Freezing of gait: pharmacological and surgical options.

PURPOSE OF REVIEW: The primary aim of this review is to describe and update the pathophysiological and relevant therapeutic strategies for freezing of gait (FoG) in patients with Parkinson's disease (PD). RECENT FINDINGS: FoG presumably involves dysfunction of multiple cortical and subcortical components, including dopaminergic and nondopaminergic circuits. In this regard, levodopa and physical therapy represent the first-choice therapeutic options for PD patients with FoG. However, the relationship between FoG and levodopa is not fully predictable. For those patients with levodopa-resistant FoG, there is promising but still controversial data on the benefits of bilateral high-frequency transcranial magnetic stimulation and deep brain stimulation on the subthalamic nuclei, substantia nigra pars reticulata, pedunculopontine nucleus, and the Fields of Forel. On the other hand, general exercise, gait training with a treadmill, focus attention on gait training, and conventional physiotherapy have demonstrated moderate to large benefits in FoG. SUMMARY: FOG requires different treatment strategies. The inclusion of adequate detection and prediction of FoG combined with double-blind, and statistically powered protocols are needed to improve patients' quality of life, the motor and nonmotor symptoms and societal burden associated with FoG.

Suicidal ideation among people with Parkinson's disease and comparison with a control group.

BACKGROUND: Detection of suicidal ideation (SI) is key for trying to prevent suicide. The aim of this study was to analyze the frequency of SI and related factors in Spanish people with Parkinson's Disease (PwPD) and to compare them with a control group. METHODS: PD patients and controls recruited from the Spanish cohort COPPADIS from January 2016 to November 2017 were included. Two visits were conducted: V0 (baseline); V2 (2-year ± 1 month follow-up). SI was defined as a score ≥1 on item nine of the Beck Depression Inventory-II (BDI-II). Regression analyses were conducted to identify factors related to SI. RESULTS: At baseline, 693 PwPD (60.2% males; 62.59 ± 8.91 years old) and 207 controls (49.8% males; 60.99 ± 8.32 years old) were included. No differences between PwPD and controls were detected in SI frequency at either V0 (5.1% [35/693] vs. 4.3% [9/207]; p = 0.421) or at V2 (5.1% [26/508] vs. 4.8% [6/125]; p = 0.549). Major depression (MD) and a worse quality of life were associated with SI at both visits in PwPD: V0 (MD, OR = 5.63; p = 0.003; PDQ-39, OR = 1.06; p = 0.021); V2 (MD, OR = 4.75; p = 0.027; EUROHIS-QOL8, OR = 0.22; p = 0.006). A greater increase in the BDI-II total score from V0 to V2 was the only factor predicting SI at V2 (OR = 1.21; p = 0.002) along with an increase in the total number of non-antiparkinsonian drugs (OR = 1.39; p = 0.041). CONCLUSION: The frequency of SI (5%) in PwPD was similar to in controls. Depression, a worse quality of life, and a greater comorbidity were related to SI.

Predictors of the change in burden, strain, mood, and quality of life among caregivers of Parkinson's disease patients.

BACKGROUND AND OBJECTIVE: Caregiver burden in Parkinson's disease (PD) has been studied in many cross-sectional studies but poorly in longitudinal ones. The aim of the present study was to analyze the change in burden, strain, mood, and quality of life (QoL) after a 2-year follow-up in a cohort of caregivers of patients with PD and also to identify predictors of these changes. PATIENTS AND METHODS: PD patients and their caregivers who were recruited from January/2016 to November/2017 from 35 centers of Spain from the COPPADIS cohort were included in the study. They were evaluated again at 2-year follow-up. Caregivers completed the Zarit Caregiver Burden Inventory (ZCBI), Caregiver Strain Index (CSI), Beck Depression Inventory-II (BDI-II), and EUROHIS-QOL 8-item index (EUROHIS-QOL8) at baseline (V0) and at 2-year follow-up (V2). General linear model repeated measure and lineal regression models were applied. RESULTS: Significant changes, indicating an impairment, were detected on the total score of the ZCBI (p < 0.0001), CSI (p < 0.0001), BDI-II (p = 0.024), and EUROHIS-QOL8 (p = 0.002) in 192 PD caregivers (58.82 ± 11.71 years old; 69.3% were females). Mood impairment (BDI-II; ß = 0.652; p < 0.0001) in patients from V0 to V2 was the strongest factor associated with caregiver's mood impairment after the 2-year follow-up. Caregiver's mood impairment was the strongest factor associated with an increase from V0 to V2 on the total score of the ZCBI (ß = 0.416; p < 0.0001), CSI (ß = 0.277; p = 0.001), and EUROHIS-QOL (ß = 0.397; p = 0.002). CONCLUSION: Burden, strain, mood, and QoL were impaired in caregivers of PD patients after a 2-year follow-up. Mood changes in both the patient and the caregiver are key aspects related to caregiver burden increase.

