交叉电脉冲在帕金森病DBS后程控中的应用

目的 探讨交叉电脉冲（ILS）在帕金森病（PD）脑深部电刺激术（DBS）后传统刺激方式疗效不佳病人中的应用效果。方法 回顾性分析2018年2月至2021年10月丘脑底核（STN）-DBS治疗的12例PD的临床资料。12例DBS后应用传统刺激方式疗效不佳,使用ILS（时间>6个月）。使用ILS后随访6~12个月,采用统一帕金森病生活量表（UPDRS Ⅱ）评分、运动量表（UPDRS Ⅲ）评分、异动症量表（UPDRS Ⅳ-A）评分评估疗效及左旋多巴等效日剂量（LEDD）评价药物使用情况。结果 与ILS前（药物关期）相比,使用ILS后（药物关期）UPDRS-Ⅱ评分、UPDRS Ⅳ-A评分、UPDRS-Ⅲ评分总分均明显改善（P<0.05）,LEDD无明显变化（P>0.05）。结论 PD病人STN-DBS后,在传统刺激模式症状改善不佳或出现刺激副反应时,ILS可明显改善PD症状、减轻刺激相关副反应。     

Efficacy and safety of simultaneous bilateral pallidotomy in advanced Parkinson's disease

BACKGROUND: Although unilateral pallidotomy is generally considered a safe and effective neurosurgical treatment for advanced Parkinson's disease (PD), controversies concerning efficacy and adverse effects of bilateral posteroventral pallidotomy (PVP) exist and need to be resolved. METHODS: We studied 8 patients with advanced PD who underwent simultaneous bilateral PVP. The patients were assessed preoperatively, immediately after surgery, and 6 and 12 months later. RESULTS: Dyskinesia was almost entirely abolished immediately after surgery, as well as being significantly lower 1 year later (p < 0.05). The 'off' medication score of the Unified Parkinson's Disease Rating Scale motor part (UPDRS III) was significantly improved after surgery (p < 0.05) but increased gradually after 6 months. The off medication score of activities of daily living tended to improve immediately after surgery, but it returned to preoperative levels at 12 months. There were no major complications of surgery. CONCLUSIONS: Simultaneous bilateral PVP may be a safe and highly effective method of reducing levodopa-induced dyskinesia. Our results suggest that simultaneous bilateral PVP may be a reasonable therapeutic option for advanced PD with severe levodopa-induced dyskinesia.     

Bilateral effects of unilateral subthalamic nucleus deep brain stimulation in advanced Parkinson's disease

To investigate the bilateral effects of unilateral subthalamic nucleus deep brain stimulation (STN-DBS), we prospectively studied 9 consecutive advanced Parkinson's disease (PD) patients (2 men and 7 women) who underwent unilateral STN-DBS. Patients were evaluated preoperatively and at 3 and 6 months postoperatively with and without dopaminergic medications ('on' and 'off' medication, respectively). Postoperatively, patients were assessed with and without stimulation. We found that, when compared with baseline, the 'off' medication scores of the Unified Parkinson's Disease Rating Scale motor part (UPDRS III) and activities of daily living (UPDRS II) were improved by 37% (p = 0.028) and 50% (p = 0.046) at 6 months after surgery, respectively. Stimulation while 'off' medication improved the total UPDRS score by 42% (p = 0.028) at 6 months. At 6 months after surgery, the subscore of UPDRS III of body parts contralateral to the DBS implantation had improved by 48% (p = 0.028), and the ipsilateral subscore of UPDRS III and the axial subscore of UPDRS III had improved by 20% (p = 0.027) and 39% (p = 0.028), respectively. Daily dosage of levodopa was reduced by 15% at 6 months. No patient exhibited permanent side effects. These findings indicate that unilateral STN-DBS may be a reasonable surgical procedure for selected PD patients who have markedly asymmetric parkinsonism.     

