Unified Huntington's Disease Rating Scale Research Articles

Association of status redox with demographic, clinical and imaging parameters in patients with Huntington's disease

Huntington's disease (HD) is an autosomal dominant, progressive neurodegenerative disorder, caused by an expanded trinucleotide CAG sequence of the huntingtin (Htt) gene, which encodes a stretch of glutamines in the Htt protein. The mechanisms of neurodegeneration associated with the accumulation of Htt aggregates still remains unclear. ObjectivesTo determine oxidative stress biomarkers in HD patients and their relationship with clinical, demographic and neuroimaging parameters. Design and methodsFourteen patients and 39 controls paired by age and sex participated in this study. Oxidative damage was assayed in blood by measuring malondialdehyde (MDA) and advanced oxidative protein products (AOPPs). Antioxidant status was determined by activities of superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), glutathione reductase (GR), reduced glutathione (GSH), protein thiols and total antioxidant capacity (FRAP). The Unified Huntington Disease Rating Scale (UHDRS) and neuroimaging studies were also employed. ResultsMDA, AOPP and GPx were significantly increased in HD patients with respect to the control group, while GR activity was decreased. FRAP correlated with age of disease onset, AOPP with motor severity (UHDRS score), age of patients and age of disease onset. Caudate atrophy was associated with lower plasma concentrations of GSH. ConclusionsThese findings point to a redox imbalance in HD patients. GR activity could be a potential biomarker for symptom onset in asymptomatic gene carriers, while plasmatic GSH could be useful in monitoring the progression of neurodegeneration – as an expression of caudate atrophy – during the course of the disease.

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.

Voxel-based analysis in neuroferritinopathy expands the phenotype and determines radiological correlates of disease severity

Neuroferritinopathy is an autosomal dominant adult-onset movement disorder which occurs due to mutations in the ferritin light chain gene (FTL). Extensive iron deposition and cavitation are observed post-mortem in the basal ganglia, but whether more widespread pathological changes occur, and whether they correlate with disease severity is unknown. 3D-T1w and quantitative T2 whole brain MRI scans were performed in 10 clinically symptomatic patients with the 460InsA FTL mutation and 10 age-matched controls. Voxel-based morphometry (VBM) and voxel-based relaxometry (VBR) were subsequently performed. Clinical assessment using the Unified Dystonia Rating Scale (UDRS) and Unified Huntington's Disease Rating Scale (UHDRS) was undertaken in all patients. VBM detected significant tissue changes within the substantia nigra, midbrain and dentate together with significant cerebellar atrophy in patients (FWE, p < 0.05). Iron deposition in the caudate head and cavitation in the lateral globus pallidus correlated with UDRS score (p < 0.001). There were no differences between groups with VBR. Our data show that progressive iron accumulation in the caudate nucleus, and cavitation of the globus pallidus correlate with disease severity in neuroferritinopathy. We also confirm sub-clinical cerebellar atrophy as a feature of the disease. We suggest that VBM is an effective technique to detect regions of iron deposition and cavitation, with potential wider utility to determine radiological markers of disease severity for all NBIA disorders.

Ubiquitin: a potential cerebrospinal fluid progression marker in Huntington's disease.

Finding early and dynamic biomarkers in Huntington's disease is a key to understanding the early pathology of Huntington's disease and potentially to tracking disease progression. This would benefit the future evaluation of potential neuroprotective and disease-modifying therapies, as well as aid in identifying an optimal time point for initiating a potential therapeutic intervention. This explorative proteomics study evaluated cerebrospinal fluid from 94 Huntington's disease gene-expansion carriers (39 premanifest and 55 manifest) and 27 Huntington's disease gene-expansion negative individuals using surface-enhanced laser desorption/ionization time-of-flight (SELDI-TOF) mass spectrometry. Differences in peak intensity from SELDI-TOF spectra were evaluated. Levels of 10 peaks were statistically significantly different between manifest gene-expansion carriers and controls. One of them identified as ubiquitin was shown to be dependent on the Unified Huntington Disease Rating Scale Total Functional Capacity, a pseudo-measure of disease severity (P=0.001), and the Symbol Digit Modalities Test (0.04) in manifest and CAG-age product score (P=0.019) in all gene-expansion carriers. Multiple studies have shown that the ubiquitin-proteasome system is involved in Huntington's disease pathogenesis and understanding of this involvement may have therapeutic potential in humans. This is the first study on cerebrospinal fluid to confirm the involvement of the ubiquitin-proteasome system in Huntington's disease. Furthermore it is shown that ubiquitin increases with disease progression and CAG-age product score and therefore may have the potential as a Huntington's disease progression marker, also prior to motor onset.