Spinocerebellar ataxia type 3: response to levodopa infusion in two cases.

INTRODUCTION: Spinocerebellar ataxia type 3 (SCA-ATXN3) is a genetic neurodegenerative disease characterized by progressive cerebellar ataxia and other variable findings, including Parkinsonian syndrome. There is no disease-modifying treatment for SCA-ATXN3, so symptom-based management predominates. We aim to illustrate the disease's phenotypic variability and describe the effectiveness of advanced therapies in Parkinsonian symptoms. CASES: We present two patients with a predominant levodopa-responsive Parkinsonian phenotype, combined with cerebellar features. We achieved an optimal control of Parkinsonian symptoms with a carbidopa-levodopa intestinal gel infusion pump. CONCLUSIONS: We should suspect an SCA-ATXN3 etiology in patients with syndromes resembling an early-onset Parkinson disease with an autosomal dominant pattern. These patients could benefit from anti-Parkinsonian treatments, including levodopa intestinal gel infusion pump.

Huntington's disease and neurovascular structure of retina.

BACKGROUND: Retinal biomarkers in neurodegenerative disorders have attracted much attention in recent years. Recent studies have reported visual dysfunction in Huntington's disease (HD). However, little is known about retinal structural changes in HD. METHODS: A total of 50 subjects, including 25 motor-manifest HD patients and 25 gender- and age-matched controls, were enrolled. Unified Huntington's Disease Rating Score-Motor part was assessed in HD patients. Spectral-domain Optical Coherence Tomography (SD-OCT) was used to evaluate the macular thickness and peripapillary retinal nerve fiber layer (pRNFL). Superficial and deep capillary plexus densities were measured using OCT angiography (OCTA). To account for inter-eye correlation, generalized estimating equation (GEE) model was used. RESULTS: HD patients had a significant reduction in macular thickness in both inner and outer superior sectors and the inferior outer sector. Inferior pRNFLs were significantly decreased in thickness. There was no significant difference in retinal capillary plexus density between the two groups. Age and disease duration were negatively correlated with macular thickness in HD patients. However, the severity of motor involvement was not correlated with SD-OCT or OCTA parameters. CONCLUSIONS: We observed attenuated pRNFL and macular retinal thickness in patients with HD, independent of macular capillary plexus parameters. It can support the hypothesis that the retina may be a potential biomarker for monitoring the neurodegenerative process in HD.

Polymorphisms in the oxytocin receptor and their association with apathy and impaired social cognition in Huntington's disease.

BACKGROUND: Huntington's disease (HD) is a neurodegenerative disorder characterized by cognitive, motor, and neuropsychiatric manifestations. Oxytocin is a neuropeptide studied for its role as a neuromodulator regulating multiple behaviors linked to social cognition. Genetic variation of oxytocin receptor (OXTR) might interact in the etiology and development of several impaired social behaviors. Our aim was to study OXTR polymorphisms and their relationship with apathy and social cognition in HD. METHODS: OXTR was sequenced in 21 cases and 22 controls. We assessed apathy, anxiety, depression, and irritability (Hospital Anxiety and Depression Scale-Snaith Irritability scale, HADS-SIS) and social cognition (Ekman 60 faces test), motor symptoms and functionality with the total functional capacity (TFC), and the Unified HD rating Scale (UHDRS). RESULTS: We identified ten variants in OXTR. Three variants were classified as possibly damaging (p.Arg40Gly) or probably damaging (p.Leu46Pro, p.Thr102Asn). Subjects carrying the wild-type genotype of the synonymous variant p.Val45 showed a significantly lower score in the HADS-SIS scale, related to lower irritability (p = 0.013). The only subject carrying the heterozygous genotype of the synonymous variant p.Leu62 showed a significantly higher score on Ekman scale, compared to wild-type (p = 0.049); however, this finding was not confirmed after bootstrapping. CONCLUSION: Variations in OXTR could have a relevant role in the correct development of social and cognitive functions. Future approaches will include the molecular study of p.Arg40Gly, p.Leu46Pro, and p.Thr102Asn to confirm their pathogenicity, as well as the validation of the influence of p.Val45 and p.Leu62 variants for their involvement in irritability and social cognition in HD.

