Welding-related parkinsonism: clinical features, treatment, and pathophysiology.
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Humans↗
Biomedical subjects
G Pezzoli
Publications and source records attributed to G Pezzoli.
Perfusion ECD/SPECT in the characterization of cognitive deficits in Parkinson's disease.
Cognitive abnormalities have been reported in a large percentage of patients with Parkinson's disease (PD). Often cognitive changes are sub-clinical and involve frontal lobe function. In other occasions they develop into full dementia. Functional neuroimaging may help characterize these abnormalities. We have studied brain perfusion with SPECT and the tracer ECD in 44 PD patients, 22 presenting with normal cognitive function and 22 with clinical and neuropsychological signs of dementia. Compared with 21 healthy controls, demented PD patients showed significant perfusion decrements in all cortical areas, particularly temporal and parietal regions; in the non-demented cohort reductions were limited to the frontal lobe area. These results suggest that brain perfusion abnormalities are present in PD patients. It is speculated that different pathological mechanisms underlie perfusion differences.
Aged↗
The status of dopamine nerve terminals in Parkinson's disease and essential tremor: a PET study with the tracer [11-C]FE-CIT.
Neuroimaging studies of the striatal dopamine transporter (DAT) are useful in the assessment of the dopaminergic system in Parkinson's disease (PD). We used positron emisson tomography (PET) and the tracer [11C]FE-CIT to measure DAT binding in the caudate nucleus and putamen of 31 patients with PD, 5 with essential tremor and 8 healthy control subjects. Of the patients with PD, 17 were drug naive, while the others were either on levodopa or dopamine agonist monotherapy. DAT binding was significantly reduced in the caudate nucleus and to a greater extent in the putamen of PD patients compared to both healthy controls and essential tremor individuals. No overlap was observed between putamen values in PD and normals. No differences were found between controls and essential tremor subjects. These data confirm that measurements of DAT binding can provide an accurate and highly sensitive measure of degeneration in the dopamine system in PD.
Carbon Radioisotopes↗
Physiologic study of the subthalamic volume.
Deep brain stimulation (DBS) obtains good control of advanced PD symptoms. Chronic stimulation of Stn may alleviate rigidity, dyskinesia and tremor. Anatomical and functional intraoperative mapping are mandatory to obtain careful target localisation. Per-operative macrostimulation was carried out in 22 patients undergoing bilateral DBS in Stn; a volume 6 mm above to 4 mm below Stn was explored. Positive, collateral and adverse effects were recorded every 2 mm. Results obtained during acute stimulation were correlated to anatomical data from stereotactic atlases. Our findings suggest a volume, encompassing the zona incerta, Forel's fields and the lowermost part of anterior thalamus, functionally homogeneous to Stn. In fact, the stimulation of this volume obtains reduction of PD symptoms comparable to Stn.
Aged↗
Hydrocarbon exposure and Parkinson's disease.
BACKGROUND: Single cases of parkinsonism have been associated with hydrocarbon solvents. OBJECTIVE: To determine whether exposure to hydrocarbon solvents is related to PD. METHODS: Cohort study of 990 patients with PD according to Core Assessment Program for Intracerebral Transplantations (CAPIT) criteria, selected from 1455 consecutive subjects presenting at a referral center; case-control study assessing Unified PD Rating Scale scores (motor score as primary endpoint) in all subjects with positive history of hydrocarbon solvent exposure (n = 188), matched for duration of disease and gender to 188 subjects selected from the remaining 802 with a negative history. Two subgroups in the case-control study included the following: 1) response to apomorphine (n = 26); 2) brain MRI (n = 15). PET imaging (n = 9) was compared with that of historic controls. RESULTS: Exposed patients were younger (61.0 +/- 9.4 versus 64.7 +/- 9.4 years, p = 0.002), predominantly male (76.4% versus 45.2%, p = 0.0001), less educated (8.4 +/- 4.2 versus 10.1 +/- 4.4 years, p = 0.0001), and younger at onset of disease (55.2 +/- 9.8 versus 58.6 +/- 10 years, p = 0.014). Exposure to hydrocarbon solvents directly correlated to disease severity (r = 0. 311) and inversely correlated to latency period (r = -0.252). Nine blue-collar occupations accounted for 91.1% of exposures. CONCLUSIONS: Occupations involving the use of hydrocarbon solvents are a risk factor for earlier onset of symptoms of PD and more severe disease throughout its course. Hydrocarbon solvents may be involved in the etiopathogenesis of PD, which does not have a major genetic component.
Adult↗
Tolerability of paroxetine in Parkinson's disease: a prospective study.
