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.     

Three simple clinical tests to accurately predict falls in people with Parkinson's disease

Falls are a major cause of morbidity in Parkinson's disease (PD). The objective of this study was to identify predictors of falls in PD and develop a simple prediction tool that would be useful in routine patient care. Potential predictor variables (falls history, disease severity, cognition, leg muscle strength, balance, mobility, freezing of gait [FOG], and fear of falling) were collected for 205 community‐dwelling people with PD. Falls were monitored prospectively for 6 months using monthly falls diaries. In total, 125 participants (59%) fell during follow‐up. A model that included a history of falls, FOG, impaired postural sway, gait speed, sit‐to‐stand, standing balance with narrow base of support, and coordinated stability had high discrimination in identifying fallers (area under the receiver‐operating characteristic curve [AUC], 0.83; 95% confidence interval [CI], 0.77–0.88). A clinical tool that incorporated 3 predictors easily determined in a clinical setting (falling in the previous year: odds ratio [OR], 5.80; 95% CI, 3.00–11.22; FOG in the past month: OR, 2.39; 95% CI, 1.19–4.80; and self‐selected gait speed < 1.1 meters per second: OR, 1.86; 95% CI, 0.96–3.58) had similar discrimination (AUC, 0.80; 95% CI, 0.73–0.86) to the more complex model (P = 0.14 for comparison of AUCs). The absolute probability of falling in the next 6 months for people with low, medium, and high risk using the simple, 3‐test tool was 17%, 51%, and 85%, respectively. In people who have PD without significant cognitive impairment, falls can be predicted with a high degree of accuracy using a simple, 3‐test clinical tool. This tool enables individualized quantification of the risk of falling. © 2013 Movement Disorder Society     

Recurrent falls and mortality in Parkinson’s disease: a prospective two‐year follow‐up study

Matinolli M, Korpelainen JT, Sotaniemi KA, Myllylä VV, Korpelainen R. Recurrent falls and mortality in Parkinson’s disease: a prospective two‐year follow‐up study.
Acta Neurol Scand: 2011: 123: 193–200.
© 2010 John Wiley & Sons A/S. Objectives – To evaluate the risk factors for recurrent falling and mortality in Parkinson’s disease (PD) in a prospective study design. Materials and methods – One hundred and twenty‐five PD patients were included in the study. Baseline medical data were collected, and patients were clinically tested for mobility and balance. Falls were prospectively recorded for 2 years. Mortality was documented 4 years after the baseline. Results – Seventy‐nine patients reported altogether 3125 falls during the follow‐up, and 59 patients were classified as recurrent fallers. Altogether 126 fall injuries including six fractures were reported. Eighteen patients had died by the time of the hospital chart review. History of falling (OR 3.02, 95% CI 1.23–7.44) and the Unified Parkinson’s Disease Rating Scale activities of daily living score (OR 1.13, 95% CI 1.04–1.22) were independent risk factors for recurrent falling in PD, whereas slow walking speed (OR 16.28, 95% CI 1.85–142.97) was an independent risk factor for mortality in PD. Conclusions – History of falling and disease severity indicate increased risk of recurrent falls in PD, while patients with slow walking speed may have an increased risk of mortality. Recurrent falling was not associated with increased risk of mortality in PD in this study.     

Gait dynamics in Parkinson's disease: relationship to Parkinsonian features,falls and response to levodopa

OBJECTIVES: Patients with Parkinson's disease (PD) have an increased risk of falling that has yet to be fully explained. To better understand the gait disturbance in PD and the factors that contribute to falls, we quantitatively evaluated: (1) the relationship between gait variability (a marker of fall risk in other populations), fall history, and other parkinsonian features, and (2) the effects of levodopa on these relationships. METHODS: The average stride time and stride-to-stride variability were measured using force-sensitive insoles during comfortable walking. Fall frequency, motor control, function, and mental health were measured using the Unified Parkinson's Disease Rating Scale (UPDRS), the Mini-Mental State Exam (MMSE), and the timed motor tests of the Core Assessment Program for Intracerebral Transplantations (CAPIT) in 32 subjects with idiopathic PD, in an "off" (unmedicated) state and again in an "on" (medicated) state. RESULTS: Average stride time was not associated with any UPDRS or CAPIT measure and was similar in fallers and non-fallers in "off" and "on" states (p>0.27). Stride time variability was significantly associated with fall frequency as well as with total scores on the CAPIT and the UPDRS, ADL abilities, and motor function. Stride time variability and falls were not related to tremor, rigidity or bradykinesia in the "off" state. 41% of subjects reported one or more falls. Stride time variability was 8.8+/-7.9% in fallers and 4.2+/-1.3% in non-fallers (p<0.009). Stride time variability significantly improved in response to levodopa, both in fallers and non-fallers, but remained increased in fallers (vs. non-fallers). CONCLUSIONS: The patho-physiology responsible for impaired stride-to-stride regulation of gait timing is apparently independent of other cardinal features of PD, i.e., tremor, rigidity, or bradykinesia, but is responsive to levodopa. Stride-to-stride variability is especially impaired among PD subjects with a history of falls, suggesting, for the first time, the possibility of exaggerated impairment of internal clock function in PD fallers.     

