Biomedical subjects

R Pahwa

Publications and source records attributed to R Pahwa.

At least 55 records · Page 3Linked to original sources

PubMed1998

Comparison of actual pallidotomy lesion location with expected stereotactic location.

Accuracy of pallidotomy lesion placement was assessed by comparing actual lesion locations with expected pallidotomy lesion locations based on stereotaxy. Actual and expected lesions were compared in anteroposterior, dorsoventral and lateral axes. In 22 pallidotomies, actual lesion locations were determined using axial MR images. Expected lesion locations were calculated using a starting point derived from preoperative computerized tomography, displacements from the starting point based on microelectrode-driven electrophysiological refinement, and the trajectory angle of the lesioning tract relative to the anterior-posterior commissural plane. On average, actual lesion locations were found 2.91 +/- 2.23 mm posterior, 3.22 +/- 2.49 mm ventral, and 0.05 +/- 1.80 mm lateral compared to the expected lesion location. Discrepancies between the actual lesion and expected lesion locations may be mostly accounted for by posterior and ventral lesion spread from the exposed electrode tip, in-plane and volume averaging effects associated with MR images, and possible brain shifting during surgery. However, despite the remaining small differences between actual and expected lesion location, good clinical outcome of reduced dyskinesias and 'off' time along with UPDRS-based improvement in mentation, motor and activity of daily living measures was observed.

Aged↗

PubMed1998

Comparative magnetic resonance image-based evaluation of thalamotomy and pallidotomy lesion volumes.

Acute thalamotomy and pallidotomy lesion volumes based on magnetic resonance (MR) images were measured in 22 patients (11 thalamotomy and 11 pallidotomy patients). Thalamotomy inner lesion volumes (0.06 +/- 0.04 ml; thermocoagulative zone) were smaller than pallidotomy inner lesion volumes (0.14 +/- 0.08 ml) as determined using T(1)-weighted 3D-MPRAGE (1.5-mm slice spacing). Similar results were found using T(1)-weighted (6-mm slice spacing) image sets (0.09 +/- 0.05 ml, thalamotomy; 0.13 +/- 0.05 ml, pallidotomy). No differences were found when comparing thalamic or pallidal inner lesion volumes when the comparison was based on T(2) weighted images. Thalamotomy total lesion volumes (thermocoagulative and surrounding edematous zones) were less than pallidotomy total lesion volumes independent of the MR protocol. The difference in thalamotomy and pallidotomy lesion volumes is most likely based on the distance between each discrete lesion placed along the lesioning tracts. In 7 of 11 thalamotomies, this distance was 1 mm with the remaining having 2 mm between each discrete lesion. All pallidotomy discrete lesions were 2 mm apart. More overlap between discrete lesioning sites for thalamotomies is likely to produce reduced lesion volumes.

Adult↗

PubMed1998

Lesion volume and clinical outcome in stereotactic pallidotomy and thalamotomy.

Postoperative lesion volume and clinical outcome were assessed in 19 Parkinson's disease (PD) patients who received posteroventral pallidotomy, and in 14 essential tremor (ET) patients who received ventrolateral thalamotomy. Before and after surgery, PD patients were evaluated using the Unified PD Rating Scale (UPDRS), and ET patients were evaluated using the Fahn-Tolosa-Marin (FTM) tremor rating scale. Inner and total lesion volumes were determined with postoperative MR imaging and three-dimensional data segmentation. Lesion volumes were compared to percent improvement in UPDRS and FTM scores, using Spearman's rank-order correlation test. No rank-order correlations were found between lesion volume and clinical improvement in either the PD or the ET patients. In performing stereotactic surgery for movement disorders, any lesion volume within a prescribed range may be equally effective in relieving symptoms associated with PD or ET.

Aged↗

PubMed1998

Reduction in voice tremor under thalamic stimulation.

We studied the effect of deep brain stimulation (DBS) of the ventral intermediate thalamic nucleus on voice symptoms in seven patients with essential tremor. All had undergone DBS for management of hand tremor. Five of the patients had received unilateral implants; two were treated bilaterally. Each reported improvement in hand tremor with thalamic stimulation (a 1-to-3-point change on a 5-point severity scale). Voice tremor was evaluated with and without stimulation using patient and clinician severity ratings, and acoustic measures (rate and amplitude). Four of the seven patients showed reductions in voice symptoms in at least two of these measures, although degree of change differed (e.g., from 1 to 3 points on the 5-point severity scale). Voice gains typically were restricted to those patients with the more severe symptoms and did not parallel improvements in the upper extremities. It appears that reduced voice tremor may be an additional benefit of DBS for some individuals.

