Non-motor symptoms in Chinese Parkinson’s disease patients

This study was designed to survey the prevalence and distribution of non-motor symptoms (NMS) in Parkinson’s disease (PD) patients in Shanghai, China, and to investigate the association between NMS and health-related quality of life (HRQoL). One hundred fifty-five PD patients were evaluated using the NMS Questionnaire 30 (NMSQuest), Unified Parkinson’s Disease Rating Scale (UPDRS) and Parkinson’s Disease Questionnaire-39 (PDQ-39). These data were compared with an international cross-sectional study, and the associations of motor and non-motor measures with HRQoL were estimated. Predictors of HRQoL were sought through multiple linear regression analyses. Each PD patient had eight different individual NMS on average. The problems of memory (65.82%), constipation (64.56%) and nocturia (61.39%) were the most frequent complaints. NMS prevalence in PD patients in Shanghai was consistent with that in the international study, although the composition proportions were different. There was a significant association of PDQ-39 score with NMSQuest score (rs = 0.433, p = 0.000), UPDRS III score (rs = 0.473, p = 0.000), Hoehn and Yahr (H-Y) stage (rs = 0.567, p = 0.000), disease duration (rs = 0.220, p = 0.005), and levodopa equivalent dosage (rs = 0.263, p = 0.001). H-Y stage (disease severity) and NMS score were the strongest predictors for PDQ-39 score. This study confirmed that NMS are common in PD, occurring across all disease stages and have a great impact on quality of life. NMS progression contributes significantly to HRQoL decline, and should be well recognized and treated.     

Sex differences in Parkinson’s disease

Sex-related differences in Parkinson’s disease (PD) have been recognised, but remain poorly understood. We aimed to further clarify real-life differences in disease experience according to sex, by evaluating quality of life (QoL), demographic and clinical characteristics of PD patients. A cross-sectional survey was conducted on 210 PD patients (129 men, 81 women) attending specialist neurological clinics across three centres. Outcome measures included the motor examination of the Unified Parkinson’s Disease Rating Scale (UPDRS-III) and QoL as measured by the 39-item Parkinson’s Disease Questionnaire (PDQ-39). A male to female ratio of 1.6:1 was observed. Men reported a greater disease burden than women as noted by higher UPDRS-III scores (27 ± 13 versus 23 ± 13, p = 0.032), daily levodopa equivalent doses (898.1 ± 481.3 mg versus 750.7 ± 427.2 mg, p = 0.037) and caregiver reliance (44% versus 29.5%, p = 0.039). The UPDRS-III score was significantly associated with sex after controlling for age and disease duration, with men more severely affected (β = −0.165, r² = 0.101, p = 0.028). The PDQ-39 showed men reported lower QoL in activities of daily living (ADL), cognition and communication sub-scales (p < 0.05). An association was identified in men between PDQ-39 ADL and cognition sub-scales (r = 0.660, p < 0.001). Men with an appointed caregiver had a higher PDQ-39 Summary Index (t = 3.222, degrees of freedom = 122, p = 0.002). PD was found to have greater overall impact on the health and well-being of male patients in sub-specialty clinical practice. Our study further supports the need for increased sex-delineated clinical assessment and consideration of potential differences required in the management of PD.     

Duration of disease does not equally influence all aspects of quality of life in Parkinson’s disease

Health related quality of life (HRQoL) is negatively impacted in patients suffering from Parkinson’s disease (PD). For the specific components that comprise HRQoL, the relationship between clinical variables, such as disease duration, is not fully characterized. In this cross-sectional study (n = 302), self-reported HRQoL on the Parkinson’s Disease Questionnaire (PDQ-39) was evaluated as a global construct as well as individual subscale scores. HRQoL was compared in three groups: those within 5 years of diagnosis, those within 6–10 years of diagnosis, and those greater than 11 years since diagnosis. Non-parametric analyses revealed lower HRQoL with increasing disease duration when assessed as a global construct. However, when subscales were evaluated, difficulties with bodily discomfort and cognitive complaints were comparable in individuals in the 1–5 years and 6–10 year duration groups. Exploratory regression analyses suggested disease duration does explain unique variance in some subscales, even after controlling for Hoehn and Yahr stage and neuropsychiatric features. Our findings show that HRQoL domains in PD patients are affected differentially across the duration of the disease. Clinicians and researchers may need to tailor interventions intended to improve HRQoL at different domains as the disease progresses.     

