XCiDaBLE is a large, prospective, observational “naturalistic” study evaluating Xeomin® for Cervical Dystonia or BLEpharospasm in the United States. We report the interim results from the blepharospasm cohort of XCiDaBLE.
Subjects (≥18 years old) with blepharospasm were followed for two treatment cycles of incobotulinumtoxinA and monitored for 4 weeks after injection via interactive voice/web response system (IVRS/IWRS). The investigator-reported scale includes the Clinical Global Impression Scale-Severity subscale (CGI-S). Patient-reported outcome measures include the Patient Global Impression Scale-Severity (PGI-S) and -Improvement (PGI-I) subscales, Jankovic Rating Scale (JRS), SF-12v2® health survey, and Work Productivity and Activity Impairment questionnaire. Subjects are seen by the investigator at baseline (including the first injection), during the second injection, and at a final study visit (12 weeks after the second injection).
One hundred seventy subjects were included in this interim analysis. The majority of subjects were female (77.1%) and white (91.8%), and had previously been treated with botulinum toxins (96.5%). The mean total dose (both eyes) was 71.5 U of incobotulinumtoxinA for the first injection. PGI-S, PGI-I, and JRS scores were significantly improved 4 weeks after treatment (all p<0.0001). No differences were noted in either quality of life (QoL) or work productivity in this short assessment period. No unexpected adverse events occurred.
This is an interim study and assessment method based on an IVRS/IWRS. In this predominantly toxin-experienced cohort, significant benefits in specific and global measures of disease severity were seen in the immediate post-incobotulinumtoxinA injection period. It will be interesting to see if there are improvements in QoL with consistent individualized injections over a longer period.
Open label; prospective; blepharospasm; incobotulinumtoxinA; Jankovic Rating Scale; Xeomin
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.
Clinical trials; Clinical trials methodology; Parkinson’s disease; Rankin scale
DYT-5 dystonia usually presents as a dopa-responsive dystonia (DRD) with early or late parkinsonian manifestations and/or dystonic features. Genetically, these patients have been described as having a wide array of independent mutations in the guanosine triphosphate cyclohydrolase 1 gene (GCH1), and these patients may also have a wide array of clinical manifestations.
A Colombian family with six affected female members was characterized.
Three members, including the index case, revealed mild parkinsonism, whereas three granddaughters of the index case showed severe generalized dystonia. No men were affected. There was anticipation, and a female predominance was uncovered. Treatment with levodopa was generally effective except in a case with severe skeletal deformities and contractions. Detailed genetic analysis in the index case revealed a new mutation in exon 1 of GCH1 (c.159delG).
This study revealed a new mutation of GCH1 that resulted in heterogeneous clinical presentations of DRD within a large family.
DRD, dopamine; Parkinson's disease; dystonia, genetics
Researchers have consistently observed in right-handed individuals across normal and disease states that the ‘dominant’ left hemisphere has greater ipsilateral control of the left side than the right hemisphere has over the right. We sought to determine whether this ipsilateral influence of the dominant hemisphere reported in Parkinson’s disease extends to treatments such as deep brain stimulation (DBS) and whether it affects outcome. We hypothesised that among Parkinson right-handers, unilateral left DBS would provide greater ipsilateral motor improvement compared with the ipsilateral motor improvement experienced on the right side.
A total of 73 Parkinson patients who underwent unilateral DBS of the subthalamic nucleus (STN) or globus palidus internus (GPi) participated. Left and right ‘composite scores’, were computed by separately adding all items on the left and right side from the motor section of the Unified Parkinson Disease Rating Scale. The change in the pre- and 4-month post-implantation score was the primary outcome measure. The mean motor scores improved by 4.96 ± 11.79 points (p < 0.001) post-surgery on the ipsilateral side of the DBS implantation. Regression analyses revealed that the side (left vs. right) and target (STN vs. GPi) did not significantly contribute in the effect of ipsilateral motor improvement (p = 0.3557).
While DBS on the ‘dominant’ left side failed to exert a greater ipsilateral influence compared with DBS on the non-dominant right side, significant ipsilateral motor improvements were observed after unilateral stimulation regardless of site of implantation and laterality.