Beta-CIT-SPECT combined with UPDRS appears to distinguish different parkinsonian conditions

OBJECTIVES: An earlier study in l-dopa responding patients with idiopathic Parkinson's disease documented that progressive nigro-striatal degeneration shown with single photon emission computed tomography (SPECT) and the cocain analog iodine-123-beta-CIT (beta-CIT) correlated linearly with increasing motor scores in the Unified Parkinson's Disease Rating Scale (UPDRS). Here we have extended the study to include 2 tremor patients with mild parkinsonism, 2 poor l-dopa responders with parkisonism and 2 non l-dopa responders with severe parkinsonism. METHODS: SPECT scanning was performed 20 h after injection of beta-CIT and UPDRS was done at the time of beta-CIT injection. RESULTS: All patients in the present study showed less nigro-striatal degeneration in relation to UPDRS motor scores than the patients with idiopathic Parkinson's disease. CONCLUSION: The results suggest that the the combination of beta-CIT-SPECT and UPDRS motor scores has the potential to differentiate idiopathic Parkinson's disease from other parkinsonian conditions.     

Piribedil and bromocriptine in Parkinson's disease: a single-blind crossover study

INTRODUCTION: Clinicians switch from one dopamine agonist to another for various reasons. However, each change may inadvertently result in certain potential risks such as decreased medication efficacy or new side-effects. OBJECTIVE: We evaluated the tolerability of a switch of bromocriptine to piribedil using two conversion ratios as a primary outcome measure, with motor function as a secondary outcome measure, in patients with mild to moderate Parkinson's disease (PD). METHODS: Twenty consecutive patients with mild to moderate PD (Hoehn and Yahr, stage II-III) on treatment with stable doses of bromocriptine and levodopa were randomized to two groups of 10 patients each, to receive piribedil based on 1:5 or 1:10 conversion ratios. Blinded evaluations were performed: 1) United Parkinson's Diseased Rating Scale (UPDRS) scores both in 'on' and 'off', 2) Open-ended interviews for adverse events, 3) Epworth Sleepiness Scale, 4) Purdue Pegboard assessment during 'on' and 'off', 5) Hand-arm movement test during 'on' and 'off', and 6) Walking test during 'on' and 'off'. RESULTS: Major adverse events included 'sleep attacks' in one patient and minor side-effects included giddiness, nausea, hallucinations, sleepiness and lethargy. However, these were mild and 19 (95%) of the 20 patients completed the study. There was a significant improvement in both the UPDRS 'off' total and motor scores at 1 month compared with baseline for the group on 1:10 ratio. The walking times during the 'off' state at 1 and 2 months were significantly better compared with baseline in the 1:5 group. There were otherwise no significant differences in the rating tests during both 'off' and 'on' states before and after the bromocriptine switch. CONCLUSIONS: We demonstrated that patients with mild to moderate PD who were on relatively low doses of bromocriptine can be safely switched to piribedil based on a conversion ratio of either 1:5 or 1:10. However, the higher conversion ratio has to be carried out with caution in patients with daytime somnolence.     

微电极导向核团毁损术和脑深部电刺激术治疗帕金森病的疗效分析

目的 观察微电极导向核团毁损术和脑深部电刺激术（DBS）治疗帕金森病的临床疗效。方法 对380例接受微电极导向立体定向核团毁损术和25例脑深部电刺激丘脑底核（STN—DBS）治疗的帕金森病患者进行随访和神经功能评估，分别获得术前、术后和DBS开启后1周、6个月、2年及5年的不同服药状态下统一帕金森病量表（UPDRS）评分资料，采用威尔科克森检验（Wilcoxontest），比较不同术后时间点UPDRS运动评分与术前评分的差异。结果 核团毁损术和DBS在术后1周、6个月及2年随访中均能明显改善术前帕金森病患者的UPDRS运动评分，减轻左旋多巴诱发的运动波动及异动症。在5年随访时间点上仅DBS治疗组较术前比较仍显示差异性。而且DBS组患者术后左旋多巴服药的剂量较术前减少。核团毁损组总体并发症的发生率为5．8％，永久性并发症的发生率为1．2％。DBS组未发生严重并发症。结论 核团毁损术和DBS两者被证实是中晚期帕金森病安全、有效的治疗方法，能显著改善术前帕金森病患者的UPDRS运动评分，减轻左旋多巴诱发的运动波动及异动症。STN—DBS较毁损术更具有独特的可控性、安全性和长效性。     

Switching dopamine agonists in advanced Parkinson's disease: is rapid titration preferable to slow?