Peripheral expression of MAPK pathways in Alzheimer’s and Parkinson’s diseases

Alteration of mitogen-activated protein kinase pathways may cause aberrant protein phosphorylation and enhanced apoptosis in Alzheimer’s disease (AD) and Parkinson’s disease (PD). Increased susceptibility of lymphocytes to apoptosis has been reported in AD. To our knowledge this is the first study to investigate the expression and phosphorylation status of p38 mitogen-activated protein kinase (p38MAPK) and c-Jun N-terminal kinase (JNK) in peripheral blood lymphocytes of 20 AD and 20 PD patients and 20 healthy controls using western blot analysis. Compared with controls, no significant difference of total p38MAPK or JNK levels were observed in AD and PD patients, whereas phosphorylated p38MAPK and phosphorylated JNK levels were significantly increased in the AD and PD groups (p < 0.001). However, the increased levels of the two phosphorylated kinases in AD versus PD patients presented no significant difference. Interestingly, phosphorylated p38MAPK and phosphorylated JNK levels were positively correlated with disease duration (r = 0.602, p = 0.005 and r = 0.561, p = 0.010, respectively) and negatively correlated with the Mini Mental State Examination score (r = −0.664, p = 0.001 and r = −0.578, p = 0.008, respectively) in AD patients. No correlations between protein levels and clinical variables were found in PD patients. Investigation of peripheral changes in the expression of p38MAPK and JNK may lead to the development of innovative biomarkers of neurodegenerative diseases, particularly for AD.     

Glucocerebrosidase enzyme activity in GBA mutation Parkinson’s disease

Mutations in the glucocerebrosidase (GBA1) gene, the most common genetic contributor to Parkinson’s disease (PD), are associated with an increased risk of PD in heterozygous and homozygous carriers. While glucocerebrosidase enzyme (GCase) activity is consistently low in Gaucher disease, there is a range of leukocyte GCase activity in healthy heterozygous GBA1 mutation carriers. To determine whether GCase activity may be a marker for PD with heterozygous GBA1 mutations (GBA1 mutation PD, GBA PD), GBA PD patients (n = 15) were compared to PD patients without heterozygous GBA1 mutations (idiopathic PD; n = 8), heterozygous GBA1 carriers without PD (asymptomatic carriers; n = 4), and biallelic mutation carriers with PD (Gaucher disease with PD, GD1 PD; n = 3) in a pilot study. GCase activity (nmol/mg protein/hour) in GD1 PD (median [interquartile range]; minimum–maximum: 6.4 [5.7]; 5.3–11) was lower than that of GBA PD (16.0 [7.0]; 11–40) (p = 0.01), while GCase activity in GBA PD was lower than idiopathic PD (28.5 [15.0]; 16–56) (p = 0.01) and asymptomatic carriers (25.5 [2.5]; 23–27) (p = 0.04). Therefore, GCase activity appears to be a possible marker of heterozygous GBA1 mutation PD, and larger studies are warranted. Prospective studies are also necessary to determine whether lower GCase activity precedes development of PD.     

