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Biomedical subjects

R Pahwa

Publications and source records attributed to R Pahwa.

At least 37 records · Page 2Linked to original sources
PubMed2001

Long-term safety and efficacy of unilateral deep brain stimulation of the thalamus in essential tremor.

Our objective was to investigate the long-term safety and efficacy of unilateral deep brain stimulation (DBS) of the VIM nucleus of the thalamus in essential tremor. Forty-nine patients were evaluated for DBS between December 1993 and March 1998. Tremor was assessed by a clinical rating scale at 3 and 12 months and then yearly. Three patients were not implanted, seven were explanted prior to 24 months, 11 were lost to long-term follow-up, and three died from unrelated causes. Twenty-five patients were evaluated with follow-up greater than or equal to 2 years. The last postsurgical follow-up occurred on average 40.2 +/- 14.7 months after surgery. Tremor scores were significantly improved with stimulation on at the long-term follow-up as compared to baseline. There was no change in tremor scores from baseline to long-term follow-up with stimulation off. There was no significant change in any stimulus parameters from 3 months to the long-term follow-up. Three patients had asymptomatic intracerebral hemorrhages and one patient had postoperative seizures. Stimulus-related adverse reactions were mild and easily controlled with changes in stimulus parameters. Device-related complications were common and required repeated surgical procedures. Unilateral DBS of the thalamus has long-term efficacy in some patients for treatment of essential tremor. However, this therapy is compromised by loss of efficacy in some patients and device complications which increase the risk of additional surgical procedures.

Adult↗
PubMed2001

Neuropsychological and quality of life changes following unilateral thalamic deep brain stimulation in Parkinson's disease: a one-year follow-up.

BACKGROUND: The long-term neuropsychological and quality of life (QOL) outcomes of unilateral thalamic deep brain stimulation (DBS) in patients with intractable Parkinson's disease (PD) have not heretofore been described. METHOD: Six patients diagnosed with PD underwent unilateral DBS implantation into a verified thalamic VIM nucleus target. Participants completed presurgical neuropsychological evaluation and follow-up assessment at approximately one year postsurgery. FINDINGS: Compared to their presurgical scores, PD patients exhibited significant improvement on measures of conceptualization, verbal memory, emotional adjustment, and QOL at one-year follow-up. A few nominal declines were observed across the battery of tests. INTERPRETATION: These data provide preliminary support for the long-term neurocognitive safety and QOL improvements following thalamic stimulation in patients with PD.

Aged↗
PubMed2001

Long term safety and efficacy of unilateral deep brain stimulation of the thalamus for parkinsonian tremor.

The objective was to investigate the long term safety and efficacy of unilateral deep brain stimulation (DBS) of the VIM nucleus of the thalamus in Parkinson's disease. Twelve patients with Parkinson's disease underwent unilateral DBS of the thalamus for medication resistant tremor between 1994 and 1997. Patients were evaluated with the motor section of the unified Parkinson's disease rating scale (UPDRS) in the medication on state at baseline, 3 months, 12 months, and yearly thereafter.Three patients were lost to follow up. Nine patients had follow up evaluations greater than 24 months and were included in the analyses. The last postsurgical follow up occurred on average 40.0 (SD 17.2) months after surgery. Tremor scores were significantly improved with stimulation on at the long term follow up compared with baseline. There was no significant change in UPDRS motor scores at long term follow up compared with baseline. There was no significant change in any stimulus parameters from 3 months to the long term follow up. Two patients had asymptomatic intracerebral haemorrhages and one patient had a subcutaneous haematoma over the implantable pulse generator site. Stimulus related adverse reactions were mild and easily controlled with changes in stimulus parameters. Two patients had replacement of the implantable pulse generator due to normal battery depletion, one patient had lead repositioning due to migration, and one patient had the lead extension wire replaced due to erosion. In conclusion, unilateral DBS of the thalamus has long term efficacy for treatment of tremor due to Parkinson's disease.

Aged↗
PubMed2001

Magnitude of microelectrode refinement in pallidotomy and thalamotomy.

The relative accuracy of starting point algorithms in microelectrode-guided stereotactic pallidotomy and thalamotomy was evaluated using postoperative magnetic resonance imaging (MRI) data. Multiplanar reformations were performed to align postoperative MRI in anterior-posterior, dorsal-ventral and mediolateral planes. Three-dimensional distance and direction from the pallidal and thalamic stereotactic starting points to the respective radiofrequency lesions were measured. Similar magnitude of microelectrode refinement in pallidotomy and thalamotomy suggested similar accuracy of algorithms used to set the stereotactic starting point. Fewer microelectrode-recording tracts were required to identify optimal lesioning sites in thalamotomy compared to pallidotomy. Lesions were consistently localized anterior and superior to the starting point and a refined starting point algorithm may reduce the number of microelectrode recording tracts.

