Search PubMed⌕ Search

Biomedical subjects

A Kishore

Publications and source records attributed to A Kishore.

34 records · Page 2Linked to original sources
PubMed2000

Evidence for impaired presynaptic dopamine function in parkinsonian patients with motor fluctuations.

We used [18F]6-fluorodopa (FD) positron emission tomography (PET) to examine the severity of nigrostriatal dopaminergic dysfunction in 67 patients with Idiopathic Parkinsonism (IP), 52 with fluctuations and 15 with a stable response to levodopa. FD uptake (Ki) was reduced by 12% in the caudate (p = 0.08) and by 28% in the putamen (p = 0.0004) of patients with fluctuations compared to those with a stable response. However, there was considerable overlap of FD Ki values between the two groups. The fluctuators had a longer symptom duration (11.6 +/- 5.7 years) than the patients with a stable response to levodopa (4.3 +/- 2.4 years; p < 0.0001) and the age of onset of symptoms was earlier in the fluctuators (43.9 +/- 8.9 versus 54.1 +/- 10.4; p = 0.0004). Similar reductions in FD Ki in the fluctuators persisted following adjustment for these variables (7.5% in the caudate and 26% in the putamen; p = n.s. and 0.007, respectively). When smaller groups (n = 15 each) were matched for duration of symptoms, the reduction in caudate Ki in the fluctuators was only 1.9% (p = n.s.), but there was still a 24% reduction in putamen Ki (p = 0.05). These findings suggest that fluctuators and non-fluctuators may differ in the severity of their nigrostriatal damage and provide modest support for the hypothesis that fluctuations may in part reflect altered "buffering" capacity of dopaminergic nerve terminals. However, the considerable overlap between groups suggests that other factors such as altered postsynaptic mechanisms and/or increased turnover of dopamine may make a substantial contribution to the development of motor fluctuations.

Antiparkinson Agents↗
PubMed2000

Nigrostriatal dopamine system and motor lateralization.

The mechanism by which most people favor use of the right hand remains unknown. It has been proposed that asymmetries in the nigrostriatal dopamine system may be related to motor lateralization in humans. We explored this hypothesis in vivo by using [18F]fluorodopa positron emission tomography. Whereas the degree of right hand preference was found to correlate with left putamen dominance as assessed by asymmetry in fluorodopa uptake (K(i)), right caudate dominance was positively correlated with the level of performance during simultaneous bimanual movements in right-handed normal subjects. In addition, right-handed patients with Parkinson's disease with higher right than left caudate K(i) performed much better in bimanual movement tests than those in whom the K(i) value of the left caudate was higher than that of the right. These findings support the notion that the nigrostriatal dopaminergic system may play a role in motor lateralization, and suggest a functional model for bimanual movements. We propose that the skill for performing simultaneous bilateral hand movements in right-handed subjects might depend upon both the activation (through the dominant left putamen circuitry) of the left supplementary motor area (SMA), and the inhibition (through the right caudate circuitry) of motor programs stored in the right SMA.

Adult↗
PubMed2000

A clinical study of vestibular schwannomas in type 2 neurofibromatosis.

All 13 patients with neurofibromatosis 2 (NF2) who presented over a period of 17 years at the Institute of Neurological Sciences, Glasgow were reviewed and compared to patients with sporadic vestibular schwannomas. The NF2 patients presented at a younger age than those with sporadic vestibular schwannomas. A significant number had normal pure tone audiograms and a small number also had normal auditory brainstem responses at presentation. Vestibular schwannomas in NF2 patients grow more often and more rapidly than sporadic unilateral ones. They are more liable to infiltrate the cochlear and facial nerves making hearing and facial nerve preservation more difficult to achieve. Because the relatives of these patients often have normal audiograms and normal auditory brain stem responses in the presence of a schwannoma, our recommended method of screening of relatives of NF2 patients is magnetic resonance image scanning with Gd-DTPA enhancement.

Adolescent↗
PubMed2000

Evidence of functional somatotopy in GPi from results of pallidotomy.

The objective of this study was to explore the functional anatomy of the globus pallidus internus (GPi) by studying the effects of unilateral pallidotomy on parkinsonian 'off' signs and levodopa-induced dyskinesias (LID). We found significant positive correlations between the preoperative levodopa responsiveness of motor signs and the levodopa responsiveness of scores in timed tests (Core Assessment Program for Intracerebral Transplantations) in the contralateral limbs and the improvement in these scores after surgery, whereas there was no correlation with the improvement in LID. We also found a highly significant correlation (P: < 0.0001, r = 0.8) between the volume of the ventral lesion in the GPi and the improvement in LID in the contralateral limbs, whereas there was no correlation between the ventral volume and the improvement in parkinsonian 'off' signs. The volumes of the total lesion cylinder and the dorsal lesion did not correlate with the outcome of either dyskinesias or parkinsonian 'off' signs. The differential predictive value of levodopa responsiveness for the outcome of parkinsonian 'off' signs and LID and the different correlations of ventral lesion volume with dyskinesias and parkinsonian 'off' signs indicate that different anatomical or pathophysiological substrates may be responsible for the generation of parkinsonian 'off' signs and dyskinesias. Whereas cells in a wider area of the GPi may be implicated in parkinsonism, the ventral GPi seems to be crucial for the manifestation of LID. We suggest that our observations are additional proof of the functional somatotopy of the systems within the GPi that mediate parkinsonism and dyskinesias, especially along the dorsoventral trajectory used in pallidotomy. The outcome of pallidotomy in which the lesion involves the ventral and dorsal GPi could be the net effect of alteration in the activity of pathways which mediate different symptoms, and hence could be variable.

