Unified Huntington's Disease Rating Research Articles

Clinical manifestations of intermediate allele carriers in Huntington disease

There is controversy about the clinical consequences of intermediate alleles (IAs) in Huntington disease (HD). The main objective of this study was to establish the clinical manifestations of IA carriers for a prospective, international, European HD registry. We assessed a cohort of participants at risk with <36 CAG repeats of the huntingtin (HTT) gene. Outcome measures were the Unified Huntington's Disease Rating Scale (UHDRS) motor, cognitive, and behavior domains, Total Functional Capacity (TFC), and quality of life (Short Form-36 [SF-36]). This cohort was subdivided into IA carriers (27-35 CAG) and controls (<27 CAG) and younger vs older participants. IA carriers and controls were compared for sociodemographic, environmental, and outcome measures. We used regression analysis to estimate the association of age and CAG repeats on the UHDRS scores. Of 12,190 participants, 657 (5.38%) with <36 CAG repeats were identified: 76 IA carriers (11.56%) and 581 controls (88.44%). After correcting for multiple comparisons, at baseline, we found no significant differences between IA carriers and controls for total UHDRS motor, SF-36, behavioral, cognitive, or TFC scores. However, older participants with IAs had higher chorea scores compared to controls (p = 0.001). Linear regression analysis showed that aging was the most contributing factor to increased UHDRS motor scores (p = 0.002). On the other hand, 1-year follow-up data analysis showed IA carriers had greater cognitive decline compared to controls (p = 0.002). Although aging worsened the UHDRS scores independently of the genetic status, IAs might confer a late-onset abnormal motor and cognitive phenotype. These results might have important implications for genetic counseling. NCT01590589.

Striatal hypometabolism in premanifest and manifest Huntington's disease patients.

To assess metabolic changes in cerebral 18F-FDG PET/CT in premanifest and manifest Huntington's disease (HD) subjects compared to a control group and to correlate 18F-FDG uptake patterns with different disease stages. Thirty-three gene-expanded carriers (Eight males; mean age: 43y/o; CAG > 39) were prospectively included. Based on the Unified Huntington's Disease Rating Scale Total Motor Score and the Total Functional Capacity, subjects were classified as premanifest (preHD = 15) and manifest (mHD = 18). Estimated time disease-onset was calculated using the Langbehn formula, which allowed classifying preHD as far-to (preHD-A) and close-to (PreHD-B) disease-onset. Eighteen properly matched participants were included as a control group (CG). All subjects underwent brain 18F-FDG PET/CT and MRI. 18F-FDG PET/CT were initially assessed by two nuclear medicine physicians identifying qualitative metabolic changes in the striatum. Quantitative analysis was performed using SPM8 with gray matter atrophy correction using the BPM toolbox. Visual analysis showed a marked striatal hypometabolism in mHD. A normal striatal distribution of 18F-FDG uptake was observed for most of the preHD subjects. Quantitative analysis showed a significant striatal hypometabolism in mHD subjects compared to CG (p < 0.001 uncorrected, k = 50voxels). In both preHD groups we observed a significant striatal hypometabolism with respect to CG (p < 0.001 uncorrected, k = 50voxels). In mHD subjects we observed a significant striatal hypometabolism with respect to both preHD groups (p < 0.001 uncorrected, k = 50voxels). 18F-FDG PET/CT might be a helpful tool to identify patterns of glucose metabolism in the striatum across the stages of HD and might be relevant in assessing the clinical status of gene-expanded HD carriers due to the fact that dysfunctional glucose metabolism begins at early preHD stages of the disease. 18F-FDG PET/CT appears as a promising method to monitor the response to disease-modifying therapies even if applied in premanifest subjects.

Wearable Sensors in Huntington Disease: A Pilot Study.

