over the past 15 years. This review primarily focuses on movement disorder applications and efficacy of DBS, but also briefly reviews other promising new and old uses of DBS. REVIEW SUMMARY: A multidisciplinary team consisting of a movement disorders neurologist, a functional neurosurgeon, and a neuropsychologist optimally selects patients for DBS. Patients must be significantly disabled despite optimal medical therapy and be cognitively healthy without significant psychiatric disorders. Although this surgery is elective, it should not be withheld until the patient suffers marked loss of quality of life. Patients must have support from caregivers and postoperatively multiple DBS programming visits may be required. DBS of the subthalamic nucleus (STN) and the globus pallidus pars interna (GPi) significantly improves motor performance, activities of daily living, and quality of life in advanced Parkinson disease. In addition, STN DBS allows for marked reductions of antiparkinson medication. Stimulation of the ventralis intermedius nucleus of the thalamus is an effective treatment for essential tremor with sustained long-term effects. The GPi may be the preferred site of stimulation for dystonia with movement scores typically improved by 75% in patients with primary dystonia. CONCLUSIONS: DBS is an effective surgical treatment for movement disorders with sustained long-term benefits. Further research is ongoing to better understand the mechanism of DBS, refine the hardware to improve efficacy and reduce adverse effects, and identify additional applications and new anatomic targets.

Kumar R. · Colorado Neurological Institute, Englewood, Colorado 80110-2778, USA. · Mov Disord. · Pubmed #11948777 No free full text.

Abstract: Globus pallidus (GPi) deep brain stimulation can markedly improve severe medication-refractory Parkinson's disease (PD) and dystonia. Appropriate perioperative patient management can assist with electrode implantation. Optimizing stimulation settings and simultaneously adjusting medications (when appropriate) can substantially improve patient outcomes. Although there are a large number of possible stimulation settings, in clinical practice, a relatively narrow range of settings has been shown to be most efficacious. A systematic approach to determining those settings that maximally improve parkinsonism and suppress drug-induced dyskinesias is outlined following a clear algorithm that uses the observation that stimulation of the dorsal and ventral pallidum has been shown to have opposite motor effects in PD. Based on the available literature, recommendations are also made for the use of GPi deep brain stimulation in dystonia.

Kumar R, Lozano AM, Sime E, Halket E, Lang AE. · Division of Neurology, University of Toronto, Ontario, Canada. · Neurology. · Pubmed #10449121 No free full text.

Abstract: OBJECTIVE: To compare the effects of unilateral subthalamic nucleus (STN) deep brain stimulation (DBS) with bilateral STN DBS in advanced PD. METHODS: Our initial 10 consecutive patients with medication-refractory motor fluctuations and levodopa-induced dyskinesias undergoing chronic bilateral STN DBS underwent a standardized evaluation of unilateral and bilateral STN DBS in the medication-off state 6 to 18 months after electrode implantation. RESULTS: Bilateral STN DBS improved the mean total Unified Parkinson's Disease Rating Scale motor score by 54%, whereas unilateral stimulation improved motor scores only 23%. Unilateral STN DBS improved postural stability and gait 14%, other axial motor features 19%, and overall parkinsonism in limbs contralateral to stimulation by 46%, including an 86% improvement in contralateral tremor. However, bilateral STN DBS resulted in greater improvement in each of these domains, including limb function, i.e., the reduction in scores from the limbs on one side was greater with bilateral than with unilateral stimulation of the contralateral STN. CONCLUSIONS: Bilateral STN DBS improves parkinsonism considerably more than unilateral STN DBS; bilateral simultaneous electrode implantation may be the most appropriate surgical option for patients with significant bilateral disability. Unilateral STN DBS results in moderate improvement in all aspects of off-period parkinsonism and improves tremor as much as is typically reported with DBS of the ventral intermedius nucleus of the thalamus (Vim). For this reason, STN DBS may be a more appropriate choice than Vim DBS or thalamotomy for parkinsonian tremor. Some patients with highly asymmetric tremor-dominant PD might be appropriately treated with unilateral instead of bilateral STN DBS.

