Comparison of therapeutic effects and mortality data of levodopa and levodopa combined with selegiline in patients with early,mild Parkinson's disease. Parkinson's Disease Research Group of the United Kingdom.

OBJECTIVE: To compare effectiveness of levodopa and levodopa combined with selegiline in treating early, mild Parkinson''s disease. DESIGN: Open, long term, prospective randomised trial. SETTING: 93 hospitals throughout United Kingdom. SUBJECTS: 520 patients with early Parkinson''s disease who were not receiving dopaminergic treatment. INTERVENTIONS: Treatment with levodopa and dopa decarboxylase inhibitor (arm 1) or levodopa and decarboxylase inhibitor in combination with selegiline (arm 2). MAIN OUTCOME MEASURES: Assessments of serial disability, frequency and severity of adverse events, and deaths from all causes. RESULTS: After average of 5-6 years'' follow up, mortality ratio in arm 2 compared with arm 1 was 1.57 (95% confidence interval 1.09 to 2.30), and difference in survival between the two arms was significant (log rank test, P = 0.015). Hazard ratio adjusted for age and sex was 1.49 (1.02 to 2.16), and after adjustment for other baseline factors it increased to 1.57 (1.07 to 2.31). Patients in arm 1 had slightly worse disability scores than those in arm 2, but differences were not significant. Functionally disabling peak dose dyskinesias and on/off fluctuations were more frequent in arm 2 than arm 1. During the trial the dose of levodopa required to produce optimum motor control steadily increased in arm 1 (median daily dose 375 mg at 1 year and 625 mg at 4 years), but median dose in arm 2 did not change (375 mg). CONCLUSIONS: Levodopa in combination with selegiline seemed to confer no clinical benefit over levodopa alone in treating early, mild Parkinson''s disease. Moreover mortality was significantly higher with combination treatment, casting doubts on its chronic use in Parkinson''s disease.     

One to Two Year Treatment of Parkinson's Disease with Levodopa

One hundred patients with Parkinson''s disease were treated with levodopa for more than a year at UCLA Medical Center. They were examined at given intervals and their improvement was graded. The optimum therapeutic dose was attained by balancing side effects against relief of symptoms and ranged from 1.5 grams to 8.0 grams per day (average 4.3 grams). There is no doubt that levodopa is the most effective treatment now available for Parkinson''s disease. At the end of the first year, 60 percent of the patients improved 50 percent or better, and 10 percent were considered symptom-free. All major symptoms of this disease, including rigidity, akinesia and tremor, improved in variable degree.There were no serious abnormalities in the routine clinical laboratory tests. The comon side effects included nausea, vomiting and choreoathetoid dyskinesias. The side effects were not life threatening, but occasionally were major therapeutic challenges.Maximal benefits with minimal side effects were achieved only by careful adjustments of the levodopa dosage as the months went by. This needed careful management by the physician and cooperation by the patient. Anticholinergic medications or amantadine hydrochloride, sometimes both, usually supplemented the effect of the levodopa.     

Comparisons of therapeutic effects of levodopa,levodopa and selegiline,and bromocriptine in patients with early,mild Parkinson's disease: three year interim report. Parkinson's Disease Research Group in the United Kingdom.

OBJECTIVE--To determine the optimum treatment for early Parkinson''s disease. DESIGN--An open, long term, prospective randomised trial conducted by the Parkinson''s Disease Research Group of the United Kingdom. SETTING--93 hospitals throughout the United Kingdom. SUBJECTS--782 patients with early Parkinson''s disease who were not receiving dopaminergic treatment. INTERVENTIONS--Patients allocated to treatment with levodopa/dopa decarboxylase inhibitor alone (arm 1), levodopa/decarboxylase inhibitor/selegiline in combination (arm 2), or bromocriptine (arm 3). MAIN OUTCOME MEASURES--Disability assessment as judged by improvement on Hoehn and Yahr, modified Webster, and North Western University disability scales. Adverse event profile and mortality ratios. RESULTS--Interim results indicate that all three treatment regimens led to improvement in baseline disabilities after 12 months'' treatment and that deterioration in control was apparent by three years. No significant differences were found between the results of treatment in arm 1 and arm 2, but both were significantly more effective than bromocriptine (arm 3) and had fewer early adverse reactions. The adjusted difference (95% confidence interval) in Webster rating for arm 3 v 1 was 0.93 points (0.27 to 1.50; p = 0.0058) and for arm 3 v 2 was 1.25 points (0.61 to 1.89; p = 0.0002). The incidence of dyskinesias and motor oscillations, however, was significantly lower in arm 3 (2% and 5%, respectively) than in arm 1 (27% and 33%, respectively) and arm 2 (34% and 35%, respectively). CONCLUSIONS--As there were no marked differences in functional improvement between the three groups the choice of treatment in the early stages of Parkinson''s disease may not be critical.     

