Sexual needs and sexual function of patients with Parkinson's disease.

BACKGROUND: Sexual dysfunction (SD) is a frequent non-motor symptom in Parkinson's disease (PD) that is rarely addressed, and sexual counseling is sporadic. OBJECTIVES: To investigate PD patients' SD and sexual counseling motivation and to propose an interventional strategy for movement disorder specialists. METHODS: All consecutive PD patients who presented to a movement disorder unit between 2018 and 2019 completed anonymous questionnaires containing the Female Sexual Function Index, the International Index of Erectile Function, and a questionnaire on sexual needs and motivation to receive sexual counseling. RESULTS: The age range of the 100 recruited patients (78 men) was 40-80 years, and the mean disease duration was 8.64 ± 6.84 years. SD appeared at all PD stages. The presence of SD pre-PD diagnosis significantly predicted SD post-diagnosis in men. Erectile dysfunction was the most common male SD (70%). Women reported frequent SD before PD diagnosis and currently. More than half of the responders (74% of the men and 40% of the women) were motivated to receive sexual counseling. Most of them (77.4%) were in a relationship. CONCLUSIONS: The findings of this analysis revealed that most PD patients had experienced SD before being diagnosed with PD and were interested in receiving sexual counseling. We propose a six-step intervention strategy for the management of SD in PD designed for application in a movement disorder unit. We also recommend that neurologists and other healthcare providers undergo training to provide basic sexual counseling tailored to the needs of PD patients.

Quality-of-life perception by Parkinson's disease patients and caregivers.

BACKGROUND: The quality-of-life (QoL) perception by Parkinson's disease (PD) patients and their caregivers (CG) has not been studied in depth. OBJECTIVE: To examine patient/proxy agreements on the PD QoL Questionnaire (PDQ-39), the Scale of Quality of Life of Care-Givers (SQLC) and the Multidimensional Caregiver Strain Index (MCSI). METHODS: Patients with PD and their CG completed the above-mentioned questionnaires about themselves and each other. The intraclass correlations between their scores (paired t test) were compared. RESULTS: Twelve patient-CG pairs were studied. Agreements for QoL items were strong and comparable for the total scores of the PDQ-39, SQLC and MCSI questionnaires (75.4% ± 14%; 78.1% ± 14.1% and 78.2% ± 14.3%, respectively). Agreements ranged from moderate to strong (0.57-0.88, P≤.05) for the patients' physical condition (PDQ-39 items 3, 5, 6, 8, 12-15, 23, 24, 35), mental concentration (item 31) and depression (item 17). Disagreements were apparent in 20%-25% of the pairs and were particularly significant for PDQ-39 items #33 and #25 (embarrassment of patients in public and distressing dreams or hallucinations), in which the CG gave higher scores than the patients. CONCLUSIONS: Agreements between patients with PD and CG were generally good for most, but not all, of the PDQ-39, SQLC and MCSI domains.

New insights into orthostatic hypotension in multiple system atrophy: a European multicentre cohort study.

OBJECTIVES: Orthostatic hypotension (OH) is a key feature of multiple system atrophy (MSA), a fatal progressive neurodegenerative disorder associated with autonomic failure, parkinsonism and ataxia. This study aims (1) to determine the clinical spectrum of OH in a large European cohort of patients with MSA and (2) to investigate whether a prolonged postural challenge increases the sensitivity to detect OH in MSA. METHODS: Assessment of OH during a 10 min orthostatic test in 349 patients with MSA from seven centres of the European MSA-Study Group (age: 63.6 ± 8.8 years; disease duration: 4.2 ± 2.6 years). Assessment of a possible relationship between OH and MSA subtype (P with predominant parkinsonism or C with predominant cerebellar ataxia), Unified MSA Rating Scale (UMSARS) scores and drug intake. RESULTS: 187 patients (54%) had moderate (> 20 mm Hg (systolic blood pressure (SBP)) and/or > 10 mm Hg (diastolic blood pressure (DBP)) or severe OH (> 30 mm Hg (SBP) and/or > 15 mm Hg (DBP)) within 3 min and 250 patients (72%) within 10 min. OH magnitude was significantly associated with disease severity (UMSARS I, II and IV), orthostatic symptoms (UMSARS I) and supine hypertension. OH severity was not associated with MSA subtype. Drug intake did not differ according to OH magnitude except for antihypertensive drugs being less frequently, and antihypotensive drugs more frequently, prescribed in severe OH. CONCLUSIONS: This is the largest study of OH in patients with MSA. Our data suggest that the sensitivity to pick up OH increases substantially by a prolonged 10 min orthostatic challenge. These results will help to improve OH management and the design of future clinical trials.

