Botulinum toxin type A for drooling in Parkinson's disease: a double-blind, randomized, placebo-controlled study.

To investigate the safety and efficacy of botulinum toxin type A (BoNTX) treatment to reduce sialorrhea in Parkinson's disease (PD), a double-blind, randomized, placebo-controlled study enrolled 32 PD patients complaining of excessive drooling. Patients received either 50 U Botox in each parotid gland or placebo without using ultrasound guidance. Subjects treated with BoNTX experienced a reduction in both drooling frequency and familial and social disability (TimexGroup effect: P<0.01), as well as in saliva production (Time x Group effect: P<0.0001). No adverse events were recorded. BoNTX injections are safe and effective treatment for the management of PD-related drooling.     

Drooling in Parkinson's disease: A review

Parkinson's disease (PD) is a neurodegenerative disease causing both motor and non-motor symptoms. Drooling, an excessive pooling and spillover of saliva out of the oral cavity, is one of the non-motor symptoms in PD patients that produces various negative physical and psychosocial consequences for patients and their caregivers. At present, the pathophysiology of drooling in PD is not completely certain; however, impaired intra-oral salivary clearance is likely the major contributor. There are neither standard diagnostic criteria nor standard severity assessment tools for evaluating drooling in PD. In accordance with the possible pathophysiology, dopaminergic agents have been used to improve salivary clearance; however, these agents are not completely effective in controlling drooling. Various pharmacological and non-pharmacological treatment options have been studied. Local injection with botulinum toxin serotypes A and B into major salivary glands is most effective to reduce drooling. Future research to explore the exact pathophysiology and develop standard diagnostic criteria and standard severity assessment tools are needed to formulate specific treatment options and improve patient care.     

Botulinum toxin A and the cutaneous nociception in humans: a prospective,double-blind,placebo-controlled,randomized study

Aside from temporary chemodenervation of skeletal muscle and potential anti-inflammatory effects, a genuine peripheral antinociceptive effect of Botulinum Neurotoxin Type A (BoNT/A) has been suspected. To evaluate the effect of BoNT/A on cutaneous nociception in humans, 50 healthy volunteers received subcutaneous injections of 100 mouse units (MU) BoNT/A (Dysport) and placebo. Both forearms of each subject were treated in a double-blind fashion, one with verum, one with placebo. Heat and cold pain thresholds within the treated skin areas were measured with quantitative sensory testing (QST) and pain thresholds were evaluated with local electrical stimulation (ES). The tests were done before treatment, and after 4 and 8 weeks. No major side effects were noted. All participants completed the study. Heat and cold pain thresholds increased from baseline to week 4 by 1.4 degrees C for verum and by 1.1 degrees C for placebo. From baseline to week 8, the thresholds increased by 2.7 degrees C for verum and by 1.2 degrees C for placebo. Electrically induced pain thresholds shifted from baseline to week 4 by -0.07 mA for verum and by 0.01 mA for placebo. From baseline to week 8, the thresholds increased by 0.10 mA for verum and by 0.11 mA for placebo. None of these differences was statistically significant. The study shows that there is no direct peripheral antinociceptive effect of BoNT/A in humans. The efficacy of BoNT/A in various pain syndromes must be explained by other pathways such as chemodenervation or anti-inflammatory effects.     

The use of famotidine in the treatment of Parkinson's disease: a pilot study

Summary Seven patients with idiopathic Parkinson's disease were enrolled in a ten week study to evaluate the efficacy of famotidine, an histamine H2-antagonist, in the treatment of bradyphrenia. Patients received famotidine 80 mg/day for a period of six weeks and were evaluated with neuropsychological tests. Overall, patients demonstrated improvement in variables measured. Some patients also reported an improvement in their motor symptoms.     