GluR1 phosphorylation and persistent expression of levodopa-induced motor response alterations in the Hemi-Parkinsonian rat

The phosphorylation of glutamate receptor 1 (GluR1) has been increasingly implicated in the formation and maintenance of plastic responses. To investigate molecular mechanisms that underlie the persisting alterations in motor response occurring with levodopa treatment of parkinsonian patients, we evaluated the time course of these changes in relation to the phosphorylation of GluR1 in 6-hydroxydopamine (6-OHDA) lesioned animals. Three weeks of twice-daily levodopa administration to rats shortened the duration of the rotational responses and increased the peak turning responses, which lasted at least 7 days after withdrawal of chronic levodopa treatment. The shortened response duration and increased peak turning, resembling human wearing-off fluctuations and dyskinesia, were associated with a marked increase in Ser-845 phosphorylated GluR1 (pGluR1S845) immunoreactivity in lesioned striatum in response to levodopa treatment. The time course of changes in GluR1 phosphorylation correlated with the time course of changes in motor behavior after withdrawal of chronic levodopa therapy. Our immunostaining data showed that these changes were confined to parvalbumin-positive neurons where GluR1 are exclusively expressed. Both the altered motor response and the degree of pGluR1S845 were attenuated by the intrastriatal administration of protein kinase A (PKA) inhibitor Rp-cAMPS or GluR1 antisense oligonucleotides. The results suggest that Ser-845 GluR1 phosphorylation within parvalbumin-positive neurons contributes to the persistence of the motor response alterations produced by chronic intermittent dopaminergic stimulation.     

Postmortem brain fatty acid profile of levodopa-treated Parkinson disease patients and parkinsonian monkeys

Fatty acids play a critical role in brain function but their specific role in the pathophysiology of Parkinson disease (PD) and levodopa-induced motor complications is still unknown. From a therapeutic standpoint, it is important to determine the relation between brain fatty acids and PD because the brain fatty acid content depends on nutritional intake, a readily manipulable environmental factor. Here, we report a postmortem analysis of fatty acid profile by gas chromatography in the brain cortex of human patients (12 PD patients and nine Controls) as well as in the brain cortex of monkeys (four controls, five drug-naive MPTP monkeys and seven levodopa-treated MPTP monkeys). Brain fatty acid profile of cerebral cortex tissue was similar between PD patients and Controls and was not correlated with age of death, delay to autopsy or brain pH. Levodopa administration in MPTP monkeys increased arachidonic acid content (+7%; P < 0 .05) but decreased docosahexaenoic acid concentration (-15%; P < 0.05) and total n-3:n-6 polyunsaturated fatty acids ratio (-27%; P < 0.01) compared to drug-naive MPTP animals. Interestingly, PD patients who experienced motor complications to levodopa had higher arachidonic acid concentrations in the cortex compared to Controls (+13.6%; P < 0.05) and to levodopa-treated PD patients devoid of motor complications (+14.4%; P < 0.05). Furthermore, PD patients who took an above-median cumulative dose of levodopa had a higher relative amount of saturated fatty acids but lower monounsaturated fatty acids in their brain cortex (P < 0.01). These results suggest that changes in brain fatty acid relative concentrations are associated with levodopa treatment in PD patients and in a non-human primate model of parkinsonism.     

Drug treatment of Parkinson's disease.

A wide variety of drugs is available for treating Parkinson''s disease, including anticholinergics, amantadine levodopa, dopamine agonists, and selegiline. In younger patients (less than 50) levodopa is usually delayed provided that adequate relief of symptoms can be achieved with other drugs. In older patients (greater than 70) levodopa should be started as soon as symptom relief is required. Between these ages there is no consensus, but at present most such patients should probably be given controlled release levodopa before a dopamine agonist is added. Fluctuations can often be alleviated by giving controlled release preparations of levodopa, by giving small doses at frequent intervals, by adding selegiline or a long acting oral agonist, or by subcutaneous apomorphine. Dyskinesia can be peak dose, diphasic, or "off period." The diphasic form is hardest to alleviate. Psychiatric side effects should initially be managed by changing the antiparkinsonian treatment before resorting to antipsychotic drugs.     