Unilateral DBS; STN; GPi; Parkinson’s disease; UPDRS
Candidacy for deep brain stimulation (DBS) in Parkinson disease (PD) is typically assessed by the preoperative motor response to levodopa along with an interdisciplinary evaluation. However, recent cases treated at our institution have achieved good outcomes with DBS despite a sub-30% improvement in motor scores. The aim of this study was to examine the outcomes of DBS in a subset of patients who failed to reach the 30% motor improvement threshold.
A review of all DBS patients treated at the University of Florida Movement Disorders Center between 2002 and 2009 was performed utilizing a DBS database. All patients with sub-30% improvement in Unified Parkinson Disease Rating Scale Part III after dopaminergic medication administration were included.
Nine patients were identified; DBS was performed for severe dyskinesia (n = 5), “on/off motor” fluctuations (n = 1) and medication-refractory tremor (n = 3). The target symptoms were improved in all patients. Postoperatively, scores on the Unified Parkinson Disease Rating Scale Part II and III and subscores on Parkinson disease questionnaire-39 improved (P < 0.05).
Although motor response to levodopa remains the primary selection criteria for DBS candidacy in Parkinson disease, patients who do not meet the 30% threshold and have disabling symptoms may still benefit from DBS. Select patients with severe dyskinesia, “on/off” motor fluctuations, and/or medication-refractory tremor may experience significant benefits from DBS and should be considered on a case by case basis through an interdisciplinary team evaluation.
deep brain stimulation; Parkinson disease; levodopa challenge test; dyskinesia; on-off motor fluctuations; tremor; quality of life
IncobotulinumtoxinA (Xeomin®, NT 201), a preparation without accessory (complexing) proteins, has shown comparable efficacy and safety to onabotulinumtoxinA in treating cervical dystonia (CD). This study evaluated the efficacy and safety of repeated incobotulinumtoxinA injections in subjects with CD. Following a ≤20-week placebo-controlled, randomized, double-blind, single-dose main period, subjects could enter a ≤68-week prospective, randomized, double-blind, repeated-dose, flexible-interval (minimum 6 weeks) extension period with 240 U or 120 U of incobotulinumtoxinA (≤5 injections). Outcome measures included the Toronto Western Spasmodic Torticollis Rating Scale (TWSTRS) and adverse events (AEs). Of 219 subjects completing the main period, 214 were randomized in the extension period to receive incobotulinumtoxinA 240 U (n = 111) or 120 U (n = 103); 169 subjects completed the extension period, with 90 receiving five injection sessions. Both doses of incobotulinumtoxinA provided statistically significant and clinically relevant improvements in mean TWSTRS-Total, -Severity, -Disability, and -Pain scores, from each injection session to respective 4-week follow-up visits. The most frequently reported AE was dysphagia (240 U: 23.4 %; 120 U: 12.6 %), which did not result in any study withdrawals. There was no impact of injection interval on the incidence of AEs (post hoc analysis). A major limitation of this study was the fixed dose design requested by regulatory authorities, which does not reflect clinical practice. However, repeated incobotulinumtoxinA injections (240 or 120 U; flexible intervals) provided sustained efficacy and were well tolerated, with no unexpected safety risks following repeated injections. The incidence of AEs was similar in subjects requiring repeated injections at shorter intervals (≤12 weeks) compared with those treated using longer intervals (>12 weeks).
Dystonia; Xeomin; IncobotulinumtoxinA; NT 201; Botulinum toxin
Dopaminergic medication-related Impulse Control Disorders (ICDs) such as pathological gambling and compulsive shopping have been reported in Parkinson disease (PD).
We hypothesized that dopamine agonists (DAs) would be associated with greater impulsive choice, or greater discounting of delayed rewards, in PD patients with ICDs (PDI).
Fourteen PDI patients, 14 PD controls without ICDs and 16 medication-free matched normal controls were tested on (i) the Experiential Discounting Task (EDT), a feedback-based intertemporal choice task, (ii) spatial working memory and (iii) attentional set shifting. The EDT was used to assess impulsivity choice (hyperbolic K-value), reaction time (RT) and decision conflict RT (the RT difference between high conflict and low conflict choices). PDI patients and PD controls were tested on and off DA.
On the EDT, there was a group by medication interaction effect [F(1,26)=5.62; p=0.03] with pairwise analyses demonstrating that DA status was associated with increased impulsive choice in PDI patients (p=0.02) but not in PD controls (p=0.37). PDI patients also had faster RT compared to PD controls F(1,26)=7.51 p=0.01]. DA status was associated with shorter RT [F(3,24)=8.39, p=0.001] and decision conflict RT [F(1,26)=6.16, p=0.02] in PDI patients but not in PD controls. There were no correlations between different measures of impulsivity. PDI patients on DA had greater spatial working memory impairments compared to PD controls on DA (t=2.13, df=26, p=0.04).