Reduced MIBG accumulation of the parotid and submandibular glands in idiopathic Parkinson's disease

IntroductionAlpha-synuclein pathology (ASP) is a characteristic histopathological finding in idiopathic Parkinson's disease (PD). The ASP involves not only the brain but also extracranial structures. In the present study we utilized MIBG scintigraphy to measure the sympathetic innervation of the major salivary glands. We were interested in whether MIBG uptake in the major salivary glands represents a potential biomarker for ASP in PD.MethodsWe investigated 77 PD patients (age 61 ± 10 years, mean ± SD), while 15 non-PD patients (age 58 ± 15 years) with arterial hypertension, who underwent MIBG scintigraphy to exclude pheochromocytoma, served as age-matched controls. The MIBG uptake of the parotid glands and the submandibular glands was quantified by means of a region of interest technique. The sublingual glands were too small for an exact measurement. We applied Generalized Estimating Equations (GEE) to identify and remove factors which may bias the statistical correlation analysis.ResultsThe PD patients showed a significantly lower MIBG uptake in the parotid and submandibular glands than the controls (p < 0.0001). MIBG uptake in the PD patients did not correlate with clinical severity (Hoehn and Yahr stage, motor part of the UPDRS) or disease duration.ConclusionMIBG uptake in the parotid and submandibular glands might be a candidate biomarker for PD. The missing correlation between MIBG uptake and clinical PD parameters suggests that ASP of the extracranial sympathetic superior cervical ganglion, which innervates the major salivary glands, develops independently from the cerebral dopaminergic nigrostriatal ASP.     

Treatment of depression in Parkinson's disease with moclobemide: A pilot open-label study

Moclobemide, a potent reversible monoamine-oxidase A (MAO-A) inhibitor, is an effective antidepressant that does not cause impairment of cognitive function in elderly patients and might be beneficial to motor deficits in Parkinson's disease (PD). In a 12-week open-label prospective study, we administered moclobemide (300–600 mg day⁻¹) as an add-on medication to twelve PD patients who met DSM-III-R criteria for depressive illness. There were two early drop-outs due to subjective worsening of Parkinsonism associated with insomnia and anorexia, respectively. The Beck Depression Inventory score decreased significantly in the ten patients who completed the study, and clinical global assessment of efficacy recorded ‘good’ or ‘excellent’ responses or in nine of the ten patients. Mean parkinsonian disability, as assessed by the Unified Parkinson's Disease Rating Scale (UPDRS) and Schwab-England Daily Life Activities scales, remained unchanged throughout the study in the group as a whole. However, worsening or onset of resting tremor occurred in five patients and the UPDRS tremor subscore in the group overall was significantly higher by week 8 (p = 0.03) when dose titration was optimal. There was a trend toward improvement in UPDRS bradykinesia subscores that did not attain statistical significance. Compared to baseline, patients complained more often of insomnia, anorexia, increased perspiration, and restlessness. Though these preliminary results need to be replicated in a large controlled trial, we suggest that moclobemide may be an effective alternative in the treatment of PD associated depression.     

Validity and inter-rater reliability of inertial gait measurements in Parkinson's disease: a pilot study

Walking models driven by centre of mass (CoM) data obtained from inertial measurement units (IMU) or optical motion capture systems (OMCS) can be used to objectively measure gait. However current models have only been validated within typical developed adults (TDA). The purpose of this study was to compare the projected CoM movement within Parkinson's disease (PD) measured by an IMU with data collected from an OMCS after which spatio-temporal gait measures were derived using an inverted pendulum model. The inter-rater reliability of spatio-temporal parameters was explored between expert researchers and clinicians using the IMU processed data.Participants walked 10 m with an IMU attached over their centre of mass which was simultaneously recorded by an OMCS. Data was collected on two occasions, each by an expert researcher and clinician.Ten people with PD showed no difference (p = 0.13) for vertical, translatory acceleration, velocity and relative position of the projected centre of mass between IMU and OMCS data. Furthermore no difference (p = 0.18) was found for the derived step time, stride length and walking speed for people with PD.Measurements of step time (p = 0.299), stride length (p = 0.883) and walking speed (p = 0.751) did not differ between experts and clinicians. There was good inter-rater reliability for these parameters (ICC3.1 = 0.979, ICC3.1 = 0.958 and ICC3.1 = 0.978, respectively).The findings are encouraging and support the use of IMUs by clinicians to measure CoM movement in people with PD.     