Fall frequency and risk assessment in early Parkinson's disease

BackgroundWe sought to define the frequency of falls in early PD and assess potential risk factors for falls in this population.MethodsWe analyzed the data from two randomized, placebo controlled trials (NET-PD FS1 and FS-TOO) of 413 individuals with early PD over 18 months of follow-up in FS1 and 12 months in FS-TOO. Falls were defined as any report of falls on the UPDRS or the adverse event log. We assessed the frequency of falls overall and by age. The relationship between prespecified fall risk markers and the probability of falling was assessed using logistic and multiple logistic regression. A hurdle Poisson model was used to jointly model the probability of remaining fall-free and the number of falls.ResultsDuring the follow-up period, 23% of participants fell, and 11% were habitual fallers. In a multiple logistic regression model, age, baseline UPDRS Falling score, and baseline PDQ-39 scores were associated with subsequent fall risk (p < 0.001). Similarly, in a hurdle Poisson regression model, age, baseline UPDRS falling item, and baseline PDQ-39 were all significantly related to the probability of falling, but only UPDRS falling >0 was associated with the number of falls.ConclusionFalls are frequent and are associated with impaired quality of life, even in early PD. Current standard rating scales do not sufficiently explain future fall risk in the absence of a prior fall history. New assessment methods for falls and postural instability are required to better evaluate this important problem in clinical trials and clinical practice.     

Excessive postural sway and the risk of falls at different stages of Parkinson's disease

Excessive postural sway may result in falls in Parkinson's disease (PD). We measured postural sway using the sensory organization test (SOT) of dynamic posturography in static (platform still) and dynamic (sway referenced platform) conditions with normal, no and inappropriate visual feedback in 102 subjects with PD, off medication. Twenty‐five healthy subjects were used as age‐matched controls. Eighteen very early stage PD subjects had never used dopaminergic medication. Postural sway was normal in those subjects in all conditions, but was abnormal in subjects with more advanced symptoms (UPDRS III > 20, P < 0.01). Postural sway increased with disease severity in all conditions except static, eyes closed (P < 0.0001). We developed the SOT Fall Severity Scale (SOTFSS) from the number of times postural sway was so large that the subject had to take a step (registered as a “fall”) and showed that falls mainly occurred in dynamic conditions, and were correlated with disease severity (P < 0.0001). In dynamic conditions the SOTFSS was correlated with the retropulsion score from the UPDRS III (N = 102, P < 0.0001) and with the subjects' self‐reported fall frequency from the UPDRS II (N = 62, SOT5: P = 0.0419, SOT6: P = 0.0034). © 2008 Movement Disorder Society     

Clinical and posturographic correlates of falling in Parkinson's disease

Various clinical tests and balance scales have been used to assess postural stability and the risk of falling in patients with idiopathic Parkinson's disease (IPD). Quantitative posturography allows a more objective assessment but the findings in previous studies have been inconsistent and few studies have investigated which posturographic measures correlate best with a history of falling. The purpose of this study was to determine the efficacy of clinical tests, balance scales, and stable‐platform posturography in detecting postural instability and discriminating between fallers and non‐fallers in a home‐dwelling PD cohort. Forty‐eight PD subjects (Hoehn & Yahr stage 1–3) and 17 age‐matched controls had the following assessments: Activities‐specific Balance Confidence scale, Berg Balance Scale, Unified Parkinson's Disease Rating Scale (UPDRS) (motor), pull‐test, timed up‐and‐go, static posturography, and dynamic posturography to assess multidirectional leaning balance. Of the clinical assessments, all but the pull‐test were closely correlated with a history of falling. Static posturography discriminated between PD fallers and controls but not between PD fallers and non‐fallers, whereas dynamic posturography (reaction time, velocity, and target hit‐time) also discriminated between fallers and non‐fallers. Our findings suggest that this combination of clinical and posturographic measures would be useful in the prospective assessment of falls risk in PD patients. A further prospective study is now required to assess their predictive value. © 2013 Movement Disorder Society     