A cross-sectional multicenter study of cognitive and behavioural features in multiple system atrophy patients of the parkinsonian and cerebellar type.

Imaging and neuropathology studies have demonstrated significant abnormalities not only in subcortical, but also in cortical regions of patients with multiple system atrophy (MSA). This raises the possibility that cognitive dysfunction may contribute to the clinical spectrum of this disorder to a greater extent than it is currently not widely appreciated. In this cross-sectional multicenter study from the European multiple system atrophy study group ( http://www.emsa-sg.org ), we applied an extensive neuropsychological test battery in a series of 61 clinically diagnosed probable MSA patients. The results demonstrated that general cognitive decline as assessed by MMSE was uncommon (2 out of 61 patients <24). In contrast, frontal lobe-related functions (as measured by FAB) were impaired in 41 % of patients, with abstract reasoning and sustained attention less compromised. This pattern was similar to our control group of 20 patients with Parkinson's disease (matched for disease duration and age at onset). There was no difference in cognitive performance between MSA patients with the parkinsonian versus the cerebellar variant. Behaviourally, MSA patients had greater depression than PD and in the case of MSA of the cerebellar variant significantly lower anxiety. Our data show that cognitive abnormalities are relatively frequent in multiple system atrophy and this involves primarily frontal-executive functions. Their contribution to clinical disability and disease progression needs to be addressed in larger prospective studies.

Subjective memory complaints in elders: depression, anxiety, or cognitive decline?

OBJECTIVES: To study the association of subjective memory complaints (SMC) with affective state and cognitive performance in elders. MATERIALS AND METHODS: We studied community dwelling elderly persons with normal physical examination. Participants completed questionnaires regarding memory difficulties and lifestyle habits, the Geriatric Depression Scale (GDS) and the Spielberger State-Trait Anxiety Inventory (STAI). Depending on their answers to the question about their memory condition, participants were divided into complainers and non-complainers and to five groups according to their MMSE scores. These data have been compared to objective cognitive performance according to Mindstreams - a computerized neuropsychological battery. A logistic regression was performed to evaluate odds ratios (OR) and 95% confidence intervals (CI) for those factors, which were associated with SMС (dependent variable). RESULTS: Of 636 consecutive subjects (61% females), 507 participants (79.7%) had SMС. Presence of SMC was inversely correlated with MMSE scores, (r = -0.108; P for trend = 0.007). GDS and STAI scores were higher among subjects with SMC (OR = 1.23: CI 95%: 1.1-1.36 and OR = 1.03: CI 95%: 1.01-1.07, respectively). SMC did not correlate with objective cognitive performance measured by Mindstreams. CONCLUSIONS: Subjective memory complaints are associated with sub-syndromal depression and anxiety in healthy cognitively normal elders.

Multicenter analysis of glucocerebrosidase mutations in Parkinson's disease.

BACKGROUND: Recent studies indicate an increased frequency of mutations in the gene encoding glucocerebrosidase (GBA), a deficiency of which causes Gaucher's disease, among patients with Parkinson's disease. We aimed to ascertain the frequency of GBA mutations in an ethnically diverse group of patients with Parkinson's disease. METHODS: Sixteen centers participated in our international, collaborative study: five from the Americas, six from Europe, two from Israel, and three from Asia. Each center genotyped a standard DNA panel to permit comparison of the genotyping results across centers. Genotypes and phenotypic data from a total of 5691 patients with Parkinson's disease (780 Ashkenazi Jews) and 4898 controls (387 Ashkenazi Jews) were analyzed, with multivariate logistic-regression models and the Mantel-Haenszel procedure used to estimate odds ratios across centers. RESULTS: All 16 centers could detect two GBA mutations, L444P and N370S. Among Ashkenazi Jewish subjects, either mutation was found in 15% of patients and 3% of controls, and among non-Ashkenazi Jewish subjects, either mutation was found in 3% of patients and less than 1% of controls. GBA was fully sequenced for 1883 non-Ashkenazi Jewish patients, and mutations were identified in 7%, showing that limited mutation screening can miss half the mutant alleles. The odds ratio for any GBA mutation in patients versus controls was 5.43 across centers. As compared with patients who did not carry a GBA mutation, those with a GBA mutation presented earlier with the disease, were more likely to have affected relatives, and were more likely to have atypical clinical manifestations. CONCLUSIONS: Data collected from 16 centers demonstrate that there is a strong association between GBA mutations and Parkinson's disease.