Early presymptomatic and long-term changes of rest activity cycles and cognitive behavior in a MPTP-monkey model of Parkinson's disease

Background

It is increasingly recognized that non-motor symptoms are a prominent feature of Parkinson''s disease and in the case of cognitive deficits can precede onset of the characteristic motor symptoms. Here, we examine in 4 monkeys chronically treated with low doses of the neurotoxin MPTP the early and long-term alterations of rest-activity rhythms in relationship to the appearance of motor and cognitive symptoms.

Methodology/Principal Findings

Behavioral activity recordings as well as motor and cognitive assessments were carried out continuously and in parallel before, during and for several months following MPTP-treatment (12–56 weeks). Cognitive abilities were assessed using a task that is dependent on the functional integrity of the fronto-striatal axis. Rest-activity cycles were monitored continuously using infrared movement detectors of locomotor activity. Motor impairment was evaluated using standardized scales for primates. Results show that MPTP treatment led to an immediate alteration (within one week) of rest-activity cycles and cognitive deficits. Parkinsonian motor deficits only became apparent 3 to 5 weeks after initiating chronic MPTP administration. In three of the four animals studied, clinical scores returned to control levels 5–7 weeks following cessation of MPTP treatment. In contrast, both cognitive deficits and chronobiological alterations persisted for many months. Levodopa treatment led to an improvement of cognitive performance but did not affect rest-activity rhythms in the two cases tested.

Conclusions/Significance

Present results show that i) changes in the rest activity cycles constituted early detectable consequences of MPTP treatment and, along with cognitive alterations, characterize the presymptomatic stage; ii) following motor recovery there is a long-term persistence of non-motor symptoms that could reflect differential underlying compensatory mechanisms in these domains; iii) the progressive MPTP-monkey model of presymptomatic ongoing parkinsonism offers possibilities for in-depth studies of early non-motor symptoms including sleep alterations and cognitive deficits.     

Novel anti-apoptotic L-DOPA precursors SuperDopa and SuperDopamide as potential neuroprotective agents for halting/delaying progression of Parkinson’s disease

Parkinson’s disease (PD) is characterized by a gradual degeneration of the dopaminergic neurons in the substantia nigra pars compacta (SNpC). Levodopa, the standard PD treatment, provides the missing dopamine in SNpC, but ultimately after a honeymoon with levodopa treatment the neurodegenerative process and the progression of the disease continue. Aimed at prolonging the life of dopaminergic cells, we prepared the levodopa precursors SuperDopa (SD) and SueprDopamide (SDA), in which levodopa is merged with the antioxidant N-acetylcysteine (NAC) into a single molecule. Rotenone is a mitochondrial complex inhibitor often used as experimental model of PD. In vivo, SD and SDA treatment show a significant relief of motor disabilities in rotenone-injected rats. SD and SDA also lower rotenone-induced-α-synuclein (α-syn) expression in human SH-SY5Y cells, and α-syn oligomerization in α-syn-overexpressing-HEK293 cells. In the neuronal SH-SY5Y cells, SD and SDA reverse oxidative stress-induced phosphorylation of cJun-N-terminal kinase (JNK) and p38-mitogen-activated kinase (p38^MAPK). Attenuation of the MAPK-inflammatory/apoptotic pathway in SH-SY5Y cells concurrent with protection of rotenone-triggered motor impairment in rats, is a manifestation of the combined antioxidant/anti-inflammatory activity of SD and SDA together with levodopa release. The concept of joined therapies into a single molecule, where levodopa precursors confer antioxidant activity by enabling NAC delivery across the BBB, provides a potential disease-modifying treatment for slowing PD progression.Subject terms: Chemical modification, Parkinson''s disease     