Dyskinesia, Drug-Induced↗
PubMed2000

Long term outcome of unilateral pallidotomy: follow up of 15 patients for 3 years.

OBJECTIVES: With the advent of new antiparkinsonian drug therapy and promising results from subthalamic and pallidal stimulation, this study evaluated the long term efficacy of unilateral pallidotomy, a technique which has gained popularity over the past decade for the management of advanced Parkinson's disease. METHODS: The 15 patients reported here are part of the original cohort of 24 patients who underwent posteroventral pallidotomy for motor fluctuations and disabling dyskinesias 3 years ago as part of a prospective study. Evaluation scales included the unified Parkinson's disease rating scale, the Goetz dyskinesia scale, and the Purdue pegboard test. RESULTS: When compared with the prepallidotomy scores, the reduction in the limb dyskinesias and off state tremor scores persisted on the side contralateral to pallidotomy at the end of 3 years (dyskinesias were reduced by 64% (p<0.01) and tremor by 63% (p<0.05). Other measures tended to deteriorate. The dosage of antiparkinsonian medications did not change significantly from 3 months prepallidotomy to 3 years postpallidotomy. CONCLUSIONS: Although unilateral pallidotomy is useful in controlling the contralateral dyskinesias and tremor 3 years after surgery, all other early benefits disappear and activities of daily living continue to worsen.

Activities of Daily Living↗
PubMed2000

Primary extracranial meningioma of the soft palate.

Extracranial meningiomas comprise two per cent of all meningiomas. Primary extracranial meningiomas are even less common. The authors report the first case of a primary extracranial meningiomas of the soft palate, which presented as an intraoral mass. This was treated by surgical excision and there was no evidence of tumour recurrence at four years of follow-up.

Adult↗
PubMed1999

Reassessment of unilateral pallidotomy in Parkinson's disease. A 2-year follow-up study.

Unilateral pallidotomy has gained popularity in treating the motor symptoms of Parkinson's disease. We present the results of a 2-year post-pallidotomy follow-up study. Using the Unified Parkinson's Disease Rating Scale (UPDRS), the Goetz dyskinesia scale and the Purdue Pegboard Test (PPBT), we evaluated 20 patients at regular intervals both off and on medications for 2 years post-pallidotomy. There were no significant changes in the dosages of antiparkinsonian medications from 3 months pre-pallidotomy to 2 years post-pallidotomy. On the side contralateral to the operation, the improvements were preserved in 'on'-state dyskinesia (83% reduction from pre-pallidotomy to 2 years post-pallidotomy, P < 0.001) and 'off'-state tremor (90% reduction from pre-pallidotomy to 2 years post-pallidotomy, P = 0.005). There were no statistically significant differences between pre-pallidotomy scores and those at 2 years post-pallidotomy in ipsilateral dyskinesia, axial dyskinesia, 'off'- or 'on'-state PPBT, 'off'-state Activities of Daily Living (ADL) and 'off'-state gait and postural stability. After 2 years, the 'on'-state ADL scores worsened by 75%, compared with pre-pallidotomy (P = 0.005). We conclude that 2 years after pallidotomy, the improvements in dyskinesia and tremor on the side contralateral to pallidotomy are preserved, while the initial improvements in most other deficits disappear, either because of progression of pathology or loss of the early efficacy achieved by surgery.

Aged↗
PubMed1999

Acute dysautonomia following mumps.

Pure acute or subacute dysautonomia is a rare entity. Its etiology is as yet unknown. However, majority of these cases have a preceding viral infection such as herpes simplex, infectious mononucleosis, rubella or coxsackie B. A unique patient in whom acute dysautonomia followed mumps is reported.

Acute Disease↗
PubMed1998

Long-term follow-up of levodopa responsiveness in generalized dystonia.

OBJECTIVES: To assign an accurate diagnosis to patients with dystonia based on the presence of sustained levodopa responsiveness and to determine whether motor fluctuations occur in patients with dystonia who are withheld from levodopa. PATIENTS AND METHODS: Patients with generalized dystonia who responded to treatment in the 1970s with levodopa/carbidopa were surveyed by phone and then examined during a 3-day levodopa holiday. Functional imaging with fluorodopa positron emission tomography was performed on a subset of patients. RESULTS: In the phone interview, 4 of 7 patients with a diagnosis of dopa-responsive dystonia reported the wearing-off effect a short while (within 4-8 hours) after missing a dose of levodopa. Five patients with dopa-responsive dystonia were examined repetitively during levodopa withdrawal, and 3 developed recurrent symptoms of dystonia as the drug was withheld. In each case, worsening of dystonia did not occur until 29 hours or more after levodopa withdrawal, providing evidence for a response profile similar to the long duration response described in Parkinson disease. No significant changes were seen in the dystonia scores of the 3 patients with idiopathic torsion dystonia who were withheld from levodopa. CONCLUSIONS: We suggest that the subjective feeling of wearing off experienced by our patients with dopa-responsive dystonia may have been for one of the nonmotor effects of levodopa, such as mood elevation. Our data provide objective evidence for the often-repeated assertion that motor fluctuations (analogous to those in levodopa-treated patients with Parkinson disease) do not occur in patients with dopa-responsive dystonia.