Natural history of falls in a population-based cohort of patients with Parkinson's disease: An 8-year prospective study

BackgroundProspective long-term studies of falls in Parkinson's disease (PD) are scarce.ObjectiveTo examine the development of falls over 8 years in a population-based cohort of ambulatory patients with PD, and to investigate predictors of future falls in non-fallers at baseline.MethodsAll patients were examined at baseline and after 4 and 8 years, including the UPDRS, MMSE, Montgomery and Aaberg Depression Rating Scale, Functional Comorbidity Index, and a clinical dementia interview. Logistic regression models were applied to investigate baseline risk factors for future falls. A total of 211 patients were included at baseline, whereas 121 and 64 were re-examined at 4 and 8 years, respectively.ResultsThe prevalence of falls increased from 41% (87 of 211) at baseline to 72% (46 of 64) after 8 years of prospective follow-up (disease duration 16.2 ± 4.8 years). Forty-seven non-falling patients at baseline completed all study visits, of these 68% (n = 32) changed fall status during follow-up. Predictive variables for current falling after 4 years were rare or occasional freezing of gait (OR 6.6, 95% CI 1.2–36.9), higher levodopa equivalent doses and more severe speech and axial impairment (both OR 1.3, 95% CI 1.0–1.7) in non-fallers at baseline. Higher baseline age was the only risk factor for current falling after 8 years.ConclusionsNearly ¾ of the PD cohort reported falling after 8 years of follow-up. Disease-specific gait and axial impairments were the major risk factors for future falls in non-fallers at baseline. This has implications for patient education and management.     

Clinical and physiological assessments for elucidating falls risk in Parkinson's disease

The study aims were to devise (1) a fall risk screen for people with PD using routine clinical measures and (2) an explanatory (physiological) fall risk assessment for guiding fall prevention interventions. One hundred thirteen people with PD (age 66 ± 95% CI 1.6 years) underwent clinical assessments and quantitative tests of sway, gait, strength, reaction time, and lower limb sensation. Participants were then followed up for 12 months to determine fall incidence. In the follow‐up year, 51 participants (45%) fell one or more times whereas 62 participants (55%) did not fall. Multivariate analyses of routine clinical measures revealed that a fall in the past year, abnormal axial posture, cognitive impairment, and freezing of gait were independent risk factors for falls and predicted 38/51 fallers (75%) and 45/62 non‐fallers (73%). A multivariate model combining clinical and physiological measures that elucidate the pathophysiology of falls identified abnormal posture, freezing of gait, frontal impairment, poor leaning balance, and leg weakness as independent risk factors. This model correctly classified 39/51 fallers (77%) and 51/62 non‐fallers (82%). Patients with PD at risk of falls can be identified accurately with routine clinical assessments and quantitative physiological tests. Many of the risk factors identified are amenable to targeted intervention. © 2009 Movement Disorder Society     

The incidence and risk factors of falls in Parkinson disease: prospective study

Background and purposeAlthough Parkinson disease (PD) patients suffer falls more frequently than other old people, only a few studies have focused on identifying the specific risk factors for falls in PD patients. The aim of this study was to assess the incidence and risk factors of falls in a prospective study in comparison to a control group.Material and methodsOne hundred patients with PD were recruited to the study along with 55 gender- and age-matched healthy controls. Both groups were examined twice; the second examination took place one year after the first one. Examination of the PD group included: medical history including falls, neurological examination, assessment of the severity of parkinsonism [Unified Parkinson's Disease Rating Scale (UPDRS), Schwab and England scale (S&E), Hoehn and Yahr scale (H&Y), Mini-Mental State Examination (MMSE)], Hamilton scale and quality of life scales (SF-36, EQ-5D) and Freezing of Gait Questionnaire (FOG-Q). In both groups falls were recorded over the 12 months. Frequent fallers are defined as having more than 3 falls a year.ResultsOver the year falls occurred in 54% of PD patients and 18% of controls. In a prospective study 28% of PD patients fell more frequently than in retrospective analysis. Frequent fallers were found in 20% of patients and in 7% of controls. Fallers showed higher scores in UPDRS, H&Y, S&E, MMSE, and Hamilton scale than non-fallers. Independent risk factors for falls were: age, previously reported falls and higher score in the FOG-Q.ConclusionsFalls in PD patients occurred three times more frequently than in controls. Independent risk factors for falls were: high score in FOG-Q, older age and presence of falls in medical history.     