Schenkman M, Hall D, Kumar R, Kohrt WM. · Physical Therapy Program, Department of Physical Medicine and Rehabilitation, University of Colorado at Denver and Health Sciences Center, 4200 E Ninth Ave, Denver, CO 80262-0244, USA. · Phys Ther. · Pubmed #17940108 links to  free full text

Abstract: BACKGROUND AND PURPOSE: Even early in Parkinson disease (PD), individuals have reduced economy of movement. In this case report, the effects of endurance exercise training are examined on walking economy and other measures for 3 individuals in early and middle stages of PD. PATIENTS: The patients were 1 woman and 2 men with PD, aged 52 to 72 years, classified at Hoehn and Yahr stages 2 to 2.5. INTERVENTION: Each patient completed 4 months of supervised endurance exercise training and 12 months of home exercise, with monthly clinic follow-up sessions. Strategies were included to enhance adherence to exercise. OUTCOMES: The main outcome measure was economy of movement (rate of oxygen consumption during gait) measured at 4 treadmill speeds. Secondary outcome measures included the Unified Parkinson's Disease Rating Scale (UPDRS), Continuous-Scale Physical Functional Performance Test (CS-PFP), Functional Reach Test (FRT), and Functional Axial Rotation Test (FAR). Economy of movement improved for all 3 patients after 4 months of supervised exercise and remained above baseline at 16 months. Two patients also had scores that were above baseline for UPDRS total score, CS-PFP, FRT, and FAR, even at 16 months. DISCUSSION AND CONCLUSION:: Evidence from these 3 individuals suggests that gains may occur with a treadmill training program that is coupled with specific strategies to enhance adherence to exercise.

Kedia S, Moro E, Tagliati M, Lang AE, Kumar R. · University of Colorado Health Sciences Center, Denver, USA. · Neurology. · Pubmed #15623715 No free full text.

Abstract: The authors systematically studied the emergence of restless legs syndrome (RLS) after subthalamic nucleus (STN) deep brain stimulation (DBS) for Parkinson disease (PD). Postoperatively, 11 of 195 patients with STN DBS reported new problematic symptoms of RLS. The mean reduction in antiparkinsonian medication was 74%. The mean RLS score at diagnosis was 15 (+/-5.9) of a possible 24 points and after symptomatic drug therapy 4.3 (+/-3.1) points. Reduction of antiparkinsonian medication during STN DBS may unmask symptoms of RLS and complicate therapy of both RLS and PD.

Kumar R, Lozano AM, Sime E, Lang AE. · Division of Neurology, Faculty of Medicine, University of Toronto, Canada. · Neurology. · Pubmed #14663050 No free full text.

Abstract: Thirteen consecutive patients with thalamic deep brain stimulation (DBS) were examined serially for 3 to 5 years. Initially, all demonstrated at least 50% improvement in contralateral tremor. At last follow-up, three of eight patients with Parkinson disease no longer used DBS because tremor had markedly improved, and for two, motor fluctuations and levodopa-induced dyskinesias became the major disability, with tremor less troublesome. Two of five patients with essential tremor had contralateral tremor improvement after ongoing stimulation for 2 years; two developed marked tolerance to DBS.

Krack P, Kumar R, Ardouin C, Dowsey PL, McVicker JM, Benabid AL, Pollak P. · Neuroscience Department, University of Grenoble, Grenoble, France. · Mov Disord. · Pubmed #11746616 No free full text.

Abstract: High-frequency stimulation of the subthalamic nucleus (STN) improves the motor signs of Parkinson's disease (PD). The three main components (motor, associative, and limbic) of the cortical-basal ganglia-cortical circuits pass through the STN. It is not known whether STN stimulation can influence the limbic loop. We present two PD patients in whom acute stimulation of an electrode located in the STN using high stimulation parameters (50% higher than therapeutic) induced funny associations, leading to infectious laughter and hilarity, whereas the therapeutic parameters induced a hypomanic behavior and marked improvement of akinesia. Our report suggests that the STN, with its sensorimotor, cognitive, and limbic parts is not only involved in motor, but also in psychomotor regulation.