Depression is a common finding in patients with Parkinson's disease (PD). Traditionally, depression has been treated with tricyclic antidepressants, which are often associated with undesirable side effects that may limit their use in PD. Few studies have been performed with selective serotonin reuptake inhibitors (SSRIs) in these patients. We assessed the tolerability of the SSRI antidepressant paroxetine (10-20 mg once per day) in 65 outpatients with PD and depression for a period of at least 3 months. Treatment was continued for 125.3+/-89.6 days (mean +/- standard deviation) in 52 patients. In these subjects the Hamilton Disease Rating Scale improved from 21.7+/-6.4 to 13.8+/-5.8 (p <0.001). Overall, 13 patients stopped paroxetine after 9.6+/-10.6 days because of adverse reactions. Two patients reported increased "off" time and tremor that reversed after treatment was stopped. No risk factors for intolerance were identified. Paroxetine is a safe and effective drug to treat depression in PD.
Aged↗
An overnight switch to ropinirole therapy in patients with Parkinson's disease. Short communication.
Patients with Parkinson's disease (n = 68) switched from pergolide or bromocriptine to ropinirole overnight (dose equivalence ratios 1:6 and 10:6, respectively). The activities of daily living score for the Unified Parkinson's Disease Rating Scale (UPDRS) was significantly improved 4 weeks after the bromocriptine-ropinirole switch. All other UPDRS scores, including that for the side-effect component, were not significantly different after either switch. Overnight switching may be a safe therapeutic approach that may reduce hospitalisation and related socio-economic costs.
Activities of Daily Living↗
T1 and T2 in the brain of healthy subjects, patients with Parkinson disease, and patients with multiple system atrophy: relation to iron content.
PURPOSE: To investigate the potential of magnetic resonance imaging for identification and quantification of brain iron in healthy subjects, patients with Parkinson disease, and patients with multiple system atrophy. MATERIALS AND METHODS: Forty-nine subjects were studied at 1.5 T. Regional T1 and T2 values were compared among groups and also with histopathologic estimates of iron concentration. RESULTS: In healthy subjects, interregional T1 and T2 differences in the cortex and basal ganglia showed a good correlation with reported values for iron concentration, and intraregional variations were generally consistent with reported variability of iron concentration. Patients with multiple system atrophy had T1 and T2 shortening in the globus pallidus consistent with reported increases in ferritin-bound iron and changes in the putamen consistent with accumulation of hemosiderin (posterior portion) and neuromelanin (remainder). Both groups of patients had changes in the cortex that are consistent with decreased ferritin concentration and T2 changes in white matter consistent with demyelination. Patients with Parkinson disease also had a (nonsignificant) T2 shortening in the substantia nigra that was suggestive of iron accumulation. CONCLUSION: Most of the T1 and T2 findings appear to be related to changes in iron content and form and may possibly be used as indicators of such changes.
Aged↗
Clinical and pathological features in hydrocarbon-induced parkinsonism.
A neuropathological examination was performed on a patient with parkinsonism induced by prolonged exposure to a mixture of aliphatic hydrocarbons, mainly n-hexane and halogenated compounds. The patient developed a rapid-course disease that progressed even after withdrawal from the toxic exposure. Pathological examination and immunohistochemical analysis of the brain revealed severe and widespread dopaminergic neuronal loss, associated with severe gliosis, in the substantia nigra, and almost complete loss of tyrosine hydroxylase immunostaining in the striatum. No Lewy bodies were detected. Neuronal loss was also observed in the periaqueductal gray matter, locus ceruleus, and pedunculopontine nucleus. These changes, combined with the moderate anemia due to marrow suppression, and the mild axonal neuropathy observed in vivo, are suggestive of a hydrocarbon toxic insult.
Female↗
n-Hexane-induced parkinsonism: pathogenetic hypotheses.
n-Hexane, similar hydrocarbons, and derivatives are common environmental pollutants and by-products of lipid peroxidation, and they may have a nigrotoxic effect like that of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine. This report describes our second case of parkinsonism in a subject exposed to n-hexane. Positron emission tomography studies demonstrated regional striatal abnormalities of the nigrostriatal dopaminergic system and of glucose metabolism that were different from those found in idiopathic Parkinson's disease.
Air Pollutants, Occupational↗
A crossover, controlled study comparing pergolide with bromocriptine as an adjunct to levodopa for the treatment of Parkinson's disease.