Identifying comorbidities and lifestyle factors contributing to the cognitive profile of early Parkinson's disease.

BACKGROUND: Identifying modifiable risk factors for cognitive impairment in the early stages of Parkinson's disease (PD) and estimating their impact on cognitive status may help prevent dementia (PDD) and the design of cognitive trials. METHODS: Using a standard approach for the assessment of global cognition in PD and controlling for the effects of age, education and disease duration, we explored the associations between cognitive status, comorbidities, metabolic variables and lifestyle variables in 533 PD participants from the COPPADIS study. RESULTS: Among the overall sample, 21% of participants were classified as PD-MCI (n = 114) and 4% as PDD (n = 26). The prevalence of hypertension, diabetes and dyslipidemia was significantly higher in cognitively impaired patients while no between-group differences were found for smoking, alcohol intake or use of supplementary vitamins. Better cognitive scores were significantly associated with regular physical exercise (p < 0.05) and cognitive stimulation (< 0.01). Cognitive performance was negatively associated with interleukin 2 (Il2) (p < 0.05), Il6 (p < 0.05), iron (p < 0.05), and homocysteine (p < 0.005) levels, and positively associated with vitamin B12 levels (p < 0.005). CONCLUSIONS: We extend previous findings regarding the positive and negative influence of various comorbidities and lifestyle factors on cognitive status in early PD patients, and reinforce the need to identify and treat potentially modifiable variables with the intention of exploring the possible improvement of the global cognitive status of patients with PD.

Mood in Parkinson's disease: From early- to late-stage disease.

BACKGROUND: Although depression is known to be frequent in Parkinson's disease (PD), it is unclear how mood can change and/or impact on patient's quality of life (QoL) over time. Our aim was to analyze the frequency of depression, mood related factors and the contribution of mood to a patient's QoL perception in regard to disease duration. METHODS: PD patients recruited from the COPPADIS cohort from January 2016 to November 2017 were included in this cross-sectional study. Three groups were defined: <5 years (Group A); from 5 to <10 years (Group B); ≥10 years (Group C). Analysis with well-planned linear regression models was conducted to determine how different factors contribute to mood (Beck Depression Inventory-II [BDI-II] as dependent variable), to health-related QoL (39-item Parkinson's Disease Questionnaire [PDQ-39SI] as dependent variable) and to global QoL (European Health Interview Survey - Quality of Life Eight-Item Index [EUROHIS-QOL8] as dependent variable). RESULTS: Six hundred and sixty-three PD patients (62.6 ± 8.9 years old, 59.6% males) were included: Group A, 50.1% (n = 332); Group B, 33.3% (n = 221) and Group C, 16.6% (n = 110). There were no differences between the three groups in terms of the frequency of depressive symptoms nor the frequency of depression type (major vs. minor vs. subthreshold) (p = 0.729). However, the unique percent variance of PDQ-39SI and EUROHIS-QOL8 explained by BDI-II total score was 2 (23.7%) and threefold (26.9%), respectively, in Group C compared to the other two groups. EUROHIS-QOL8 total score provided the highest unique contribution to mood (16.8%). CONCLUSIONS: Although depression-type frequency does not appear to change over time in PD; the contribution of mood on QoL perception is greater in patients with longer disease duration.

Global Survey on Telemedicine Utilization for Movement Disorders During the COVID-19 Pandemic.