CYP2D6 phenotypes and Parkinson's disease risk: A meta-analysis

BackgroundCYP2D6 polymorphisms have been reported to be associated with Parkinson's disease (PD) susceptibility, but the results of these previous studies were inconsistent.ObjectivesTo explore whether PD patients with CYP2D6 gene variation have different risk to PD to those with normal function of CYP2D6.MethodsSystematic review with meta-analysis of case-controlled studies on the association between CYP2D6 and PD risk was conducted. Studies published up to August 1, 2013 were identified by searching electronic databases PubMed and Embase. Odds ratios (ORs) together with their corresponding 95% confidence intervals (CIs) were used to estimated the association between CYP2D6 polymorphisms and PD risk in different phenotype models. Meta-regression, subgroup analysis, sensitivity analysis and publication bias were also performed.ResultsA total of 3521 PD Patients and 4476 controls from 29 case–control studies were identified. Overall, a borderline significant influence of the CYP2D6 polymorphisms on PD risk was observed (OR: 1.07, 95%CI: 0.99–1.16, p = 0.106). Significant association was found when comparisons were performed in different phenotypes in PM versus EM (OR = 1.33, 95% CI = 1.01–1.74, p = 0.044) and PM versus IM + EM (OR = 1.32, 95% CI = 1.11–1.56, p = 0.002). In subgroup analysis stratified by country, significant association was demonstrated in British but not in other white subjects. No significant association was detected in subgroup analysis according to the age of onset and the source of patients.ConclusionThe present meta-analysis demonstrated that the poor metabolizer phenotype of CYP2D6 confers a significant genetic susceptibility to PD in Caucasians, especially in British white subjects.     

Health related quality of life in parents of six to eight year old children with Down syndrome

Raising a child with Down syndrome (DS) has been found to be associated with lowered health related quality of life (HRQoL) in the domains cognitive functioning, social functioning, daily activities and vitality. We aimed to explore which socio-demographics, child functioning and psychosocial variables were related to these HRQoL domains in parents of children with DS. Parents of 98 children with DS completed the TNO-AZL adult quality of life questionnaire (TAAQOL) and a questionnaire assessing socio-demographic, child functioning and psychosocial predictors. Using multiple linear regression analyses for each category of predictors, we selected relevant predictors for the final models. The final multiple linear regression models revealed that cognitive functioning was best predicted by the sleep of the child (β = .29, p < .01) and by the parent having given up a hobby (β = ?.29, p < .01), social functioning by the quality of the partner relation (β = .34, p < .001), daily activities by the parent having to care for an ill friend or family member (β = ?.31, p < .01), and vitality by the parent having enough personal time (β = .32, p < .01). Overall, psychosocial variables rather than socio-demographics or child functioning showed most consistent and powerful relations to the HRQoL domains of cognitive functioning, social functioning, daily activities and vitality. These psychosocial variables mainly related to social support and time pressure. Systematic screening of parents to detect problems timely, and interventions targeting the supportive network and the demands in time are recommended.     

Forehead sympathetic skin responses in determining autonomic involvement in Parkinson’s disease

ObjectiveThe purpose of this study was to evaluate forehead sympathetic skin response (SSR) and demonstrate any differences with extremity SSR in determining autonomic nervous system (ANS) involvement in patients with Parkinson’s disease (PD).MethodsTwenty early stage, 20 advanced stage idiopathic PD patients and 20 healthy controls participated in this study. SSR of forehead, hands and feet, heart rate variability (HRV), orthostatic intolerance, QT intervals and dysautonomic symptoms were evaluated.ResultsAbsent forehead SSR was determined unilaterally in 4, bilaterally in 7 early stage patients, and unilaterally in 4, bilaterally in 8 advanced stage PD patients; there was significant difference between early and advanced stage PD and control groups in terms of the lack of SSR (p = 0.000). Absent extremity SSR was determined in at least 1 extremity of 3 advanced stage PD patients, and none of the early stage PD patients. No difference was noted in HRV at rest between early and advanced stage PD and control groups (p = 0.218); but HRV at deep breathing was lower in both early and advanced PD patients compared to controls (p = 0.014, p = 0.002, respectively).ConclusionForehead SSR is more sensitive in determining ANS dysfunction not only in late but also in early stage of PD.SignificanceWith further supportive research, forehead SSR might be used as a simple diagnostic electrophysiological test in the early diagnosis of ANS dysfunction enabling proper treatment and increasing the quality of life of PD patients.     