Asymmetrical Effect of Levodopa on the Neural Activity of Motor Regions in PD

Parkinson''s disease (PD) is a neurodegenerative illness often characterized by asymmetrical symptoms. However, the reason for this asymmetry and the cerebral correlates underlying symptom asymmetry are still not well understood. Furthermore, the effects of levodopa on the cerebral correlates of disease asymmetry have not been investigated. In this study, right-handed PD patients performed self-initiated, externally triggered and repetitive control finger movements with both their right and left hands during functional magnetic resonance imaging (fMRI) to investigate asymmetrical effects of levodopa on the hemodynamic correlates of finger movements. Patients completed two experimental sessions OFF and ON medication after a minimum of 12 hours medication withdrawal. We compared the effect of levodopa on the neural activation patterns underlying the execution of both the more affected and less affected hand for self-initiated and externally triggered movements. Our results show that levodopa led to larger differences in cerebral activity for movements of the more affected, left side: there were significant differences in activity after levodopa administration in regions of the motor cortico-striatal network when patients performed self-initiated and externally triggered movements with their left hand. By contrast, when patients used their right hand, levodopa led to differences in cerebellar activity only. As our patients were affected more severely on their left side, we propose that levodopa may help provide additional dopaminergic input, improving movements for the more severely affected side. These results suggest that the impact of reduced dopamine in the cortico-striatal system and the action of levodopa is not symmetrical.     

Differential Neural Activation Patterns in Patients with Parkinson's Disease and Freezing of Gait in Response to Concurrent Cognitive and Motor Load

Freezing of gait is a devastating symptom of Parkinson''s disease (PD) that is exacerbated by the processing of cognitive information whilst walking. To date, no studies have explored the neural correlates associated with increases in cognitive load whilst performing a motor task in patients with freezing. In this experiment, 14 PD patients with and 15 PD patients without freezing of gait underwent 3T fMRI while performing a virtual reality gait task. Directions to walk and stop were presented on the viewing screen as either direct cues or as more cognitively indirect pre-learned cues. Both groups showed a consistent pattern of BOLD response within the Cognitive Control Network during performance of the paradigm. However, a between group comparison revealed that those PD patients with freezing of gait were less able to recruit the bilateral anterior insula, ventral striatum and the pre-supplementary motor area, as well as the left subthalamic nucleus when responding to indirect cognitive cues whilst maintaining a motor output. These results suggest that PD patients with freezing of gait are unable to properly recruit specific cortical and subcortical regions within the Cognitive Control Network during the performance of simultaneous motor and cognitive functions.     

等速肌力康复训练对阿尔茨海默病患者认知功能及运动功能的影响

目的:探讨等速肌力康复训练对阿尔茨海默病患者认知功能及运动功能的影响。方法:符合入组条件的40例阿尔茨海默病患者随机分为试验组和对照组,两组常规治疗相同,试验组在常规治疗的同时予等速肌力康复训练,两组治疗时间均为2个月。在纳入研究1周内和研究结束1周内进行认知功能和运动功能评价,对前后两次评分进行对比分析。结果:试验组患者与对照组比较,剑桥老年认知量表、Berg平衡、功能伸展测试、起立-行走计时测试改善差异有统计学意义,试验组明显优于对照组(P0.05)。结论:等速肌力康复训练能明显促进阿尔茨海默病患者的认知功能和运动功能的改善。     

Comparative Effects of Acute or Chronic Administration of Levodopa to 6-OHDA-lesioned Rats on the Expression and Phosphorylation of <Emphasis Type="Italic">N</Emphasis>-methyl-<Emphasis Type="SmallCaps">d</Emphasis>-aspartate Receptor NR1 Subunits in the Striatum

N-methyl-d-aspartate receptor (NMDA) has been increasingly implicated in the formation and maintenance of various forms of behavioral and synaptic plasticity. Recent evidence has linked striatal NMDA function to the adverse effects of long-term dopaminergic treatment in Parkinson’s disease. The subcellular distribution and phosphorylation of NMDA subunit, NR1, reflects NMDA receptor activity. To elucidate molecular mechanisms that underlie the persisting alterations in motor response occurring with levodopa treatment of parkinsonian patients, we evaluated the effects of unilateral nigrostriatal depletion with 6-hydroxydopamine and subsequent levodopa treatment on motor responses and NR1 alterations. Three weeks of levodopa administration to rats shortened the rotational duration and increased the peak turning responses, which lasted after withdrawal of chronic levodopa treatment. We found a significant reduction in the abundance of both phosphorylated NR1 on serine residues 890 and 896 (pNR1S890 and pNR1S896) and NR1 in the cell plasma membrane of lesioned striatum. Chronic treatment of lesioned rats with levodopa markedly upregulated pNR1S890, pNR1S896, and pNR1S897 in lesioned striatum with a concomitant normalization of the plasma membrane NR1 abundance. The magnitude of increased pNR1S890, pNR1S896, and pNR1S897 is dependent on the number of levodopa injections and is paralleled by a sensitization of the rotational response. Our data indicate that glutamate signaling is triggered during the levodopa administration. Activated NMDA receptor NR1-mediated mechanisms are involved in the persistent expression of the motor response alterations that appear during chronic levodopa therapy of parkinsonian rats and continue after treatment withdrawal. M. Kong and M. Ba are contributed equally to this work.     