Aged↗

PubMed1998

Advances in the treatment of Parkinson's disease.

Pharmacological treatment of Parkinson's disease has been advanced by a better understanding of how to use currently existing drugs as well as by the introduction of newer drugs. Three new dopaminergic agonists, ropinirole, pramipexole and cabergoline, have been introduced recently for the treatment of Parkinson's disease. A new class of drugs, COMT inhibitors, such as tolcapone, also have been introduced into clinical practice. These drugs extend the effect of levodopa therapy. The results of clinical trials such as the 5-year Sinemet study indicate that low-dose levo-dopa therapy can control motor symptoms up to 5 years with the minimal prevalence of adverse reactions. Pharmacology, efficacy and adverse reactions of these compounds will be discussed as well as their place in the treatment of Parkinson's disease.

Journal Article↗

PubMed1998

Surgical treatment options in Parkinson's disease.

Surgical treatment of Parkinson's disease has become an important mode of therapy for advanced disease. Both ablative lesions and, more recently, deep brain stimulation have been employed. Various brain areas, including the thalamus, globus pallidus, and subthalamus, have been target sites.

Decision Making↗

PubMed1997

Magnetic resonance image evaluation of pallidotomy lesions: a volumetric and shape analysis.

Determination of acute pallidotomy-produced lesion volumes, pre- and postpallidotomy globus pallidus (GP) volumes, and assessment of lesion shape using magnetic resonance (MR) imaging-based computerized segmentation (contouring) and three-dimensional rendering was made in 19 patients. Magnetic resonance image slice thickness (1.5 mm or 6 mm) was not found to be a significant factor influencing contour-based pallidotomy lesion volume estimates. Previously reported lesion volumes produced by pallidotomy have often been estimated using the ellipsoid volume formula. Using 1.5-mm-thick MR sections, contour-based pallidotomy-produced lesion volumes were significantly different from those volumes estimated by the ellipsoid formula. Globus pallidus volumes, estimated by contouring T2-weighted MR images, were bilaterally similar (2.4 +/- 0.37 ml [right]; 2.2 +/- 0.45 ml [left]). Postoperative GP volumes were found on the contralateral, unlesioned side to be 2 +/- 0.45 ml and on the lesioned side to be 1.25 +/- 0.45 ml. Using the contralateral, unlesioned side as a reference volume, approximately 39 +/- 14% of the GP was visibly affected on the lesioned side. Seventeen of 18 patients had a favorable outcome with reduced dyskinesias and "off" time with improvement in parkinsonian symptoms. Analysis of computerized three-dimensional rendering of pallidotomy-produced lesions based on MR images showed no relationship between lesioning technique and resulting lesion shape. Important factors in the volumetric analysis of pallidotomy lesions are identified and allow reasonable assessment of the pallidotomy lesion volume and shape and the extent of the affected GP.

Journal Article↗

PubMed1997

High-frequency unilateral thalamic stimulation in the treatment of essential and parkinsonian tremor.

Pharmacologic treatment for essential tremor and the tremor of Parkinson's disease is often inadequate. Stereotaxic surgery, such as thalamotomy, can effectively reduce tremors. We performed a multicenter trial of unilateral high-frequency stimulation of the ventral intermedius nucleus of the thalamus in 29 patients with essential tremor and 24 patients with Parkinson's disease, using a blinded assessment at 3 months after surgery to compare clinical rating of tremor with stimulation ON with stimulation OFF and baseline and a 1-year follow-up. Six patients were not implanted because of lack of intraoperative tremor suppression (2 patients), hemorrhage (2 patients), withdrawal of consent (1 patient), and persistent microthalamotomy effect (1 patient). A significant reduction in both essential and parkinsonian tremor occurred contralaterally with stimulation. Patients reported a significant reduction in disability. Measures of function were significantly improved in patients with essential tremor. Complications related to surgery in implanted patients were few. Stimulation was commonly associated with transient paresthesias. Other adverse effects were mild and well tolerated. Efficacy was not reduced at 1 year. Chronic high-frequency stimulation is safe and highly effective in ameliorating essential and parkinsonian tremor.

Aged↗

PubMed1997

Effects of thalamic deep brain stimulation based on tremor type and diagnosis.