Factors predicting incremental administration of antihypertensive boluses during deep brain stimulator placement for Parkinson’s disease

Hypertension is common in deep brain stimulator (DBS) placement predisposing to intracranial hemorrhage. This retrospective review evaluates factors predicting incremental antihypertensive use intraoperatively. Medical records of Parkinson’s disease (PD) patients undergoing DBS procedure between 2008–2011 were reviewed after Institutional Review Board approval. Anesthesia medication, preoperative levodopa dose, age, preoperative use of antihypertensive medications, diabetes mellitus, anxiety, motor part of the Unified Parkinson’s Disease Rating Scale score and PD duration were collected. Univariate and multivariate analysis was done between each patient characteristic and the number of antihypertensive boluses. From the 136 patients included 60 were hypertensive, of whom 32 were on angiotensin converting enzyme inhibitors (ACEI) or angiotensin receptor blockers (ARB), told to hold on the morning of surgery. Antihypertensive medications were given to 130 patients intraoperatively. Age (relative risk [RR] 1.01; 95% confidence interval [CI] 1.00–1.02; p = 0.005), high Joint National Committee (JNC) class (p < 0.0001), diabetes mellitus (RR 1.4; 95%CI 1.2–17; p < 0.0001) and duration of PD >10 years (RR 1.2; 95%CI 1.1–1.3; p = 0.001) were independent predictors for antihypertensive use. No difference was noted in the mean dose of levodopa (p = 0.1) and levodopa equivalent dose (p = 0.4) between the low (I/II) and high severity (III/IV) JNC groups. Addition of dexmedetomidine to propofol did not influence antihypertensive boluses required (p = 0.38). Intraoperative hypertension during DBS surgery is associated with higher age group, hypertensive, diabetic patients and longer duration of PD. Withholding ACEI or ARB is an independent predictor of hypertension requiring more aggressive therapy. Levodopa withdrawal and choice of anesthetic agent is not associated with higher intraoperative antihypertensive medications.     

Factors that predict a change in quality of life among Parkinson's disease patients participating in a patient education program

BackgroundPatient education is essential in Parkinson's disease (PD). However, it is not known which aspects of patient education are associated with an improvement in quality of life (QoL).ObjectiveTo identify factors that predicted an improvement in QoL in PD patients that participate in an education program.MethodsEduPark is a community-hospital patient education program. PD Patients that had participated in the program between September 2013 and March 2017 were retrospectively included. QoL was prospectively evaluated (using the PDQ-8 questionnaire) before and after the patient's participation. We used mixed linear models (adjusted for the initial value of the PDQ-8) to determine socio-demographic and clinical variables that predicted the change in the PDQ-8 score.ResultsA total of 181 patients were included (mean ± standard deviation age: 62.9 ± 8.2 years; disease duration: 9.1 ± 5.3 years). 76.7% of the 103 patients having undergone a cognitive evaluation did not display cognitive impairment. We did not identify any factors that predicted the program's impact on the patient's QoL. Participation in the program was associated with a significant decrease (improvement) in the PDQ-8 score (39.4 ± 17.81 before and 35.6 ± 15.9 afterwards, P < 0.001).ConclusionWe did not identify any factors that were predictive of the patient education program's impact on QoL in patients with PD. Participation in the program was associated with a significant improvement in QoL. Our results suggest that Patient Education Programs should be more widely prescribed and developed in the management of PD.     