The Unified Huntington's Disease Rating Scale (UHDRS) is the principal means of assessing motor impairment in Huntington disease but is subjective and generally limited to in-clinic assessments. To evaluate the feasibility and ability of wearable sensors to measure motor impairment in individuals with Huntington disease in the clinic and at home. Participants with Huntington disease and controls were asked to wear five accelerometer-based sensors attached to the chest and each limb for standardized, in-clinic assessments and for one day at home. A second chest sensor was worn for six additional days at home. Gait measures were compared between controls, participants with Huntington disease, and participants with Huntington disease grouped by UHDRS total motor score using Cohen's d values. Fifteen individuals with Huntington disease and five controls completed the study. Sensor data were successfully captured from 18 of the 20 participants at home. In the clinic, the standard deviation of step time (time between consecutive steps) was increased in Huntington disease (p < 0.0001; Cohen's d = 2.61) compared to controls. At home with additional observations, significant differences were observed in seven additional gait measures. The gait of individuals with higher total motor scores (50 or more) differed significantly from those with lower total motor scores (below 50) on multiple measures at home. In this pilot study, the use of wearable sensors in clinic and at home was feasible and demonstrated gait differences between controls, participants with Huntington disease, and participants with Huntington disease grouped by motor impairment.

Huntington's Disease: Prevalence and Psychological Indicators of Pain.

Huntington's disease (HD) is a genetic neurodegenerative condition that involves impairments in movement, cognition, and mood. Research is lacking in HD with regard to the prevalence of pain and the relationships between psychological factors and pain. The aim of this research was to investigate the prevalence of pain and identify the psychological factors associated with pain severity in people with HD. This data-mining study used data from 1474 people who participated in the European Huntington's Disease Network (EHDN) REGISTRY study. Pain severity was measured using the Medical Outcome Study 36-item short-form health survey. Separate ordinal regression analyses were conducted with participant-rated and interviewer-rated psychological measures (the Hospital Anxiety and Depression Scale-Snaith Irritability Scale and the Unified Huntington's Disease Rating Scale). The psychological factors considered were anxiety, depression, irritability, aggression, low self-esteem, and apathy. The prevalence of pain in the total sample was 41% (stage I, 42%; stage II, 44%; stage III, 39%; stages IV and V, 50%). After controlling for confounding variables, pain severity was significantly associated with participant-rated anxiety and depression. Interviewer-rated anxiety, depression, and irritability also were significantly associated with severity of pain after controlling for confounding variables. This research confirmed that pain is indeed an issue for people with HD, particularly during the later stages of the disease. Caregivers and health professionals should consider the possibility that people with HD might be experiencing pain, particularly if they are showing signs of anxiety, depression, or irritability.

Resting-state fMRI reveals potential neural correlates of impaired cognition in Huntington's disease

BackgroundHuntington's Disease (HD) is characterized by motor, cognitive and psychiatric dysfunction. Functional MRI (fMRI) provides new insight into the pathologic mechanism underlying the cognitive symptoms. Previous fMRI studies of HD focused on functional synchronization of various brain areas by measuring functional connectivity, a method that is unable to identify regional intrinsic neural activity changes in the brain. To fill in this gap, we utilized amplitude of low frequency fluctuations (ALFF). ObjectiveTo investigate alterations in regional brain activity and their association with clinical characteristics in the early stages of HD. MethodsTen early stage HD patients and 20 age- and sex-matched healthy controls were scanned to obtain imaging data. HD patients were assessed with the Unified Huntington's Disease Rating Scale, Mini-Mental State Exam (MMSE), Stroop test, Symbol Digit Modalities Test (SDMT), Verbal Fluency Test and Beck Depression Index. ResultsGray matter volume (GMV) reduction was detected in bilateral striatum and left calcarine cortex in the HD group. After correcting for GMV, HD patients demonstrated significantly decreased ALFF in the right precuneus and angular gyrus, and increased ALFF in bilateral inferior temporal gyrus (ITG) and left superior frontal gyrus. Increased mean values of ALFF in the left ITG were correlated with worse performance in SDMT, and decreased mean values of ALFF in the precuneus were correlated with worse performance in the Stroop test and SDMT. ConclusionsOur results suggest that intrinsic brain activity alterations in the precuneus and cortico-striatal circuit may be the mechanism underlying impaired cognition in early HD.