Kumar R, Lang AE, Rodriguez-Oroz MC, Lozano AM, Limousin P, Pollak P, Benabid AL, Guridi J, Ramos E, van der Linden C, Vandewalle A, Caemaert J, Lannoo E, van den Abbeele D, Vingerhoets G, Wolters M, Obeso JA. · Division of Neurology and Neurosurgery, University of Toronto Medical School, Ontario, Canada. · Neurology. · Pubmed #11188973 No free full text.

Abstract: Pallidotomy is now widely performed for the treatment of advanced Parkinson's disease (PD). Preliminary reports of the effect of globus pallidus pars interna deep brain stimulation (GPi DBS) have also been promising. We have analyzed a cohort of 22 consecutive patients enrolled in a multicenter study. Surgery was bilateral in 17 and unilateral in five patients. At 6-month follow-up, the bilaterally GPi-implanted patients demonstrated a marked improvement when examined after drug withdrawal ("off") and under optimal medication ("on") using the Unified Parkinson's Disease Rating Scale (UPDRS). The benefit induced by the stimulation in the "off" medication condition in the total motor score was 31% and in the activities of daily living (ADL) scores was 39%. During the "on" medication period, the reduction in the total "on" dyskinesias score was 66% and in the ADL score was 32%. A similar pattern of improvement was seen in the group of patients with unilateral GPi stimulation, although a second cohort of 12 patients not included in the multicenter study showed greater improvements in "on" motor functioning. Although the effect of DBS is predominantly reversible, electrode insertion alone resulted in measurable clinical effects in the absence of stimulation. Thus, at 6-month follow-up, the benefit observed without stimulation was up to 44% in the "on" dyskinesias score and 29% in timed tapping scores undertaken in the "off" medication state. Complications among 34 patients from all centers included perioperative infection (n=3), hardware fracture (n=2), and premature battery failure (n=3). These results show a positive antiparkinsonian effect of pallidal DBS. No specific complications were observed with bilateral procedures.

Dromey C, Kumar R, Lang AE, Lozano AM. · Department of Speech-Language Pathology, Toronto Western Hospital, Ontario, Canada. · Mov Disord. · Pubmed #11104196 No free full text.

Abstract: Seven patients with Parkinson's disease were implanted with deep brain stimulators to provide chronic electrical stimulation to the subthalamic nucleus bilaterally. Acoustic recordings and neurologic assessments were undertaken before surgery in the medication-off and medication-on conditions and after surgery with and without electrical stimulation in the medication-off and medication-on conditions. The data showed significant improvements in limb motor performance in response to medication before surgery and when the subthalamic nucleus was stimulated after surgery. Six months after surgery, there were small but statistically significant increases in sound pressure level and fundamental frequency variability in response to stimulation in the medication-on condition. No other statistically significant speech changes were measured. These findings are consistent with several other studies that have reported disparity between limb and speech improvements after neurosurgical intervention for Parkinson's disease.

Saint-Cyr JA, Trépanier LL, Kumar R, Lozano AM, Lang AE. · Department of Medicine, Division of Neurology, University Health Network, Toronto Western Hospital Research Institute, University of Toronto and The Toronto Western Hospital, Ontario, Canada. · Brain. · Pubmed #11004126 links to  free full text