Cerebrospinal fluid inflammatory markers in Parkinson’s disease – Associations with depression,fatigue, and cognitive impairment

Neuroinflammation may be involved in the pathophysiology of Parkinson’s disease (PD) and specifically in non-motor symptoms such as depression, fatigue and cognitive impairment. The aim of this study was to measure inflammatory markers in cerebrospinal fluid (CSF) samples from PD patients and a reference group, and to investigate correlations between non-motor symptoms and inflammation.We quantified C-reactive protein (CRP), interleukin-6, tumor necrosis factor-alpha, eotaxin, interferon gamma-induced protein-10, monocyte chemotactic protein-1 (MCP-1), and macrophage inflammatory protein 1-β in CSF samples from PD patients (N = 87) and the reference group (N = 33). Sixteen of the PD patients had a dementia diagnosis (PDD). We assessed symptoms of fatigue, depression, anxiety and cognitive function using the Functional Assessment of Chronic Illness Therapy-Fatigue, the Hospital Anxiety and Depression Scale, and the Mini Mental State Examination, respectively.There were no significant differences in mean levels of inflammatory markers between PD patients and the reference group. After controlling for age, gender and somatic illness, patients with PDD had significantly higher levels of CRP compared to non-demented PD patients (p = 0.032) and the reference group (p = 0.026). Increased levels of inflammatory markers in CSF were significantly associated with more severe symptoms of depression, anxiety, fatigue, and cognition in the entire PD group. After controlling for PD duration, age, gender, somatic illness and dementia diagnosis, high CRP levels were significantly associated with more severe symptoms of depression (p = 0.010) and fatigue (p = 0.008), and high MCP-1 levels were significantly associated with more severe symptoms of depression (p = 0.032).Our results indicate that non-motor features of PD such as depression, fatigue, and cognitive impairment are associated with higher CSF levels of inflammatory markers.     

Rankin scale as a potential measure of global disability in early Parkinson’s disease

We conducted an exploratory analysis of the utility of the modified Rankin Scale (mRS) as a global measure of disability in early Parkinson’s diesase (PD) using the baseline data from a large cohort of PD patients enrolled in a longitudinal study of creatine. The mRS is scored 0–6 with lower scores reflecting less disability. For the analysis the mRS score was dichotomized at <2 versus ?2. We explored the association of the mRS with multiple measures of PD-related impairments, including the Unified Parkinson Disease Rating Scale (UPDRS); cognitive function characterized by the Symbol Digit Modalities – verbal, and Scales for Outcomes in Parkinson’s disease – cognition (SCOPA-COG); quality of life (Parkinson’s disease questionnaire [PDQ-39]) and EuroQOL; Beck Depression Inventory II (BDI); and Total Functional Capacity (TFC). We also investigated the interaction between variables. One thousand seven hundred forty-one patients were included in the analysis of which 374 had a mRS score of 2 or above. In the univariate model, all interested measures except SCOPA-COG (p = 0.23) had significant association with mRS (p < 0.001) after controlling for confounders. In the multivariate model, UPDRS Part II and III (activities of daily living and motor), BDI, TFC and PDQ-39 were significant (p < 0.05). The mRS has a significant association with the wide spectrum of measures of impairment and quality of life in early PD and shows good potential to be a global measure of disability in early PD. The sensitivity of the mRS to change and performance of the scale in more advanced PD will have to be established longitudinally.     

A cross-sectional study of clinical management,and provision of health services and their utilisation,by patients with Parkinson’s disease in urban and regional Victoria

Our objective was to evaluate and compare clinical management, utilisation of health services and quality of life (QoL) in patients with Parkinson’s disease (PD) attending clinics in urban and regional Victoria. A cross-sectional survey was conducted on 210 patients with PD attending specialist neurological clinics in a regional area (Ballarat) (n = 97), and an urban area (Melbourne) (n = 113), Victoria. Demographic characteristics of patients with PD, QoL, patterns of disease and management and utilisation of medical and allied health services were analysed. Compared to patients with PD from urban clinics, patients in the regional clinic were significantly older and were diagnosed at a later age with a shorter duration of treatment (all p < 0.05). Despite no significant difference in disease severity (measured by Unified Parkinson’s Disease Rating Scale scores) between the groups, patients in the urban clinic reported a lower QoL (p = 0.003). Patients in the regional clinic were more satisfied with their treatment, despite seeing their medical specialist less frequently (p < 0.001) and having a higher rate of early misdiagnosis (p = 0.015). Patients from regional clinics reported a poorer understanding of their illness than patients in the urban clinic (p = 0.049). Half of all respondents were interested in using telemedicine services. Two-thirds (71%) of all patients used allied health services, with patients in the urban clinic utilising more and desiring greater access to these services (p < 0.05). In conclusion, we found significant differences in the presentation, management and use of health services between patients accessing regional and urban PD clinics in Victoria. Telemedicine may be an effective, and even desirable, method for facilitating improved diagnosis and referral for appropriate therapies.     