Greater impulsive choice, faster RT, faster decision conflict RT and executive dysfunction may contribute to ICDs in PD.
dopamine agonist; gambling; impulse control; Parkinson disease; delay discounting
Several case reports have linked solvent exposure to Parkinson’s disease (PD), but few studies have assessed associations with specific agents using an analytic epidemiologic design. We tested the hypothesis that exposure to specific solvents is associated with PD risk using a discordant twin pair design.
99 twin pairs discordant for PD ascertained from the National Academy of Science/National Research Council (NAS/NRC) World War II Veteran Twins Cohort were interviewed regarding lifetime occupations and hobbies using detailed job-task-specific questionnaires. Exposures to 6 specific solvents selected a priori were estimated by expert raters unaware of case status.
Ever exposure to trichloroethylene (TCE) was associated with significantly increased risk of PD (OR 6.1, 95%CI 1.2 – 33; p = 0.034), and exposure to perchloroethylene (PERC) and carbon tetrachloride (CCl4) tended toward significance (respectively: OR 10.5, 95%CI 0.97-113, p = 0.053; OR 2.3, 95%CI 0.9-6.1, p = 0.088). Results were similar for estimates of exposure duration and cumulative lifetime exposure.
Exposure to specific solvents may increase risk of PD. TCE is the most common organic contaminant in groundwater, and PERC and CCl4 are also ubiquitous in the environment. Our findings require replication in other populations with well-characterized exposures, but the potential public health implications are substantial.
Levodopa–carbidopa intestinal gel (LCIG) delivered continuously via percutaneous endoscopic gastrojejunostomy (PEG-J) tube has been reported, mainly in small open-label studies, to significantly alleviate motor complications in Parkinson’s disease (PD). A prospective open-label, 54-week, international study of LCIG is ongoing in advanced PD patients experiencing motor fluctuations despite optimized pharmacologic therapy. Pre-planned interim analyses were conducted on all enrolled patients (n = 192) who had their PEG-J tube inserted at least 12 weeks before data cutoff (July 30, 2010). Outcomes include the 24-h patient diary of motor fluctuations, Unified Parkinson’s Disease Rating Scale (UPDRS), Clinical Global Impression-Improvement (CGI-I), Parkinson’s Disease Questionnaire (PDQ-39), and safety evaluations. Patients (average PD duration 12.4 yrs) were taking at least one PD medication at baseline. The mean (±SD) exposure to LCIG was 256.7 (±126.0) days. Baseline mean “Off” time was 6.7 h/day. “Off” time was reduced by a mean of 3.9 (±3.2) h/day and “On” time without troublesome dyskinesia was increased by 4.6 (±3.5) h/day at Week 12 compared to baseline. For the 168 patients (87.5%) reporting any adverse event (AE), the most common were abdominal pain (30.7%), complication of device insertion (21.4%), and procedural pain (17.7%). Serious AEs occurred in 60 (31.3%) patients. Twenty-four (12.5%) patients discontinued, including 14 (7.3%) due to AEs. Four (2.1%) patients died (none deemed related to LCIG). Interim results from this advanced PD cohort demonstrate that LCIG produced meaningful clinical improvements. LCIG was generally well-tolerated; however, device and procedural complications, while generally of mild severity, were common.
Parkinson’s disease; Levodopa–carbidopa intestinal gel; Motor fluctuations; PEG-J procedure; Pump administration
We report the interim results from XCiDaBLE, a large, prospective, observational “naturalistic” study evaluating Xeomin® (incobotulinumtoxinA) for Cervical Dystonia or BLEpharospasm in the United States.
Subjects (≥ 18 years old) with cervical dystonia (CD) are followed for two treatment cycles and monitored via Interactive Voice/Web Response. The subject's physician must have chosen to treat with incobotulinumtoxinA prior to and independent of enrollment in this study. Subject-reported scales include the Subject Global Impression-Severity and Improvement and Cervical Dystonia Impact Profile (CDIP-58), and Work Productivity and Quality of Life (QoL) are assessed by means of an employment questionnaire and work history and the SF-12v2 Health Survey (SF-12v2). Subjects are seen by the investigator for three visits, which include a baseline visit (including the first injection), a second injection visit, and a final study visit (12 weeks after the second injection).
