Unified Huntington's Disease Rating Scale Research Articles

Deficits in temporal processing correlate with clinical progression in Huntington's disease.

Precise temporal performance is crucial for several complex tasks. Time estimation in the second-to-minutes range-known as interval timing-involves the interaction of the basal ganglia and the prefrontal cortex via dopaminergic-glutamatergic pathways. Patients with Huntington's disease (HD) present deficits in cognitive and motor functions that require fine control of temporal processing. The objective of the present work was to assess temporal cognition through a peak-interval time (PI) production task in patients with HD and its potential correlation with the Unified Huntington's Disease Rating Scale (UHDRS). Patients with molecular diagnosis of HD and controls matched by age, sex and educational level (n=18/group) were tested for interval timing in short- (3seconds), medium- (6seconds) and long (12seconds)-duration stimuli. Significant differences were observed in the PI task, with worse performance in HD compared to controls. Patients underestimated real time (left-shifted Peak location) for 6- and 12-second intervals (P<.05) and presented decreased temporal precision for all the intervals evaluated (P<.01). Importantly, a significant correlation was found between time performance and the UHDRS (P<.01). Patients' responses also deviated from the scalar property. Our results contribute to support that timing functions are impaired in HD in correlation with clinical deterioration. Recordings of cognitive performance related to timing could be a potential useful tool to measure the neurodegenerative progression of movement disorder-related pathologies.

Children with Mild CAG Repeat Expansion in HTT Gene Showing Psychiatric but not Neurological Presentation: Is It One More Shade of Huntington Disease?

Objective: Huntington disease (HD) generally manifests in adulthood. Large mutations with CAG repeat expansion in HTT gene may rarely cause juvenile Huntington disease (JHD) in early childhood or adolescence with atypical clinical features, i.e., atypical parkinsonism, if compared to adult patients. Our objective is to characterize the rare occurrence of clinical manifestations in children carrying mutations in the low-mild size, generally causing adult HD with typical choreic movements. Methods: We are following up a subgroup of young subjects with HD mutation who manifested with disabling psychiatric condition since early childhood or adolescence. We are collecting data by the observational studies Registry and ENROLL-HD since 2004. Among 60 JHD patients we are currently following-up, we selected people who carry a mutation in the mild range of CAG expansions (i.e., expected to manifest in adulthood), psychiatric manifestations and no neurological signs or movement disorders suggestive of HD. All patients were genetically (i.e., CAG size analysis) and clinically (i.e., total motor score within the Unified HD Rating Scale) characterized. Results: We found four subjects who showed the characteristics for this analysis. All four subjects presented a CAG expansion size <45 repeats. Two patients manifested a schizophrenia-like disturbance during their adolescence, with the later appearance of motor signs after age 20. In the other two cases, patients presented symptoms of autistic spectrum disorder, since infancy. One of them showed also a schizophrenia-like disturbance and, later, HD onset with motor signs after 20. A 45 year old patient is currently manifesting an autistic disorder in absence of others neurological signs. Conclusion: The description of JHD includes sometimes children with psychiatric manifestations associated with adult motor onset. We advise to pay careful attention to such rare conditions that might represent either psychiatric conditions erroneously classified as JHD or prodromic adult HD cases.

66. Effects of cranio-spinal tDCS in the treatment of cognitive and motor symptoms in early Huntington’s Disease

Transcutaneous Direct Current Stimulation (tDCS) is a safe technique for modulating central nervous system excitability. We assessed clinical changes in early Huntington’s Disease (HD) following tDCS by evaluating Unified Huntington Disease Rating Scale (UHDRS). tDCS electrodes were applied over the thoracic spinal cord (T9–T11) and parietal cortex of right hemisphere, respectively as anode and cathode. We applied current at a density of 0.071 mA/cm2 and delivered a total charge density of 85.7 mC/cm2. The stimulation consisted in a daily session of treatment during 5 days, of 20 min (2.0 mA) each one. The clinical evaluation was performed before tDCS (T0), after 5 days of treatment (T1) and after 2 weeks from the last session (T2). After tDCS a significant improvement both in motor (T0 vs. T1: 17 vs. 12) and behavioral scores was found (T0 vs. T1 vs. T2: 25 vs. 18 vs. 13). We showed significant effects of tDCS on motor and behavioral symptoms in early HD. The configuration we used likely reduces the abnormal peripheral afferent input, possibly restoring at the same time the balance of interhemispheric communication by interfering with right parietal hyperactivity.

Comparison of Huntington's Disease in Europe and North America.

