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1.
J Neurol Neurosurg Psychiatry ; 77(4): 450-3, 2006 Apr.
Article in English | MEDLINE | ID: mdl-16543520

ABSTRACT

BACKGROUND: The clinical condition of advanced Parkinson's disease (PD) patients is often complicated by motor fluctuations and dyskinesias which are difficult to control with available oral medications. OBJECTIVE: To compare clinical and neuropsychological 12 month outcome following subcutaneous apomorphine infusion (APO) and chronic deep brain stimulation of the subthalamic nucleus (STN-DBS) in advanced PD patients. METHODS: Patients with advanced PD and medically untreatable fluctuations underwent either APO (13 patients) or STN-DBS (12 patients). All patients were clinically (UPDRS-III, AIMS, 12 h on-off daily) and neuropsychologically (MMSE, Hamilton-17 depression, NPI) evaluated at baseline and at 12 months. APO was discontinued at night. RESULTS: At 12 months APO treatment (74.78+/-24.42 mg/day) resulted in significant reduction in off time (-51%) and no change in AIMS. Levodopa equivalent medication doses were reduced from 665.98+/-215 mg/day at baseline to 470+/-229 mg/day. MMSE, NPI, and Hamilton depression scores were unchanged. At 12 months STN-DBS resulted in significant clinical improvement in terms of reduction in daily off time (-76%) and AIMS (-81%) as well as levodopa equivalent medication doses (980+/-835 to 374+/-284 mg/day). Four out of 12 patients had stopped oral medications. MMSE was unchanged (from 28.6+/-0.3 to 28.4+/-0.6). Hamilton depression was also unchanged, but NPI showed significant worsening (from 6.58+/-9.8 to 18.16+/-10.2; p<0.02). Category fluency also declined. CONCLUSIONS: Both APO and STN-DBS resulted in significant clinical improvement in complicated PD. STN-DBS resulted in greater reduction in dopaminergic medications and provided 24 h motor benefit. However, STN-DBS, unlike APO, appears to be associated with significant worsening on NPI resulting from long term behavioral problems in some patients.


Subject(s)
Antiparkinson Agents/therapeutic use , Apomorphine/therapeutic use , Cognition Disorders/diagnosis , Cognition Disorders/etiology , Deep Brain Stimulation/instrumentation , Parkinson Disease/complications , Parkinson Disease/therapy , Subthalamic Nucleus/physiology , Aged , Antiparkinson Agents/administration & dosage , Apomorphine/administration & dosage , Drug Administration Schedule , Female , Follow-Up Studies , Humans , Injections, Subcutaneous , Levodopa/therapeutic use , Male , Middle Aged , Neuropsychological Tests , Parkinson Disease/drug therapy , Severity of Illness Index
2.
Neurol Sci ; 22(1): 111-2, 2001 Feb.
Article in English | MEDLINE | ID: mdl-11487185

ABSTRACT

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.


Subject(s)
Parkinsonian Disorders/physiopathology , Parkinsonian Disorders/therapy , Subthalamic Nucleus/anatomy & histology , Subthalamic Nucleus/physiopathology , Aged , Brain Mapping , Electric Stimulation Therapy , Electrodes, Implanted , Humans , Models, Neurological , Neural Pathways/anatomy & histology , Neural Pathways/physiopathology , Recovery of Function/physiology , Stereotaxic Techniques , Substantia Nigra/anatomy & histology , Substantia Nigra/physiopathology , Subthalamus/anatomy & histology , Subthalamus/physiopathology , Treatment Outcome , Ventral Thalamic Nuclei/anatomy & histology , Ventral Thalamic Nuclei/physiopathology
3.
Mov Disord ; 15(5): 986-9, 2000 Sep.
Article in English | MEDLINE | ID: mdl-11009210

ABSTRACT

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.


Subject(s)
Depression/drug therapy , Parkinson Disease/drug therapy , Paroxetine/therapeutic use , Selective Serotonin Reuptake Inhibitors/therapeutic use , Aged , Antiparkinson Agents/therapeutic use , Clinical Protocols , Depression/etiology , Dose-Response Relationship, Drug , Drug Therapy, Combination , Female , Humans , Male , Middle Aged , Parkinson Disease/complications , Parkinson Disease/physiopathology , Parkinson Disease/psychology , Paroxetine/administration & dosage , Paroxetine/adverse effects , Prospective Studies , Selective Serotonin Reuptake Inhibitors/administration & dosage , Selective Serotonin Reuptake Inhibitors/adverse effects , Treatment Outcome
4.
Neurology ; 55(5): 667-73, 2000 Sep 12.
Article in English | MEDLINE | ID: mdl-10980731

ABSTRACT

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.


Subject(s)
Hydrocarbons/adverse effects , Occupational Exposure/adverse effects , Parkinson Disease, Secondary/chemically induced , Adult , Aged , Female , Humans , Male , Middle Aged , Risk Factors , Solvents/adverse effects
5.
J Neural Transm (Vienna) ; 106(9-10): 925-9, 1999.
Article in English | MEDLINE | ID: mdl-10599874

ABSTRACT

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.