BACKGROUND: New dopamine agonists are available, but no study has examined safe and effective ways to switch from one agonist to another. OBJECTIVE: To compare rapid- versus slow-titration schedules for starting a new dopamine agonist in patients already on chronic agonist therapy for Parkinson's disease. METHODS: Sixteen patients on stable carbidopa/levodopa and a dopamine agonist (bromocriptine or pergolide) switched to pramipexole using a conversion calculation of 1:1 for pergolide dose and 10:1 for bromocriptine dose. Patients were randomized to two titration schedules-either slow titration, following the package insert and taking up to 8 weeks to reach their equivalent dosage (8 patients), or rapid titration, receiving the full converted dose the day after stopping the former agonist (8 patients) with subsequent weekly dose adjustments. Using a blinded observer, the primary outcome variable was the time required to a Unified Parkinson's Disease Rating Scale (UPDRS) motor score superior to baseline without increased adverse effects. RESULTS: Both groups showed equivalent and statistically significant improvement after switching to the new agonist. The mean time to reach a UPDRS score that was superior to baseline without increased adverse effects was significantly shorter in the rapid-titration group (mean 2.1 weeks versus 5.3 weeks). Furthermore, with slow titration two patients experienced enhanced parkinsonian serious adverse effects requiring hospitalization (two falls with fractures). CONCLUSION: The switchover from one agonist to another can be safely and successfully accomplished with a rapid titration based on an equivalency dose calculation.     

微电极引导立体定向核团毁损和脑深部电刺激治疗帕金森病

目的研究微电极引导立体定向颅内核团毁损和脑深部电刺激手术(deep brain stimulation,DBS)治疗帕金森病的临床疗效。方法分析我院116例应用微电极引导立体定向核团毁损术和85例应用脑深部电刺激术治疗的帕金森病患者的临床资料,获得术前、术后和DBS开启后6个月、1年、3年及5年的不同服药状态下帕金森病联合评分量表(UPDRS)的评分,比较手术前后UPDRS运动评分的差异。结果核团毁损术和DBS在术后6个月、1年和3年的随访中均能显著改善患者术前UPDRS运动评分,在第5年仅DBS组UPDRS运动评分较术前有改善,同时DBS组患者术后抗帕金森病药物用量较术前减少。结论核团毁损和脑深部电刺激手术均能显著改善帕金森病患者的UPDRS运动评分,DBS疗效更为长久。     

Dopamine levels after repetitive transcranial magnetic stimulation of motor cortex in patients with Parkinson's disease: preliminary results.

BACKGROUND: Repeated session of repetitive transcranial magnetic stimulation (rTMS) over motor cortex have been reported to produce significant improvement of motor performance in patients with parkinson's disease (PD). In addition, it is known that a single session of rTMS over motor cortex transiently increases DA in striatum. Here, we test whether repeated sessions of rTMS increase serum dopamine in PD patients and whether this correlates with changes in clinical rating scales. MATERIAL AND METHODS: Twenty untreated PD patients with moderate to severe symptoms (Hoehn & Yahr state III-V 1967) were assessed on the Unified Parkinson's Disease Rating Scale (UPDRS), and with an enzyme immunoassay for quantitative determination of plasma dopamine before and after six daily sessions of 25 Hz rTMS with 3,000 stimuli over the right and left hand and leg motor cortex. RESULTS: There was significant improvement in UPDRS compared with the baseline. Serum dopamine level also was significantly elevated over the same interval. There was a significant correlation between UPDRS and serum dopamine level before and after treatment. CONCLUSION: Improved motor performance in PD after repeated session of rTMS may be related to an elevation of serum dopamine concentration.     