Adult↗
PubMed2000

Health-related quality of life in Parkinson's disease after pallidotomy and deep brain stimulation.

This study explored the multidimensional outcome of three neurosurgical interventions for Parkinson's disease (PD): pallidotomy (N = 23), pallidal deep brain stimulation (DBS) (N = 9), and thalamic DBS (N = 7). All patients completed the Sickness Impact Profile (SIP) and the Beck Depression Inventory. Pallidotomy patients also completed the Profile of Mood States, the Beck Anxiety Inventory, and a disease-specific quality of life (QOL) measure, the Parkinson's Disease Questionnaire (PDQ-39). Three months after surgery, all neurosurgical groups showed significant improvements in mood and function, including physical, psychosocial, and overall functioning. Pallidal DBS and pallidotomy patients who completed additional QOL measures reported decreased anxiety and tension, increased vigor, improved mobility and ability to perform activities of daily living, and decreased perceived stigma. Psychosocial dysfunction scores from the SIP were related to depressed mood both at baseline (r = .42) and at followup (r = .45), but the physical dysfunction subscale was not related to mood at either time point, suggesting that disruption of social relationships due to PD may have more impact on affective distress than physical symptoms alone. Results suggest that neurosurgical interventions for PD improve disabling PD motor symptoms and also improve several domains of quality of life.

Activities of Daily Living↗
PubMed2000

Surgical treatment of essential tremor.

Surgical treatment for essential tremor (ET) has been used since the early 1950s. Initially, different areas were targeted for tremor control. However, the optimal target was eventually determined to be the ventralis intermedius (VIM) nucleus of the thalamus. Thalamotomy improves contralateral tremor in more than 90% of patients. Long-term studies of thalamotomy indicate that the benefits continue in most patients. Persistent morbidity associated with thalamotomy, which occurs in less than 10% of patients, includes dysarthria, dysequilibrium, weakness, and cognitive impairment. Bilateral thalamotomy is associated with substantial morbidity and is usually avoided. Studies demonstrate that chronic stimulation of the VIM is safe and effective for tremor. Adverse effects of chronic stimulation include paresthesia, dysarthria, dysequilibrium, and localized pain. In many patients, bilateral thalamic stimulation is performed without a substantial increase in morbidity. ET patients with disabling medication-resistant tremor are reasonable candidates for these stereotactic procedures.

Essential Tremor↗
PubMed1999

Neuropsychological and quality of life outcome after thalamic stimulation for essential tremor.

OBJECTIVE: To evaluate short-term effects of unilateral thalamic deep brain stimulation (DBS) on cognition, mood state, and quality of life in patients with essential tremor (ET). BACKGROUND: Unilateral thalamotomy and thalamic DBS are effective in alleviating refractory tremor contralateral to the side of surgery. Thalamotomy can lead to cognitive morbidity, and DBS might be a preferable surgical intervention given potential avoidance or reversibility of such morbidity. Although unilateral thalamic DBS is cognitively safe and leads to quality of life improvement in PD, its neurobehavioral effects in ET are unknown. METHODS: Forty patients with ET were administered a broad neuropsychological test battery, measures of mood state, and generic and disease-specific quality of life measures approximately 1 month before and 3 months after surgery (left hemisphere, 38 patients). RESULTS: Unilateral thalamic DBS was associated with significant improvements in tremor and dominant-hand fine visuomotor coordination. Statistically significant but clinically modest gains were observed on tasks of visuoperceptual and constructional ability, visual attention, delayed word list recognition, and prose recall. Only lexical verbal fluency declined significantly after surgery. Patients rated themselves as less anxious after surgery, and they perceived their quality of life as improved significantly. In particular, patients reported improved quality of life with respect to activities of daily living, stigma, emotional well-being, and communication. CONCLUSIONS: Unilateral thalamic DBS for ET is cognitively safe and associated with improvements in anxiety and quality of life in the near term and in the absence of operative complications. Patients were better able to carry out activities of daily living after surgery, and they reported improvement in several psychosocial domains of quality of life.

Aged↗
PubMed1999

Bilateral thalamic stimulation for the treatment of essential tremor.