Lifestyle-related risk factors for Parkinson's disease: a population-based study

OBJECTIVES: To investigate the association of major lifestyle-related risk factors with the prevalent cases of Parkinson's disease (PD) identified by the Italian Longitudinal Study on Aging. METHODS: A total of 5632 individuals randomly selected from the population registers of eight centers were screened for parkinsonism using both a questionnaire and a neurologic examination. Screened positives underwent a structured clinical work-up for the diagnosis of parkinsonism and parkinsonism subtypes. RESULTS: We identified 113 prevalent cases of PD. Age, male gender, and pesticide-use license were significantly related to PD. Heavy smoking was inversely related to PD. Age (OR = 1.1; 95% CI, 1.06-1.15) and pesticide-use license (OR = 3.7; 95% CI, 1.6-8.6) kept their significant correlation with the disease in the multivariate analysis to adjust for all the variables under investigation. Multivariate analyses were made for men and women separately: pesticide exposure was positively associated with PD only in men. CONCLUSIONS: Pesticide exposure might represent a candidate for environmental factors involved in PD.     

Activity and acceptability of piribedil in Parkinson's disease: a multicentre study

Several controlled trials have shown that the dopamine agonist, Trivastal (piribedil), is active in the treatment of Parkinson's disease, particularly with regard to tremor. To determine its efficacy as monotherapy in patients previously untreated with levodopa, a 3-month multicentre study was conducted with Trivastal 50 mg LP in 113 patients with idiopathic Parkinson's disease. The study population consisted of 66 men and 47 women, aged 63.1, SD 0.6 (43–79) years with a 2.1, SD 0.2 (1–15) year history of Parkinson's disease. Mean disease stage was 1.82 (1–4) by the Hoehn and Yahr classification. Tremor was the predominant clinical feature in 42 patients; the remaining 71 patients displayed the full parkinsonian syndrom. Trivastal 50 mg LP was prescribed stepwise up to doses of 150–250 (207, SD 6.4) mg/day at the end of 3 months. No concomitant antiparkinsonian medication was given. Patients were clinically assessed at 1, 2 and 3 months on the Webster scale, a specific tremor scale and the HARD depression scale. Mean results were as follows in the 90 patients completing the study. On the Webster scale, tremor fell from 1.7 to 1 (–41%,P<0.001), bradykinesia=" from=" 1.5=" to=" 0.8=">P<0.001) and=" rigidity=" from=" 1.3=" to=" 0.9=">P < 0.001);=" on=" the=" specific=" scale,=" rest=" tremor=" decreased=" in=" daily=" duration=" and=" amplitude=" from=" 3.9=" to=" 2.4=">P < 0.001)=" and=" from=" 2.9=" to=" 2.1=">P < 0.001),=" respectively.=" the=" 32=" patients=" in=" whom=" tremor=" was=" the=" predominant=" feature=" improved=" their=" total=" score=" on=" the=" webster=" scale=" from=" 5.8=" to=" 4.7=">P<0.05) and=" their=" tremor=" score=" from=" 1.7=" to=" 1.2=">P < 0.05).=" the=" 58=" patients=" with=" the=" full=" parkinsonian=" syndrom=" improved=" their=" total=" webster=" score=" from=" 11.8=" to=" 6.9=">P < 0.001).=" eight=" of=" the=" ten=" items=" on=" the=" scale=" were=" significantly=" reduced,=" from=" between=" 33%=" (facial=" expression)=" to=" 53%=" (manual=" bradykinesia).=" the=" depression=" rating=" fell=" from=" 10.2=" to=" 7.3=">P < 0.001),=" the=" most=" marked=" improvement=" being=" in=" mood=" and=" inhibition.=" in=" conclusion,=" monotherapy=" with=" trivastal=" 50=" mg=" lp=" at=" a=" mean=" dose=" of=" 200=" mg/day=" is=" effective=" within=" 1=" month=" regarding=" the=" major=" features=" of=" parkinson's=">     