Liver function in Huntington's disease assessed by blood biochemical analyses in a clinical setting

Huntington's disease (HD) is a dominantly inherited, progressive neurological disorder caused by a CAG repeat elongation in the huntingtin gene. In addition to motor-, psychiatric- and cognitive dysfunction, peripheral disease manifestations in the form of metabolic changes and cellular dysfunction are seen. Blood levels of a wide range of hormones, metabolites and proteins have been analyzed in HD patients, identifying several changes associated with the disease. However, a comprehensive panel of liver function tests (LFT) has not been performed. We investigated a cohort of manifest and premanifest HD gene-expansion carriers and controls, using a clinically applied panel of LFTs. Here, we demonstrate that the level of alkaline phosphatase is increased in manifest HD gene-expansion carriers compared to premanifest HD gene-expansion carriers and correlate with increased disease severity indicated by the Unified Huntington's disease rating scale-Total Functional Capacity Score (UHDRS-TFC). For gamma-glutamyl transferase, elevated levels were more frequent in the manifest groups than in both the HD gene-expansion negative controls and premanifest HD gene-expansion carriers. Finally, the manifest HD gene-expansion carriers displayed moderate increases in total cholesterol and blood glucose relative to the premanifest HD gene-expansion carriers, as well as increased C-reactive protein relative to HD gene-expansion negative controls. Our results show that LFT values are elevated more frequently in manifest compared to premanifest HD gene-expansion carriers and controls. The majority of the manifest HD gene-expansion carriers receive medication, and it is possible that this can influence the liver function tests performed in this study.

Spectral-Domain Optical Coherence Tomography as a Potential Biomarker in Huntington's Disease.

Spectral-domain optical coherence tomography has been used in several neurological conditions, and peripapillary and macular measurements have been proposed as potential biomarkers in these disorders. The aim of this study was to investigate retinal and choroidal changes in Huntington's disease and to evaluate any potential correlation with the stage of the disease. A cross-sectional observational study compared patients with Huntington's disease and controls. Patients were evaluated using the Unified Huntington's Disease Rating Scale. Spectral-domain optical coherence tomography with enhanced depth imaging was used, and peripapillary choroidal and retinal nerve fiber layer thickness and macular retinal and choroidal thickness were evaluated. Fifteen eyes of 8 patients and 16 eyes of 8 sex-, age-, and mean refractive error-matched healthy controls were included. Average (231.3 ± 52.8 vs 296.2 ± 57.1, P = 0.033), central (341.8 ± 70.5 vs 252.0 ± 57.9, P = 0.015), and inferior (225.3 ± 57.9 vs 313.8 ± 55.2, P = 0.007) macular choroidal thickness were significantly reduced in patients, in comparison with controls. No differences were observed in macular retina or peripapillary retinal and choroidal measurements. However, there was a negative correlation between Total Motor Score of the Unified Huntington's Disease Rating Scale and average (r(2) = 0.585, P = 0.027), superior (r(2) = 0.653, P = 0.015), nasal (r(2) = 0.642, P = 0.017), and inferior (r(2) = 0.574, P = 0.029) macular retinal thickness. Our results suggest that both the choroidal and retinal macula are altered in Huntington's disease and may become useful biomarkers for monitoring neurodegeneration in this disease. The involvement of the choroid may also support the recent findings of vascular involvement in Huntington's disease.

Change in PDE10 across early Huntington disease assessed by [18F]MNI-659 and PET imaging.

To evaluate whether striatal [(18)F]MNI-659 PET imaging of phosphodiesterase 10A (PDE10) serves as a sensitive and reliable biomarker of striatal neurodegeneration in a longitudinal cohort of participants with early Huntington disease (HD). A cohort of participants with HD, including both participants premanifest or manifest with motor signs, underwent clinical assessments, genetic determination, and 2 [(18)F]MNI-659 PET imaging sessions approximately 1 year apart. Eleven healthy control (HC) participants underwent clinical assessments and [(18)F]MNI-659 PET imaging once. Striatal binding potentials (BPnd) were estimated for brain regions of interest, specifically within the basal ganglia, and compared between baseline and follow-up imaging. Clinical measures of HD severity were assessed at each visit. Eight participants with HD (6 manifest; 2 premanifest) participated. Of those with manifest HD, all had relatively early stage disease (stage 1, n = 2; stage 2, n = 4) and a Unified Huntington's Disease Rating Scale total motor score <45. As expected, the HD cohort as a whole had a reduction in the basal ganglia BPnd to approximately 50% of that seen in HC. On follow-up scans, [(18)F]MNI-659 uptake declined in the putamen and caudate nucleus in all 8 participants. The mean annualized rates of decline in signal in the caudate, putamen, and globus pallidus and the putamen were 16.6%, 6.9%, and 5.8%, respectively. In HC, the annualized reduction in signal in striatal regions was less than 1%. Longitudinal data in this small cohort of participants with early HD support [(18)F]MNI-659 PET imaging of PDE10 as a useful biomarker to track HD disease progression.