BACKGROUND: The COVID-19 pandemic restricted usual healthcare management for movement-disorders patients, with a consequent upsurge in telemedicine to bridge the gap. OBJECTIVE: To assess global telemedicine usage in the context of the pandemic. METHODS: The Movement Disorder Society (MDS) Telemedicine Study Group surveyed telemedicine experts from 40 countries across all continents in March-April 2020. Four domains of telemedicine were assessed: legal regulations, reimbursement, clinical use, and barriers; comparing emerging responses to the pandemic versus the baseline scenario. RESULTS: All forms of telemedicine for movement disorders increased globally, irrespective of country income categorization, as an immediate response to the pandemic. This was aided by widespread availability of technology and updated government regulations. However, privacy concerns, lack of reimbursement, limited access, and lack of telemedicine training were barriers highlighted worldwide. CONCLUSIONS: Questions remain about the longevity and extent of changes in regulations and reimbursement regarding telemedicine in the aftermath of the pandemic. © 2020 International Parkinson and Movement Disorder Society.

Survival in Restless Legs Syndrome: An 11-Year Surveillance, Community-Based Population Study.

BACKGROUND: A growing body of evidence relates restless legs syndrome (RLS) to an increased risk of mortality attributable to both cerebrovascular and cardiovascular events. The aim was to investigate survival in patients with RLS. METHODS: This was an observational, retrospective longitudinal study of a cohort of patients followed up for 11 years. RLS was diagnosed by a physician using the International RLS Study Group criteria. Mortality was analyzed using age-standardized mortality ratios (SMR: observed/expected deaths) and Cox regression analysis. RESULTS: Vital status was studied in a cohort of 232 patients: 181 women (78%), 96 with RLS (41.4%) with a mean age at baseline of 49.8 ± 15.0 years and a mean RLS duration of 14.1 ± 1.9 years, and 136 non-RLS (58.6%) with a mean age of 51.3 ± 14.9 years. This RLS cohort was followed up for a period of 10.4 ± 2.0 years. As of September 2019, 17 (7.3%) patients died (6 with RLS, 6.3%), and the most frequent cause was oncological (66.7%). A total of 944 person-years of observations were available for survival analysis. RLS was not associated with increased mortality in adjusted Cox regression analysis (HR = 1.12, 95% CI: 0.40-3.15), and survival was similar to that expected for the general population (SMR = 0.61, 95% CI: 0.27-1.36). CONCLUSIONS: RLS seems not to be associated with increased mortality compared to the general population. Still, studies with prospective data collection with large samples are needed to study the long-term mortality risk factors in RLS cohorts.

The impact of freezing of gait on functional dependency in Parkinson's disease with regard to motor phenotype.

BACKGROUND AND OBJECTIVE: Freezing of gait (FOG) is a disabling symptom more frequent in Parkinson's disease (PD) patients with postural instability gait difficulty (PIGD) phenotype. The aim of this study was to determine the prevalence of self-reported FOG in a large group of PD patients as well as assess its relationship with functional dependency with regard to motor phenotype. METHODS: The data correspond to the baseline evaluation of the COPPADIS-2015 study. Patients with FOG were identified as those with a score of 1 or greater on item-3 of the freezing of gait questionnaire (FOG-Q). Functional dependency was defined as a Schwab and England (S&E) ADL scale score less than 80%. PIGD and non-PIGD (tremor dominant + indeterminate) groups were considered regarding to motor phenotype. RESULTS: Among the 689 PD patients (62.6 ± 8.9 years old, 59.8% males), 240 reported FOG (34.8%), whereas 63 presented functional dependency (9.1%). A total of 22.1% of patients with FOG presented functional dependency vs. only 2.2% of those without FOG (p < 0.0001). FOG was related to functional dependency (OR = 3.470; 95%CI 1.411-8.530; p = 0.007) after adjustment to age, gender, disease duration, daily equivalent levodopa dose, comorbidity (number of non-antiparkinsonian drugs/day), motor status (UPDRS-III), PIGD phenotype, motor complications (UPDRS-IV), NMS burden (NMSS total score), cognition (PD-CRS), and mood (BDI-II). However, according to motor phenotype, FOG was related to functional dependency only in PIGD patients (OR = 7.163; 95%CI 1.206-42.564; p = 0.030). CONCLUSIONS: Self-reported FOG is associated with functional dependency in PIGD but not in non-PIGD motor phenotype patients.