This ongoing study includes 145 subjects with a diagnosis of CD. The majority were female (82.3%) and white (91.0%) and had previously been treated with botulinum toxins (77.2%). There were 106 employed at the time of disease onset, but 12.6 years later only 44% were still employed at the time of enrolment into the study, and 20% were either receiving or seeking disability benefits. The mean total dose/treatment of CD was 225.2 units for the first injection. The CDIP-58 total score was significantly improved 4 weeks after the first injection compared to baseline (p≤0.0001). Most subjects noted improvement in their global impression assessment. No new or unexpected adverse events occurred.
The results from these interim analyses confirm previous controlled, single-dose studies of incobotulinumtoxinA in terms of efficacy and safety.
incobotulinumtoxinA; botulinum toxin type A; NT 201; cervical dystonia; CDIP-58
IncobotulinumtoxinA (Xeomin®, NT 201) is a purified botulinum toxin type A free from accessory (complexing) proteins. Previous studies evaluated single sets of incobotulinumtoxinA injections for the treatment of blepharospasm. Individualized injection intervals and other potential determinants of efficacy and safety need to be evaluated in a prospective, longitudinal study. Subjects with blepharospasm who completed a ≤20 weeks double-blind, placebo-controlled main period entered a ≤69 weeks open-label extension period (OLEX) and received ≤5 additional incobotulinumtoxinA treatments at flexible doses (≤50 U per eye) and flexible injection intervals (minimum of 6 weeks). Outcome measures included Jankovic Rating Scale (JRS) (sumscore, severity subscore and frequency subscore), Blepharospasm Disability Index, and adverse events. All 102 subjects who completed the main period entered the OLEX; 82 subjects completed the study, 56 received the maximum five injections. From each injection visit to a control visit 6 weeks later, investigator-rated JRS sumscores and subscores, and patient-rated Blepharospasm Disability Index were significantly improved (p ≤ 0.001 for all). All scores were still significantly improved at trial termination compared with the first injection visit (p < 0.05 for all). The most frequently reported adverse events were eyelid ptosis (31.4 %) and dry eye symptoms (17.6 %). The injection interval had no impact on the incidence of adverse events (post hoc analysis). No subject developed neutralizing antibodies during the study. Repeated incobotulinumtoxinA injections, administered at flexible doses and injection intervals from 6 to 20 weeks according to subjects’ needs, provide sustained efficacy in the treatment of blepharospasm with no new or unexpected safety risks.
Blepharospasm; Botulinum toxin; IncobotulinumtoxinA; Dystonia; Xeomin
To test whether the synucleinopathies Parkinson’s disease and multiple system atrophy (MSA) share a common genetic etiology, we performed a candidate single nucleotide polymorphism (SNP) association study of the 384 most associated SNPs in a genome-wide association study of Parkinson’s disease in 413 MSA cases and 3,974 control subjects. The 10 most significant SNPs were then replicated in additional 108 MSA cases and 537 controls. SNPs at the SNCA locus were significantly associated with risk for increased risk for the development of MSA (combined p = 5.5 × 1012; odds ratio 6.2).
Fatigue is a common and disabling nonmotor symptom seen in Parkinson's disease (PD). While deep brain stimulation surgery (DBS) improves motor symptoms, it has also been associated with non-motor side effects. To date no study has utilized standardized instruments to evaluate fatigue following DBS surgery. Our objective was to determine the prevalence of fatigue following DBS surgery in PD its impact on quality of life and explore predictive factors. We recruited 44 PD subjects. At least one year following DBS placement, we administered the Fatigue Severity Scale (FSS), the Parkinson's Disease Questionnaire (PDQ-39), the Beck Depression Inventory, the Beck Anxiety Inventory, the UPDRS, and a neuropsychological battery. Fifty-eight percent of subjects had moderate to severe fatigue. Fatigue was significantly associated with quality of life, depression, and anxiety. Depression preoperatively was the only predictive factor of fatigue. Fatigue is common following DBS surgery and significantly impacts quality of life.
Parkinson’s patients, on average, gain weight following DBS.
To determine potential differences in weight gain when comparing the STN versus the GPi target.