In a rare disorder such as Huntington's disease (HD), a global network of clinical trial sites with access to patients speeds up recruitment into clinical trials. The objective was to test the hypothesis that demographics, HTT genotype, clinical spectrum, and progression are similar in HD participants of two large observational HD studies, the European Huntington's Disease Network's European REGISTRY study and the North American COHORT study. REGISTRY cross-sectional data were available from a total of 7,384 participants (1,125 [15.2%] premanifest and 6,259 [84.8%] manifest HD). COHORT cross-sectional data from 1,499 participants at 44 study sites were available (175 pre-HD [11.7%], 1,324 manifest HD [88.3%]). Participants were assessed clinically using the Unified Huntington's Disease Rating Scale (UHDRS). Longitudinal data were available for total motor score and cognitive performance in more than 50% of REGISTRY participants and more than 70% of COHORT participants. Demographics, HTT genotypes, phenotype, and progression were similar in the two studies. Patients in Europe were prescribed antidyskinetics more frequently, and antidepressants less frequently, than in North America. In either study, participants on antidyskinetic medication had higher UHDRS total motor scores, worse function assessment scores, and worse cognitive scores than those taking antidepressants or no medication. In contrast, motor, function assessment, and cognitive scores were broadly similar in participants taking antidepressants or no medication. The differences in cognitive performances between languages were small. Our data suggest that HD patients, and the way they are assessed, are similar across two continents with different cultures and languages.

Assistive Technology for Cognition andHealth-related Quality of Life inHuntington's Disease.

Background: Assistive technology for cognition (ATC) can be defined as external devices aimed at supporting cognitive function. Studies in neurological populations suggest that use of ATC is a promising strategy to ameliorate negative effects of cognitive impairment and improve Health-related Quality of Life (HRQoL). There is a lack of studies on the effects of ATC in HD.Objective: This study aimed to describe the use of ATC in patients with HD, and to investigate the association between ATC and HRQoL.Methods: A cross-sectional population-based study, including eighty-four patients with a clinical HD diagnosis (stages I–V). Socio-demographic and clinical data were collected, including information regarding various aspects of ATC use and an evaluation of cognitive impairment was performed. The Unified Huntington’s Disease Rating Scale (UHDRS) Total Functional Capacity scale (TFC) and the EQ-5D Visual Analogue Scale were used to evaluate functional ability and HRQoL. Descriptive analyses were conducted to describe ATC use and regression analyses to investigate associations between ATC and HRQoL.Results: Thirty-seven percent of the patients had ATC, and ATC was used most frequently in stages I-III. Information about ATC, needs evaluation and training was provided to 44%, 32.1% and 20.2% respectively. The regression analysis showed a significant association between TFC and HRQoL (β value = –0.564, p = 0.001), but there was no association between ATC and HRQoL.Conclusions: One-third of all patients used ATC, mainly those with mild to moderate cognitive impairment (stage I –III). No association between ATC and HRQoL was found. More research is needed to investigate effects of ATC in HD.

Hypernasality associated with basal ganglia dysfunction: evidence from Parkinson's disease and Huntington's disease.

BackgroundAlthough increased nasality can originate from basal ganglia dysfunction, data regarding hypernasality in Parkinson’s disease (PD) and Huntington’s disease (HD) are very sparse. The aim of the current study was to analyze acoustic and perceptual correlates of velopharyngeal seal closure in 37 PD and 37 HD participants in comparison to 37 healthy control speakers.MethodsAcoustical analysis was based on sustained phonation of the vowel /i/ and perceptual analysis was based on monologue. Perceptual analysis was performed by 10 raters using The Great Ormond Street Speech Assessment ’98. Acoustic parameters related to changes in a 1/3-octave band centered on 1 kHz were proposed to reflect nasality level and behavior through utterance.ResultsPerceptual analysis showed the occurrence of mild to moderate hypernasality in 65% of PD, 89% of HD and 22% of control speakers. Based on acoustic analyses, 27% of PD, 54% of HD and 19% of control speakers showed an increased occurrence of hypernasality. In addition, 78% of HD patients demonstrated a high occurrence of intermittent hypernasality. Further results indicated relationships between the acoustic parameter representing fluctuation of nasality and perceptual assessment (r = 0.51, p < 0.001) as well as the Unified Huntington Disease Rating Scale chorea composite subscore (r = 0.42, p = 0.01).ConclusionsIn conclusion the acoustic assessment showed that abnormal nasality was not a common feature of PD, whereas patients with HD manifested intermittent hypernasality associated with chorea.