Gamma-aminobutyric acid (GABA) receptors genes polymorphisms and risk for restless legs syndrome.

The possible role of gammaaminobutyric acid (GABA) in the pathophysiology of restless legs syndrome (RLS) is suggested by the symptomatic improvement achieved with GABAergic drugs. Thalamic GABA levels have shown positive correlation with periodic limb movements indices and with RLS severity. We tried to investigate the possible association between the most common single nucleotide polymorphisms (SNPs) in the GABA receptors (GABR) genes rho1, 2, and 3 (GABRR1, GABRR2, GABRR3), alpha4 (GABRA4), epsilon (GABRE), and theta (GABRQ) with the risk of developing RLS. We studied the genotype and allelic variant frequencies of the most common SNPs in the GABRR1(rs12200969, rs1186902), GABRR2(rs282129), GABRR3(rs832032), GABRA4(rs2229940), GABRE(rs1139916), and GABRQ(rs3810651) genes in 205 RLS patients and 230 age- and gender-matched healthy controls using specific TaqMan assays. The frequencies of the GABRR3 rs832032TT genotype and the allelic variant GABRR3 rs832032T were significantly higher in RLS patients than in controls (odds ratio [95% confidence intervals] 7.08[1.48-46.44] and 1.66[1.16-2.37], respectively), although only the higher frequency of the rs832032T allele remained as significant after multiple comparison analysis, both in the whole series and in the female gender. The frequencies of the other genotypes of allelic variants did not differ significantly between RLS patients and controls. RLS patients carrying the GABRA4 rs2229940TT genotype showed a significantly younger age at onset of RLS symptoms than those with the other two genotypes. These results suggest association between GABRR3rs832032 polymorphism and the risk for RLS, and a modifier effect of GABRA4 rs2229940 on the age of onset of RLS.

Quality of Life in Huntington's Disease: Critique and Recommendations for Measures Assessing Patient Health-Related Quality of Life and Caregiver Quality of Life.

The compromise of quality of life in Huntington's disease is a major issue, both for individuals with the disease as well as for their caregivers. The International Parkinson and Movement Disorder Society commissioned a review of the use and clinimetric validation status of measures used in Huntington's disease to assess aspects related with quality of life and to make recommendations on their use following standardized criteria. We included both patient-centered measures (patient health-related quality-of-life measures) and caregiver-centered measures (caregiver quality-of-life measures). After conducting a systematic literature search, we included 12 measures of patient health-related quality of life and 2 measures of caregiver quality of life. Regarding patient-centered measures, the Medical Outcomes Study 36-Item Short-Form Health Survey is "recommended" as a generic assessment of health-related quality of life in patients with Huntington's disease. The 12-Item Short Form Health Survey, the Sickness Impact Profile, the 12-item World Health Organization Disability Assessment Schedule, and the Huntington's Disease Health-Related Quality of Life questionnaire are "suggested." No caregiver-centered quality-of-life measure obtained a "recommended" status. The Alzheimer's Carer's Quality of Life Inventory and the Huntington's Disease Quality of Life Battery for Carers are "suggested." Recognizing that the assessment of patient health-related quality of life can be challenging in Huntington's disease, as patients may lack insight and there is insufficient clinimetric testing of these scales, the committee concluded that further validation of currently available health-related quality-of-life measures should be undertaken, namely, those Huntington's disease-specific health-related quality-of-life measures that have recently been reported and used. © 2018 International Parkinson and Movement Disorder Society.

Rating scales for cognition in Huntington's disease: Critique and recommendations.