重复经颅磁刺激治疗帕金森病

目的探讨重复经颅磁刺激对帕金森病患者的治疗作用。方法采用重复经颅磁刺激方法对8例帕金森病患者进行治疗,另选择7例帕金森病患者作为对照。采用改进的H&Y(HoehnandYahr)评分标准、SchwabandEngland日常生活能力评分量表以及帕金森病症状评分量表(UPDRS)进行疗效评估。结果8例接受重复经颅磁刺激治疗的患者,于治疗第3、6和9个月时进行H&Y评分和UPDRS评分,与治疗前相比,这两种评分均明显下降(P<0.05),而SchwabandEngland日常生活能力评分则明显提高,治疗前后相比差异具有显著性意义(P<0.05);对照组治疗前后相比差异无显著性意义(P>0.05)。结论重复经颅磁刺激有助于缓解帕金森病患者的症状。     

Efficacy of piribedil as early combination to levodopa in patients with stable Parkinson's disease: a 6-month, randomized, placebo-controlled study.

Piribedil is a non-ergot D2/D3 agonist with a significant antagonist action on alpha2A and alpha2C adrenergic receptor subtypes. This double-blind placebo-controlled study was undertaken to confirm the efficacy of 150 mg/day piribedil po in improving motor symptoms of idiopathic Parkinson's disease (PD) in nonfluctuating patients insufficiently controlled by a stable daily dose of levodopa (L-dopa). Efficacy was assessed using the Unified Parkinson's Disease Rating Scale (UPDRS) III score as primary criterion over 4 months. A second comparison was planned at 6 months, after possible adjustment of L-dopa. At 4 months, the rate of response, defined as a 30% decrease from baseline on UPDRS III score, was significantly greater with piribedil compared with placebo (56.4% vs. 37.7%; P = 0.040). At 6 months, the better efficacy of piribedil was maintained (61.8% of responders vs. 39.6% on placebo; P = 0.020). The difference between groups on UPDRS III change from baseline reached statistical significance only at 6 months: -10.0 points in the piribedil group vs. -6.7 points in the placebo group (P = 0.037). Secondary end-points were not significantly different. The most frequently reported adverse events were gastrointestinal symptoms (27 of 61 patients in the piribedil group vs. 13 of 54 patients in the placebo group). In conclusion, a 6-month oral administration of 150 mg/day piribedil in combination with L-dopa is well tolerated, except for minor gastrointestinal symptoms at the beginning of the treatment and significantly improves motor symptoms compared with placebo in PD nonfluctuating patients.     

The role of sensory cues in the rehabilitation of parkinsonian patients: a comparison of two physical therapy protocols.

We devised a single-blind study to assess the role of providing external sensory cues in the rehabilitation of patients with idiopathic Parkinson's disease (PD). Twenty stable, nondemented patients with PD entered a 6-week rehabilitation program and were randomly assigned to two balanced protocols which were differentiated by the use of external sensory cues ("non-cued" vs "cued"). Patients were evaluated by a neurologist, who was blind to group membership, with the Unified Parkinson's Disease Rating Scale (UPDRS) at baseline, end of treatment, and after 6 weeks. Patient groups were comparable for age, disease duration, and severity. A significant reduction of UPDRS scores (activities of daily living and motor sections) was present after the rehabilitation phase in both groups. However, at follow up, while this clinical improvement had largely faded in the "non-cued" group, mean UPDRS scores of the "cued" group were still significantly lower than baseline values. The incorporation of external sensory cues in the rehabilitation protocol can extend the short-term benefit of physical therapy in moderately disabled patients with PD, possibly as a result of the learning of new motor strategies. "Cued" physical therapy for PD should be targeted to compensate for the defective physiological mechanisms.     

End-of-dose akinesia after a single intravenous infusion of the dopaminergic agonist piribedil in Parkinson's disease patients: a pharmacokinetic/pharmacodynamic, randomized, double-blind study.

This randomized, double-blind trial was designed to define the possible relationship between piribedil plasma concentrations and the decrease of the Unified Parkinson's Disease Rating Scale (UPDRS) motor score or the switch from off to on state after single intravenous infusion. Ten fluctuating patients with idiopathic Parkinson's disease (PD) received escalating doses of piribedil (2-16 mg) and placebo. Starting from 2 mg, piribedil was effective in reducing the motor deficit (UPDRS, motor score) including akinesia at the first evaluation time point of 15 minutes, and in reversing off state of 7 of 10 patients. The doses were equally effective, although the effect was more sustained with the highest dose of 16 mg. Piribedil was well tolerated up to a 16-mg dose and pharmacokinetics were linear up to the 16-mg dose. Plasma levels of piribedil were not correlated to the motor score improvement or switch from off-->on. In conclusion, a short single infusion of piribedil at 2 to 16 mg was safe and effective in improving motor symptoms, including akinesia, of fluctuating PD patients.     