Sleep disorders in Chinese patients with Parkinson's disease: validation study of a Chinese version of Parkinson's disease sleep scale

To evaluate the Chinese version of the Parkinson's disease sleep scale (PDSS) as an instrument for measuring sleep disorders in Chinese patients with Parkinson's disease (PD). The objective of the present study was to carry out a metric analysis of a Chinese version of PDSS using a cross-sectional study of 126 patients with PD who participated in the study. Usual measures for PD patients including the Pittsburgh sleep quality index (PSQI), the Epworth sleepiness scale (ESS), the Geriatric Depression Scale (GDS), and the Hamilton Anxiety Scale (HAMA) were applied by neurologists. The intra-class correlation coefficient was 0.880, and test-retest reliability for total PDSS score was 0.914. The Mean total PDSS score was 118.38+/-26.07. There was a significant correlation between the PDSS and PSQI, between the PDSS and ESS, between the PDSS and GDS, between the PDSS and HAMA, between the PDSS and the disease durations, and between the PDSS and the LDE, respectively. The Chinese version of PDSS met some basic standards required for sleep disorders measures. It could lead to better understanding the sleep disorders of PD of China in future studies.     

Botulinum toxin type A potentiates the effect of neuromotor rehabilitation of Pisa syndrome in Parkinson disease: A placebo controlled study

IntroductionPisa syndrome (PS) is a tonic lateral flexion of trunk that represents a disabling complication of advanced Parkinson disease (PD).Conventional rehabilitation treatment (CT) ameliorates axial posture and trunk mobility in PD patients, but the improvement tends to wane in 4–6 months. Botulin toxin (BT) may reduce muscle hyperactivity, therefore improving CT effectiveness. We evaluated whether the injection of incabotulinum toxin type A (iBTA) into the hyperactive trunk muscles might improve the effectiveness of rehabilitation in a group of PD patients with PS.MethodsTwenty-six PD patients were enrolled in a randomized placebo-controlled trial. Group A was treated with iBTA before undergoing CT (a 4-week intensive programme), while Group B received saline before the 4-week CT treatment. Patients were evaluated at baseline, at the end of the rehabilitative period, 3 and 6 months with kinematic analysis of movement, UPDRS, Functional Independence Measure and Visual Analog Scale for pain.ResultsAt the end of the rehabilitation period, both groups improved significantly in terms of static postural alignment and of range of motion. Group A showed a significantly more marked reduction in pain score as compared with Group B and a more prolonged efficacy on several clinical and kinematic variables.ConclusionsOur preliminary data suggest that BT may be considered an important addition to the rehabilitation programme for PD subjects with PS for improving axial posture and trunk mobility, as well as for a better control of pain.     

The effect of botulinum toxin injections to the calf muscles on freezing of gait in parkinsonism: a pilot study

Background Freezing of gait (FOG) is a common and very disabling parkinsonian symptom, which is poorly understood and responds unsatisfactorily to medical treatment. We recently reported a unique patient with Parkinson's disease (PD) who had significant alleviation of FOG shortly after she was injected with botulinum toxin type A (BTX-A) for foot dystonia (Giladi et al. 1997). Objective To assess the effect of BTX-A injections into the calf muscles of parkinsonian patients on FOG. Method BTX-A was injected in an open fashion into the calf muscles of 10 parkinsonian patients (age 55–75 years) with FOG as a predominant symptom. Response of FOG was assessed subjectively by the patient from worsening (–1) to marked improvement (+3). One patient was injected in a single blind fashion with saline or BTX-A after he had an initial good response. Results Seven patients reported different rates of improvement of FOG severity in 15 out of 17 therapeutic sessions. Four patients (40%) reported marked improvement (+3) of FOG in 5 sessions. Two patients reported no effect in two sessions. The mean duration of improvement was 6 weeks (range 1–12 weeks) with definite deterioration afterwards. The patient who was injected in a single blind fashion did not respond to saline injections but improved significantly with BTX-A treatment. Conclusions We observed a clear temporal relationship between BTX-A injections into the calf muscles of parkinsonian patients and improvement of FOG. A double blind placebo controlled prospective study is needed before any conclusions can be drawn about the role of BTX-A injection in FOG. Received: 31 August 2000 / Received in revised form: 24 October 2000 / Accepted: 19 January 2001     