Factors Associated with Low Body Mass Index in Huntington's Disease: A Spanish Multicenter Study of the European Huntington's Disease Registry.

Patients with Huntington's disease (HD) are at risk for body weight loss and increased risk for institutionalization, morbidity, and mortality. The aim of this study was to determine the factors associated with low body mass index (BMI) in patients with HD. In this national, observational, cross-sectional study of the European Huntington's Disease Network, the frequency of food consumption, calories, and nutrient intake in patients with HD was assessed using questionnaires validated for the Spanish population and were calculated using the software package Alimentación and Salud (Diet and Health), version 2.0. Nutritional status was estimated using the BMI, and disease severity was assessed using the Unified Huntington's Disease Rating Scale and a total functional capacity (TFC) score. Linear regression models were performed using BMI as the dependent variable and using energy balance (energy caloric intake - energy expenditure); the TFC score; the presence of a caregiver; dysphagia; cytosine, adenine, guanine (CAG) repeats; comorbidities; intake of supplements; pharmacologic treatments; age; gender; education; and physical activity as the independent variables. Two hundred twenty-four patients with HD were included (59% women), and their mean age was 47.41 ± 14.26 years, a median TFC score of 9 (range, 3-13), normal BMI in 124 patients (55.4%), and low BMI in 13 patients (6.7%). In the linear regression model, older age (β = 0.003; P = 0.01), male gender (β = 0.13; P = 0.003), and lower energy balance (β = -0.0001; P = 0.0003) were associated with a higher log-transformed BMI. Younger female HD patients are at risk for low BMI. To counteract the influence of the HD gene mutation on decreased BMI, an increase in kilocalories per day should be encouraged.

Clinical and genetic investigation of a Brazilian family with Huntington's disease.

The aim of this study was to investigate a Brazilian family carrying full penetrance alleles for Huntington's disease (HD) in order to correlate each member's genetic and clinical features. To this end, the following scales were administered in each patient: the Beck Depression Inventory, the Mini-Mental State Examination (MMSE) and the Unified Huntington's Disease Rating Scale (UHDRS). The patterns of CAG and CCG polymorphic regions in the HTT gene were determined, the disease burden score was calculated, and genotypes were correlated with phenotypes within this family. We suggest that HD duration, the number of years of formal education, and UHDRS status variables can explain 96.6% of the MMSE variability in HD patients. A strong significant correlation was found between the disease burden score and the UHDRS (r = 0.76; p-value = 0.049) and the MMSE (r = -0.90; p-value = 0.006). The correlations between CAG allele size and the three clinical evaluations performed in the HD patients were not statistically significant.

Social Cognition, Executive Functions and Self-Report of Psychological Distress in Huntington's Disease.

Objective: Huntington’s disease (HD) is characterized by motor symptoms, psychiatric symptoms and cognitive impairment in, inter alia, executive functions and social cognition. The aim of this study was to investigate the relationship between subjective feeling of psychological distress using a self-report questionnaire and performances on tests of executive functions and social cognition in a large consecutive cohort of HD patients.Method: 50 manifest HD patients were tested in social cognition and executive functions and each answered a self-report questionnaire about current status of perceived psychological distress (the Symptom Checklist-90-Revised (SCL-90-R)). Correlation analyses of test performance and SCL-90-R scores were made as well as stepwise linear regression analyses with the SCL-90-R GSI score and test performances as dependent variables.Results: We found that less psychological distress was significantly associated with worse performances on social cognitive tests (mean absolute correlation .34) and that there were no significant correlations between perceived psychological distress and performance on tests of executive functions. The correlations between perceived psychological distress and performance on social cognitive tests remained significant after controlling for age, Unified Huntington’s Disease Rating Scale-99 total motor score and performance on tests of executive functions.Conclusions: Based on previous findings that insight and apathy are closely connected and may be mediated by overlapping neuroanatomical networks involving the prefrontal cortex and frontostriatal circuits, we speculate that apathy/and or impaired insight may offer an explanation for the correlation between self-report of psychological distress and performance on social cognitive tests in this study.