A meta-analysis of six prospective studies of falling in Parkinson's disease.

Recurrent falls are a disabling feature of Parkinson's disease (PD). We have estimated the incidence of falling over a prospective 3 month follow-up from a large sample size, identified predictors for falling for PD patients repeated this analysis for patients without prior falls, and examined the risk of falling with increasing disease severity. We pooled six prospective studies of falling in PD (n = 473), and examined the predictive power of variables that were common to most studies. The 3-month fall rate was 46% (95% confidence interval: 38-54%). Interestingly, even among subjects without prior falls, this fall rate was 21% (12-35%). The best predictor of falling was two or more falls in the previous year (sensitivity 68%; specificity 81%). The risk of falling rose as UPDRS increased, to about a 60% chance of falling for UPDRS values 25 to 35, but remained at this level thereafter with a tendency to taper off towards later disease stages. These results confirm the high frequency of falling in PD, as almost 50% of patients fell during a short period of only 3 months. The strongest predictor of falling was prior falls in the preceding year, but even subjects without any prior falls had a considerable risk of sustaining future falls. Disease severity was not a good predictor of falls, possibly due to the complex U-shaped relation with falls. Early identification of the very first fall therefore remains difficult, and new prediction methods must be developed.     

Double-blind, single-dose, cross-over study of the effects of pramipexole, pergolide, and placebo on rest tremor and UPDRS part III in Parkinson's disease.

Tremor is one of the cardinal signs of Parkinson's disease (PD) but its response to antiparkinsonian medication is variable. It has been postulated that pramipexole may have a stronger antiparkinsonian tremor effect than pergolide, another direct acting dopamine agonist medication, possibly because the former has preferential affinity for the dopamine D3 receptor. The purpose of this pilot study was to compare the effects of a single oral dose of either pramipexole (Pr) or pergolide (Pe) or placebo (Pl) on parkinsonian tremor and the motor (part III) subsection of the UPDRS. Ten patients (6 men, 4 women), mean age 65.3 years, mean duration from diagnosis of 2.6 years, with tremor dominant PD were recruited. On three separate occasions a single dose of pramipexole (salt) 500 microg, pergolide 500 microg or placebo were administered in random order to each patient, who were pretreated with domperidone and had their antiparkinsonian medication withheld from midnight before study. After each medication patients were assessed at baseline and then every 30 min for 4 hr using a 0 to 10 tremor rating scale and the UPDRS (part III) in a double-blind protocol. Adverse effects were systematically recorded. The results demonstrate that 500 microg of either pramipexole or pergolide reduced PD rest tremor scores to a similar degree, which at peak effect was significantly greater than placebo (respectively Pe v Pl: P < 0.006, Pr v Pl: P < 0.033). The two active drugs also had weaker beneficial effects on the UPDRS part III. Pergolide, however, was significantly more likely than pramipexole to cause nausea (P = 0.005) or vomiting (P = 0.014).     

Cardiovascular physiology in premotor Parkinson's disease: a neuroepidemiologic study

Changes in cardiovascular physiology in Parkinson's disease (PD) are common and may occur prior to diagnostic parkinsonian motor signs. We investigated associations of electrocardiographic (ECG) abnormalities, orthostasis, heart rate variability, and carotid stenosis with the risk of PD diagnosis in the Cardiovascular Health Study, a community-based cohort of older adults. ECG abnormality, orthostasis (symptomatic or asymptomatic), heart rate variability (24-hour Holter monitoring), and any carotid stenosis (≥1%) by ultrasound were modeled as primary predictors of incident PD diagnosis using multivariable logistic regression. Incident PD cases were identified by at least 1 of the following: self-report, antiparkinsonian medication use, and ICD-9. If unadjusted models were significant, they were adjusted or stratified by age, sex, and smoking status, and those in which predictors were still significant (P ≤ .05) were also adjusted for race, diabetes, total cholesterol, low-density lipoprotein, blood pressure, body mass index, physical activity, education level, stroke, and C-reactive protein. Of 5888 participants, 154 incident PD cases were identified over 14 years of follow-up. After adjusting models with all covariates, those with any ECG abnormality (odds ratio [OR], 1.45; 95% CI, 1.02-2.07; P = .04) or any carotid stenosis (OR, 2.40; 95% CI, 1.40-4.09; P = .001) at baseline had a higher risk of incident PD diagnosis. Orthostasis and heart rate variability were not significant predictors. This exploratory study suggests that carotid stenosis and ECG abnormalities occur prior to motor signs in PD, thus serving as potential premotor features or risk factors for PD diagnosis. Replication is needed in a population with more thorough ascertainment of PD onset.     