OBJECTIVE: To determine the safety and efficacy of bilateral thalamic stimulation in the treatment of essential tremor (ET). METHODS: Nine ET patients with disabling tremor refractory to pharmacotherapy underwent bilateral staged implants. Tremor was assessed by the Fahn-Tolosa-Marin Tremor Rating Scale at baseline 1 (before first implant), baseline 2 (before second implant), and at 6-month and 1-year follow-up. Blinded evaluations were performed at 3 months. Associated changes in speech were evaluated in six patients. There were seven men and two women with a mean age of 73.8 years. RESULTS: There was a significant improvement in the mean total tremor score from a baseline of 66.1+/-11.6 to 28.4+/-12.8 12 months after the second surgery. Similarly, the mean motor tremor subscore was 20.1+/-5.0 before the first surgery and improved significantly to 14.1+/-3.6 before the second surgery. Motor tremor scores 6 months after the second surgery (6.0+/-3.7) and 12 months after the second surgery (7.5+/-3.9) also improved significantly relative to the preoperative scores. The mean activities of daily living (ADL) subscore at baseline was 18.2+/-2.9 and improved significantly before the second surgery to 9.0+/-3.2. These ADL scores further improved 6 months (6.2+/-5.2) and 12 months (7.9+/-5.7) following the second surgery, but these gains were not significant. Blinded evaluations also revealed a similar degree of improvement. Complications were noted in five patients: asymptomatic intracranial hematoma (1), postoperative seizures (1), a hematoma over the implanted pulse generator (IPG) (1), lead repositioning (1), and IPG malfunction (1). Adverse effects related to stimulation were mild and resolved with adjustment of the stimulation parameters. Three of the six patients demonstrated worsening of dysarthria with both stimulators on. CONCLUSIONS: Bilateral thalamic stimulation is effective in reducing tremor and functional disability in ET; however, dysarthria is a possible complication.

Activities of Daily Living↗
PubMed1999

Surgical treatment of Parkinson's disease.

Stereotaxtic surgery is an effective therapeutic maneuver in the management of advanced Parkinson's disease (PD). Thalamotomy is an effective measure to control tremor but other PD symptoms are not changed. Bilateral operations are associated with a risk of severe speech impairment. Deep brain stimulation (DBS) of the thalamus is as effective as thalamotomy and is associated with fewer side effects. Pallidotomy is effective in reducing contralateral dyskinesias and the cardinal symptoms of PD. Bilateral pallidotomy often results in cognitive dysfunction. Deep brain stimulation of the pallidum replicates the positive effects of pallidotomy and appears to be safer than ablative lesions. Subthalamic DBS is currently under investigation. This procedure may control all PD symptoms, and the dose of levodopa can often be dramatically reduced. Neurotransplantation is a promising surgical approach to PD. However, further investigation is needed to optimize this approach.

Brain Tissue Transplantation↗
PubMed1999

Efficacy of unilateral deep brain stimulation of the VIM nucleus of the thalamus for essential head tremor.

Essential tremor is a common movement disorder. Deep brain stimulation of the VIM nucleus of the thalamus has been reported to be efficacious for reducing essential hand tremor. The effect of deep brain stimulation of the thalamus on essential head tremor has not been well studied. Therefore, we evaluated the effect of DBS of the thalamus in 38 patients with essential head tremor. Head tremor scores prior to surgery were compared with scores at 3, 6, and 12 months postimplant with stimulation "on" and "off." The 3-month evaluations were blinded for 24 patients and all others were open-label. There was a significant improvement in head tremor at all postimplant evaluations compared with baseline. Essential head tremor can be reduced with deep brain stimulation of the VIM nucleus of the thalamus and, pending the results of other controlled trials, should be considered as a treatment option for patients with disabling essential head tremor unresponsive to medication.

Aged↗
PubMed1999

Progressive supranuclear palsy.

Richardson observed an unusual clinical syndrome in the 1950s, which he later designated progressive supranuclear palsy (PSP). Over the past 25 years, although knowledge of this disorder has gradually improved, its cause is still unknown, pathogenesis is unclear, and there is still no definitive treatment for this disorder. This article reviews the epidemiology, clinical features, diagnostic criteria, neuropathology, neuroimaging, and treatment of PSP.

Brain↗
PubMed1999

Cognitive outcome following staged bilateral pallidal stimulation for the treatment of Parkinson's disease.