High Protein Diet and Huntington's Disease.

Huntington’s disease (HD) is a neurodegenerative disorder caused by the huntingtin (HTT) gene with expanded CAG repeats. In addition to the apparent brain abnormalities, impairments also occur in peripheral tissues. We previously reported that mutant Huntingtin (mHTT) exists in the liver and causes urea cycle deficiency. A low protein diet (17%) restores urea cycle activity and ameliorates symptoms in HD model mice. It remains unknown whether the dietary protein content should be monitored closely in HD patients because the normal protein consumption is lower in humans (~15% of total calories) than in mice (~22%). We assessed whether dietary protein content affects the urea cycle in HD patients. Thirty HD patients were hospitalized and received a standard protein diet (13.7% protein) for 5 days, followed by a high protein diet (HPD, 26.3% protein) for another 5 days. Urea cycle deficiency was monitored by the blood levels of citrulline and ammonia. HD progression was determined by the Unified Huntington’s Disease Rating Scale (UHDRS). The HPD increased blood citrulline concentration from 15.19 μmol/l to 16.30 μmol/l (p = 0.0378) in HD patients but did not change blood ammonia concentration. A 2-year pilot study of 14 HD patients found no significant correlation between blood citrulline concentration and HD progression. Our results indicated a short period of the HPD did not markedly compromise urea cycle function. Blood citrulline concentration is not a reliable biomarker of HD progression.

Cholinesterase inhibitors for rarer dementias associated with neurological conditions

Cholinesterase inhibitors for rarer dementias associated with neurological conditions

Clinical evaluation of eye movements in spinocerebellar ataxias: a prospective multicenter study.

Ocular motor abnormalities reflect the varied neuropathology of spinocerebellar ataxias (SCAs) and may serve to clinically distinguish the different SCAs. We analyzed the various eye movement abnormalities detected prospectively at the baseline visit during a large multicenter natural history study of SCAs 1, 2, 3, and 6. The data were prospectively collected from 12 centers in the United States in patients with SCAs 1, 2, 3, and 6, as part of the Clinical Research Consortium for Spinocerebellar Ataxias (NIH-CRC-SCA). Patient characteristics, ataxia rating scales, the Unified Huntington Disease Rating Scale functional examination, and clinical staging were used. Eye movement abnormalities including nystagmus, disorders of saccades and pursuit, and ophthalmoparesis were recorded, and factors influencing their occurrence were examined. A total of 301 patients participated in this study, including 52 patients with SCA 1, 64 with SCA 2, 117 with SCA 3, and 68 with SCA 6. Although no specific ocular motor abnormality was pathognomonic to any SCA, significant differences were noted in their occurrence among different disorders. SCA 6 was characterized by frequent occurrence of nystagmus and abnormal pursuit and rarity of slow saccades and ophthalmoparesis and SCA 2 by the frequent occurrence of slow saccades and infrequent nystagmus and dysmetric saccades. SCA 1 and SCA 3 subjects had a more even distribution of eye movement abnormalities. Prospective data from a large cohort of patients with SCAs 1, 2, 3, and 6 provide statistical validation that the SCAs exhibit distinct eye movement abnormalities that are useful in identifying the genotypes. Many of the abnormalities correlate with greater disease severity measures.