It has been suggested that deep brain stimulation (DBS) is less effective in alleviating proximal than distal postural arm tremor reduction is said to be less in essential tremor (ET) than in Parkinson's disease (PD). We analyzed blinded rater's tremor scores and subjects' disability ratings at 3-month follow-up to examine the effects of DBS based on tremor type (rest, kinetic, distal postural, proximal postural) and diagnosis (ET, PD). An independent examiner provided tremor scores using randomized videotaped footage of 19 ET and 10 PD subjects at baseline and at follow-up with DBS "on." Subjects provided self-ratings of disability at baseline and at follow-up. Comparisons of baseline and follow-up tremor scores and disability ratings were made using the Mann-Whitney U and Wilcoxon rank sum W test; correlation analyses were performed using Spearman rank order correlation test. There were significant and essentially equal improvements in tremor scores of test, kinetic, distal postural, and proximal postural tremor at follow-up. Only one subject had no improvement in tremor. Tremor improved significantly and to the same extent in ET and PD subjects in each position except "at rest," which was most improved in PD (p = 0.0003). ET and PD subjects did not differ in the extent of disability improvement. Improved disability correlated only with improved postural tremor scores; proximal postural and distal postural (r = 0.41, p = 0.03; r = 0.47, p = 0.01). DBS is effective in alleviating tremor and disability in both ET and PD. Resting, kinetic, distal postural, and proximal postural tremor can be reduced to an equal degree. However, DBS produces the greatest improvement in disability in association with improved postural tremor in both ET and PD.

Adolescent↗

PubMed1997

Comparison of standard carbidopa-levodopa and sustained-release carbidopa-levodopa in Parkinson's disease: pharmacokinetic and quality-of-life measures.

We compared clinical, pharmacokinetic, and quality-of-life measures in patients with Parkinson's disease (PD) who were on standard carbidopa-levodopa (Std-L) and after conversion to sustained-release carbidopa-levodopa 50/200 (L-CR). A total of 20 PD patients with motor fluctuations participated in the study and 18 completed it. There were 10 women and eight men, with a mean age of 67.5 years and a mean disease duration of 9.9 years. All patients underwent 10-h pharmacokinetic and clinical evaluations while on Std-L and again while on L-CR. The patients maintained diaries for 2 days before the 10-h evaluations and completed a sickness impact profile (SIP) while on Std-L and again while on L-CR. The total daily levodopa intake was significantly greater with L-CR because of the reduced bioavailability of the L-CR. The mean daily levodopa dosage was 569 mg for Std-L compared with 751 mg for L-CR. The patients performed better in walking time, Unified Parkinson's Disease Rating Scale (motor score), and tapping total with L-CR, although the improvement was not statistically significant. There was no significant difference in dyskinesias between the two preparations. The plasma levodopa levels and the areas under the curve were significantly greater with L-CR. "On" time as measured by patient diaries was significantly greater for L-CR. There was no significant difference in the total SIP scores for patients on the two preparations, but patients had significantly better home management and mobility while on L-CR. In conclusion, L-CR resulted in more "on" time with greater plasma levodopa levels, which resulted in better home management and mobility.

Activities of Daily Living↗

PubMed1997

Clinical expression of essential tremor: effects of gender and age.

Essential tremor (ET) is considered to be a monosymptomatic disorder consisting primarily of postural hand tremor. Nevertheless, clinical expression can vary based on the body region affected by tremor and the coexistence of other neurologic signs, such as tandem gait disturbance. We conducted a two-part study to test the hypothesis that variability in ET clinical expression is influenced by gender and age. In part 1, we examined a large ET clinical database (n = 450), comparing ratings of postural hand and head/voice tremor based on gender. Head/voice tremor was significantly more frequent and more severe among female ET patients; men had more severe postural hand tremor. In part 2, ET patients (n = 40) had significantly more missteps when tandem walking in comparison to age-matched controls. Poor tandem walk in ET cases was associated with more advanced age, but not gender, disease duration, or ratings of postural hand or head/voice tremor. We conclude that gender influences the body region most affected by ET possibly through the effects of the sex chromosomes or hormones. Ataxia (tandem gait difficulty) is common in ET and may be an accentuation of cerebellar dysfunction due to aging.

Age Distribution↗

PubMed1997

Motor complications of chronic levodopa therapy in Parkinson's disease.

