Huntington’s disease from the patient, caregiver and physician’s perspectives : three sides of the same coin?

The aim of this study was to identify determinants of functional disability, patient’s quality of life (QoL) and caregivers’ burden in Huntington’s disease (HD). Eighty HD patients participated in the study. Motor and behavioral disturbances as well as cognitive impairment were assessed using motor, behavioral and cognitive parts of the Unified Huntington Disease Rating Scale (UHDRS); Hamilton Depression Rating Scale was used to assess depression. Disability, health-related QoL and the impact of the disease on the caregivers were assessed using the following methods: UHDRS Functional Assessment Score, SF-36 Scale and Caregiver Burden Inventory. Multiple regression analysis showed that motor disturbances, cognitive impairment, apathy and disease duration were the independent predictors of disability. Depression and cognitive disturbances were the determinants of patient’s QoL, while motor disturbances and depression were the predictors of the caregiver burden. Patient’s disability and QoL as well as caregivers’ burden should be taken into consideration while planning treatment strategy and the results of the present study show that the predictors of those treatment targets are different

The effects of physiotherapy with PNF concept on gait and balance of patients with Huntington's disease : pilot study

Background and purpose Huntington's disease (HD) is a neurodegenerative, progressive disorder of the central nervous system which causes significant gait and balance disturbances. This is a pilot study which aims to determine the effects of a physiotherapy programme with use of Proprioceptive Neuromuscular Facilitation (PNF) on gait and balance in HD patients. Material and methods 30 HD patients aged 21-60 with genetically confirmed diagnosis participated in the study. Participants followed a 3-week-long PNF-based physiotherapy programme. Gait and balance were evaluated twice in each participant: first at baseline and then after the course of physiotherapy. The following methods were used for gait disturbances: Tinetti Gait Assessment Tool, Up and Go Test, Timed Walking Tests for 10m and 20m (TWT10m, TWT20m). Balance was assessed with use of Berg Balance Scale, Pastor Test and Functional Reach Test. Results There was a significant improvement in all measures of balance and gait. Conclusion PNF-based physiotherapy is effective and safe in HD patients

The effects of physiotherapy with PNF concept on gait and balance of patients with Huntington's disease – pilot study

Background and purpose Huntington's disease (HD) is a neurodegenerative, progressive disorder of the central nervous system which causes significant gait and balance disturbances. This is a pilot study which aims to determine the effects of a physiotherapy programme with use of Proprioceptive Neuromuscular Facilitation (PNF) on gait and balance in HD patients. Material and methods 30 HD patients aged 21–60 with genetically confirmed diagnosis participated in the study. Participants followed a 3-week-long PNF-based physiotherapy programme. Gait and balance were evaluated twice in each participant: first at baseline and then after the course of physiotherapy. The following methods were used for gait disturbances: Tinetti Gait Assessment Tool, Up and Go Test, Timed Walking Tests for 10m and 20m (TWT10m, TWT20m). Balance was assessed with use of Berg Balance Scale, Pastor Test and Functional Reach Test. Results There was a significant improvement in all measures of balance and gait. Conclusion PNF-based physiotherapy is effective and safe in HD patients

The influence of motor ability rehabilitation on temporal-spatial parameters of gait in Huntington's disease patients on the basis of a three-dimensional motion analysis system: An experimental trial

Objective There is no existing standard, evidence-based, scientific model for motor ability improvement in Huntington's Disease (HD) patients aimed at maintaining independent gait for as long as possible, or performing activities of daily living, the effectiveness of which would be supported by the results of studies using objective research tools. Under these circumstances, the aim of this study was to analyze the influence of motor ability rehabilitation on the spatial-temporal parameters of gait in HD patients. Design It was an experimental trial. The studied group consisted of 30 patients (17 women and 13 men) with HD. In hospital conditions, the patients participated in the 3-week motor ability l rehabilitation programme tailored to individual needs. The study group was tested using the Vicon 250 three-dimensional gait analysis system before and after the physical exercise programme. Results Walking speed after therapy increased for the left lower limb from 1.06 (SD 0.24) [m/s] to 1.21 (SD 0.23) [m/s], and for the right lower limb from 1.07 (SD 0.25) [m/s] to 1.20 (SD 0.25) [m/s]. The cycle length increased after the applied therapy for the left lower limb from 1.17 (SD 0.20) [m] to 1.23 (SD 0.19) [m]. Conclusion The three-week motor ability rehabilitation programme positively influences spatial-temporal gait parameters in HD patients