Domains and correlates of clinical balance impairment associated with Huntington's disease

This study sought to (a) determine the domains of clinical balance impairments associated with Huntington's disease (HD), and (b) evaluate associations between balance test scores and other disease-related impairments. Eighteen subjects with genetically definite HD and 17 age-matched control subjects were evaluated on the Mini-BESTest for their clinical balance impairments as well as the Unified HD Rating Scale (UHDRS) motor and total functional capacity scales, Activity-Specific Balance Confidence (ABC) Scale-short form, Montreal Cognitive Assessment (MoCA), and Symbol Digit Modalities Test (SDMT). Results showed that subjects with HD exhibited significantly lower total Mini-BESTest scores than subjects without HD (mean (95% CI)=76 (64–87)% with HD, 98 (96–99)% without HD; p=0.0011). Mini-BESTest item scores were significantly lower for subjects with HD on one-leg stance, postural responses, standing with eyes closed on foam, and dual-task timed up-and-go. Mini-BESTest scores significantly correlated with UHDRS motor (r2=0.68; p=0.00003) and total functional capacity (r2=0.75; p=0.000006) scores as well as with scores on the ABC short form (r2=0.45; p=0.0024), SDMT (r2=0.42; p=0.0036), and MoCA (r2=0.23; p=0.046) assessments. This study, therefore, demonstrates that balance impairments associated with HD span domains of anticipatory postural adjustments, postural responses, stance in challenging sensory conditions, and gait. Although preliminary, clinical balance impairment appears to be an efficient proxy evaluation of multiple HD-related factors due to associations with functional capacity, other motor impairments, balance confidence, and cognitive abilities.

Substantia nigra hyperechogenicity in hypokinetic Huntington's disease patients.

Substantia nigra (SN) hyperechogenicity can be detected by transcranial sonography (TCS) to assist the early diagnosis of idiopathic Parkinson's disease (IPD). This study prospectively investigated whether SN hyperechogenicity is also present in Huntington's disease (HD) patients with symptoms of hypokinesia and/or rigidity. All patients recruited to the study (n = 15) were characterised by hypokinesia and/or rigidity while nine of these patients also displayed chorea and/or dystonia. The control group included 15 individuals. Clinical examination was documented using the Unified Huntington's Disease Rating Scale (UHDRS). TCS examination revealed SN hyperechogenicity in 14/15 (93.3 %) patients (9/14 unilateral, 5/14 bilateral). Hyperechogenicity of the caudate and lentiform nuclei (CN, LN) was less frequent (CN: 80 % total, LN: 53.3 % total). This is the first study to assess SN hyperechogenicity in hypokinetic HD patients. Assuming that the primary sites of pathology in IPD and HD are the SN and the striatum, respectively, our observations suggest a functional impairment of the nigrostriatal system in HD, an effect that is potentially independent of the primarily-affected basal ganglia nucleus.

Relationship between Nutritional Status and the Severity of Huntington's Disease. A Spanish Multicenter Dietary Intake Study

Little is known about the impact of nutrition status on Huntington’s disease (HD) severity. To analyze the association of nutritional factors with HD severity. Observational, cross-sectional, national multicenter study. Participants were selected from a Spanish cohort of patients who participate in the European Huntington Disease Network (EHDN). The frequency of food consumption, caloric and nutrients intake in patients with HD were assessed using validated questionnaires for the Spanish population, and calculated using Alimentaci´on and Salud, version 2.0, and the Spanish Dietary Recommended Intakes were used as the gold standard. Disease severity was assessed using the Unified HD Rating Scale (UHDRS) and Total Functional Capacity (TFC). Logistic regression models were performed using the TFC as the dependent variable, and the macro-micronutrients as the independent variables, adjusted for age, gender, education, physical activity, and intake of supplements. Two hundred and twenty four patients with HD were included (59% women), mean age of 47.41±14.26 years, median TFC 9 (3–13), median UHDRS motor score of 33.5 (3.75–56), 75.8% with normal-high caloric intake, 55.4% normal BMI, and 54.4% with medium-high adherence to the Mediterranean diet. Compared to patients with mild-moderate HD, patients with severe HD had higher caloric intake (p = 0.02), and similar BMI (p = 0.33). Advanced HD was associated with higher intake of water-soluble vitamins (OR = 2.08; 95% CI = 1.12–3.85, p = 0.02), and minerals (OR = 1.86; 95% CI = 1.09– 3.19, p = 0.02). An adequate dietary intake prevents against weight loss in patients with advanced HD, but it is not associated with better functional state.

Modelling the natural history of Huntington's disease progression

BackgroundThe lack of reliable biomarkers to track disease progression is a major problem in clinical research of chronic neurological disorders. Using Huntington's disease (HD) as an example, we describe a...