Ten-year follow-up of Parkinson's disease patients randomized to initial therapy with ropinirole or levodopa.

In a 5-year, double-blind study, subjects with Parkinson's disease (PD) who were randomized to initial treatment with ropinirole had a significantly lower incidence of dyskinesia compared with subjects randomized to levodopa, although Unified Parkinson's Disease Rating Scale (UPDRS) motor scores were significantly more improved in the levodopa group. Subjects who completed the original study were eligible to participate in a long-term extension study conducted according to an open, naturalistic design and were evaluated approximately every 6 months until they had been followed for a total of 10 years. Comparing subjects randomized to initial treatment with ropinirole (n = 42) and levodopa (n = 27), the incidence of dyskinesia was significantly lower in the ropinirole group (adjusted odds ratio [OR] = 0.3; 95% confidence interval [CI]: 0.1, 1.0; P = 0.046) and the median time to dyskinesia was significantly longer (adjusted hazard ratio = 0.4; 95% CI: 0.2, 0.8; P = 0.007). The incidence of at least moderate wearing off ("off" time >/=26% of the awake day) was also significantly lower in the ropinirole group (adjusted OR = 0.3; 95% CI: 0.09, 0.03; P = 0.03). There were no significant differences in change in UPDRS activities of daily living or motor scores, or scores for the 39-item PD questionnaire, Clinical Global Impression, or the Epworth Sleepiness Scale. Early treatment decisions for individual patients depend largely on the anticipated risk of side effects and long-term complications. Both ropinirole and levodopa are viable treatment options in early PD.     

Causes and risk factors of falls in patients with Parkinson's disease

BACKGROUND AND PURPOSE: Falls are a common and serious problem among Parkinson's disease (PD) patients. However, knowledge about the causes and risk factors of falls is limited. There have been a few attempts to classify the causes of falls. The classification suggested by Olanow seems to be the most comprehensive one. The aim of this study was to analyze retrospectively the causes of falls and risk factors of falls in PD patients. MATERIAL AND METHODS: One hundred and four patients with moderately advanced PD were included in the study. The patients were asked to describe the circumstances and consequences of falls which occurred during 12 months preceding the examination. The falls were classified according to the Olanow classification of causes of falls. RESULTS: Fifty-two patients (50%) reported at least one fall during the previous year with a mean number of 1.5 falls per year. The most common causes of falls were environmental factors, sudden falls and postural instability. There were no falls caused by severe dyskinesia, drugs or cardiovascular disorders. The only independent risk factors of the recurrent falls identified in this study were UPDRS part II score (OR 1.17, 95% CI: 1.02-1.37) and Mini Mental State Examination score (OR 0.85, 95% CI: 0.72-0.99). CONCLUSIONS: Considering these results we may be able to prevent most falls by means of the education of patients about environmental factors and using adequate rehabilitation techniques concentrating on postural stability and gait.     

Remote smartphone gait monitoring and fall prediction in Parkinson’s disease during the COVID-19 lockdown

Background

Falls could be serious events in Parkinson’s disease (PD). Patient remote monitoring strategies are on the raise and may be an additional aid in identifying patients who are at risk of falling. The aim of the study was to evaluate if balance and timed-up-and-go data obtained by a smartphone application during COVID-19 lockdown were able to predict falls in PD patients.

Methods

A cohort of PD patients were monitored for 4 weeks during the COVID-19 lockdown with an application measuring static balance and timed-up-and-go test. The main outcome was the occurrence of falls (UPDRS-II item 13) during the observation period.