Przyczyny i konsekwencje upadków w chorobie Parkinsona – badanie prospektywne

Background and purpose Falls are common events in Parkinson disease (PD) but only a few prospective studies have focused on causes and consequences of falls in PD patients. The aim of the study was prospective analysis of direct causes and consequences of falls in PD patients in comparison to the control group. Material and methods One hundred PD patients and 55 age-matched controls were enrolled in the study. The diagnostic workup in all patients included neurological examination, Unified Parkinson's Disease Rating Scale, magnetic resonance imaging, electroencephalography, ultrasonography, otolaryngological, ophthalmological and autonomic function examination. During 12 months of follow-up, falls were registered in both groups, direct causes were classified according to the St. Louis and Olanow classification, and consequences were established. Results Falls occurred in 54% of PD patients and in 18% of control subjects. Analysis of direct causes of falls revealed that sudden falls were the most common (31%), followed by episodes of freezing and festination (19.6%), neurological and sensory disturbances (mostly vertigo) (12%), environmental factors (12%), postural instability (11%), orthostatic hypotension (4%), and severe dyskinesia (3.6%); 6.19% of falls were unclassified; 22% of patients had the same etiology of subsequent falls. In PD patients, intrinsic factors were dominant, whereas in the control group intrinsic and extrinsic factors occurred with the same frequency. Every third fall intensified fear of walking. 34% of falls caused injuries; among them bruises of body parts other than the head were most frequent. Conclusions Intrinsic factors are the most common causes of falls in PD. Every third fall intensifies fear of walking and causes injuries.Wstęp i cel pracy Upadki są częstymi objawami choroby Parkinsona (ChP). Dotychczas jednak tylko w kilku badaniach oceniano przyczyny i konsekwencje upadków w ChP. Celem badania była prospektywna analiza przyczyn bezpośrednich oraz konsekwencji upadków u pacjentów z ChP w porównaniu z grupą kontrolną. Materiał i metody Do badania zostało włączonych 100 chorych na ChP oraz 55 dobranych pod względem wieku osób z grupy kontrolnej. U wszystkich chorych przeprowadzono badanie neurologiczne, ocenę za pomocą Unified Parkinson's Disease Rating Scale, badanie za pomocą rezonansu magnetycznego, elektroencefalografię i ultrasonografię, badanie otolaryngologiczne i okulistyczne oraz badanie czynności autonomicznych. Podczas 12-miesięcznej obserwacji upadki rejestrowano w obu badanych grupach. Przyczyny bezpośrednie upadków podzielono zgodnie z klasyfikacją St. Louis i Olanowa, określano także konsekwencje upadków. Wyniki Upadki wystąpiły u 54% chorych na ChP i 18% osób z grupy kontrolnej. Najczęstsze były upadki nagłe (31%), następnie epizody zamrożeń i dreptania (19,6%), zaburzenia neurologiczne i czuciowe (zawroty głowy) (12%), czynniki zewnętrzne (12%), niestabilność postawy (11%), niedociśnienie ortostatyczne (4%), nasilone dyskinezy (3,6%). Upadki niesklasyfikowane stanowiły 6,19%. U 22% chorych etiologia kolejnych upadków była jednakowa. U chorych na ChP dominowały czynniki wewnętrzne, a w grupie kontrolnej częstości czynników wewnętrznych i zewnętrznych były podobne. Co trzeci upadek nasilał lęk przed chodzeniem, 34% upadków powodowało obrażenia, najczęściej sduczenia. Wnioski Czynniki wewnętrzne są najczęstszymi przyczynami upadków w ChP. Co trzeci upadek nasila lęk przed chodzeniem oraz powoduje obrażenia