Abstract: The aim of this study was to examine possible neuropsychological changes in patients with advanced idiopathic Parkinson's disease treated with bilateral deep brain stimulation (DBS) of the subthalamic nucleus (STN). Eleven patients (age = 67 +/- 8 years, years with Parkinson's disease = 15 +/- 3, verbal IQ = 114 +/- 12) were evaluated (in their best 'on state') with tests assessing processes reliant on the functional integrity of frontal striatal circuitry, prior to the procedure (n = 11), at 3-6 months (n = 11) and at 9-12 months (n =10) post-operatively. Six of these patients were older than 69 years. Despite clinical motor benefits at 3-6 months post-operative, significant declines were noted in working memory, speed of mental processing, bimanual motor speed and co-ordination, set switching, phonemic fluency, long-term consolidation of verbal material and the encoding of visuospatial material. Declines were more consistently observed in patients who were older than 69 years, leading to a mental state comparable with progressive supranuclear palsy. 'Frontal' behavioural dyscontrol without the benefit of insight was also reported by half (three of six) of the caregivers of the elderly subgroup. At 9-12 months postoperative, only learning based on multiple trials had recovered. Tasks reliant on the integrity of frontal striatal circuitry either did not recover or gradually worsened over time. Bilateral STN DBS can have a negative impact on various aspects of frontal executive functioning, especially in patients older than 69 years. Future studies will evaluate a larger group of patients and examine the possible reversibility of these effects by turning the DBS off.

Trépanier LL, Kumar R, Lozano AM, Lang AE, Saint-Cyr JA. · Toronto Western Hospital--Research Institute, University of Toronto and The Toronto Hospital, Ontario, Canada. · Brain Cogn. · Pubmed #10753483 No free full text.

Abstract: This paper highlights the neuropsychological sequelae of posteroventral pallidotomy (PVP) and deep brain stimulation (DBS) of the subthalamic nucleus (STN) and the internal segment of the globus pallidus (GPi) at 3/6 months postoperatively. Results are based on our extensive experience with PVP and our preliminary observations with DBS. Patients with borderline cognitive or psychiatric functioning risk postoperative decompensation. Nonlateralizing attentional and hemisphere-specific impairments of frontostriatal cognitive functions followed unilateral PVP. "Frontal" behavioral dyscontrol was observed in approximately 25% of patients. Three cases of staged bilateral PVP suggest that premorbid factors may predict outcome, although lesion size and location are also critical. Older patients are at risk for significant cognitive and behavioral decline after bilateral STN DBS, while GPi DBS may be safer.

Ashby P, Kim YJ, Kumar R, Lang AE, Lozano AM. · Playfair Neuroscience Unit, University of Toronto,Toronto Western Hospital, Toronto, Canada. · Brain. · Pubmed #10506093 links to  free full text

Abstract: The effects of stimulation through macroelectrodes implanted in the subthalamic nucleus (STN) were studied in 14 patients with parkinsonism. Single stimuli delivered directly to the STN electrodes with an external stimulator modulated voluntary electromyography (EMG) of contralateral muscles in most patients. A short-latency facilitation ('peak') was attributed to the activation of the corticospinal system. A longer latency inhibition ('dip'), often preceded or followed by facilitations, appeared to arise from the activation of large-diameter fibres running parallel to the electrode and to be transmitted through the motor cortex. It is possible that the dip could result from the inhibition of thalamocortical neurons. With high-frequency stimulation ( approximately 100 Hz) the peaks occurred at the stimulus frequency; the dips became confluent and outlasted the duration of the stimulus train. There was no evidence that high-frequency stimulation produced 'blocking'. The studies were repeated in 12 patients a mean of 5.8 months after implantation of the stimulator. The same short-latency effects were obtained. They were present on 7 out of 23 sides at the settings in use and on the majority of sides if the stimulus intensity was slightly increased. There was no clear relationship between these short-latency effects and the patients' overall clinical improvement; the effects may result from the spread of current to large-fibre systems near the STN. In five patients, high-frequency stimulation on one side immediately reduced tremor in the contralateral limbs. This effect arose from the activation of large-diameter fibres and, like the dip, had about the same threshold at each of the contacts. Frequencies as low as 70 Hz were sufficient. We conclude that the control of tremor by STN stimulation is due to the activation of a large-fibre system.

Kumar R, Krack P, Pollak P. · No affiliation provided · N Engl J Med. · Pubmed #10498481 No free full text.

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