Vasomotor reactivity as a predictor for syncope in patients with orthostatism.

OBJECTIVES: Syncope in patients with orthostatic hypotension (OH) may be the result of impaired cerebral autoregulation. Cerebral autoregulation status can be determined by assessing cerebral vasomotor reactivity (VMR). We assessed and compared VMR in patients with OH with and without syncope. MATERIAL AND METHODS: Twenty-nine patients with OH underwent transcranial Doppler (TCD) and the Diamox test (1 g acetazolamide IV) for assessing VMR during elaboration of their OH syndrome. The percent difference between cerebral blood flow velocities (BFV) in the middle cerebral (MCA) and vertebral (VA) arteries before and after acetazolamide was defined as VMR%. We considered increases of BFV of ≥ 40% as being indicative of good VMR and classified our study patients as having good or impaired VMRs accordingly. RESULTS: Mean VMR% values of the MCA and VA in patients with OH with syncope (n = 12) were significantly lower as compared with patients with OH without syncope (n = 17): 25.2 ± 20.5% and 42.5 ± 18.6%; 20.9 ± 15.5% and 40.8 ± 28.5%, respectively (P < 0.05). CONCLUSIONS: Among patients with OH, we found an association between the presence of syncope and impaired VMR. Assessment of VMR among patients with OH may predict those who are at higher risk to faint and fall and to support more aggressive intervention.

LRRK2 and GBA mutations differentially affect the initial presentation of Parkinson disease.

GBA and LRRK2 mutations increase susceptibility to Parkinson disease (PD), which is characterized by various disabling symptoms. An extended cohort of 600 Ashkenazi PD patients was screened for the LRRK2 G2019S and for eight GBA mutations. Reported initial symptoms were compared between three genotypic groups of patients: carriers of GBA mutations, carriers of LRRK2 G2019S mutation, and non-carriers. More LRRK2 G2019S carriers reported muscle stiffness (rigidity, p = 0.007) and balance disturbances (p = 0.008), while more GBA mutation carriers reported slowness (bradykinesia, p = 0.021). These results suggest distinct effects of LRRK2 or GBA mutations on the initial symptoms of PD.

Progression of dysautonomia in multiple system atrophy: a prospective study of self-perceived impairment.

To assess severity and progression of self-perceived dysautonomia and their impact on health-related quality of life (Hr-QoL) in multiple system atrophy (MSA), twenty-seven patients were recruited by the European MSA Study Group (EMSA-SG). At baseline, all patients completed the Composite Autonomic Symptom Scale (COMPASS) and the 36 item Short Form Health Survey (SF-36), and they were assessed using the 3-point global disease severity scale (SS-3) and the Unified MSA Rating Scale (UMSARS). After 6 months follow-up, the self completed COMPASS Change Scale (CCS), the SF-36, SS-3, and UMSARS were obtained. MSA patients showed marked self-perceived dysautonomia at baseline visit and pronounced worsening of dysautonomia severity on the CCS at follow-up. Severity and progression of dysautonomia did not correlate with age, disease duration, motor impairment and overall disease severity at baseline. There were no significant differences between genders and motor subtypes. Baseline COMPASS scores were, however, inversely correlated with SF-36 scores. Progression of self-perceived dysautonomia did not correlate with global disease progression. Hr-QoL scores were stable during follow-up. This is the first study to investigate self-perceived dysautonomia severity in MSA and its evolution over time. Our data suggest that dysautonomia should be recognized as a key target for therapeutic intervention in MSA.

Clinical characteristics of elderly patients with a cautious gait of unknown origin.