Impact of tetrabenazine on gait and functional mobility in individuals with Huntington's disease

Chorea may contribute to balance problems and walking difficulties that lead to higher fall rates in individuals with Huntington's disease (HD). Few studies have examined the effects of tetrabenazine (TBZ), an anti-choreic drug, on function and mobility in HD. The purpose of this study was to compare: 1) gait measures in forward walking, 2) balance and mobility measures, and 3) hand and forearm function measures on and off TBZ. We hypothesized that use of TBZ would improve gait, transfers and hand and forearm function. Eleven individuals with HD on stable doses of TBZ were evaluated while off medication and again following resumption of medication. Significant improvements were found on the Unified Huntington's Disease Rating Scale (UHDRS) motor scores, Tinetti Mobility Test (TMT) total (t=4.20, p=0.002) and balance subscale (t=−4.61, p=0.001) scores, and the Five Times Sit-to-Stand test (5TSST, t=3.20, p=.009) when on-TBZ compared to off-TBZ. Spatiotemporal gait measures, the Six Condition Romberg test, and UHDRS hand and forearm function items were not changed by TBZ use. Improved TMT and 5TSST performance when on drug indicates that TBZ use may improve balance and functional mobility in individuals with HD.

J23 Evaluation of Validity of UHDRS Translations in the Registry Study

Background The REGISTRY study was designed to obtain natural history data on a wide spectrum of HD patients in Europe over the course of 15 years. Several scales were administered to characterise and evaluate HD patients’ progression, which included the Unified Huntington’s Disease Rating Scale (UHDRS). Aims The aim of this study was to evaluate the validity of translations of UHDRS to German, French, Italian, Dutch, Polish, Portuguese and Spanish as applied in the REGISTRY study. Methods/techniques This study was submitted to European Huntington’s Disease Network Scientific Bio-ethics Assessment Committee for authorisation and access to the REGISTRY data. Data was provided with baseline and follow up evaluations, by country and site. The analysis was performed for translated versions of the UHDRS if a minimum of 100 cases were observed per language and limited to HD gene expansion carriers with manifest disease. Statistical analysis included Cronbach’s alpha and Confirmatory Factorial Analysis (CFA) trough SPSS and R software. Results/outcome A total of 6.009 manifest HD patients were analysed from 8 different languages (English was used as a control language), 53% female with a mean age of 48.2 years (SD 13.8), age-at-onset of 45 years (SD 12.3) and a CAG of 44.3 (SD 4.9). Cronbach’s alpha results showed a high internal consistency in each of the four components of the UHDRS for all translated languages. Regardless the language assessed, CFA analysis demonstrated that motor items of dystonia, chorea and arms rigidity, and most of the behavioural items are not well explained by their respective latent component, with loadings below 0.7. Conclusions Results demonstrate that the translation process used in the REGISTRY did not affect UHDRS structure and basic clinemetrics indices across the different languages. However, this analysis revealed structural issues concerning UHDRS and its latent dimensions which require further evaluation.

N06 Rasagiline For The Treatment Of Parkinsonism In Huntington's Disease

Background Parkinsonism is a common and invalidating feature of Huntington’s disease (HD) that results difficult to manage since levodopa and/or dopaminergic agonists may exacerbate chorea and psychiatric symptoms. Methods Two patients exhibiting a rigid-akinetic form of HD, -with apathetic symptoms and slight depression in patient A and major depression in patient B were treated with Rasagiline (a monoaminoxidasa-B inhibitor used in Parkinson’s disease) 1mg/day. Motor function, cognition and affect were explored through the Unified Huntington Disease Rating Scale (UHDRS), neuropsychological assessment, the Hospital Anxiety and Depression Scale and the Starkstein’s Apathy Scale. Results One month after initiation of Rasagiline, motor function improved on rigidity/bradykinesia (measured with finger taps, pronate supinate-hands, bradykiensia-body and rigidity items). Patient A improved nine points (Initial UHDRS = 33, final 24) and patient B ten (Initial UHDRS = 24, final 14). No worsening on chorea neither in other items was seen. Significant amelioration of apathy and depression was also evidenced in both cases. In Patient A, apathy score decreased from 18 to 12 points and from 12 to 7 for depression. In patient B, apathy decreased from 22 to 13, while depression from 14 to 6. The Global impression of change was rated by the patients up to 70% of improvement in both cases. Neurologist rated up to 50% for patient A and 70% for patient B. Both remained stable after 3-month follow-up. Conclusions In our reported cases of HD, rasagiline appeared effective to treat parkinsonism. Future studies are needed to clarify the potential usefulness of Rasagiline for the management of HD.