A retrospective analysis was performed on the prospective randomized cohort of NIH COMPARE DBS patients who received unilateral STN or GPi DBS. Baseline weights were recorded prior to DBS surgery and at 6, 12, and 18 months post-operatively. Relationships between weight change and changes in BDI score, UPDRS motor score (part III) (also the dyskinesia duration and disability subscores from UPDRS IV), and HY stage were determined via Spearman’s rank order correlation coefficients. Regression analyses were performed to investigate the effects of potential factors on weight change over time.
Patients in the COMPARE DBS cohort gained a significant amount of weight-a mean of 4.86 lbs (SD 8.73) (p-value = 0.0006), but there was no significant difference between STN and GPi targets (weight gain of 4.29± 6.79 and 5.38±10.32 pounds, respectively; p-value = 0.684). Weight gain did not correlate with BDI score change, UPDRS motor score, dyskinesia duration, dyskinesia disability change, or the HY stage (p-values were0.617, 0.210, and 0.305 respectively). No specific variable was associated with weight gain, and there were no differences in binge eating post-surgery in either target.
There were significant changes in weight over time following DBS therapy. However, neither BDI score change nor UPDRS score change or dyskinesia was correlated with weight gain. No significant factor was associated with the weight change.
Deep brain stimulation; hypothalamus; diet; outcome; binge
Impulse control disorders are common in Parkinson's; disease, occurring in 13.6% of patients. Using a pharmacological manipulation and a novel risk taking task while performing functional magnetic resonance imaging, we investigated the relationship between dopamine agonists and risk taking in patients with Parkinson's; disease with and without impulse control disorders. During functional magnetic resonance imaging, subjects chose between two choices of equal expected value: a ‘Sure’ choice and a ‘Gamble’ choice of moderate risk. To commence each trial, in the ‘Gain’ condition, individuals started at $0 and in the ‘Loss’ condition individuals started at −$50 below the ‘Sure’ amount. The difference between the maximum and minimum outcomes from each gamble (i.e. range) was used as an index of risk (‘Gamble Risk’). Sixteen healthy volunteers were behaviourally tested. Fourteen impulse control disorder (problem gambling or compulsive shopping) and 14 matched Parkinson's; disease controls were tested ON and OFF dopamine agonists. Patients with impulse control disorder made more risky choices in the ‘Gain’ relative to the ‘Loss’ condition along with decreased orbitofrontal cortex and anterior cingulate activity, with the opposite observed in Parkinson's; disease controls. In patients with impulse control disorder, dopamine agonists were associated with enhanced sensitivity to risk along with decreased ventral striatal activity again with the opposite in Parkinson's; disease controls. Patients with impulse control disorder appear to have a bias towards risky choices independent of the effect of loss aversion. Dopamine agonists enhance sensitivity to risk in patients with impulse control disorder possibly by impairing risk evaluation in the striatum. Our results provide a potential explanation of why dopamine agonists may lead to an unconscious bias towards risk in susceptible individuals.
Parkinson's; disease; dopamine; gambling; decision making; risk
McLeod syndrome (MLS) is a rare, X-linked, late-onset, disease involving hematological, brain, and neuromuscular systems, caused by mutations in XK that result in either defective XK or complete loss of XK protein. Acanthocytosis of erythrocytes is a typical feature. We report novel mutations in two patients who exhibited typical clinical characteristics of MLS. The coding and flanking intronic regions of XK were amplified by PCR, sequenced, and compared with the normal XK sequence. XK protein, and its complexed partner protein, Kell, were assessed by Western blot analysis. Patient 1 was found to have a single base insertion, 605insA at 175Ile creating a frame shift within the coding sequence of XK. Patient 2 had a single base substitution in the 3′ splice sequence of intron 2 (IVS2–2a>g). In both cases mutations resulted in the absence of XK protein.