OBJECTIVE: To evaluate and systematically characterize a group of older adults with disturbed gait of unknown origin. DESIGN: Cross-sectional study. SETTING: Outpatient clinic in a movement disorders unit. PARTICIPANTS: Twenty-five patients (mean age 78.4 years) with a disturbed gait of unknown origin were compared with twenty-eight age matched "healthy" controls (mean age 78.2). MEASUREMENT: Detailed medical history, geriatric and neurological assessments. RESULTS: Patients walked more slowly (P<0.0001) and with shorter strides (P<0.0001) compared with controls. Muscle strength was lower, and static and dynamic balance and gait performance were worse among the patients (P<0.0001). The patients also tended to be more depressed (P<0.0001),more anxious (P<0.002), had a greater fear of falling (P<0.0001) and had lower scores on the Mini-Mental State Examination (P<0.005). There was no difference in the frequency of cerebellar or pyramidal signs in the two groups. However, neurological testing revealed that extrapyramidal (P<0.0001) and frontal release signs (P<0.0001) were more common among the patients. Neuroradiological findings were rare among the patients and they did not explain the changes in gait speed or fear of falling. CONCLUSIONS: Older adults with a disturbed gait of unknown origin appear to share common characteristics. They walk more slowly than "healthy" controls with increased unsteadiness and with excessive fear of falling. The extrapyramidal, frontal lobe, and limbic systems apparently play an important role, to different degrees, in what can be viewed as a multisystem neurodegenerative syndrome clearly different from "aging."

Gait instability and fractal dynamics of older adults with a "cautious" gait: why do certain older adults walk fearfully?

Many older adults walk with a cautious and impaired gait of unknown origin, however, the relationship between fear of falling and the observed gait changes is not well understood. To better understand the "cautious" gait of the elderly, we tested the hypothesis that temporal gait variability, putatively a marker of intrinsic walking unsteadiness, is increased among older adults with a cautious gait and a higher-level gait disorder (HLGD), an altered gait that cannot be attributed to a well-defined cause. Twenty-five older adults (mean age: 78 years) with a HLGD were compared to healthy controls of similar age and sex (n=28). The clinical characteristics (e.g., neurological status, fear of falling), the magnitude of the stride-to-stride variations in gait cycle timing (a measure of temporal gait variability), and a fractal index of gait (a measure of the stride dynamics independent of the magnitude of the variability) were studied in both groups. Gait variability was significantly increased (P<0.0001) in HLGD subjects (52+/-26 ms) compared to controls (27+/-9 ms). Changes in frontal lobe and extra-pyramidal function were also found in the patient group. Among HLGD subjects, gait variability was not associated (P>0.05) with age, gender, MMSE score, muscle strength, # of co-morbidities, balance, cerebellar signs, or pyramidal signs, but was significantly associated with scores on the Geriatric Depression Scale (r=0.46, P<0.02) and fear of falling (r=0.69, P<0.0001). Among HLGD subjects, only a fractal index was significantly different in fallers and non-fallers. These findings underscore the idea that the gait changes in older adults who walk with fear may be an appropriate response to unsteadiness, are likely a marker of underlying pathology, and are not simply a physiological or psychological consequence of normal aging.

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.

Quality of sexual life in Parkinson's disease.

Ninety-one consecutive patients with Parkinson's disease (PD) were asked to grade their general satisfaction from life (GSL) and completed the PDQ-39 and the quality of sexual life questionnaire (QoSL-Q). The reliability of the QoSL-Q was 0.74. Satisfaction from sexual life as reflected by the QoSL-Q significantly decreased with aging (P<0.01) and advanced disease (P<0.05). No correlation was found between the PDQ-39 and the QoSL index. The correlation between the PDQ-39 and GSL (r=-0.334) improved by adding the QoSL-Q, as a 9th dimension to the PDQ-39 (r=-0.405). The QoSL-Q is a reliable tool assessed a unique and important dimension not evaluated by the PDQ-39.

[Modulated kinesitherapy in rehabilitation of patients with cardiovascular diseases]. / Modulirovannaia kineziterapiia v reabilitatsii bol'nykh s zabolevaniiami serdechno-sosudistoi sistemy.

Modulated kinesitherapy (MK) is a new method based on synchronization of vegetative and motor components in walking at a pace corresponding to actual heart rate which is maintained during the procedure with cardiotrainer Marafon. MK produced the following therapeutic effects: optimization of cardiovascular functions (weakening of postload on the heart with lowering of arterial pressure; improvement of coronary blood flow, stabilization of the heart rate and cardiac pump function); marked antiarrhythmic effect, normalization of autonomic nervous system tonicity, neurohumoral and psychoemotional state. MK is indicated in ischemic heart disease, essential hypertension, cardiac arrhythmia, vegetovascular asthenia.

Mobility, mood and site of care impact health related quality of life in Parkinson's disease.