A single-blind, crossover study was carried out to compare the efficacy and safety of pergolide against that of bromocriptine in 57 patients with Parkinson's disease who showed a declining response to levodopa therapy. Patients were randomly assigned to receive either bromocriptine followed by pergolide, or pergolide followed by bromocriptine. Both drugs were administered for 12 weeks. Patients were assessed by a clinician blinded to treatment assignment using the New York University Parkinson's Disease Scale. The average daily dose of pergolide was 2.3 +/- 0.8 mg and of bromocriptine 24.2 +/- 8.4 mg. Addition of pergolide or bromocriptine resulted in a significant improvement in total scores when compared with the previous treatment of levodopa alone (pergolide, p = 0.0001; bromocriptine, p = 0.0005). Pergolide was more effective than bromocriptine in daily living scores (p = 0.02) and motor scores (p = 0.038). No differences in the incidence of dyskinesias, dystonias, or psychosis were observed between groups. Fewer adverse events were recorded in the pergolide group, and most patients and physicians preferred pergolide to bromocriptine. Pergolide as adjunctive therapy to levodopa was more effective than bromocriptine in this short-term trial.
Aged↗
Cerebrospinal fluid and plasma concentrations of SRIH, beta-endorphin, CRH, NPY and GHRH in obese and normal weight subjects.
Numerous hypothalamic peptides are involved in the control of eating behaviour. We assessed plasma and cerebrospinal fluid (CSF) levels of SRIH, beta-endorphin (beta-EP), CRH, NPY and GHRH in a group of massively obese patients and in normal weight subjects. In the obese patients, CSF SRIH and beta-EP levels were significantly reduced and increased, respectively, compared with controls (20.6 +/- 2.62, mean +/- s.e.m., vs 34.5 +/- 2.14 pg/ml, P < 0.05, for SRIH and 111.2 +/- 5.00 vs 80.4 +/- 5.32 pg/ml, P < 0.001, for beta-EP). Considering the data of obese and control subjects altogether, SRIH and beta-EP concentrations correlated negatively and positively, respectively, with BMI values (r = -0.641, P < 0.005 and r = 0.518, P < 0.05). No significant differences were observed in CSF levels of CRH, NPY and GHRH between obese and normal weight subjects, though GHRH levels were close to the assay sensitivity. CSF concentrations of CRH were positively correlated with those of SRIH in obese patients (r = 0.60, P < 0.05) and with those of NPY both in obese (r = 0.69, P < 0.02) and in control subjects (r = 0.83, P < 0.005). Plasma levels of SRIH, beta-EP, NPY and GHRH did not differ significantly in the two groups of subjects; plasma CRH was undetectable. Our results argue against the hypothesis of an enhanced SRIH tone as the cause of impaired GH secretion in obese patients, a primary defect in GHRH or GH release seems more likely. Moreover, they emphasise the importance of an increased tone of endogenous opioids in the pathophysiology of human obesity.
Adult↗
Pergolide mesylate in Parkinson's disease treatment.
In the past 15 years, clinical data of over 1,500 patients treated with pergolide mesylate have been published. Pergolide is a dopamine agonist with a potent stimulating effect on D2 and also on D1 receptors. This pharmacodynamic characteristic seems the most effective in increasing the motility in Parkinson's disease. Pergolide has been used almost exclusively as an adjunct to levodopa treatment. Its positive effects seems to be related to its long plasma half life, about 27 hours, and 5-6 hours of clinical activity; it has shown to be effective on all parkinsonian symptoms except for the reduction of postural reflexes, it reduces off periods and compared to bromocriptine, it considerably improves the activities of daily living. Adverse reactions are, for the most part, mild and reversible, they mostly include nausea and gastroenteric disturbances.
Antiparkinson Agents↗
Pergolide compared with bromocriptine in Parkinson's disease: a multicenter, crossover, controlled study.
We compared the efficacy and safety of pergolide and bromocriptine in 57 patients with Parkinson's disease (PD) with a declining response to levodopa therapy in a single-blind, crossover study. Patients were placed randomly on the sequence bromocriptine-pergolide (12 + 12 weeks) or vice versa. Regular evaluations using the New York University Parkinson's Disease Scale were performed by a clinician blinded to treatment assignment. Patients' and clinicians' impressions also were recorded. The average daily dose of pergolide was 2.3 +/0- 0.8 mg, and that of bromocriptine was 24.2 +/- 8.4 mg. Significantly greater efficacy was demonstrated by both drugs as adjunctive therapy to levodopa compared with previous treatment of levodopa alone (pergolide, p = 0.0001; bromocriptine, p = 0.0005; Wilcoxon t test). Pergolide was more effective than bromocriptine in daily living scores (p = 0.020) and motor scores (p = 0.038). No difference in dyskinesias, dystonias, and psychosis was observed. Adverse events were more frequent in bromocriptine-treated patients. Most patients and physicians preferred pergolide to bromocriptine. Pergolide as adjunctive therapy to levodopa was more effective than bromocriptine in this short-term trial.