Drooling rating scales in Parkinson's disease: A systematic review

BackgroundDrooling is a clinically relevant non-motor symptom of people with Parkinson's disease (PwP). Several drooling rating scales are available. Nevertheless, the compelling scientific evidence supporting their validity is limited. This study aims to evaluate clinical rating scales for drooling, assessing their characteristics, clinimetric properties, and clinical utility classification.MethodsA systematic review was undertaken. Two reviewers performed independent literature searches using the CENTRAL®, CINAHL®, Embase®, MEDLINE®, SciElo®, and SPEECH BITE® databases. We used consensus-based standards for the selection of health measurement instruments (COSMIN) and the International Parkinson's disease and the Movement Disorders (MDS) criteria to evaluate the included rating scales.ResultsThe following six rating scales were identified: Drooling Impact Scale (DIS), Sialorrhea Scoring Scale (SSS), Drooling Severity and Frequency Scale (DSFS), Drooling Rating Scale (DRS), Sialorrhea Clinical Scale for Parkinson Disease (SCS-PD), and the Radboud Oral Motor inventory for Parkinson's disease – Saliva (ROMP-saliva). The scales had heterogeneous characteristics: (i) not all were created/adapted for PwP; (ii) different dimensions associated with drooling are assessed; (iii) cross-cultural adaptations are limited to some languages. The clinimetric properties showed: (i) target population size limitations; (ii) incomplete reliability analysis; (iii) lack of robust validity; (iv) sensitivity to change not fully explored. Following the MDS criteria, only one tool was classified as “recommended”, the ROMP-saliva.ConclusionsThis review provides information for an adequate selection of a drooling rating scale for clinical and/or research purposes. To date, ROMP-saliva is the only scale with substantial evidence of its clinimetric properties adequacy and data in PwP.     

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.     

Mobility and balance in Parkinson's disease: a population-based study

Background and purpose:  To assess the clinical correlates of mobility and balance, and to identify the risk factors for falls in Parkinson's disease (PD).
Methods:  One-hundred and nineteen PD patients underwent clinical examination and tests for mobility and balance using the Timed Up & Go (TUG) test, walking speed, and the measurement of postural sway.
Results:  The fallers (35% of the subjects) performed significantly worse in the TUG test than the non-fallers, and they also had a slower walking speed ( P  =   0.037 and P  =   0.006, respectively). The total Unified Parkinson's Disease Rating Scale (UPDRS) score and age were positively associated with the TUG-test score. The severity of the disease and the use of walking aids correlated negatively with the walking speed, whereas the use of dopamine agonists was positively associated with the walking speed. The UPDRS total score [odds ratio (OR) 1.04, 95% confidence intervals (CI) 1.01–1.07] and increased postural sway (OR 1.25, 95% CI 1.02–1.54) were independent risk factors for falling in PD.
Conclusion:  Advanced age and severity of the disease are related to impaired mobility and balance in PD patients. The severity of the disease and increased postural sway seem to be the most important independent risk factors for falling in PD.     

Botulinum toxin A may be efficacious as treatment for jaw tremor in Parkinson's disease.