Results

Thirty-three patients completed the study, and 4 (12%) reported falls in the observation period. The rate of falls was reduced with respect to patient previous falls history (24%). The stand-up time and the mediolateral sway, acquired through the application, differed between “fallers” and “non-fallers” and related to the occurrence of new falls (OR 1.7 and 1.6 respectively, p?<?0.05), together with previous falling (OR 7.5, p?<?0.01). In a multivariate model, the stand-up time and the history of falling independently related to the outcome (p?<?0.01).

Conclusions

Our study provides new data on falls in Parkinson’s disease during the lockdown. The reduction of falling events and the relationship with the stand-up time might suggest that a different quality of falls occurs when patient is forced to stay home — hence, clinicians should point their attention also on monitoring patients’ sit-to-stand body transition other than more acknowledged features based on step quality.

     

Early piribedil monotherapy of Parkinson's disease: A planned seven-month report of the REGAIN study.

Piribedil is a D2 dopamine agonist, which has been shown to improve symptoms of Parkinson's disease (PD) when combined with L-dopa. The objective of this study was to compare the efficacy of piribedil monotherapy to placebo in patients with early PD over a 7-month period. Four hundred and five early PD patients were randomized (double-blind) to piribedil (150-300 mg/day) or placebo. L-dopa open-label supplementation was permitted. Unified Parkinson Disease Rating Scale part III (UPDRS III) score as the last observation on monotherapy over 7 months was the primary outcome measure. Secondary outcomes were proportion of responders (UPDRS III improvement > 30%), patients remaining on monotherapy after 7 months, UPDRS III subscores, and UPDRS II. UPDRS III improved on piribedil (-4.9 points) versus a worsening on placebo (2.6 points; estimated effect = 7.26 points; 95% CI = 5.38-9.14; P < 0.0001). The proportion of responders was significantly higher for piribedil (42%) than for placebo (14%) (OR = 4.69; 95% CI = 2.82-7.80; P < 0.001). Piribedil significantly improved several UPDRS III subscores. UPDRS II improved on piribedil by -1.2 points, while it deteriorated by 1.5 points on placebo (estimated effect = 2.71; 95% CI = 1.8-3.62; P < 0.0001). The proportion of patients remaining on monotherapy after 7 months was greater in the piribedil group (OR = 3.72; 95% CI = 2.26-6.11; P < 0.001). Safety was consistent with that reported for other dopamine agonists, gastrointestinal side effects being the most common (22% of patients in piribedil group vs. 14% on placebo). Piribedil is effective and safe as early PD therapy.     

Estrogen improves motor disability in parkinsonian postmenopausal women with motor fluctuations

OBJECTIVE: To test the efficacy, tolerance, and safety of low-dose oral estrogen in postmenopausal women with PD associated with motor fluctuations. BACKGROUND: Motor fluctuations in PD may be predictable or unpredictable, and eventually affect most patients after long-term levodopa therapy. Although estrogen can modulate nigrostriatal dopamine levels, its effects on PD are unclear. METHODS: Patients were randomized to receive conjugated estrogen (oral Premarin 0.625 mg daily; n = 20) or placebo (n = 20) in a double-blind, parallel-group, prospective study over 8 weeks. Existing antiparkinsonian drug regimes were kept unchanged. Changes in "on" and "off" periods using patient diaries, Unified Parkinson's Disease Rating Scale (UPDRS) score, timed tapping score, and Hamilton Depression Scale score were determined by one rater. Subgroup analyses were also performed on patients with only predictable motor fluctuations. RESULTS: Both treatment groups were similar in age, duration of disease and menopause, antiparkinsonian medication, and compliance with test medication and diary assessments. "On" and "off" times, and motor score (UPDRS subscale III) improved with estrogen, using the Mann-Whitney U test (p < 0.05 after Bonferroni adjustment). Mean "on" time improved by 7% (9 hours/week of awake time) in estrogen-treated patients versus a deterioration of 0.5% (1.4 hours) in placebo-treated patients (95% confidence interval, [CI] of mean difference, 5.73 to 14.9). Mean "off" time improved by 4% (4.4 hours/week of awake time) in estrogen-treated patients versus no change in placebo-treated patients (95% CI, 1.54 to 7.16). Mean subscale III score improved by 3.5 points in estrogen-treated patients versus 0.4 in placebo-treated patients (95% CI, 1.02 to 5.18). No other significant changes were observed (p > 0.05). Subgroup analyses in patients with only predictable motor fluctuations showed similar results, except improvement in mean subscale III score was marginally not significant (p = 0.07; 95% CI, 1.06 to 6.24). Five patients on estrogen had facial flushing, three had lower abdominal discomfort, and two had mild withdrawal vaginal bleeding. The adverse events were mild and resolved without sequelae. CONCLUSION: Low-dose estrogen is a safe and effective adjunct therapy to existing antiparkinsonian treatment in reducing motor disability in postmenopausal women with PD associated with motor fluctuations.     