H15 Prevalence And Phenomenology Of Psychotic Symptoms In Huntington's Disease

Introduction Neuropsychiatric features are characteristic symptoms in Huntington’s disease (HD). Compelling evidence proved high prevalence of alterations on mood and affect. However, little is known about psychotic symptoms in HD. Objective Describe the characteristics and phenomenology of psychotic symptoms in a Spanish cohort of Huntington’s disease patients. Methods From the Spanish Registry cohort, genetically positive patients with psychiatric, cognitive and motor assessment were included. We analysed demographic, genetic and clinical data. Cognitive and motor functions were measured with Unified Huntington Disease Rating Scale (UHDRS), psychiatric disturbances with the Problem Behaviour Assessment Scale (PBA-s) and function with the total functional capacity (TFC). Results 264 patients were included (46.2% males; mean age of 45.2 ± 12.5y; disease duration 5.5 ± 5.5y and mean CAG 44.1 ± 4.7). Delusions were present in the 10.2% of the patients and hallucinations in 4.5%. Visual hallucinations were the more frequent 3.4% followed by auditory 1.9%. UHDRS cognitive score (p = 0.05) and TFC (p = 0.01) were more impaired in patients with psychotic symptoms. No other differences or correlations between delusions/hallucinations and cognitive, motor or functional scores were found. Formal diagnosis of schizoaffective disorder was present in two patients, previous acute psychotic episode in one, dementia in one and young HD in one. Conclusions Psychotic symptoms are infrequent in HD. Delusions are more frequent than hallucinations being the visual ones the more recurrent. Despite not found correlation, patients presenting psychosis/hallucinations are significantly more impaired on cognition and functional capacity.

J40 The Relationship Between Macro- And Micronutrients Intake With Huntington's Disease Severity

Background Weight loss is common among patients with Huntington’s disease (HD), although the mechanisms contributing to this phenomenon are not well known. Objective To analyse the relationship between dietary intake and HD severity. Methods National, multicenter, observational, cross-sectional study (EHDN). The frequency of food consuming, caloric and nutrients intake at an individual, and population level in pre-symptomatic and symptomatic patients with HD were assessed using validated questionnaires for the Spanish population, and the Spanish Dietary Recommended Intakes (SDRI). In addition, nutritional state was estimated by the body mass index (BMI), disease severity using the Unified HD Rating Scale (UHDRS), psychiatric status (PBA-s), dysphagia (EAT-10), caregiver burden (summacare), comorbidities (CIRS-G), and quality of life (SF-36 questionnaire). Results Two hundred and twenty four patients with HD were included (59% women) with a mean age of 47.41 ± 14.26, median Total Functional Capacity (TFC) 9 (13–3), and median UHDRS motor score 33.5 (56–3.75). In this population, 55% had moderate-high adherence to the Mediterranean diet, 24% had low caloric intake, 6,7% were underweight, 55.4% had normal weight; 37.9% were overweight-obese, 22% were on vitamins/supplements (VS) and 2% PEG. The use of antidopaminergic was associated with normal BMi (p = 0.02), and patients on VS had lower comorbidities (p = 0.03). Both, high and low functional capacity (TFC score > and Conclusions In this study, conducted in the Spanish HD population, patients9 dietary intake was mostly associated with normal weight and normal nutritional intake. Longitudinal studies are warranted to evaluate the efficacy of supplementary dietary intakes to prevent HD related comorbidities.