Cognitive impairment is one of the main features of Huntington's disease and is present across the disease spectrum. As part of the International Parkinson's Disease and Movement Disorder Society-sponsored project to review all clinical rating scales used in Huntington's disease, a systematic review of the literature was performed to identify cognitive scales used in Huntington's disease and make recommendations for their use. A total of 17 cognitive scales were identified and evaluated. None of the scales met criteria for a "recommended" status. For assessing severity of cognitive dysfunction, the Montreal Cognitive Assessment was "recommended with caveats." The UHDRS Cognitive Assessment, the UHDRS-For Advanced Patients cognitive section, the Alzheimer's Disease Assessment Scale-Cognitive Subscale, the Frontal Assessment Battery, the Mattis Dementia Rating Scale, the Mini-Mental State Examination, and the Repeatable Battery for the Assessment of Neuropsychological Status were "suggested" for evaluating severity of cognitive impairment. The MoCA was "suggested" as a screening tool for cognitive impairment. The major challenge in the assessment of cognition in Huntington's disease is the lack of a formal definition of dementia and/or mild cognitive impairment in this disease. The committee concluded that there is a need to further validate currently available cognitive scales in Huntington's disease, but that it is premature to recommend the development of new scales. Recently developed Huntington's disease-specific scales, such as the Huntington's Disease-Cognitive Assessment Battery, hold promise but require the completion of more comprehensive clinimetric development. © 2017 International Parkinson and Movement Disorder Society.

Telemedicine Use for Movement Disorders: A Global Survey.

BACKGROUND: Telemedicine is increasingly used to care for patients with movement disorders, but data regarding its global use are limited. INTRODUCTION: To obtain baseline international data about telemedicine use among movement disorder clinicians. METHODS: An online survey was sent to all 6,056 Movement Disorder Society members in 2015. Scope, reimbursement, and perceived quality of telemedicine were assessed. RESULTS: There were 549 respondents (9.1% overall response rate) from 83 countries. Most (85.8%) were physicians, and most (70.9%) worked in an academic or university practice. Half of respondents (n = 287, from 57 countries) used telemedicine for clinical care; activities included e-mail (63.2%), video visits (follow-up [39.7%] and new [35.2%]), and video-based education (35.2%). One hundred five respondents personally conducted video visits, most frequently to outpatient clinics (53.5%), patient homes (30.8%), and hospital inpatients (30.3%). The most common challenges were a limited neurological examination (58.9%) and technological difficulties (53.3%), and the most common benefits were reduced travel time (92.9%) and patient costs (60.1%). The most frequent reimbursements were none (39.0%), public insurance (24.5%), and patient payment (9.3%). Half of respondents planned to use telemedicine in the future, and three-quarters were interested in telemedicine education. CONCLUSIONS: More than 250 respondents around the world engage in telemedicine for movement disorders; most perceived benefit for patients, despite challenges and reimbursement for clinicians. Formal instruction on telemedicine is highly desired. Although the survey response was low and possibly biased to over represent those with telemedicine experience, the study provides baseline data for future comparison and to improve telemedicine delivery.

New neurosurgical approaches for tremor and Parkinson's disease.

PURPOSE OF REVIEW: The objective of this review is to gather the newest advances in the surgical treatment of tremor and Parkinson's disease. We will briefly discuss the potential applications of the new technologies of deep brain stimulation (DBS), and we will focus on MRI-guided focused ultrasound (MRgFUS). RECENT FINDINGS: Novel DBS devices are being progressively adopted, particularly electrodes allowing a longer stimulating surface (suitable for multiple targets stimulation) and current radial steering (to minimize side effects of stimulation). New implantable pulse generators are also able to record neurons and are generating enough knowledge to advance the implementation of adaptive (closed-loop) DBS.Over the last years, 'minimally-invasive' neurosurgical approaches for the treatment of movement disorders have been developed: gamma knife radiosurgery and MRgFUS. Uncontrolled and recent controlled studies have shown the benefits of MRgFUS targeting the thalamus and pallidus for the treatment of tremor and Parkinson's disease. SUMMARY: The initial clinical data are certainly promising and have expanded the current portfolio of neurosurgical treatments of movement disorders. Many issues are yet to be addressed, particularly safety of MRgFUS-and how these new treatments compare with the existing ones.

The Association of Poor Academic Performance with Tic Disorders: A Longitudinal, Mainstream School-Based Population Study.