OBJECTIVE: Examine the correlates of Health Related Quality of Life (HRQL) in a large cohort of Parkinson's disease (PD) patients from National Parkinson Foundation (NPF) Centers of Excellence (COEs). BACKGROUND: Improving outcomes for PD will depend upon uncovering disease features impacting HRQL to identify targets for intervention and variables for risk-adjustment models. Differences in HRQL outcomes between COEs could uncover modifiable aspects of care delivery. METHODS: This cross-sectional study examined the relative contribution of demographic, social, clinical and treatment features potentially related to HRQL, as measured by the PDQ-39, in 4601 consecutive subjects from 18 COEs. Stepwise linear regression was utilized to identify correlates of HRQL. RESULTS: The variability in the PDQ-39 summary index score correlated with H&Y stage (R(2) = 22%), Timed up and Go (TUG) (17%), disease duration (11%), comorbidities (8%), cognitive status (8%), antidepressant use (6%) and center at which a patient received care (5%). Stepwise regression reordered the importance of the variables, with the H&Y first and TUG and the center becoming equal and the second most important variables determining the PDQ-39 total score. All independent variables together accounted for 44% of the variability in HRQL. CONCLUSIONS: We confirmed many but not all HRQL associations found in smaller studies. A novel observation was that the site of care was an important contributor to HRQL, suggesting that comparison of outcomes and processes among centers may identify best practices.

Estimation of Parkinson's disease survival in Israeli men and women, using health maintenance organization pharmacy data in a unique approach.

The aim of this work was to estimate in an incident cohort of pharmacy-based PD patients the survival of men and women accounting for age at treatment initiation and to compare their gender-specific survival with that of the general Israeli population. A population-based cohort of 4,848 incident pharmacy-based PD cases with definite/probable/possible certainty was previously identified using a drug-tracer approach for 1999-2008. Survival analysis was performed for two time scales: survival after treatment initiation (disease duration), and life-time survival (life expectancy). Kaplan-Meier curves and Cox regressions were used to compare survival across gender. Gender-specific SMRs were calculated from national rates and were compared using Poisson regression. During the follow-up from first purchase of any anti-parkinsonian drug (mean 4.0 ± 2.6 years, range 2 months-10 years), 1,266 (26 %) of the cases died. Younger age at first anti-parkinsonian drug purchase and female gender were associated with increased survival after treatment initiation (HR = 1.089, 95 % CI 1.080-1.098 for 1-year age increase; HR = 0.716, 95 % CI 0.640-0.800, females vs. males). Life-time survival increased with older age at first anti-parkinsonian drug purchase and female gender (HR = 0.759, 95 % CI 0.746-0.771 for 1-year age increase; HR = 0.694, 95 % CI 0.621-0.776, females vs. males). Sensitivity analysis on a sub-cohort of definite cases (n = 2501) yielded similar results. In comparison to the general Israeli population, mortality among pharmacy-based PD patients was significantly increased (SMR(men) = 1.69, 95 % CI 1.57-1.81, SMR(women) = 1.49, 95 % CI 1.37-1.62), differently between genders (p < 0.01). Female gender was associated with longer, perhaps more benign disease course, and longer life expectancy. Earlier age at anti-parkinsonian drug initiation increased disease duration, but was associated with shorter life expectancy.

Progressive nature of a higher level gait disorder: a 3-year prospective study.

The objective of the study was to characterize the natural history of patients with a higher level gait disorder (HLGD) of the cautious/disequilibrium type in a 3-year prospective study. Subjects were taken from an outpatient setting in a movement disorders clinic. Twenty-two mobile, community-living patients with a HLGD of the cautious/disequilibrium type and 26 age- and gender-matched healthy controls were evaluated at baseline and approximately 3 years later. Detailed medical history, a complete, structured geriatric and neurological examination, mental and affective state, gait and balance assessment were obtained. At follow-up, marked declines were observed in gait, mobility and functional independence in the patients, but not in the controls. For example, 23% of the patients could not complete the Timed Up and Go test, compared to only 4% of the control group, and among those who could complete the test, time to completion was almost three times longer (P < 0.0001) in the patients (23 s), compared to the controls (8 s). At follow-up, 50% of the patients required a personal live-in caregiver compared to only 4% of the controls (P < 0.0001). Although mild extra-pyramidal, pyramidal, cognitive and affective alterations were observed at baseline in the patients, those symptoms were stable over time. Unexpectedly, there was no association between the presence of HLGD or its progression and vascular risk factors. HLGD is a debilitating, rapidly progressive disease. The profound deterioration in functional independence in a relatively short period of time suggests that early multidisciplinary interventions may be the appropriate clinical approach to the treatment of these patients who are at risk for a rapid decline in functional abilities.