The quality of life of Spanish patients with Huntington's disease measured with H-QoL-I and EQ-5D

Background and objectiveHuntington's disease (HD) is an inherited neurodegenerative disorder that heavily affects the patient's motor, cognitive, and psychological functions. Yet, very few studies have measured the impact of this disease on the patient's health-related quality of life (HRQoL) with specific and validated instruments. The aim of this study was to explore the impact of HD on the HRQoL of Spanish HD patients using the self-reported, Huntington Quality of Life Instrument (H-QoL-I) and the generic instrument EuroQoL five dimensions (EQ-5D-3L) and thereafter compare the results obtained with the two instruments.MethodsFifty-five patients and an equal number of caregivers participated. Patient assessments included the questionnaires of the Huntington Self-Assessment Instrument's four parts: background information assessment, Huntington clinical self-reported instrument, disease-specific HRQoL assessment (H-QoL-I instrument) and Huntington resource utilisation interview, and the EQ-5D-3L questionnaire. Levels of disease severity were also determined based on the Unified Huntington's Disease Rating Scale that was completed by caregivers. Pearson's correlation tests were computed between H-QoL-I and EQ-5D-3L scores.ResultsThe scores obtained with the H-QoL-I instrument showed that motor dimension was the most altered followed by the psychological dimension while the social dimension was the least altered. Increase of disease severity resulted in lower patient QoL. The usual activities and anxiety/depression were the most severely altered dimensions according to the EQ-5D-3L results. Mobility was also altered to a great extent while pain was the least altered dimension. All correlations between H-QoL-I and EQ-5D-3L scores were moderate to high and statistically significant (p<0.01) with the exception of the correlation between H-QoL-I socialising score and EQ-5D-3L anxiety score. The highest correlations were found between H-QoL-I motor score and three EQ-5D-3L scores: mobility, self-care, and usual activity.ConclusionsThe quality of life of the Spanish HD patients included in this study was severely affected by HD as demonstrated by the results of the generic EQ-5D-3L and the specific H-QoL-I instruments, which showed considerable impact of the disease on the motor and psychological functions. The H-QoL-I instrument was able to discern psychological and motor functioning dimensions that were altered by the disease with more specificity and accuracy than the generic instrument.

Reaction time and rhythm of movement in Huntington's disease

Huntington disease (HD) is characterized by several hyperkinesias though motor slowness is also another cardinal in this disease. In addition, self-paced timing movements are also disturbed in HD, which may also affect several rhythmic voluntary movements such as gait. Motor slowness can be measured with clinical scales such as the Unified Huntington's Disease Rating Scale (UHDRS) and timed tests, but also with the reaction time (RT) paradigm.We evaluated RT as a measure of motor slowness in 30 patients with genetically confirmed Huntington's disease and 24 control subjects. We also evaluated self-paced timing precision (SPTP) by applying a simple software program devised by our group. Clinical assessment was performed according to the UHDRS, including motor section, total functional capacity (TFC) and cognitive section (verbal fluency test, symbol digit, and Stroop test)The mean values obtained for RT and SPTP were statistically different in HD as compared with those from controls (p<0.0005). We observed a statistically significant correlation between RT and TFC scores (rs=−0.57, p<0.005 Spearman's correlation) and also between SPTP values and TFC scores (rs=-0.40, p<0.05 Spearman's correlation). In addition, RT and SPTP significantly correlated with cognitive scores (including digit symbol, verbal fluency and Stroop tests).Simple tests such as RT and SPTP provide an objective evaluation of motor impairment in HD yielding measures that correlate with clinical assessment and functional disability.