Bromocriptine in Parkinsonism.

A review of the effects of using bromocriptine in Parkinson''s disease showed that it rarely helps patients not primarily improved by levodopa. Patients who show late failure with levadopa and whose response to treatment is declining are helped by combining the two drugs. High cost and severe psychosis are the main disadvantages of bromocriptine, and, although it is not recommended for patients who are doing well on levodopa, it is the best available drug for hospital use in patients who show late failure with levodopa.     

Awareness of Memory Deficits in Early Stage Huntington's Disease

Patients with Huntington''s disease (HD) are often described as unaware of their motor symptoms, their behavioral disorders or their cognitive deficits, including memory. Nevertheless, because patients with Parkinson''s disease (PD) remain aware of their memory deficits despite striatal dysfunction, we hypothesize that early stage HD patients in whom degeneration predominates in the striatum can accurately judge their own memory disorders whereas more advanced patients cannot. In order to test our hypothesis, we compared subjective questionnaires of memory deficits (in HD patients and in their proxies) and objective measures of memory dysfunction in patients. Forty-six patients with manifest HD attending the out-patient department of the French National Reference Center for HD and thirty-three proxies were enrolled. We found that HD patients at an early stage of the disease (Stage 1) were more accurate than their proxies at evaluating their own memory deficits, independently from their depression level. The proxies were more influenced by patients'' functional decline rather than by patients'' memory deficits. Patients with moderate disease (Stage 2) misestimated their memory deficits compared to their proxies, whose judgment was nonetheless influenced by the severity of both functional decline and depression. Contrasting subjective memory ratings from the patients and their objective memory performance, we demonstrate that although HD patients are often reported to be unaware of their neurological, cognitive and behavioral symptoms, it is not the case for memory deficits at an early stage. Loss of awareness of memory deficits in HD is associated with the severity of the disease in terms of CAG repeats, functional decline, motor dysfunction and cognitive impairment, including memory deficits and executive dysfunction.     

Two phases of the contingent negative variation in humans: connection with motor and mental functions

The question of dependence of the contingent negative variation (CNV) on the regulating mechanisms of motor and mental functions is not sufficiently studied. The tasks of the present work were: to investigate the dependence of the CNV early and late phases on the state of motor and mental functions in patients with Parkinson's disease (PD), and to elucidate the levodopa influence on the CNV parameters. 18 healthy subjects and 56 patients with PD were studied. In PD patients, significant reductions of amplitudes and squares of two CNV phases were observed. A negative correlation of the degree of coordinating muscle relationships disturbance with amplitudes of two CNV phases was found (p < 0.01). A positive interdependence between values of the both CNV phases and the state of mental functions was established, memory in particular (p < 0.05). After levodopa administration in PD patients, the early CNV phase did not significantly change, whereas the late CNV phase significantly increased (p < 0.05). Results of the investigation suggest an important role of the structures ensuring both direct motor control and mental functions in two CNV phases formation. A more obvious levodopa influence on the late CNV phase suggest participation of the basal ganglia efferent system in generation of the late CNV phase rather than in organization of the early CNV phase.     

Relationship between Motor Symptoms,Cognition, and Demographic Characteristics in Treated Mild/Moderate Parkinson’s Disease

Background

Although Parkinson’s disease (PD) is a progressive neurodegenerative disorder characterized primarily by motor symptoms, PD patients, at all stages of the disease, can experience cognitive dysfunction. However, the relationships between cognitive and motor symptoms and specific demographic characteristics are not well defined, particularly for patients who have progressed to requiring dopaminergic medication.