Age,drugs, or disease: What alters the macrostructure of sleep in Parkinson’s disease?

ObjectiveTo describe the alterations in the macrostructure of sleep in a large cohort of sleep-disturbed patients with Parkinson’s disease (PD) and investigate influencing factors.MethodsA cohort of sleep-disturbed but otherwise unselected PD patients (n = 351) was investigated with video-supported polysomnography. We analyzed the influence of age, disease duration, disease severity, and dopaminergic medication on subjective sleep perception, sleep efficiency, the amount of slow wave sleep, awakenings, periodic leg movements in sleep (PLMS), and REM sleep behavior disorder (RBD).ResultsSleep efficiency and slow wave sleep decreased with age (p = 0.003 and p = 0.041, respectively). The number of awakenings and the frequency of RBD increased with age (p = 0.028 and p = 0.006, respectively). Higher Hoehn & Yahr stages were associated with more PLMS (p = 0.017). A higher daily dose of levodopa corresponded to more RBD (p < 0.001). Neither disease duration nor levodopa dosage had any influence on sleep efficiency, slow wave sleep, awakenings, or PLMS. Dopamine agonists increased awakenings (p < 0.001) and lowered PLMS (p < 0.001). Subjective sleep perception was not influenced by any of the factors analyzed. The only path model that could be replicated identified disease severity and dopamine agonists as interdependent factors influencing awakenings and PLMS.ConclusionAge leads to less sleep and a higher risk for RBD, and disease severity increases motor phenomena such as PLMS; dopamine agonists reduce PLMS but increase awakenings. No single factor analyzed influenced subjective sleep perception in this cohort of sleep disturbed PD patients.     

Parkinson’s disease and REM sleep behavior disorder result in increased non-motor symptoms

ObjectiveRapid eye movement (REM)-sleep behavior disorder (RBD) is often comorbid with Parkinson’s disease (PD). The current study aimed to provide a detailed understanding of the impact of having RBD on multiple non-motor symptoms (NMS) in patients with PD.MethodsA total of 86 participants were evaluated for RBD and assessed for multiple NMS of PD. Principal component analysis was utilized to model multiple measures of NMS in PD, and a multivariate analysis of variance was used to assess the relationship between RBD and the multiple NMS measures. Seven NMS measures were assessed: cognition, quality of life, fatigue, sleepiness, overall sleep, mood, and overall NMS of PD.ResultsAmong the PD patients, 36 were classified as having RBD (objective polysomnography and subjective findings), 26 as not having RBD (neither objective nor subjective findings), and 24 as probably having RBD (either subjective or objective findings). RBD was a significant predictor of increased NMS in PD while controlling for dopaminergic therapy and age (p = 0.01). The RBD group reported more NMS of depression (p = 0.012), fatigue (p = 0.036), overall sleep (p = 0.018), and overall NMS (p = 0.002).ConclusionIn PD, RBD is associated with more NMS, particularly increased depressive symptoms, sleep disturbances, and fatigue. More research is needed to assess whether PD patients with RBD represent a subtype of PD with different disease progression and phenomenological presentation.     