N02 Safety And Tolerability Of Selisistat For The Treatment Of Huntington's Disease: Results From A Randomised, Double-blind, Placebo-controlled Phase Ii Trial

Background Selisistat is a first-in-class SirT1 inhibitor shown to be safe and well tolerated in healthy volunteers and HD patients in short-term studies. Objective To evaluate safety and tolerability of selisistat over 12 weeks in patients with Huntington’s disease (HD). Design/methods This was a double-blind, placebo-controlled, international multi-centre study of selisistat in individuals with Stage I-III HD. Participants (30–70 yrs) with genetically confirmed HD, a Unified Huntington Disease Rating Scale (UHDRS) Total Motor Score of ≥ 5 and a Total Functional Capacity ≥ 5 were randomised (1:1:1) to selisistat 50 or 200 mg or placebo once daily for 12 weeks. Safety and tolerability were evaluated by monitoring adverse events, vital signs, ECG and laboratory safety data throughout the study. Blood sampling for pharmacokinetics and soluble mutant huntingtin levels were collected throughout. Results/outcome A total of 144 patients were randomised and 125 patients (87%) completed the study. There were 9 serious adverse events, three in each treatment group, including one death in the placebo group. The most common adverse events were reversible increases in liver function tests without accompanying increases in bilirubin. All of these occurred in the selisistat groups; while most of these increases were Conclusions Apart from increases in liver function tests in a subset of patients, selisistat was safe and well tolerated, and a trend for modulation of the levels of soluble mutant huntingtin was observed. Acknowledgement Supported by Siena Biotech SpA.

H13 Apathy Is Underecognised By Patients With Huntington's Disease

Background Although apathy can be disabling in Huntington’s disease (HD) and seems to increase with disease progression, most patients, in contrast with their caregivers, do not complain about it. Objective 1) To assess the presence and severity of apathy in patients with HD using a structured interview for patients and their caregivers. 2) To correlate the severity of apathy with disease duration, the presence of mood alterations and motor, cognitive and functional impairment. Methods 30 subjects (16M/14F; 6 presymptomatic carriers, 24 patiens with early-intermediated HD) and 26 caregivers participated in the study after informed consent was obtained. 1) Demographic data from patients were recruited. 2) Apathy was assessed using the Lille apathy rating scale (LARS), which was administered to patients and their caregivers separately. 3) The Unified Huntington Disease Rating Scale (UHDRS) was used for motor, cognitive, functional and behavioural assessment. 4) Other assessments: Mattis Dementia Rating Scale, Hospital Anxiety and Depression Scale (HADS) and the SF-36 health survey. Results LARS scores obtained from the patients differed from their caregivers. Abnormal scores were found in 4 presymptomatic patients. The scores obtained from their caregivers led to classify apathy as severe in 16 patients. We found that apathy correlated to disease duration and motor, cognitive and functional impairment, but not to depression. Conclusions Apathy is frequent and severe in most HD patients and can be even present in presymptomatic cases. The severity of apathy increases with disease progression. The discordant scores between patients and their caregivers suggest the presence of low disease awareness in patients and reinforce the role of caregivers in the assessment of many clinical aspects of the disease.

K13 First Middle Eastern Focus On Research And Assistance On Huntington Disease In Oman

<h3>Background</h3> Huntington disease (HD) was sporadically described in the Arabic population, so far. Since Arabic people frequently marry within the same family, the mutation risk is reiterating in offspring. In Oman, only few and anecdotal reports, are known. <h3>Aims</h3> To set a HD Centre in the Middle East. <h3>Methods</h3> A Neurogenetic Centre with outpatient and molecular diagnostic services focused on HD, was inaugurated by Ministry of Health at Royal Hospital, Oman, in November 2013. We analysed clinical, genetic and demographic features of affected and at risk subjects from a large and inbred family from Muscat and surroundings. <h3>Results</h3> In this six generations family we have visited 23 alive symptomatic subjects of 42 reported by genealogical retrospective analysis. We counted about 84, 50% and 86, 25%, at risk individuals. We found 18 people with a theoretical risk &gt;50%, due to intermarriages and four with a risk of homozygousity for CAG mutation. DNA testing was provided, after informed consent, with the support of genetic counselling, and clinical data were collected by the Unified HD Rating Scale. Age at onset ranged between 2 and 79 years, (CAG)n between 39 (oldest onset) and over 80 (earliest onset) repeats. By careful interview of family members, we deduced that the ancestor carrying the HD mutation to Oman immigrated from Tanzania, Africa. <h3>Conclusions</h3> Our collaborative effort aims to improve medical assistance and social awareness on HD and related diseases in Middle East. Accordingly, we have now contributed to set the first HD family association in Middle East (www.hdom.org), in strict collaboration with Italian LIRH (www.lirh.it).