Subject(s)
Antiparkinson Agents/therapeutic use , Bromocriptine/therapeutic use , Indoles/therapeutic use , Parkinson Disease/drug therapy , Pergolide/therapeutic use , Activities of Daily Living , Aged , Antiparkinson Agents/pharmacokinetics , Bromocriptine/pharmacokinetics , Female , Humans , Indoles/pharmacokinetics , Male , Middle Aged , Pergolide/pharmacokinetics , Therapeutic Equivalency
6.
Mov Disord ; 10(3): 279-82, 1995 May.
Article in English | MEDLINE | ID: mdl-7651443

ABSTRACT

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.


Subject(s)
Air Pollutants, Occupational/adverse effects , Brain/drug effects , Hexanes/adverse effects , Occupational Diseases/chemically induced , Parkinson Disease, Secondary/chemically induced , Tomography, Emission-Computed , Blood Glucose/metabolism , Brain/diagnostic imaging , Brain Mapping , Corpus Striatum/diagnostic imaging , Corpus Striatum/drug effects , Humans , Lipid Peroxidation/drug effects , Lipid Peroxidation/physiology , Male , Middle Aged , Neurologic Examination/drug effects , Occupational Diseases/diagnostic imaging , Parkinson Disease, Secondary/diagnostic imaging , Receptors, Dopamine/drug effects , Receptors, Dopamine/physiology , Substantia Nigra/diagnostic imaging , Substantia Nigra/drug effects , Tanning
7.
J Neural Transm Suppl ; 45: 203-12, 1995.
Article in English | MEDLINE | ID: mdl-8748627

ABSTRACT

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.


Subject(s)
Antiparkinson Agents/therapeutic use , Dopamine Agonists/therapeutic use , Neuroprotective Agents/therapeutic use , Pergolide/therapeutic use , Antiparkinson Agents/adverse effects , Bromocriptine/therapeutic use , Controlled Clinical Trials as Topic , Dopamine Agonists/adverse effects , Humans , Lisuride/therapeutic use , Neuroprotective Agents/adverse effects , Pergolide/adverse effects
8.
J Neural Transm Suppl ; 45: 281-5, 1995.
Article in English | MEDLINE | ID: mdl-8748636

ABSTRACT

In order to investigate the effect of n-hexane and its metabolites on the Central Nervous System (CNS), we treated mice with n-hexane and 2,5-hexanedione (2,5-HD) by intraperitoneal (i.p.) administration. Gascromatographic mass spectrometric (GCMS) analyses of striatum and cerebellum revealed a consistent increase of 2,5-HD concentration at 0.5 and 2 hours after treatment and a decline to baseline levels at 24 hours. Traces of 2,5-HD were detected in the brain of control animals. Biochemical analyses revealed a precocious, short lasting, significant increase of striatal dopamine (DA) and homovanillic acid (HVA) levels. A significant increase of striatal synaptosomal DA uptake, suggesting a DA releasing effect on the dopaminergic terminals, was also observed. These results support the hypothesis of a possible role of n-hexane and its metabolites in inducing parkinsonism in humans and animals.


Subject(s)
Corpus Striatum/drug effects , Dopamine/physiology , Hexanes/pharmacology , Hexanones/pharmacology , 3,4-Dihydroxyphenylacetic Acid/metabolism , Animals , Corpus Striatum/metabolism , Dopamine/metabolism , Homovanillic Acid/metabolism , Injections, Intraperitoneal , Male , Mice , Mice, Inbred ICR , Time Factors
9.
Brain Res ; 531(1-2): 355-7, 1990 Oct 29.
Article in English | MEDLINE | ID: mdl-1705155

ABSTRACT

A case of human parkinsonism, due to n-hexane exposure, was recently described. On the basis of this observation, we treated mice and rats with n-hexane and its principle toxic metabolite 2,5-hexanedione. The mice underwent a chronic treatment intraperitoneum, the rats were treated stereotaxically into the substantia nigra. At biochemical analysis of the striata, dopamine and homovanillic acid levels were significantly lower compared with control animals; norepinephrine, serotonin, 5-hydroxindolacetic acid levels were unchanged. The rats treated with 2,5-hexanedione showed an apomorphine-induced rotational behavior significantly higher compared to controls. Since n-hexane and its metabolites are environmental contaminants and by-products of endogenous metabolic pathways, we propose that they may play a role in inducing parkinsonism in humans.


Subject(s)
Corpus Striatum/metabolism , Hexanes/toxicity , Parkinson Disease, Secondary/metabolism , Animals , Corpus Striatum/drug effects , Dopamine/metabolism , Hexanones/pharmacology , Homovanillic Acid/metabolism , Hydroxyindoleacetic Acid/metabolism , Male , Mice , Mice, Inbred ICR , Motor Activity/drug effects , Norepinephrine/metabolism , Rats , Rats, Inbred Strains , Reference Values , Serotonin/metabolism , Substantia Nigra/drug effects , Substantia Nigra/metabolism
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