Finger tapping analysis in patients with Parkinson’s disease and atypical parkinsonism

The goal of this study was to investigate repetitive finger tapping patterns in patients with Parkinson’s disease (PD), progressive supranuclear palsy–Richardson syndrome (PSP-R), or multiple system atrophy of parkinsonian type (MSA-P). The finger tapping performance was objectively assessed in PD (n = 13), PSP-R (n = 15), and MSA-P (n = 14) patients and matched healthy controls (HC; n = 14), using miniature inertial sensors positioned on the thumb and index finger, providing spatio-temporal kinematic parameters. The main finding was the lack or only minimal progressive reduction in amplitude during the finger tapping in PSP-R patients, similar to HC, but significantly different from the sequence effect (progressive decrement) in both PD and MSA-P patients. The mean negative amplitude slope of −0.12°/cycle revealed less progression of amplitude decrement even in comparison to HC (−0.21°/cycle, p = 0.032), and particularly from PD (−0.56°/cycle, p = 0.001), and MSA-P patients (−1.48°/cycle, p = 0.003). No significant differences were found in the average finger separation amplitudes between PD, PSP-R and MSA-P patients (p_msa-pd = 0.726, p_msa-psp = 0.363, p_psp-pd = 0.726). The lack of clinically significant sequence effect during finger tapping differentiated PSP-R from both PD and MSA-P patients, and might be specific for PSP-R. The finger tapping kinematic parameter of amplitude slope may be a neurophysiological marker able to differentiate particular forms of parkinsonism.     

Attachment style,relationship quality,and psychological distress in patients with psychogenic non-epileptic seizures versus epilepsy

ObjectivesPsychopathology levels are elevated in patients with psychogenic non-epileptic seizures (PNES) and those with epilepsy. However, patients with PNES report higher rates of trauma and neglect, poorer health-related quality of life (HRQoL), and an increased prevalence of insecure attachment. We examined to what extent attachment style and relationship quality with their main informal carer impact on levels of HRQoL, depression, and anxiety in patients with PNES versus those with epilepsy.MethodConsecutive patients with PNES (N = 23) and epilepsy (N = 72) completed questionnaires about attachment style, quality of their relationship with their main informal carer, seizure severity, HRQoL, depression, and anxiety.ResultsPatients with PNES reported higher levels of anxiety and depression and lower HRQoL than those with epilepsy. PNES: No significant correlations were found with HRQoL but depression correlated positively with attachment avoidance, attachment anxiety, and relationship conflict. Anxiety correlated positively with attachment avoidance, attachment anxiety, and relationship conflict, and negatively with relationship depth and support. Epilepsy: HRQoL correlated negatively with seizure severity, depression, anxiety, attachment avoidance, and attachment anxiety. Depression correlated positively with attachment avoidance, attachment anxiety, and relationship conflict. Anxiety correlated positively with seizure severity, attachment avoidance, and attachment anxiety. Correlations between measures of relationship quality and anxiety were stronger in patients with PNES versus those with epilepsy (zs = 2.66 to 2.97, ps < 0.004). Attachment style and relationship quality explained larger amounts of variance in depression (45%) and anxiety (60%) in the patients with PNES than those with epilepsy (16% and 13%).SignificanceLevels of anxiety and depression were higher in patients with PNES than those with epilepsy. Interpersonal problems were much more closely associated with anxiety and depression in patients with PNES than those with epilepsy. The findings support the use of therapeutic interventions for PNES focusing on attachment and relationship issues.     

Dynamic posturography in evaluation of balance in patients of Parkinson’s disease with normal pull test: Concept of a diagonal pull test