Cerebrospinal fluid total tau concentration predicts clinical phenotype in Huntington's disease.

Huntington's disease (HD) is a hereditary neurodegenerative condition with no therapeutic intervention known to alter disease progression, but several trials are ongoing and biomarkers of disease progression are needed. Tau is an axonal protein, often altered in neurodegeneration, and recent studies pointed out its role on HD neuropathology. Our goal was to study whether cerebrospinal fluid (CSF) tau is a biomarker of disease progression in HD. After informed consent, healthy controls, pre‐symptomatic and symptomatic gene expansion carriers were recruited from two HD clinics. All participants underwent assessment with the Unified HD Rating Scale ’99 (UHDRS). CSF was obtained according to a standardized lumbar puncture protocol. CSF tau was quantified using enzyme‐linked immunosorbent assay. Comparisons between two groups were tested using ancova. Pearson's correlation coefficients were calculated for disease progression. Significance level was defined as p < 0.05. Seventy‐six participants were included in this cross‐sectional multicenter international pilot study. Age‐adjusted CSF tau was significantly elevated in gene expansion carriers compared with healthy controls (p = 0.002). UHDRS total functional capacity was significantly correlated with CSF tau (r = −0.29, p = 0.004) after adjustment for age, and UHDRS total motor score was significantly correlated with CSF tau after adjustment for age (r = 0.32, p = 0.002). Several UHDRS cognitive tasks were also significantly correlated with CST total tau after age‐adjustment. This study confirms that CSF tau concentrations in HD gene mutation carriers are increased compared with healthy controls and reports for the first time that CSF tau concentration is associated with phenotypic variability in HD. These conclusions strengthen the case for CSF tau as a biomarker in HD. In the era of novel targeted approaches to Huntington's disease, reliable biomarkers are needed. We quantified Tau protein, a marker of neuronal death, in cerebrospinal fluid and found it was increased in patients with Huntington's disease and predicted motor, cognitive, and functional disability in patients. It is therefore likely to be a biomarker of disease progression, and possibly of therapeutic response. Read the Editorial Highlight for this article on page 9.

EP 34. Effects of deep brain stimulation of the globus pallidus interna on Huntington’s disease at 1 year

Introduction Huntington’s disease (HD) is an autosomal dominant and progressive neurodegenerative disorder. The disease is caused by a strongly increased number of trinucleotide CAG repeats in the Huntingtin gene and characterized by a progressive loss of striatal neurons. Phenotypically, patients present with severe motor symptoms, such as chorea, dystonia, and bradykinesia. Deep brain stimulation (DBS) of the globus pallidus interna (GPi) has been proposed to treat abnormal movements in HD. Here, we report the clinical outcomes of DBS of the GPi in three HD patients followed for 1 year respectively. Objectives Our main objective was to assess the efficacy and safety of DBS of the GPi in alleviating motor symptoms, particularly chorea. Materials and methods Patients with major functional disability due to pharmacoresistant chorea, preserved or mildly altered cognitive function and no severe psychiatric disorder were selected. Due to the severity of chorea, DBS of the GPi were performed under general anesthesia. Microelectrode recording were also used in the preoperative period in all patients. They were followed for 1 year respectively. Outcome measure were scored by the change of the chorea and total motor scores of the Unified Huntington’s Disease Rating Scale (UHDRS) between pre- and last postoperative assessments. Results Chorea improved in all patients (13%, 86% and 29%) and total motor score decreased in 1 patient (%24) postoperatively. 1 patient had a transient dysarthria because of frontal cerebral contusion after operation. Conclusion Based on these results and previous published reports, DBS of the GPi may be considered as an alternative treatment in non-demented HD patients with severe chorea.