Jaw tremor in Parkinson's disease (PD) may not respond well to conventional treatment. It causes embarrassment and social handicap. We piloted the use of botulinum toxin (BTX) injections in three patients with PD jaw tremor. BTX A (Dysport; mean, 53 U; range, 30-100 U) was given into each masseter muscle. Outcome was assessed by subjective and clinical improvement and by video recording before and 4 to 9 weeks after injections. There was an excellent response in all without side effects. BTX injections into the masseter may effectively improve jaw tremor and be useful in PD and other conditions.     

Levodopa-induced striatal activation in Parkinson's disease: A functional MRI study

ObjectiveTo assess the effect of a single levodopa dose (200 mg levodopa, 50 mg carbidopa = sdLD) on cortical and subcortical motor-circuit activation during bimanual grip force in patients with Parkinson's disease (PD).Patients and methodsWe studied 12 right-handed patients with PD (Hoehn–Yahr stages I–II) after a period of at least 12 h without medication (OFF state) and a second time 1 h after oral administration of sdLD (ON state) using functional magnetic resonance imaging (fMRI). Blood-oxygenation-level-dependency (BOLD) fMRI was measured while participants underwent two unilateral and two bimanual grip force movements with a defined movement amplitude and force (10 N) in a block design. 12 age matched healthy subjects were studied as controls (without administration of sdLD).ResultsBimanual grip force tasks activated a specific pattern of cortical and subcortical structures in all patients during the OFF state and after levodopa administration with statistically significant differences in putamen and thalamus comparing the OFF and ON condition. In contrast, no such significant changes were observed in cortical structures. Between-group analysis revealed higher putaminal activity in controls compared to OFF state in bimanual tasks, while these differences disappeared after administration of levodopa.ConclusionsOur results indicate that the putamen and thalamus are the regions within the cortico-subcortical motor-circuit with most prominent response to levodopa. In our study, cortical motor areas did not respond to levodopa as one could have expected from previous studies. These findings contribute to the increasing evidence that an extended model of the underlying pathophysiology of motor dysfunctions in PD is warranted.     

帕金森病患者双眼竞争的研究

目的 采用双眼竞争范式,探讨帕金森病（PD）患者的双眼竞争交替速率及其可能的神经机制。方法 选取临床确诊的原发性PD患者32例（PD组）以及与其人口学资料相匹配的健康对照者32例（HC组）作为研究对象,采用双眼竞争范式进行双眼竞争交替速率的检查。结果 PD组双眼竞争交替速率[（0.24±0.07）Hz]较健康对照组[（0.35±0.11）Hz]显著减慢,且二者差异有统计学意义（t=-4.653,P=0.000）。结论 PD患者双眼竞争交替速率较健康对照组显著减慢,推测因其额叶﹣基底节的神经通路损伤从而削弱了知觉的交替变化而影响了双眼竞争交替速率。     

Environmental risk factors of young onset Parkinson's disease: a case-control study

While the cause of Parkinson's disease (PD) remains unknown, recent evidence suggests certain environmental factors, such as well water drinking, herbicides and pesticides exposure, and neurotoxins, may trigger the chain of oxidative reactions culminating in the death of dopaminergic neurons in substantia nigra to cause parkinsonism. Most studies to date focused on PD with old age onset. However, there is a peculiar group of parkinsonian patients, the young onset Parkinson's disease (YOPD), in whom the age of onset is before 40. It is intriguing to know whether earlier exposure to the putative neurotoxin(s) may contribute to the earlier onset. We therefore conducted this case-control study in which 60 PD patients, 30 YOPD patients and the same number of age- and sex-matched young controls were included. Using logistic regression, we found well water drinking and head injury were risk factors for the development of YOPD. When YOPD patients were compared with PD, we found head injury and exercise were the significant predictors. Keeping all other variables constant, head injury was a risk factor and exercise appeared to be a protective factor. We conclude early exposure to well water drinking and head trauma may trigger and expedite the appearance of parkinsonian features, but such acceleration may be prevented through regular exercise.