Therapeutic effect of repetitive transcranial magnetic stimulation in Parkinson's disease.

The therapeutic effect of repetitive transcranial magnetic stimulation (r-TMS) on clinical performance was studied in 8 patients with Parkinson's disease (PD). Seven patients were used as controls and underwent sham stimulation. The modified Hoehn and Yahr (H & Y) Staging Scale, Schwab and England Activities of Daily Living (ADL) Scale and Unified Parkinson's Disease Rating Scale (UPDRS) were used to assess changes in clinical performance. Eight patients were assessed prior to and following 3, 6 and 9 months of R-TMS. R-TMS was applied manually 60 times (30 times each side) to the frontal areas using a large circular coil, a pulse intensity of 700 V, and a frequency of 0.2 Hz. Sessions were performed once weekly for 9 months. The 7 control patients showed no differences in clinical symptoms between initial evaluations and evaluations after 3 months of sham R-TMS. In all 8 patients, the modified H & Y staging and UPDRS scores decreased significantly, and the Schwab and England ADL Scale increased significantly after 3, 6 and 9 months of R-TMS therapy. These results suggest that R-TMS is beneficial for the treatment of Parkinsonian symptoms.     

帕金森病丘脑底核脑深部电刺激术后的长期随访研究

目的 研究丘脑底核脑深部电刺激(STN-DBS)术治疗帕金森病(PD)的长期临床效果.方法 对采用STN-DBS术治疗的75例PD患者进行术后长期随访.对患者手术前抗PD药物“关”与“开”状态进行统一帕金森病评定量表(UPDRS)评估;术后第1、3、5和10年,在STN-DBS持续治疗下对患者药物“关”与“开”状态进行...     

Therapeutic and "dose-dependent" effect of repetitive microelectroshock induced by transcranial magnetic stimulation in Parkinson's disease.

Transcranial magnetic stimulation (TMS) has been used in the diagnosis of neurological lesions and has been introduced into the therapy of central nervous diseases. Lately it has been claimed that TMS would be useful not only in the treatment of depression, but also in relieving symptoms of Parkinson's disease. In this study, we sought evidence of the effect of repetitive TMS on the symptoms of Parkinson's disease, the dose dependency between the applied elecromagnetic field and the Parkinsonian symptoms, and the maintenance of the improvement. Forty-nine patients with Parkinson's disease were divided into four groups, each given one stimulus, repeated 30 times, once or twice a day ( approximately 0.34Tesla (T), approximately 0.57T, approximately 0.80T). Patients were followed for 3 months and assessed using two different parkinsonian scales: the graded clinical rating scale and Unified Parkinson Disability Rating Scale (UPDRS), and with a short-term memory test (Ziehen-Ranschburg word pair test). No effect was seen in the group treated with approximately 0.34T\30 stimuli once a day. In all of the groups receiving TMS twice a day, the parkinsonian scores were significantly decreased compared with that of baselines after 1 month of treatment. The greatest improvement in the hypokinesia was detected in the group treated with approximately 0.57T\30 stimuli twice a day (baseline total UPDRS: 30.62 +/- 15.23; 1 month after treatment: 17.08 +/- 7.04, P < 0.01; 3 months after treatment: 16.08 +/- 7.06, P < 0.01). A dose-dependent difference was observed between the two groups after 3 months. The total UPDRS in Group II ( approximately 0.34T\30 stimuli twice a day) significantly differed from Group III ( approximately 0.57T\30 stimuli twice a day; 22.43 +/- 8.87, 16.08 +/- 7.06, P < 0.05). The long-lasting improvement effect with TMS would seem to suggest it as an appropriate tool in the therapy of Parkinson's disease.     