Aged↗
Biochemical and physiological aspects of 2,5-hexanedione: endogenous or exogenous product?
This article reports results regarding two different physiological aspects of 2,5-hexanedione (2,5-HD). The first is the relationship between "free" 2,5-HD (the fraction of "real" 2,5-HD) and "total" 2,5-HD (2,5-HD obtained from acid hydrolysis) in urine and blood of workers exposed to n-hexane. The second part of the study is an attempt to clarify "physiological" excretion of 2,5-HD in subjects not occupationally exposed to n-hexane. The concentration of free 2,5-HD in urine of workers exposed to n-hexane is about 8% of total urinary 2,5-HD. In blood, free 2,5-HD is about 50% of the total. The serum concentration range of total and free 2,5-HD in workers from whom blood was taken was 33-418 micrograms/l and 14-283 micrograms/l respectively. In subjects not exposed to n-hexane, urinary concentration of 2,5-HD ranged between 0.17 and 0.98 mg/l, the urinary excretion rate between 0.23 and 0.57 microgram/min, and renal clearance between 14 and 66 ml/min. The blood concentration of 2,5-HD in nonexposed subjects was 6-30 micrograms/l. Fluctuations typical of a circadian rhythm were not observed for 2,5-HD in blood or urine. We think that 2,5-HD is mainly a product of intermediate metabolism in the human body. Only a minimal part could derive from n-hexane as a ubiquitous micropollutant.
Circadian Rhythm↗
[Pergolide mesylate in the treatment of Parkinson's disease resistant to other treatments. First Italian experience].
Sixteen parkinsonian patients, mean age 57 (range 41-71), with a mean 9 year duration of Parkinson's disease, with "on-off" motor fluctuations were treated with pergolide mesylate 1.6 mg/die (range 1-5) for three months. The treatment resulted in an improvement of akinesia, tremor and rigidity, of the severity of phase "off" and of the duration of time "on". No significant improvements were obtained in the severity of dyskinesia. Three patients considered the treatment excellent and capable of restoring their working abilities. The drug was generally well tolerated. Pergolide was discontinued because of orthostatic hypotension in two patients and because of hallucinations in one patient. We consider these results a favorable progress in the treatment of Parkinson's disease.
Adult↗
Stereotaxic implantation of autologous adrenal medulla into caudate nucleus in four patients with parkinsonism. One-year follow-up.
Four patients with levodopa-responsive parkinsonism (aged 26, 35, 45, and 49 years) received autologous adrenal medullary implants into or near the left caudate nucleus by stereotaxic implantation after flank adrenalectomy. All patients had an immediate response to implantation lasting several days, during which parkinsonian signs and symptoms decreased. This period was followed by a gradual reappearance of symptoms in all but one patient. This patient had had a dramatic increase in "on" time without dyskinesias and a decrease in the severity and duration of "off" time. He died of multifocal glioblastoma 1 year after transplantation. Autopsy revealed no surviving adrenal cells. In one case, the stereotaxic implantation missed the basal ganglia, resulting in the placement of the adrenal medullary tissue into the medial thalamus and near the third ventricle; the patient did not improve. In the other two cases, a modest but definite increase in "on" time without dyskinesia and a reduction in the severity and duration of "off" time has been observed. The role of autologous adrenal medullary transplantation in patients with parkinsonism remains to be determined. Patients with a family history of cerebral malignancy may be at increased risk for the development of transplant-induced malignancy.
Adrenal Medulla↗
Intraventricular infusion of epidermal growth factor restores dopaminergic pathway in hemiparkinsonian rats.
We assessed the effect of a 35-day delayed intracerebroventricular (ICV) infusion of epidermal growth factor (EGF) on the survival and function of the substantia nigra (SN) dopaminergic neurons after a unilateral mechanical transection of rat nigrostriatal pathway. EGF infusion for 28 days resulted in a twofold increase in the number of surviving tyrosine-hydroxylase (TH)-positive SN neurons and a significant increase in ipsilateral striatal TH-positive fiber staining compared to controls at 200 days following the injury. In addition, there was a persistent enhancement of behavioral recovery, as indicated by a reduction in amphetamine-induced rotations. We conclude that EGF exerts a neurotrophic effect on the dopaminergic neurons in this experimental model of parkinsonism.
Animals↗