Antiparkinson Agents↗
PubMed1998

Striatal D2 receptors in symptomatic and asymptomatic carriers of dopa-responsive dystonia measured with [11C]-raclopride and positron-emission tomography.

We tested the hypothesis that asymptomatic carriers of dopa-responsive dystonia (DRD) have increased dopamine D2 receptors in the striatum that protect them from the clinical manifestations of dopaminergic deficiency. We examined striatal D2-receptor binding in (1) symptomatic subjects (treated and untreated) and (2) asymptomatic gene carriers. Using [11C]-raclopride PET, we found elevated striatal D2-receptor binding in both groups. In one of our drug-naive symptomatic subjects, 7 months of treatment with levodopa/carbidopa did not affect the receptor binding as measured on a second scan. We conclude that increased D2-receptor binding in DRD may be a homeostatic response to the dopaminergic deficit in subjects carrying the DRD gene, but is not the sole factor determining the clinical state of these individuals.

Adult↗
PubMed1997

Contributions of positron emission tomography to elucidating the pathogenesis of idiopathic parkinsonism and dopa responsive dystonia.

The metabolic mapping of brain activity, using PET, confirms the conventional wisdom of neurophysiology. In studies of pathophysiology, PET has yielded evidence that has generated new hypotheses. Progression of the lesion detectable with fluorodopa, in human subjects exposed to MPTP, raises the possibility of a transient environmental event being a cause of progressive neurodegeneration. Studies with fluorodopa in Idiopathic Parkinsonism indicate that the rate of loss of neurons is faster initially, and then tends to approach the normal age-related decline. In dopa responsive dystonia, the finding of normal fluorodopa PET led to the prediction that the lesion would be functional rather than anatomical; this has been confirmed by the identification of a defect in dopamine synthesis in this disorder. Filally, new PET ligands show promise for future studies designed to unravel the pathogenesis of diseases involving the basal ganglia.

Brain↗
PubMed1997

Efficacy, stability and predictors of outcome of pallidotomy for Parkinson's disease. Six-month follow-up with additional 1-year observations.

We tested the efficacy, stability and predictors of outcome of unilateral pallidotomy used to treat patients with Parkinson's disease inadequately controlled with pharmacotherapy (IP). The surgical procedure was as simple as possible; we used CT rather than MRI, and we omitted microelectrode recording. We studied 24 patients with IP; 22 of these patients had drug-induced dyskinesias. There was a significant and stable improvement in all the major parkinsonian motor signs in the OFF (medication) state on the contralateral side. In the ON (medication) state peak-dose dyskinesias were alleviated on the contralateral side. The only significant and stable change on the ipsilateral side was improvement in dyskinesias less marked than on the contralateral side. The improvement in Unified Parkinson's Disease Rating Scale motor scores in the OFF state increased with age. The improvement in total dyskinesia scores occurred irrespective of age, but increased with duration of disease, duration of dyskinesias and baseline severity of dyskinesias. Five patients had transient neurological complications while facial paresis was permanent in one subject. Our results are similar to those obtained by others who used the time consuming microelectrode recording technique for localization. By simplifying the procedure in the way that we describe, the operation could become available to a greater number of patients.

Adult↗
PubMed1996

Presynaptic nigrostriatal function in genetically tested asymptomatic relatives from the pallido-ponto-nigral degeneration family.

Pallido-ponto-nigral degeneration (PPND) is a dominantly inherited disorder with parkinsonism. We performed PET with [18F]fluorodopa (FD) and, later, gene testing in 12 asymptomatic relatives at risk from a family with PPND and compared the striatal FD uptake constant (Ki) in them with 4 symptomatic individuals and 10 normal control subjects. Four relatives with positive linkage had a significantly reduced Ki from the normal control subjects but to a lesser degree than the symptomatic patients. The mean Ki in the relatives with negative linkage (n = 8) did not differ from normal control subjects. In conclusion, we identified reduced dopaminergic function in asymptomatic relatives with positive genetic linkage from the PPND family. Most of the reduction in this disorder occurs in the fifth decade, when the disease manifests clinically.

Adult↗
PubMed1996

Drug management of Parkinson's disease.

Levodopa remains the cornerstone for managing Parkinson's disease. Physician's preference usually determines the dopamine agonist chosen for the early phases of treatment. The concept of neuro-protection, however, remains unproven. A better understanding of the cause of the disease and treatment-related complications could make managing Parkinson's disease more rewarding.

Amantadine↗