ObjectivesTo assess subclinical balance impairment in patients of Parkinson’s disease (PD) with normal “pull test”, using dynamic posturography.MethodsTwenty PD patients (H&Y stage 2) and 20 matched healthy controls were studied. The patients were evaluated in best ‘ON’ state using UPDRS and Dynamic Posturography. The latter measured dynamic balance indices and limits of stability (LOS) in 8 directions: forward (FW), backward (BW), right (RT), left (LT), forward-right (FW-RT), forward-left (FW-LT), backward-right (BW-RT) and backward-left (BW-LT).ResultsThe dynamic balance indices and total LOS scores did not differ significantly between PD and controls. Direction-wise analysis of LOS showed significantly lower scores (suggesting impaired balance) in PD compared to controls only in FW-RT (21.2 ± 13.8 vs 34.5 ± 17.5, p = 0.005) and BW-LT (20.8 ± 9.8 vs 31.8 ± 15.1, p = 0.018) directions. In LOS test, controls had better stability in FW than BW (p = 0.002) and on RT than LT directions (p = 0.0005). Analysis in diagonal directions showed greater stability in FW-RT than FW-LT, in BW-LT than BW-RT, in FW-RT than BW-RT, and BW-LT than FW-LT directions. Though PD patients maintained greater stability in FW direction like controls, they lost the advantage in other directions.ConclusionsDespite normal “pull test”, PD patients had subclinical direction-specific balance impairment, more apparent in forward-right and backward-left directions. This information may be useful in modifying the standard “pull test” with addition of pull in diagonal directions for detection of early balance impairment.     

Lack of differential motor outcome with subthalamic nucleus region stimulation in Parkinson’s disease

Deep brain stimulation (DBS) has emerged as a viable therapy for Parkinson’s disease (PD). The impact of subthalamic nucleus (STN) lead placement (lateral versus medial) on motor outcome, however, has not been systematically evaluated. Forty-eight patients with PD underwent STN-DBS surgery and were evaluated postoperatively for 48 weeks for motor improvement as measured by the Unified Parkinson’s Disease Rating Scale (UPDRS) part III (standardized motor examination) and levodopa equivalent daily dose (LEDD). Postoperative MRI was used to identify the location of the active stimulating contact and motor outcome was analyzed. STN-DBS was associated with significant improvement in motor outcome as determined by a reduction in the UPDRS part III subscore from 34.44 ± 1.29 at baseline to 18.76 ± 1.06 at end visit (p < 0.0001) and a reduction in LEDD from 1721 ± 152 mg/day at baseline to 1134 ± 119 mg/day at end visit (p = 0.0024). Patients with stimulating contacts in the medial STN compared to the lateral STN did not demonstrate any significant differences in motor outcome (UPDRS, p = 0.5811; LEDD, p = 0.7341). No significant differences were found in motor outcome between patients with STN stimulation compared to stimulation of surrounding fiber tracts (p = 0.80). No significant difference in stimulation voltage was noted with respect to lead location. Our study did not find a significant effect for the location of active contact and motor outcome neither within the subregions of the STN nor between the STN and surrounding fibers. Further research is needed to better understand the neurophysiological basis for these results.     

Association of a polymorphism in the ABCB1 gene with Parkinson's disease

The ATP-binding cassette, sub-family B, member 1 (ABCB1) gene encoding the protein P-glycoprotein (P-gp) has been implicated in the pathophysiology of Parkinson's disease (PD) due to its role in regulating transport of endogenous molecules and exogenous toxins. In the present study, we analyzed the ABCB1 single nucleotide polymorphisms (SNPs) 1236C/T (exon 12), 2677G/T/A (exon 21) and 3435C/T (exon 26) in 288 Swedish PD patients and 313 control subjects and found a significant association of SNP 1236C/T with disease (p = 0.0159; χ² = 8.28), whereas the distributions of wild-type and mutated alleles were similar for 2677G/T/A and 3435C/T in patients and controls. Haplotype analysis revealed significant association of the 1236C–2677G haplotype with PD (p = 0.026; χ² = 4.955) and a trend towards association with disease of the 1236C–2677G–3435C haplotype (p = 0.072; χ² = 3.229). Altered ABCB1 and/or P-pg expression was recently shown in PD patients, and impaired drug efflux across barriers such as the gastrointestinal and nasal mucosal linings or the blood–brain barrier, might result in accumulation of drugs and/or endogenous molecules in toxic amounts, possibly contributing to disease. ABCB1 polymorphisms thus constitute an example of how genetic predisposition and environmental influences may combine to increase risk of PD.