As neurosurgical treatment of parkinsonian symptoms has become increasingly popular, concern about the cognitive morbidity which may result from such interventions has risen proportionately. Previous reports of cognitive difficulties associated with pallidotomy and thalamotomy, especially in bilateral cases, have provided the impetus for research into chronic electrical deep brain stimulation procedures which are believed to be safer than ablation. Given the lack of neurobehavioral research following bilateral deep brain stimulation procedures, this preliminary study of six Parkinson's disease patients undergoing staged bilateral pallidal stimulation was undertaken. A battery of tests assessing attention, executive function, visuomotor coordination, language, visuoperceptual function, learning memory and mood revealed no significant change in overall level of cognitive functioning after either unilateral or bilateral pallidal deep brain stimulation. No significant declines were observed about three months following bilateral stimulation, and in fact, significant gains in delayed recall and relief of anxiety symptoms were noted. It was concluded from this preliminary data that bilateral pallidal stimulation for the treatment of Parkinson's disease, at least in the absence of operative complications, offers a cognitively safe alternative to ablation.

Cognition↗
PubMed1998

Clozapine use in Parkinson's disease: a retrospective analysis of a large multicentered clinical experience.

We conducted a multicentered, retrospective review of clozapine's (CZP) effects on a range of psychiatric, sleep, cognitive, motor, and sensory disorders in Parkinson's disease (PD). Therapeutic outcomes and adverse events were compared with varying prescribing practices at participating sites. The medical records of 172 consecutive PD patients treated with CZP at four movement disorder clinics were reviewed. Low-dose CZP improved psychiatric symptoms of psychosis, anxiety, depression, hypersexuality, sleep disturbance, and akathisia. Tremor, torticollis, limb dystonia, and pain showed modest rates of improvement. Twenty-three percent of patients withdrew as a result of adverse events or treatment failure. Inpatient CZP initiation did not improve therapeutic efficacy, or reduce adverse events or the withdrawal rate. Low-dose CZP in the outpatient setting is generally an effective and well-tolerated treatment for many of the psychiatric, sleep, motor, and sensory disturbances common to late-stage PD.

Aged↗
PubMed1998

Double-blind controlled trial of gabapentin in essential tremor.

Gabapentin has been reported to be effective for essential tremor (ET) based on open-label trials. We studied gabapentin (1800 mg/day) and placebo in a double-blind crossover design in 20 ET patients. Eighteen patients completed the study and two patients dropped out as a result of adverse effects which resolved when the medication was discontinued. Tremor was assessed at baseline and after 2 weeks of gabapentin and placebo treatment. One patient was mildly improved and another was moderately improved with placebo. Similarly, one patient reported mild improvement and another patient had marked improvement with gabapentin. All the remaining patients either reported no change or were worse with both treatment arms. There was no significant difference for total tremor score, hand tremor score, handwriting scores, or pouring scores. Sickness Impact Profile scores were no different between placebo and gabapentin. Our results suggest that as an adjuvant therapy in ET, gabapentin has limited benefit.

Acetates↗
PubMed1998

Improvements in daily functioning after deep brain stimulation of the thalamus for intractable tremor.

Deep brain stimulation (DBS) of the thalamus reduces tremor in patients with essential tremor (ET). However, few studies have determined the degree of improvement in daily functioning associated with DBS. We developed a self-report Tremor Activities of Daily Living Scale (TADLS) to compare daily functioning with the stimulator turned on and off. Patients rated their performance on the 30 items of the TADLS with the stimulator turned off and then on. They also performed 10 activities under the supervision of a clinician who rated their functional ability with stimulation off and then on. There was a 58% improvement in self-rated TADLS scores in patients with DBS with the stimulator on compared with stimulation off. When activities were rated by the clinician, the average improvement in functioning with the stimulator on was 54%. There were reasonably high correlations between patient and clinician ratings of functioning. ET patients have a marked improvement in daily functioning with thalamic DBS.

Activities of Daily Living↗
PubMed1998

Characterization of natural suppressor cells in human bone marrow.

Natural suppressor (NS) cells, which exert nonspecific suppressive activity in an unprimed manner, have been found in mouse, rabbit and monkey bone marrow (BM). In the present study, we characterize NS cells in human BM. NS activity was found in a fraction of low density (1.055-1.065 g/ml) BM cells that had been depleted of T cells, B cells, and monocytes. The NS activity was significantly decreased by the depletion of CD34+ or CD33+ cells but not CD56+ cells. The NS activity was indeed detected in isolated CD34+ cells and further enriched in CD34+CD33+ cells. Hematopoietic progenitor cells committed to the myeloid lineage were also enriched in the CD34+CD33+ cells, which significantly correlated to the NS activity. From these findings, it is strongly suggested that NS activity in human BM is exerted by the myeloid hematopoietic progenitors. Since cell-to-cell contact was not necessary for the action, NS cells seemed to secrete soluble mediator(s). Transforming growth factor-beta 1 and leukemia inhibitory factor were, however, not the candidates, based on experiments using neutralizing antibodies.

Antigens, CD↗