Depression and clinical progression in spinocerebellar ataxias

BackgroundDepression is a common comorbidity in spinocerebellar ataxias (SCAs) but its association with ataxia progression is not well understood. ObjectivesTo study the prevalence and influence of depressive symptoms in SCAs. MethodsWe studied 300 participants with SCA 1, 2, 3 and 6 from the Clinical Research Consortium for Spinocerebellar Ataxias (CRC-SCA) and repeatedly measured depressive symptoms by the 9-item Patient Health Questionnaire (PHQ-9) along with other clinical features including ataxia, functional status, and quality of life every 6 months for 2 years. We employed regression models to study the effects of depressive symptoms on clinical progression indexed by Scale for Assessment and Rating of Ataxia (SARA), Unified Huntington's Disease Rating Scale Part IV (UHDRS-IV) and EQ5D after adjusting for age, sex and pathological CAG repeats. ResultsComorbid depression is common in SCAs (26%). Although the baseline prevalence of depression was similar among different SCA types, suicidal ideation was more frequently reported in SCA3 (65%). Depressive symptoms were associated with SARA scores but did not significantly progress over time within 2 years or deteriorate by increased numbers of pathological CAG repeats. The effects of depression on ataxia progression varied across different SCA types. Nevertheless, depression had consistently negative and significant impact on functional status and quality of life in all SCAs, even after accounting for ataxia progression. ConclusionsDepressive symptoms are not simply the consequence of motor disability in SCAs. Comorbid depression per se contributes to different health outcomes and deserves more attention when caring patients with SCAs.

Male sexual function in presymptomatic gene carriers and patients with Huntington's disease

AimsTo report sexual dysfunction in a systematically studied cohort of men with Huntington's disease (HD), and compare them with control men of a similar age. MethodsIn men with HD and asymptomatic HD gene carriers, the male sexual dysfunction questionnaire (International Index of Erectile Function – IIEF, covering erectile and orgasmic function, sexual desire, intercourse satisfaction and overall satisfaction), neurologic assessment using the Unified Huntington's Disease Rating Scale (UHDRS) and the Total Functional Capacity (TFC) Score were utilized. ResultsResponses were obtained from 23 HD patients and 2 HD gene carriers. HD patients reported more problems with erection, intercourse satisfaction and overall satisfaction (p<0.05) compared to 41 controls. HD patients generally reported reduced sexual desire and performance. Sexual dysfunction progressed in parallel with patients' decline in motor (UHDRS) and TFC, but was not related to patients' age and duration of disease. ConclusionsOur study demonstrated a significant impact of HD on male sexual function that progressed in parallel with motor and total patient (TFC) dysfunction. Physicians helping HD patients should also consider this largely neglected aspect of the disease.

Informativeness of Early Huntington Disease Signs about Gene Status.

The cohort-level risk of Huntington disease (HD) is related to the age and symptom level of the cohort, but this relationship has not been made precise. To predict the evolving likelihood of carrying the Huntington disease (HD) gene for at-risk adults using age and sign level. Using data from adults with early signs and symptoms of HD linked to information on genetic status, we use Bayes' theorem to calculate the probability that an undiagnosed individual of a certain age and sign level has an expanded CAG repeat. Both age and sign levels have substantial influence on the likelihood of HD onset, and the probability of eventual diagnosis changes as those at risk age and exhibit (or fail to exhibit) symptoms. For example, our data suggest that in a cohort of individuals age 26 with a Unified Huntington's Disease Rating Scale (UHDRS) motor score of 7-10 70% of them will carry the HD mutation. For individuals age 56, the same motor score suggests only a 40% chance of carrying the mutation. Early motor signs of HD, overall and the chorea subscore, were highly predictive of disease onset at any age. However, body mass index (BMI) and cognitive performance scores were not as highly predictive. These results suggest that if researchers or clinicians are looking for early clues of HD, it may be more foretelling to look at motor rather than cognitive signs. Application of similar approaches could be used with other adult-onset genetic conditions.

Motor onset and diagnosis in Huntington disease using the diagnostic confidence level.

Huntington disease (HD) is a neurodegenerative disorder characterized by motor dysfunction, cognitive deterioration, and psychiatric symptoms, with progressive motor impairments being a prominent feature. The primary objectives of this study are to delineate the disease course of motor function in HD, to provide estimates of the onset of motor impairments and motor diagnosis, and to examine the effects of genetic and demographic variables on the progression of motor impairments. Data from an international multisite, longitudinal observational study of 905 prodromal HD participants with cytosine-adenine-guanine (CAG) repeats of at least 36 and with at least two visits during the followup period from 2001 to 2012 was examined for changes in the diagnostic confidence level from the Unified Huntington's Disease Rating Scale. HD progression from unimpaired to impaired motor function, as well as the progression from motor impairment to diagnosis, was associated with the linear effect of age and CAG repeat length. Specifically, for every 1-year increase in age, the risk of transition in diagnostic confidence level increased by 11% (95% CI 7-15%) and for one repeat length increase in CAG, the risk of transition in diagnostic confidence level increased by 47% (95% CI 27-69%). Findings show that CAG repeat length and age increased the likelihood of the first onset of motor impairment as well as the age at diagnosis. Results suggest that more accurate estimates of HD onset age can be obtained by incorporating the current status of diagnostic confidence level into predictive models.