We report on motor complications of chronic levodopa therapy among 811 levodopa-responsive patients with idiopathic Parkinson's disease (PD), stratified by duration after diagnosis. Predictable "offs" were noted in 20.2% of patients in the first 5 years, in 58.3% after 15 years. Unpredictable or sudden offs and early morning dystonia were less common. Longer duration was associated with greater percentages of patients with off periods or dyskinesias (up to 70% after 15 years), although patients with 6-15 years' duration saw relatively little increase in frequency of those complications, and a minority of patients (approximately 30%) with duration into the second decade did not experience off periods or dyskinesia. Across groups, mean Hoehn and Yahr stage and daily levodopa dosage progressively increase (and mean Schwab and England disability ratings decrease), but more conservatively than in prior reports in the postlevodopa era. We note that with advancing PD duration, levodopa complications are more common, but in many cases there appear to be relatively stable periods in terms of levodopa dosage and disease severity, and a minority of patients will be relatively free of motor complications into the second decade of their disease.

Adult↗

PubMed1997

Analysis of pallidotomy lesion positions using three-dimensional reconstruction of pallidal lesions, the basal ganglia, and the optic tract.

OBJECTIVE: To assess the position of radiofrequency pallidotomy lesions placed using microelectrode stimulation and cellular recordings in relation to a stereotactically defined starting point. Radiofrequency lesion locations were also evaluated in relation to the putamen, posterior limb of the internal capsule, and optic tract. METHODS: Magnetic resonance images obtained from 23 patients with Parkinson's disease who underwent pallidotomy at the University of Kansas Medical Center were analyzed. Using computerized techniques, lesion positions in relation to the midcommissural point and a hypothetical starting point were determined. Data segmentation and three-dimensional reconstruction of pallidal lesions, the internal capsule, and the optic tract allowed assessment of lesion position in relation to internal anatomy. Clinical outcome of pallidotomy was assessed using both the Unified Parkinson's Disease Rating Scale and the Dementia Rating Scale. RESULTS: Pallidal lesions were usually placed anterior and dorsal to the stereotactically defined starting point. The position of pallidal lesions in the men were observed, in four trials, to be significantly more dorsal than the lesions in the women. The outer zone of the lesion was usually adjacent to the internal capsule and the putamen and relatively close to the optic tract. The inner zone of the lesion was usually several millimeters removed from anatomic boundaries of the putamen, internal capsule, and optic tract. Patients achieved favorable outcomes, with reduced dyskinesias and "off" time and improvement of their Parkinsonian symptoms, as evidenced by clinical assessment, the Unified Parkinson's Disease Rating Scale, and the Dementia Rating Scale. CONCLUSION: Microelectrode stimulation and cellular recordings usually led to a final pallidotomy lesion position that deviated from the stereotactically defined starting point. The pallidotomy lesions in the men were observed to be more dorsal than the lesions in the women. Clinical outcomes were not correlated with either lesion location relative to the starting point or distances between the pallidal lesion and the putamen, internal capsule, or optic tract. Kinesthetically responsive cells may be localized generally more anterior and dorsal to the starting point (within the globus pallidus) and may be grouped variably from patient to patient in relation to other basal ganglia structures. Although the primary lesion site is most likely within the sensorimotor region of the globus pallidus internus, the more dorsal locations of responsive cell groups may indicate that some lesion sites may be localized within the globus pallidus externus.

Aged↗

PubMed1997

High-frequency stimulation of the globus pallidus for the treatment of Parkinson's disease.

Long-term treatment of Parkinson's disease (PD) with levodopa is complicated by the development of motor fluctuations and dyskinesias. Posteroventral pallidotomy can improve tremor, bradykinesia, rigidity, and dyskinesias in PD. We performed chronic stimulation of the globus pallidus (CSGP) to duplicate the positive results of pallidotomy with reduced risk of permanent neurologic deficit in patients with advanced PD. The lead for CSGP was stereotactically implanted with the aid of microelectrode recordings in the globus pallidus pars interna. An electrical pulse generator was implanted in the subclavicular region. Stimulation settings were adjusted by computer. Five PD patients (four men, one woman) with disabling symptoms were enrolled. Three of the patients had bilateral implants. At 3 months following the last implant, four patients rated themselves as markedly improved, and one patient was moderately improved. The amount of time in the "on" state increased from 21% at baseline to 65% at 3-month follow-up (p < 0.05). There was a significant improvement in all subscales of the UPDRS (p < 0.05). One patient had an asymptomatic intracranial bleed, one patient had transient hemiparesis during surgery with stimulation, and one patient required surgical repositioning of the lead. Adverse effects caused by stimulation were minimal. CSGP is a safe and effective procedure in PD patients with motor fluctuations and dyskinesias.

Aged↗

PubMed1997

Unilateral pallidal stimulation for Parkinson's disease: neurobehavioral functioning before and 3 months after electrode implantation.