Objective

To examine relationships between motor and cognitive symptoms and various demographic factors in mild to moderate, PD patients requiring anti-PD medication.

Methods

Cognitive function was assessed in 94 subjects with a variety of neuropsychological tests during baseline evaluations as part of an experimental treatment study. Data were analyzed in relation to Unified Parkinson’s Disease Rating Scale motor scores and demographic variables.

Results

Of the UPDRS subscores analyzed, posture/balance/gait was associated with the highest number of adverse cognitive outcomes followed by speech/facial expression, bradykinesia, and rigidity. No associations were detected between any of the cognitive performance measures and tremor. Motor functioning assessed in the “off” condition correlated primarily with disease duration; neuropsychological performance in general was primarily related to age.

Conclusion

In PD patients who have advanced to requiring anti-PD therapies, there are salient associations between axial signs and cognitive performance and in particular, with different aspects of visuospatial function suggesting involvement of similar circuits in these functions. Associations between executive functions and bradykinesia also suggest involvement similar circuits in these functions.     

Treatment of Cushing's disease with low dose radiation therapy.

Nineteen patients with Cushing''s disease were treated with low dose external pituitary irradiation (20 Gy (2000 rad) in eight fractions over 10 days). While awaiting the effects of pituitary irradiation all patients were treated with metyrapone. Seven patients had a complete remission of their disease within six to 12 months of irradiation. They did not require any further treatment and were followed up for a mean of three and a half (range one to eight) years. Another patient had a complete remission after a second course of pituitary irradiation. A further two patients showed a significant biochemical improvement after irradiation, although they were not rendered eucorticoid. There were no complications after this dose of irradiation. These results compare favourably with those reported after pituitary irradiation at conventional doses (40-50 Gy (4000-5000 rad) over four or five weeks) but were not associated with any complications. It is therefore recommended that low dose external pituitary irradiation be used as definitive first line treatment for Cushing''s disease.     

Subthalamic Nucleus Deep Brain Stimulation Modulate Catecholamine Levels with Significant Relations to Clinical Outcome after Surgery in Patients with Parkinson’s Disease

Aims

Although subthalamic nucleus deep brain stimulation (STN-DBS) is effective in patients with advanced Parkinson’s disease (PD), its physiological mechanisms remain unclear. Because STN-DBS is effective in patients with PD whose motor symptoms are dramatically alleviated by L-3,4-dihydroxyphenylalanine (L-DOPA) treatment, the higher preoperative catecholamine levels might be related to the better clinical outcome after surgery. We aimed to examine the correlation between the preoperative catecholamine levels and postoperative clinical outcome after subthalamic nucleus deep brain stimulation. The effectiveness of STN-DBS in the patient who responded well to dopaminergic medication suggest the causal link between the dopaminergic system and STN-DBS. We also examined how catecholamine levels were modulated after subthalamic stimulation.

Methods

In total 25 patients with PD were enrolled (Mean age 66.2 ± 6.7 years, mean disease duration 11.6 ± 3.7 years). Mean levodopa equivalent doses were 1032 ± 34.6 mg before surgery. Cerebrospinal fluid and plasma catecholamine levels were measured an hour after oral administration of antiparkinsonian drugs before surgery. The mean Unified Parkinson’s Disease Rating Scale scores (UPDRS) and the Parkinson’s disease Questionnaire-39 (PDQ-39) were obtained before and after surgery. Of the 25 patients, postoperative cerebrospinal fluid and plasma were collected an hour after oral administration of antiparkinsonian drugs during on stimulation at follow up in 11 patients.