Causes and consequences of falls in Parkinson disease patients in a prospective study

Background and purpose: Falls are common events in Parkinson disease (PD) but only a few prospective studies have focused on causes and consequences of falls in PD patients. The aim of the study was prospective analysis of direct causes and consequences of falls in PD patients in comparison to the control group. Material and methods: One hundred PD patients and 55 age-matched controls were enrolled in the study. The diagnostic workup in all patients included neurological examination, Unified Parkinson’s Disease Rating Scale, magnetic resonance imaging, electroencephalography, ultrasonography, otolaryngological, ophthalmological and autonomic function examination. During 12 months of follow-up, falls were registered in both groups, direct causes were classified according to the St. Louis and Olanow classification, and consequences were established. Results: Falls occurred in 54% of PD patients and in 18% of control subjects. Analysis of direct causes of falls revealed that sudden falls were the most common (31%), followed by episodes of freezing and festination (19.6%), neurological and sensory disturbances (mostly vertigo) (12%), environmental factors (12%), postural instability (11%), orthostatic hypotension (4%), and severe dyskinesia (3.6%); 6.19% of falls were unclassified; 22% of patients had the same etiology of subsequent falls. In PD patients, intrinsic factors were dominant, whereas in the control group intrinsic and extrinsic factors occurred with the same frequency. Every third fall intensified fear of walking. 34% of falls caused injuries; among them bruises of body parts other than the head were most frequent. Conclusions: Intrinsic factors are the most common causes of falls in PD. Every third fall intensifies fear of walking and causes injuries

Identification of genetic variants associated with Huntington's disease progression: a genome-wide association study

Background Huntington's disease is caused by a CAG repeat expansion in the huntingtin gene, HTT. Age at onset has been used as a quantitative phenotype in genetic analysis looking for Huntington's disease modifiers, but is hard to define and not always available. Therefore, we aimed to generate a novel measure of disease progression and to identify genetic markers associated with this progression measure. Methods We generated a progression score on the basis of principal component analysis of prospectively acquired longitudinal changes in motor, cognitive, and imaging measures in the 218 indivduals in the TRACK-HD cohort of Huntington's disease gene mutation carriers (data collected 2008–11). We generated a parallel progression score using data from 1773 previously genotyped participants from the European Huntington's Disease Network REGISTRY study of Huntington's disease mutation carriers (data collected 2003–13). We did a genome-wide association analyses in terms of progression for 216 TRACK-HD participants and 1773 REGISTRY participants, then a meta-analysis of these results was undertaken. Findings Longitudinal motor, cognitive, and imaging scores were correlated with each other in TRACK-HD participants, justifying use of a single, cross-domain measure of disease progression in both studies. The TRACK-HD and REGISTRY progression measures were correlated with each other (r=0·674), and with age at onset (TRACK-HD, r=0·315; REGISTRY, r=0·234). The meta-analysis of progression in TRACK-HD and REGISTRY gave a genome-wide significant signal (p=1·12 × 10−10) on chromosome 5 spanning three genes: MSH3, DHFR, and MTRNR2L2. The genes in this locus were associated with progression in TRACK-HD (MSH3 p=2·94 × 10−8 DHFR p=8·37 × 10−7 MTRNR2L2 p=2·15 × 10−9) and to a lesser extent in REGISTRY (MSH3 p=9·36 × 10−4 DHFR p=8·45 × 10−4 MTRNR2L2 p=1·20 × 10−3). The lead single nucleotide polymorphism (SNP) in TRACK-HD (rs557874766) was genome-wide significant in the meta-analysis (p=1·58 × 10−8), and encodes an aminoacid change (Pro67Ala) in MSH3. In TRACK-HD, each copy of the minor allele at this SNP was associated with a 0·4 units per year (95% CI 0·16–0·66) reduction in the rate of change of the Unified Huntington's Disease Rating Scale (UHDRS) Total Motor Score, and a reduction of 0·12 units per year (95% CI 0·06–0·18) in the rate of change of UHDRS Total Functional Capacity score. These associations remained significant after adjusting for age of onset. Interpretation The multidomain progression measure in TRACK-HD was associated with a functional variant that was genome-wide significant in our meta-analysis. The association in only 216 participants implies that the progression measure is a sensitive reflection of disease burden, that the effect size at this locus is large, or both. Knockout of Msh3 reduces somatic expansion in Huntington's disease mouse models, suggesting this mechanism as an area for future therapeutic investigation