BACKGROUND: Little is known about the academic performance of students with tic disorders (TD). Our aim was to investigate the association of TD and poor academic performance over time. METHODS: Longitudinal, observational study of mainstream schoolchildren comparing grade retention (GR) and learning disorders (LD) in students with vs. without TD between 2010 and 2014. Students with vs. without TD based on DSM-IV-TR criteria, or with vs. without GR and LD were compared in terms of comorbidities, school, and environmental characteristics. The association of TD with GR was analyzed using hazard ratios (HRs) with 95% CIs, and with LD using logistic regression analysis [Odds ratio (OR)]. RESULTS: Two hundred fifty-eight students were included (mean age 14.0 ± 1.71 years, 143 [55.4%] males). The incident rate for TD and GR was 2.6 and 3.3 per 100 persons-year, respectively. LD found in 21 (9.9%) students was associated with TD (OR 11.62, 95% CI 2.21-60.90, p = 0.004), and attention deficit hyperactivity disorder (ADHD; OR 6.63, 95% CI 1.55-28.37, p = 0.01). Low psychological support (HRs 12.79, 95% CI 3.39-48.17) and low sport participation (HRs 6.41, 95% CI 1.54-26.78) were risk factors for GR. CONCLUSIONS: TD was associated with academic difficulties, namely, LD in conjunction with ADHD but not GR. The diagnosis of TD and comorbidities, and the initiation of proper treatment could have a favorable impact on school performance, and consequently on social development.

Thr105Ile (rs11558538) polymorphism in the histamine-1-methyl-transferase (HNMT) gene and risk for restless legs syndrome.

A recent meta-analysis suggests an association between the rs11558538 single nucleotide polymorphism in the histamine-N-methyl-transferase (HNMT) gene and the risk for Parkinson's disease. Based on the possible relationship between PD and restless legs syndrome (RLS), we tried to establish whether rs11558538 SNP is associated with the risk for RLS. We studied the genotype and allelic variant frequencies of HNMT rs11558538 SNP 205 RLS patients and 410 healthy controls using a TaqMan assay. The frequencies of the HNMT rs11558538 genotypes allelic variants were similar between RLS patients and controls, and were not influenced by gender, family history of RLS, or RLS severity. RLS patients carrying the genotype rs11558538TT had an earlier age at onset, but this finding was based on three subjects only. These results suggest a lack of major association between HNMT rs11558538 SNP and the risk for RLS.

Spanish Validation of the Problem Behaviors Assessment-Short (PBA-s) for Huntington's Disease.

A prospective, observational multicenter study was carried out assessing neuropsychiatric symptoms in a sample of 117 subjects in order to validate the Spanish version of the Problem Behaviors Assessment-Short (PBA-s). The psychometric properties of this version were analyzed. Inter- and intra-rater reliability were good: the mean weighted Cohen's kappa was 0.90 for severity scores and 0.93 for frequency scores. Four factors accounting for 56% of the total variance were identified after an exploratory factor analysis: apathy, irritability, depression, and perseveration. The PBA-s correlates strongly with the Neuropsychiatric Inventory, demonstrating its accuracy for assessing neuropsychiatric symptoms in patients with Huntington's disease.

Rating scales for behavioral symptoms in Huntington's disease: Critique and recommendations.

Behavioral symptoms are an important feature of Huntington's disease and contribute to impairment in quality of life. The Movement Disorder Society commissioned the assessment of the clinimetric properties of rating scales in Huntington's disease to make recommendations regarding their use, following previously used standardized criteria. A systematic literature search was conducted to identify the scales used to assess behavioral symptoms in Huntington's disease. For the purpose of this review, 7 behavioral domains were deemed significant in Huntington's disease: irritability, anxiety, depression, apathy, obsessive-compulsive behaviors, psychosis, and suicidal ideation. We included a total of 27 behavioral rating scales, 19 of which were of a single behavioral domain and the remaining 8 scales included multiple behavioral domains. Three rating scales were classified as "recommended" exclusively for screening purposes: the Irritability Scale for irritability, the Beck Depression Inventory-II, and the Hospital Anxiety and Depression Scale for depression. There were no "recommended" scales for other purposes such as diagnosis, severity, or change in time or to treatment. The main challenges identified for assessment of behavioral symptoms in Huntington's disease are the co-occurrence of multiple behavioral symptoms, the particular features of a behavioral symptom in Huntington's disease, and the need to address stage- and disease-specific features, including cognitive impairment and lack of insight. The committee concluded that there is a need to further validate currently available behavioral rating scales in Huntington's disease to address gaps in scale validation for specific behavioral domains and purpose of use. © 2016 International Parkinson and Movement Disorder Society.