EP 39. Clinical experience with deep brain stimulation in Huntington’s disease

Introduction Deep brain stimulation (DBS) of the subthalamic nucleus (STN) or globus pallidus internus (GPi) are well-established standard procedures for various movement disorders, e.g. Parkinson’s disease or dystonia. Until now, application of DBS in Huntington’s disease (HD) has been performed only as an individual and experimental treatment option reported in a few cases. Objective We present a prospective controlled case series of six patients with HD and bilateral DBS of the GPi. Material and Methods Indication for DBS was stated in six patients with severe, treatment-refractory chorea. The procedure was performed in general, intravenous anaesthesia. Bilateral lead placement in the GPi was achieved with stereotactic MRI-coordinates and intraoperative microrecordings. Stereotactic coordinates were as follows: (x) 19–20 mm lateral the midline of the intercommissural line, (y) 3 mm anterior and (z) 2–3 mm inferior the midpoint of the intercommissural line. Also intraoperative stimulation via the implanted leads was performed to evaluate stimulation induced-side effects like dystonic movements, eye movements etc. After insertion of the leads a second stereotactic MRI was performed to rule out any intracerebral complications and to document the definite position of the lead. Clinical evaluation included the motor score of the Unified Huntington‘s disease rating scale (UHDRS), Total Functional Capacity score (TFC), the Functional Assessment score (FA) and the 26-item version of the World Health Organisation questionnaire (WHO Bref) preoperatively and six months postoperatively. Results In all 6 patients leads were successfully implanted bilaterally in general anaesthesia. In one case one lead needed to be revised due to dislocation detected in the control, second MRI. Also in one case, second MRI revealed a small local haemorrhage in the course of one lead, but no clinical neurological deficits were observed in the patient postoperatively. Standard stimulation parameters were programmed and adjusted individually (mono- or bipolar mode, 30–130 hertz, 50–100 microseconds, amplitude 2–5.0 milliampere). The chorea subscore of the UHDRS motor score improved by 47% (range 21–86%; p Conclusion DBS of the GPi is an additional invasive treatment option for well-selected patients with HD. Risks and complications of the procedure and related to the implanted materials are low and acceptable. Continuous clinical experience and long-term follow-up of these patients are needed to evaluate the significance and evidence of DBS in HD.

Clinical and genetic characteristics in patients with Huntington’s disease from China

Huntington’s disease (HD) is a neurodegenerative disease caused by the expansion of unstable CAG repeats in the HTT gene. There are scarce data about HD in China. Fifty-eight HD patients were consecutively recruited and assessed using the Unified HD Rating Scale (UHDRS) motor section and UHDRS behaviour assessment (UHDRS-b). Genetic analyses were also conducted. Thirty-three women and Twenty -five men were diagnosed with a mean age of 46.1 ± 11.2 years and a mean number of CAG triplet repeats 44.6 ± 4.4. CAG triplet repeat number was negatively correlated with age at onset, and positively correlated with UHDRS-b total score, and its subdomains including depressed mood, low self-esteem, anxiety and irritability. On the other hand, negative correlations were identified between age at onset and UHDRS-b total score, and its subdomains include low self-esteem, anxiety, suicidal thought, irritability and apathy. Disease durations were correlated with UHDRS motor scores and anxiety domain of UHDRS-b. This is the largest series of Chinese HD patients with demographic, clinical and genetic data confirms the demographic features of Chinese HD patients are comparable to those in other ethnic backgrounds. CAG triplet repeat number may also predict the severity of behaviour problems in HD patients besides its predication for age of onset.

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.

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.

A double-blind, randomized, cross-over, placebo-controlled, pilot trial with Sativex in Huntington's disease.

Huntington's disease (HD) is a neurodegenerative disease for which there is no curative treatment available. Given that the endocannabinoid system is involved in the pathogenesis of HD mouse models, stimulation of specific targets within this signaling system has been investigated as a promising therapeutic agent in HD. We conducted a double-blind, randomized, placebo-controlled, cross-over pilot clinical trial with Sativex(®), a botanical extract with an equimolecular combination of delta-9-tetrahydrocannabinol and cannabidiol. Both Sativex(®) and placebo were dispensed as an oral spray, to be administered up to 12 sprays/day for 12weeks. The primary objective was safety, assessed by the absence of more severe adverse events (SAE) and no greater deterioration of motor, cognitive, behavioral and functional scales during the phase of active treatment. Secondary objectives were clinical improvement of Unified Huntington Disease Rating Scale scores. Twenty-six patients were randomized and 24 completed the trial. After ruling-out period and sequence effects, safety and tolerability were confirmed. No differences on motor (p=0.286), cognitive (p=0.824), behavioral (p=1.0) and functional (p=0.581) scores were detected during treatment with Sativex(®) as compared to placebo. No significant molecular effects were detected on the biomarker analysis. Sativex(®) is safe and well tolerated in patients with HD, with no SAE or clinical worsening. No significant symptomatic effects were detected at the prescribed dosage and for a 12-week period. Also, no significant molecular changes were observed on the biomarkers. Future study designs should consider higher doses, longer treatment periods and/or alternative cannabinoid combinations.Clincaltrals.gov identifier: NCT01502046.