McLeod syndrome; Neuroacanthocytosis; XK protein; Kell protein; Acanthocytosis; McLeod blood group; Kx erythrocyte antigen; Kell blood group antigens
Parkinson's disease (PD) management has traditionally focused largely on motor symptoms. Deep brain stimulation (DBS) of the subthalamic nucleus (STN) and globus pallidus internus (GPi) are effective treatments for motor symptoms. Nonmotor symptoms (NMSs) may also profoundly affect the quality of life. The purpose of this pilot study was to evaluate NMS changes pre- and post-DBS utilizing two recently developed questionnaires. Methods. NMS-Q (questionnaire) and NMS-S (scale) were administered to PD patients before/after unilateral DBS (STN/GPi targets). Results. Ten PD patients (9 STN implants, 1 GPi implant) were included. The three most frequent NMS symptoms identified utilizing NMS-Q in pre-surgical patients were gastrointestinal (100%), sleep (100%), and urinary (90%). NMS sleep subscore significantly decreased (−1.6 points ± 1.8, P = 0.03). The three most frequent NMS symptoms identified in pre-surgical patients using NMS-S were gastrointestinal (90%), mood (80%), and cardiovascular (80%). The largest mean decrease of NMS scores was seen in miscellaneous symptoms (pain, anosmia, weight change, and sweating) (−7 points ± 8.7), and cardiovascular/falls (−1.9, P = 0.02). Conclusion. Non-motor symptoms improved on two separate questionnaires following unilateral DBS for PD. Future studies are needed to confirm these findings and determine their clinical significance as well as to examine the strengths/weaknesses of each questionnaire/scale.
X-linked dystonia-parkinsonism (XDP; DYT3; Lubag) is an adult-onset hereditary progressive dystonia/parkinsonism which is typically minimally responsive to pharmacological treatment.
We report a 63- year-old man with a diagnosis of XDP who underwent bilateral globus pallidus internus deep brain stimulator (GPi-DBS) placement. His course initially began with right hand tremor and dystonia at age 57 and progressed to also include bradykinesia and rigidity. The patient tolerated the procedure without significant complications. GPi-DBS improved his right hand dystonia, but did not significantly improve his parkinsonism.
DBS may be a therapeutic option for select cases of XDP, but its specificindications must be carefully discussed, as the available cases have had mixed responses. Whether other targets may be more effective is not known.
X-linked dystonia-parkinsonism; Globus pallidus internus; Cognitive impairment; Medication-resistant parkinsonism
A substantial number of individuals with Parkinson’s disease who display impaired postural stability experience accelerated cognitive decline and an increased prevalence of dementia. To date, studies suggest that this relationship, believed to be due to involvement of nondopaminergic circuitry, occurs later in the disease process. Research has yet to adequately investigate this cognitive-posturomotor relationship especially when examining earlier disease states. To gain greater understanding of the relationship between postural stability and cognitive function/dysfunction we evaluated a more stringent, objective measure of postural stability (center of pressure displacement), and also more specific measures of cognition in twenty-two patients with early to moderate stage Parkinson’s disease. The magnitude of the center of pressure displacement in this cohort was negatively correlated with performance on tests known to activate dorsolateral frontal regions. Additionally, the postural stability item of the UPDRS exhibited poor correlation with the more objective measure of center of pressure displacement and all specific measures of cognition. These results may serve as rationale for a more thorough evaluation of postural stability and cognition especially in individuals with mild Parkinson’s disease. Greater understanding of the relationship between motor and cognitive processes in Parkinson’s disease will be critical for understanding the disease process and its potential therapeutic possibilities.
neurodegenerative disease; dementia; balance
Of 96 Parkinson’s disease (PD) patients at the University of Florida Movement Disorders Center, one (1%) met diagnostic criteria for binge eating disorder (BED). Eight (8.3%) exhibited subthreshold BED. Psychometric criteria classified problem gambling in 17.8%, hoarding in 8.3%, buying in 11.5%, hypersexuality in 1.0%, and mania in 1.0% of patients. More overeaters met psychometric criteria for at least one additional impulse control disorder (67% vs. 29%). No more overeaters than non-overeaters were taking a dopamine agonist (44% vs. 41%). More overeaters had a history of subthalamic DBS (44% vs. 14%). History of DBS was the only independent predictor of overeating.
Parkinson’s disease; binge eating; impulse control disorders
Background. Nonmotor symptoms (NMS) of Parkinson's disease (PD) may be more debilitating than motor symptoms. The purpose of this study was to determine the frequency and corecognition of NMS among our advanced PD cohort (patients considered for deep brain stimulation (DBS)) and caregivers.