GPi pallidotomy for Parkinson's disease with drug-induced psychosis

Levodopa-induced psychosis may seriously threaten the ability of patients with Parkinson's disease (PD) to continue leading an independent life. A retrospective assessment of the therapeutic effects of the globus pallidus internus (GPi) pallidotomy on the activities of daily living (ADL) of seven PD patients presenting with mild or moderate degrees of psychosis was carried out. Their scores according to the Unified Parkinson's Disease Rating Scale (UPDRS) Part I-2 (maximum=4) were 2 or 3 (mean +/- SD=2.4 +/- 0.5). Bilateral procedure was needed in 5 out of 7 patients to obtain sufficient improvement of motor symptoms. At 3 months after surgery, UPDRS part III motor scores in the 'off' state were significantly decreased and motor fluctuations were abolished. Nevertheless, their score of Schwab and England (S-E) ADL scale scores responded poorly to the surgery, while the scores in other 12 patients without psychosis was significantly improved after pallidotomy. The data indicate that GPi pallidotomy ameliorates the motor symptoms in patients with drug-induced psychosis (DIP), but has no significant impact on their consequent daily activities. A regression model for all 19 patients who underwent pallidotomy revealed that postoperative S-E scale was affected by the preoperative UPDRS Part I-2 rather than by Part III motor score. The present study suggested that DIP, even if its degree is not severe, may be a limiting factor of the therapeutic potential of pallidotomy in patients with PD.     

Does severity of Parkinson's disease vary according to season?

In temperate climates, many factors that may influence function in Parkinson's disease (PD) vary according to season. We examined whether severity of PD, as measured by the Unified Parkinson's Disease Rating Scale (UPDRS), varied with the season of evaluation. We found no evidence for seasonal fluctuation in the UPDRS scores, suggesting that, although considerable day-to-day variation may exist in PD, there is little monthly or seasonal variation.     

Risperidone treatment of drug-related psychosis in patients with parkinsonism.

Risperidone, a novel neuroleptic with approximately equal D2 and 5HT2A receptor blocking properties, has been used to treat drug-related hallucinations in patients with Parkinson's disease. However, the results of only small numbers of patients have been reported with the drug demonstrating limited usefulness. We report our experience with this drug in 39 patients (25 women and 19 men) with parkinsonism. Monitored clinical data included duration of disease, Hoehn and Yahr score, Mini-Mental State Score, Unified Parkinson's Disease Rating Scale (UPDRS) prior to drug administration and after 3 and 6 months of treatment, and response to treatment. Twenty-three patients with Parkinson's disease had either complete or near-complete resolution of hallucinations whereas an unsatisfactory response (N = 6) or worsening of parkinsonism (N = 6) was noted in 12 patients, only six of whom had Parkinson's disease. Excluding patients with diffuse Lewy body disease, there was no significant worsening of the UPDRS scores after either 3 or 6 months of treatment. The presence of dementia did not predict response to treatment. Our results suggest that risperidone is a useful treatment for hallucinations in patients with parkinsonism.     

Deep brain stimulation of the subthalamic nucleus: effectiveness in advanced Parkinson's disease patients previously reliant on apomorphine

OBJECTIVES: To assess the efficacy of bilateral subthalamic nucleus (STN) deep brain stimulation (DBS) in patients with advanced Parkinson's disease previously reliant on apomorphine as their main antiparkinsonian medication. METHODS: Seven patients with motor fluctuations despite optimal medical treatment given as predominantly apomorphine infusion (n=6), or intermittent apomorphine injections (n=1) underwent bilateral STN DBS using frameless stereotactic surgery. Standard assessments of parkinsonism and motor fluctuations, using Unified Parkinson's Disease Rating Scale (UPDRS) were performed before and six months after surgery. Assessments were performed both on and off medication, and postoperative with the stimulators switched on and off. RESULTS: Bilateral STN DBS improved motor scores (UPDRS III) by 61% when off medication (p<0.05). Clinical fluctuations (UPDRS IV items 36-39) were reduced by 46.2% (p<0.05). Total daily apomorphine dose was reduced by 68.9% (p<0.05) and apomorphine infusion via a pump was no longer required in four patients. There were no operative complications. Two patients required treatment for hallucinations postoperatively but there was no significant change in mini-mental state examination. CONCLUSIONS: In patients with advanced Parkinson's disease, previously reliant on apomorphine, bilateral STN DBS is an effective treatment to reduce motor fluctuations and enable a reduction in apomorphine use.