Factors associated with Mediterranean diet adherence in Huntington's disease

Little is known about the importance of the Mediterranean Diet (MeDi) and dietary intake as environmental neuroprotective factors in Huntington's disease (HD); so, we evaluated and analyzed the prevalence and factors associated with MeDi adherence, and dietary intake in HD. Spanish participants of the European Huntington Disease Network (EHDN) Registry study diagnosed with HD or premanifest HD gene carriers were included from June 2012 to August 2013. Self-reported dietary intake was collected by 3-day dietary record, MeDi adherence was assessed by 0-9 range (proposed by Trichopoulou etal.) and, other contributing factors related to nutrition were collected by telephone. Demographics and clinical variables were obtained from the EHDN Registry study database. Association of HD with MeDi adherence and nutritional characteristics were performed using logistic regression models. Ninety eight participants were included in the study, median age of 48 years (38-60 range), and median total functional capacity (TFC) 9 (5-13 range). HD severity was similar between participants with low vs moderate/high MeDi; however, quality of life (P=0.009) was significantly higher among participants with moderate/high MeDi adherence. In terms of nutrients, higher MUFA/SFA intake was moderately correlated with better TFC and Unified HD Rating Scale (UHDRS) cognitive. Better TFC was associated with having a caregiver (OR=11.86, P<0.001), and non-smoking (OR=0.21, P=0.013). Moderate adherence to MeDi, was associated with older participants (OR=1.19, P=0.031), lower comorbidity (OR=0.18, P=0.018), lower UHDRS motor (OR=0.90, P=0.041), and lower risk for abdominal obesity (OR=0.02, P=0.011). In HD the moderate MeDi adherence is associated with better quality of life, lower comorbidity, lower motor impairment and lower risk for abdominal obesity compared to those participants with low MeDi adherence.

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.

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.

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.

Examining Huntington’s disease patient and informant concordance on frontally mediated behaviors

Introduction: Huntington’s disease (HD) is a genetic, neurodegenerative disease that affects cognitive, psychiatric and motor functioning. Frontal subcortical circuits are impacted by disease pathology, resulting in frontally mediated behavioral dysfunction. The purpose of this study was (a) to examine the relationship between both patient and informant reports of frontally mediated behaviors and disease progression and (b) to determine rate of agreement between patient and informant reports of these behaviors in relation to disease progression. Method: Twenty-six HD patients and their informants participated in the study at the University of South Florida. Patient–informant pairs completed the Frontal Systems Behavior Scale (FrSBe) Self and Family ratings forms, respectively. UHDRS (Unified Huntington’s Disease Rating Scale) motor scores were obtained from medical records as an index of disease progression. Results: Only informant report of frontally mediated behaviors of apathy, disinhibition, and executive dysfunction was related to neurological examination results. On average, ratings by patients with less severe motor symptoms were comparable to informant ratings, suggesting intact awareness of deficits. In contrast, ratings of patients with more severe motor symptoms were discrepant from informant data, with informants providing more severe ratings than patients. Conclusions: HD patients may show intact awareness of frontally mediated behaviors in less severe stages but become increasingly unaware in more severe stages of the disease. This underscores the importance of clinical decisions regarding patient versus informant report at various stages of the disease.

Optical coherence tomography findings in Huntington's disease: a potential biomarker of disease progression.

Previous reports of ocular abnormalities in Huntington's disease (HD) have detailed eye movement disorders. The objective of this case-control study was to investigate optic nerve and macular morphology in HD using optical coherence tomography (OCT). A total of 26 HD patients and 29 controls underwent a thorough ophthalmic examination including spectral domain OCT scans of the macula and peripapillary retinal nerve fibre layer (RNFL). Genetic testing results, disease duration, HD disease burden scores and Unified HD Rating Scale motor scores were acquired for HD patients. Temporal RNFL thickness was significantly reduced in the HD group (62.3 vs. 69.8 μm, p = 0.005), and there was a significant negative correlation between temporal RNFL thickness and disease duration (R (2) = -0.51, p = 0.04). Average peripapillary RNFL thickness was not significantly different between the HD and control groups. There was a significant negative correlation between macular volume and disease duration (R (2) = -0.71, p = 0.002), and motor scores (R (2) = -0.56, p = 0.01). Colour vision was significantly poorer in the HD group. Temporal RNFL is preferentially thinned in HD patients, possibly implicating mitochondrial dysfunction as the temporal RNFL is reduced in the patients with some mitochondrial disorders, including Leber's hereditary optic neuropathy. The correlation between the decrease in macular volume and temporal RNFL, and increasing disease severity suggests that OCT may be a useful biomarker for disease progression in HD. Larger, longitudinal studies are required.