Prospective assessment of falls in Parkinson's disease

We studied prospectively the epidemiology, clinical impact and prediction of falls in 59 moderately affected patients with Parkinson's disease (PD) (mean UPDRS motor score 31.5; mean age 61 years) and 55 controls (mean age 60 years). At baseline, balance and gait were evaluated extensively. The retropulsion test (response to sudden shoulder pull) was executed first unexpectedly and five more times following prior warning. All persons used standardised scoring forms to document their falls during six months. Thirty patients (50.8 %) and eight controls (14.5 %) fell at least once (relative risk [RR] 6.1; 95 % confidence interval [CI] 2.5–15.1, p < 0.001). Recurrent (≥ 2) falls occurred in 15 patients (25.4 %), but in only two controls (RR 9.0; 95 % CI 2.0–41.7; p=0.001). Recurrent falls were more common among persons taking benzodiazepines (RR 5.0; 95 % CI 1.6–15.5; p < 0.01). Sixty-two percent of the falls in patients caused soft tissue injuries, but no fractures occurred. A fear of future falls was common (45.8 % of patients) and was accompanied by restriction of daily activities (44.1 % of patients). Seventy percent of falls reported by patients were ‘intrinsic’ (due to patient-related factors), but falls in controls were mainly (50 %) ‘extrinsic’ (due to environmental factors). None of the baseline posture and gait variables predicted falls adequately. The first ‘unexpected’ retropulsion test was more often abnormal than all subsequent (predictable) tests. Irrespective of its method of execution, the retropulsion test did not predict falls. A combination of asking for prior falls, disease severity and the Romberg test yielded the best overall diagnostic utility (sensitivity 65 % and specificity 98 %). Recurrent fallers were best predicted by disease severity (RR for Hoehn and Yahr stage 3 was > 100; 95 % CI 3.1–585) and asking for prior falls (RR 5.0; 95 % CI 1.2–20.9). We conclude that falls are common and disabling, even in relatively early stage PD. Recurrent fallers were best predicted by disease severity and presence of prior falls. Strategies to prevent falls in PD should particularly focus at intrinsic (patient-related) factors, such as minimising the use of benzodiazepines. Received: 18 December 2000, Received in revised form: 15 March 2001, Accepted: 25 March 2001     

Subthalamic DBS replaces levodopa in Parkinson's disease: two-year follow-up

BACKGROUND: Subthalamic nucleus (STN) deep brain stimulation (DBS) of patients with PD allows reduction of antiparkinsonian medication but has only a mild direct effect on dyskinesia. Since antiparkinsonian medication has short- and long-term effects that may prevent an estimate of the maximal possible impact of STN DBS, such medication was used at the lowest possible dosage after DBS implantation. OBJECTIVE: To study the maximal and long-term effects of STN DBS using the lowest dose of medication. METHODS: Twenty consecutive patients with PD with motor fluctuations and dyskinesia underwent bilateral implantation under stereotactic guidance, microrecording, and clinical control. All medications were stopped before implantation and reintroduced, at the lowest dosage needed, only if the postoperative motor score did not reach the baseline level. Unified PD Rating Scale (UPDRS) motor (subscale III) scores were measured at baseline and after 3, 6, 12, and 24 months. RESULTS: After 21 plus minus 8 months, the UPDRS III "off-medication" score was decreased by 45% and was similar to the preoperative UPDRS III "on" score. Overall, medication was reduced by 79%, being completely withdrawn in 10 patients. Fluctuations and dyskinesia showed an overall reduction of >90%, disappearing completely in patients without medication. These improvements were maintained for 2 years. CONCLUSIONS: These results show that STN DBS could replace levodopa and allowed all antiparkinsonian medication to be discontinued in 50% of patients with PD. Fluctuations and dyskinesia disappeared completely in these patients but persisted in those still on medication. These improvements were maintained for 2 years.