Unilateral pallidotomy is thought to have a low risk for cognitive morbidity. Nonetheless, recent research suggests that some patients experience declines in memory and language and that pallidal stimulation might be a safer treatment for Parkinson's disease (PD). We investigated the neurobehavioral effects of unilateral pallidal stimulation. Nine consecutive PD patients undergoing unilateral deep brain-stimulating electrode implantation in the globus pallidus interna were evaluated with a neuropsychological test battery approximately 1 month before and 3 months after surgery. Patients reported significantly fewer symptoms of anxiety and greater vigor after surgery. There was a trend toward fewer depressive symptoms. Semantic verbal fluency and visuoconstructional test scores declined significantly after surgery. However, among five patients showing declines in semantic verbal fluency, only one patient's score declined by more than 2 SD. No patient showed significant decline or improvement in the overall level of cognitive functioning. This study supports the relative safety, in terms of cognitive function, of unilateral pallidal stimulation in PD.

Adult↗

PubMed1996

Pharmacokinetic comparison of Sinemet and Atamet (generic carbidopa/levodopa): a single-dose study.

We compared the pharmacokinetic and motor responses of Sinemet and Atamet (generic carbidopa/levodopa) in patients with Parkinson's disease. Thirty Parkinson's disease patients (10 previously untreated, 10 with early disease, and 10 with motor fluctuations/dyskinesia) participated in a single-dose double-blind study. Following administration of an equivalent oral dose of Sinemet and Atamet on two separate days, we compared the peak plasma concentration, time to peak plasma concentration, area under the curve, total motor score, tapping score, and walking time. The mean time to peak plasma concentrations was 49 min with Sinemet and 47 min with Atamet, the mean peak plasma concentration was 1,273 ng/ml with Sinemet and 1,153 ng/ml with Atamet, and the mean area under the curve was 2,295 micrograms/ml/h with Sinemet and 2,330 micrograms/ml/h with Atamet. Similarly, there was no significant difference between total motor score, tapping score, or walking time. In this single-dose study, there were no significant differences in pharmacokinetic and motor responses between Sinemet and Atamet.

Administration, Oral↗

PubMed1996

Early morning akinesia in Parkinson's disease: effect of standard carbidopa/levodopa and sustained-release carbidopa/levodopa.

We examined the effects of supplemental standard carbidopa/levodopa (Std-L) on early morning akinesia in patients with Parkinson's disease (PD) who were being treated with sustained-release carbidopa/levodopa (L-CR). We compared plasma dopa levels and clinical response in 15 PD patients after a dose of Std-L and L-CR (2 hours later) and after a dose of L-CR and placebo in a double-blind, placebo-controlled, crossover study. Plasma dopa levels, total motor score, walking time, and finger tapping time were assessed every 15 minutes for the first 2 hours and then every 30 minutes for the next 3 hours. The time of onset in clinical benefit was significantly earlier with Std-L (47 minutes, range 15 to 75 minutes) as the first dose as compared with L-CR (58 minutes, range 30 to 105 minutes). Similarly, there was a significant difference in the peak plasma dopa levels (Cmax) and the time to reach peak plasma dopa levels (Tmax) with administration of Std-L (Tmax 36 minutes; Cmax 1,501 micrograms/ml) as compared with L-CR (Tmax 111 minutes, Cmax 1,260 micrograms/ml). There was no significant difference in dyskinesias between the two treatment arms. An initial morning dose of Std-L alleviates the problem of delayed-onset clinical response that commonly occurs with L-CR.

Aged↗

PubMed1996

Multicenter, placebo-controlled trial of cabergoline taken once daily in the treatment of Parkinson's disease.

Cabergoline is a dopaminergic agonist relatively specific for the D2 receptor and much longer-acting than other dopamine agonists. We conducted a randomized, placebo-controlled, double-blind study of cabergoline in 188 levodopa/carbidopa-treated patients with suboptimally controlled Parkinson's disease (PD). The cabergoline patients had significantly better Activities of Daily Living (p = 0.032) and Motor Examination (p = 0.031) scores at the conclusion of the trial compared with the placebo group. The daily levodopa dose for the cabergoline patients decreased 18% compared with a 3% reduction for the placebo group (p < 0.001). The amount of time in the "on" state increased more in the cabergoline group (p = 0.022). The side-effect was similar to that seen with other dopamine agonists, and cabergoline was generally well tolerated. We conclude that cabergoline is an effective adjunct to levodopa for the treatment of PD.

Activities of Daily Living↗