Body composition analysis as an indirect marker of skeletal muscle mass in Huntington's disease

BackgroundSkeletal muscle wasting is likely to play an important role in the Huntington's disease (HD) pathogenesis. Our aim was to analyze the body composition, and specifically fat-free mass (FFM), as an indirect marker of skeletal muscle in patients with HD, and its association with HD severity and energy balance. MethodsCross-sectional, case–control study. Body composition was analyzed using bioelectrical impedance. Information was collected as regards of the anthropometrics, disease severity [Unified Huntington Disease Rating (UHDRS) and Total functional capacity (TFC) scores], CAG repeats, protein catabolism, energy intake and energy expenditure. ResultsTwenty two patients with HD [mean age 50.3±15.6, mean UHDRS of 27.9±23.7, median TFC of 11 (IQR: 7; 13); median body mass index 23.6 (IQR: 26.8; 22.5)], and 18 controls were included. Both groups were similar in terms of age, gender, body mass index, body composition, physical activity level, and protein catabolism. FFM was correlated with energy intake (r=0.73, p<0.001), resting energy expenditure (r=0.64, p=0.001) and physical activity (r=0.54, p=0.003), but not with CAG repeats, or HD severity. ConclusionsOur results do not support the presence of significant muscle wasting in patients with early-moderate Huntington's disease. However, to prevent muscle wasting in HD, dietary strategies, in addition to physical exercise, should be further investigated.

Dysphagia in Huntington's Disease: Correlation with Clinical Features

Huntington's disease (HD) is an inherited neurodegenerative disorder characterised by motor impairment, cognitive decline and psychiatric disorders. Dysphagia is a pathologic condition that increases morbidity and mortality of the affected people. Our aim was to evaluate dysphagia in a group of HD patients in view of motor, cognitive and functional decline. Thirty-seven genetically confirmed HD patients were submitted to clinical evaluations of swallowing. Bedside Swallowing Assessment Scale (BSAS) was used. Dysphagia Outcome and Severity Scale (DOSS) was applied for a preliminary classification of swallowing difficulties. All patients were also evaluated by the Unified Huntington's Disease Rating Scale (UHDRS). A group of 39 controls comparable for sex and age were recruited for BSAS scores normalisation. The BSAS scores indicated that in our HD cohort, 32.4% presented relevant or severe dysphagia. The DOSS levels were significantly correlated with main clinical features, such as age, disease duration and motor impairment, with special regard to lingual protrusion ability, dysarthria and bradykinesia. The total functional capacity (TFC) and cognitive scales did not show significant correlation with DOSS levels. The results of clinical examination of swallowing indicated that dysphagia is a prevalent motor symptom of HD.

Ethyl-eicosapentaenoic acid treatment in Huntington's disease: A placebo-controlled clinical trial.

It has been suggested that treatment with ethyl-eicosapentaenoic acid (EPA) may improve motor function in patients with Huntington's disease (HD) with cytosine-adenine-guanine repeat numbers of <45. This multicenter, randomized, double-blind, placebo-controlled 6-month trial compared the effects of ethyl-EPA versus placebo on 290 subjects with mild-to-moderate HD. The primary endpoint was the change from baseline to 6 months in the Total Motor Score 4 (TMS-4) component of the Unified Huntington's Disease Rating Scale (UHDRS). Secondary endpoints included change from baseline in UHDRS subscores and Clinical Global Impression (CGI). No significant differences in TMS-4 scores were noted between treatment groups. Similarly, there were no significant differences between groups on any of the UHDRS subscores or CGI scores. Ethyl-EPA was not beneficial in patients with HD during 6 months of placebo-controlled evaluation.