Żółtakowatość mózgowo-ścięgnista : rzadka przyczyna zespołu rdzeniowo-móżdżkowego

A 34-year-old patient demonstrating pyramidal and cerebellar signs, accompanied by epilepsy, peripheral neuropathy, mental retardation and bilateral cataract was diagnosed with cerebrotendinous xanthomatosis based on the clinical picture, magnetic resonance imaging of the brain and serum sterol analysis. Tendon xanthomas were not observed in this case. After establishing the diagnosis, treatment with chenodeoxycholic acid and statin was introduced. During the next two years of the follow-up, serum cholestanol and 7α-hydroxycholesterol levels decreased in response to the therapy, but this was not reflected in the patient's neurological condition, which was slowly progressing. Treatment effectiveness in cerebrotendinous xanthomatosis is variable, notably better in patients who had started therapy before the injury to the nervous system took place. The present case report points to cerebrotendinous xanthomatosis as a rare cause of spinocerebellar syndrome, which might be treatable if diagnosed in early life

Żółtakowatość mózgowo-ścięgnista: rzadka przyczyna zespołu rdzeniowo-móżdżkowego

A 34-year-old patient demonstrating pyramidal and cerebellar signs, accompanied by epilepsy, peripheral neuropathy, mental retardation and bilateral cataract was diagnosed with cerebrotendinous xanthomatosis based on the clinical picture, magnetic resonance imaging of the brain and serum sterol analysis. Tendon xanthomas were not observed in this case. After establishing the diagnosis, treatment with chenodeoxycholic acid and statin was introduced. During the next two years of the follow-up, serum cholestanol and 7α-hydroxycholesterol levels decreased in response to the therapy, but this was not reflected in the patient's neurological condition, which was slowly progressing. Treatment effectiveness in cerebrotendinous xanthomatosis is variable, notably better in patients who had started therapy before the injury to the nervous system took place. The present case report points to cerebrotendinous xanthomatosis as a rare cause of spinocerebellar syndrome, which might be treatable if diagnosed in early life.U 34-letniego chorego z objawami piramidowymi i móżdżkowymi, padaczką, neuropatią obwodową, upośledzeniem umysłowym oraz obustronną zaćmą na podstawie obrazu klinicznego, badania rezonansu magnetycznego mózgu i oznaczenia stężenia steroli w surowicy rozpoznano żółtakowatość mózgowo-ścięgnistą. Nie obserwowano u tego chorego żółtaków ścięgien. Do leczenia włączono kwas chenodeoksycholowy oraz statynę. Chociaż podczas kolejnych dwóch lat obserwacji stwierdzono zmniejszenie stężenia cholestanolu i 7α-hydroksycholesterolu w surowicy chorego w odpowiedzi na leczenie, jego stan neurologiczny stopniowo się pogarszał. Odpowiedź na leczenie żółtakowatości mózgowo-ścięgnistej jest zróżnicowana; lepsza u chorych, u których leczenie rozpoczęto, zanim wystąpiły zmiany w ośrodkowym układzie nerwowym. Przedstawiany opis przypadku zwraca uwagę na żółtakowatość mózgowo-ścięgnistą jako rzadką przyczynę zespołu rdzeniowo-móżdżkowego, który mógłby być uleczalny, jeśli zostałby rozpoznany na wczesnym etapie życia