Methods. NMS-Questionnaire (NMS-Q), a self-administered screening questionnaire, and NMS Assessment-Scale (NMS-S), a clinician-administered scale, were administered to PD patients and caregivers. Results. We enrolled 33 PD patients (23 males, 10 females) and caregivers. The most frequent NMS among patients using NMS-Q were gastrointestinal (87.9%), sleep (84.9%), and urinary (72.7%), while the most frequent symptoms using NMS-S were sleep (90.9%), gastrointestinal (75.8%), and mood (75.8%). Patient/caregiver scoring correlations for NMS-Q and NMS-S were 0.670 (P < 0.0001) and 0.527 (P = 0.0016), respectively. Conclusion The frequency of NMS among advanced PD patients and correlation between patients and caregivers varied with the instrument used. The overall correlation between patient and caregiver was greater with NMS-Q than NMS-S.
Mitochondrial dysfunction and oxidative stress are pathophysiologic mechanisms implicated in experimental models and genetic forms of Parkinson’s disease (PD). Certain pesticides may affect these mechanisms, but no pesticide has been definitively associated with PD in humans.
Our goal was to determine whether pesticides that cause mitochondrial dysfunction or oxidative stress are associated with PD or clinical features of parkinsonism in humans.
We assessed lifetime use of pesticides selected by mechanism in a case–control study nested in the Agricultural Health Study (AHS). PD was diagnosed by movement disorders specialists. Controls were a stratified random sample of all AHS participants frequency-matched to cases by age, sex, and state at approximately three controls: one case.
In 110 PD cases and 358 controls, PD was associated with use of a group of pesticides that inhibit mitochondrial complex I [odds ratio (OR) = 1.7; 95% confidence interval (CI), 1.0–2.8] including rotenone (OR = 2.5; 95% CI, 1.3–4.7) and with use of a group of pesticides that cause oxidative stress (OR = 2.0; 95% CI, 1.2–3.6), including paraquat (OR = 2.5; 95% CI, 1.4–4.7).
PD was positively associated with two groups of pesticides defined by mechanisms implicated experimentally—those that impair mitochondrial function and those that increase oxidative stress—supporting a role for these mechanisms in PD pathophysiology.
aging; agricultural epidemiology; environmental epidemiology; epidemiology; fungicides; herbicides; insecticides; persistent organic pollutants; pesticides
It is essential to recognize and treat psychosis in Parkinson disease (PD) for several reasons. Multiple studies have shown that psychosis in PD patients is a strong risk factor for nursing home placement. Psychosis may be the single greatest stress for caretakers of PD patients, it is often persistent, and its presence markedly increases the risk of mortality.
Treatment of psychotic symptoms should occur only after potential medical and environmental causes of delirium have been eliminated or addressed. Initial pharmacologic changes should include limiting the patient’s anti-PD medications to those that are necessary to preserve motor function. Should that fail, an atypical antipsychotic agent is presently the treatment of choice. An emerging treatment option is the use of acetylcholinesterase inhibitors. This article reviews what is currently known about the course, prognosis and treatment strategies in PD psychosis.
Psychotic symptoms in Parkinson’s disease (PD) are relatively common, and in addition to being a disturbance to patients’ daily lives, they have consistently been shown to be associated with poor outcome. Our understanding of the pathophysiology of psychosis in PD has expanded dramatically over the past fifteen years, from an initial interpretation of symptoms as dopaminergic drug side effects to the current view of a complex interplay of extrinsic and disease-related factors. The present article reviews the unique clinical features of psychosis as expressed in PD, associated risk factors, and current theories behind its pathogenesis, including medications, visual processing deficits, sleep disturbances, genetics, and neurochemical and structural abnormalities. Finally, we review both traditional and emergent management strategies for PD psychosis, including antipsychotic agents, cholinesterase inhibitors, electroconvulsive therapy (ECT), and other pharmacological and psychological interventions.
Psychosis is a leading reason for nursing home placement of patients with Parkinson’s disease (PD). It may also be the single greatest stressor for caregivers of PD patients, it is generally persistent, and its presence markedly increases the risk of mortality. For these reasons, it is essential to recognize and appropriately treat psychosis in PD. Treatment of psychotic symptoms should be initiated after potential medical and environmental causes of delirium (eg, infection) have been eliminated or addressed. Initial pharmacologic changes should include limiting the patient’s anti-PD medications to those that are necessary to preserve motor function (ie, eliminating adjunctive agents). Should that fail, an atypical antipsychotic agent is the treatment of choice. Clozapine is presently the gold standard, and quetiapine represents another option because of its ease of use and good tolerability profile. Emerging treatment options include the use of acetylcholinesterase inhibitors, antidepressants, and cognitive behavioral therapy. This article reviews what is currently known about treatment strategies in PD psychosis.