Results

Mean levodopa equivalent doses significantly decreased after surgery with improvement in motor functions and quality of life. The preoperative catecholamine levels had basically negative correlations with postoperative motor scores and quality of life, suggesting that higher preoperative catecholamine levels were related to better outcome after STN-DBS. The preoperative plasma levels of L-DOPA had significantly negative correlations with postoperative UPDRS- III score in off phase three months after STN-DBS. The preoperative cerebrospinal fluid (CSF) 3,4-dihydroxyphenylacetic acid (DOPAC) and 5-hydroxytryptamine (5-HT) levels had significantly negative correlations with postoperative UPDRS- III score in off phase one year after STN-DBS and the preoperative CSF homovanilic acid (HVA) levels had significant negative correlations with postoperative UPDRS- III score in on phase three months after STN-DBS. In PDQ-39 SI (summary index), preoperative plasma dopamine (DA) level had significantly negative correlations with postoperative PDQ-39 SI one year after STN-DBS suggesting that higher preoperative plasma DA level resulted in better quality of life (QOL) one year after STN-DBS. The stepwise multiple linear regression study revealed that higher preoperative plasma HVA levels had negative influence on the postoperative motor symptoms (i.e., increase in the score of UPDRS), whereas higher preoperative CSF L-DOPA levels had positive influence on the postoperative motor symptoms and QOL (decrease in the score of UPDRS and PDQ-39 SI) The catecholamine levels were not significantly reduced postoperatively in 11 patients despite the significant reduction in levodopa equivalent doses. Unexpectedly, CSF HVA levels significantly increased from 0.00089±0.0003 ng/μl to 0.002±0.0008 ng/μl after STN-DBS.

Conclusion

The preoperative catecholamine levels might affect the postoperative motor symptoms and quality of life. The catecholamine levels were not significantly reduced postoperatively despite the significant reduction in levodopa equivalent doses.     

文拉法辛联合认知行为疗法治疗帕金森病抑郁、认知功能障碍的临床疗效评价

目的:探讨文拉法辛联合认知行为疗法治疗帕金森病(PD)抑郁、认知功能障碍的临床疗效和安全性。方法:选择我院收治的60例PD合并抑郁、认知功能障碍患者并将其随机分为三组,分别为对照组(单用文拉法辛治疗),联合奥氮平组(文拉法辛联合奥氮平),联合认知行为疗法组(文拉法辛联合认知行为疗法),每组20例,于治疗前及治疗后4、8周末采用汉密尔顿抑郁量表(HAMD)进行抑郁程度评定,简易精神状态评价量表(MMSE)和事件相关电位(event-related potentials,ERPs)P300进行认知功能评定。结果:治疗4、8周时,三组的HAMD评分均较治疗前有不同程度下降,P300潜伏期较治疗前有不同程度缩短,P300波幅、MMSE评分有不同程度升高(P0.05),联合奥氮平组和联合认知行为疗法组HAMD评分较对照组明显下降,P300潜伏期较对照组明显缩短,P300波幅、MMSE评分明显升高(P0.05),联合认知行为疗法组HAMD评分较联合奥氮平组明显下降,P300潜伏期明显缩短,P300波幅、MMSE评分明显升高(P0.05)。三组均无特殊不良反应。结论:文拉法辛联合认知行为疗法治疗PD抑郁、认知功能障碍疗效确切,能显著改善患者抑郁症状,提高患者的认知功能,疗效较单用文拉法辛或文拉法辛联合奥氮平治疗更好,且安全性高。     

美金刚联合普拉克索治疗帕金森患者临床疗效及对CysC、Hcy水平影响

目的:探究美金刚联合普拉克索在治疗帕金森患者中的临床疗效,并就治疗对患者胱抑素C(cystatin C,CysC)以及血同型半胱氨酸(homocysteine,Hcy)水平的影响。方法:选择2018年1月至2020年1月于我院接受治疗的98例帕金森患者,随机数字表法均分为两组(每组各49例),对照组单纯接受美金刚治疗,研究组在对照组基础上加用普拉克索进行治疗,对比两组治疗有效率,治疗前后CysC、Hcy水平,以及治疗前后简易智能精神状态检查量表(mini mental state examination,MMSE)以及帕金森病评定量表III(parkinson comprehensive rating scale,UPDRS III)评分,最后对两组患者治疗中不良反应发生率进行统计对比。结果:(1)研究组患者治疗有效率明显高于对照组患者(P0.05);(2)治疗前两组患者CysC、Hcy水平对比差异不具有统计学意义(P0.05),治疗后研究组患者CysC、Hcy水平低于对照组(P0.05);(3)治疗前两组患者MMSE及UPDRS III量表评分对比差异不具有统计学意义(P0.05),治疗后研究组患者MMSE得分高于对照组,UPDRS III量表评分低于对照组(P0.05);(4)两组治疗不良反应诸如胃肠道反应、嗜睡、体位性低血压等对比无差异(P0.05)。结论:美金刚联合普拉克索对帕金森具有较好的治疗效果,能够显著改善患者认知及运动功能,降低CysC、Hcy水平,同时治疗安全性较高。